bluuebunny/crossref_metadata_2025 huggingface dataset:
P624 Long-term effectiveness of anti-TNF therapy in pediatric-onset inflammatory bowel diseases: a population-based study
Authors: Fumery M , Savoye G , Ley D , Dupont C , Bertrand V , Spyckerelle C , Guillon N , Desreumaux P , Gower-Rousseau C , Sarter H , Turck D , Leroyer A
Published: January 2022

Background

Anti-TNFs antibodies are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD.

Methods

All patients diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in a population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNFs, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model.

Results

Among a total of 1007 patients with CD (median disease duration, 3.2 years IQR (1.2–7.6) and median follow-up 8.8 years (IQR, 4.6–14.2)) and 337 patients with UC (median disease duration, 2.5 years IQR [1.1–4.5] and median follow-up 7.2 years (IQR, 3.8–13.0)), respectively 481 (48%) and 81 (24%) were treated with anti-TNFs. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1–20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0–59.9). In CD, the probability of failure of 1st line anti-TNF therapy at

1, 3 and 5 years was respectively 29.3%, 47.0% and 54.6% for infliximab (n = 397) and 22.6%, 37.7% and 48.0% for adalimumab (n = 83). In UC, the probability of failure of 1st line anti-TNF therapy at 1, 3 and 5 years was respectively 37.3%, 49.0% and 61.0% for infliximab (n = 71) and 12.5% for these 3 timepoints for adalimumab (n = 10). In CD, probabilities of primary failure, loss of response and intolerance at 5 years were 10.4%, 36.7% and 6.8% (n = 480), respectively; in UC, these same probabilities were 7.5%, 39.2% and 11.3% (n = 81), respectively. Female sex (Hazard Ratio (HR) 1.43, 95% CI 1.09–1.87; p = 0.010) and intestinal resection prior anti-TNF initiation (HR 1.73, 95% CI 1.21–2.47, p = 0.003) were associated with anti-TNF failure in multivariate analysis.

Conclusion

In a population-based study of pediatric-onset IBD, approximately half of anti-TNFs users discontinue use within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC.
P625 Predictors of pancreatitis among patients with inflammatory bowel disease (IBD) treated with vedolizumab (VDZ): Observation from a large global safety database
Authors: Wernicke J , Verstak T , Zhang T , Spalding W , Lee L , Cheng Y , Ademi A
Published: January 2022

Background

Patients (pts) with IBD are at increased risk of pancreatitis. Here, we report a post-marketing safety analysis to identify predictors of pancreatitis utilising data captured during treatment with VDZ in a large Global Safety Database (GSD).

Methods

Takeda’s GSD was queried for case reports (CRs) of adverse events (AEs) following VDZ treatment, from licensure (20 May, 2014) through 31 March, 2021. Unsolicited and solicited CRs of pancreatitis were coded using the Medical Dictionary for Regulatory Activities (version 24.0) high-level term “Acute and chronic pancreatitis”. A comparator was created using data from 600 CRs of random, non-pancreatitis AEs; cases meeting the regulatory definition of serious criteria were compared with serious CRs (SAEs) of pancreatitis. Unadjusted comparisons were performed using t-tests for continuous data and Chi-square tests, Fisher’s exact tests for categorical data. Logistic regression analysis was performed to adjust for covariates that allowed backward selection. Baseline characteristics included in the model were: age, gender, indication, medical history, concomitant medications and comorbid conditions. To account for differences in pt baseline characteristics between pancreatitis and random CRs, an adjusted analysis was performed using inverse probability treatment weighting to reduce biases on estimates of average group (gp) effects. A p value below 0.05 was considered statistically significant.

Results

Over the approximate 7 years since regulatory approval of VDZ, 196 pts reported pancreatitis. A higher proportion of pts reported SAEs in the pancreatitis gp (99.5%, n=195/196) vs the random gp (32.5%, n=195/600). An unadjusted comparison between pts with SAEs showed that females (p=0.015) and Crohn’s disease (p=0.001) were more common in the random gp vs the pancreatitis gp. In the pancreatitis gp, 17 pts (8.7%) with SAEs had a known history of pancreatitis vs none in the random gp. Fourteen pts (7.2%) with SAEs had concurrent cholelithiasis in the pancreatitis gp vs none in the random gp. Results of the logistic regression analysis are shown in the Table. A number of factors, including age, VDZ indication use, the use of concomitant medications, a history of pancreatitis and several comorbid conditions strongly associated with the development of pancreatitis.

Conclusion

This retrospective analysis identified several factors associated with 196 spontaneous CRs of pancreatitis captured in our large GSD of over 700,000 patient-years of exposure to VDZ. This offers useful insights into potential predictive factors that could be important to inform clinical management of patients with IBD regarding the risk of pancreatitis, but further research to confirm these observations is warranted.
P647 Idiopathic Thrombocytopenic Purpura associated with Inflammatory Bowel Disease: a multi-centre ECCO CONFER case series
Authors: Mahajna H , Verstockt B , Bergemalm D , Castiglione F , Rodríguez-Moranta F , Vincenzo Savarino E , Hoentjen F , Bessissow T , Pokryszka J , Cremer A , Eder P , Truyens M , Yershalmy-Feler A , García M J , Kopylov U
Published: January 2022

Background

Idiopathic Thrombocytopenic Purpura (ITP) is an acquired haematological disorder with an incidence of 1 to 6 per 100.000, with reported comorbidity in patients with Inflammatory Bowel Disease (IBD). The current study aimed to evaluate the clinical presentation and outcome of ITP in IBD patients.

Methods

This multicenter retrospective case series was performed as part of the ECCO Collaborative Network of Exceptionally Rare case reports (CONFER) project. Cases of patients with ITP and IBD were collected by participating investigators. Clinical data were recorded in a standardised collection form.

Results

This report includes 20 patients with concurrent ITP and IBD: 15 were males, median age was 34 [Interquartile range (IQR) 25–56]. 12 subjects had a diagnosis of ulcerative colitis and 8 of Crohn’s disease. The diagnosis of IBD preceded the ITP diagnosis in 17 patients (median time between diagnosis was 7 years [IQR 1–14 years]). Among those, 10 patients were in IBD clinical remission at ITP diagnosis. Nine were treated with mesalamine, one with thiopurine, 4 with tumor necrosis factor-alpha (TNF) blockers, and 3 with no treatment. The mean platelet count at the presentation of ITP was 41.7±38.6 ×109/L. 6 patients had rectal bleeding, 8 had purpura, 6 had mucosal petechia, 2 had epistaxis, and 6 patients were asymptomatic. Regarding ITP treatment, 11 were treated with corticosteroids, 1 with Anti-RhD immunoglobulin, 7 with intravenous immunoglobulins (IVIG), 2 with rituximab and 2 patients eventually required splenectomy. All patients whose first presentation of ITP was rectal bleeding were treated medically with successful control of the ITP and IBD, None of them required splenectomy. 3 patients required colectomy with long-term follow-up, indicated by the IBD and not due to massive bleeding as a complication of ITP. With long-term follow-up, all patients had thrombocytes count above 50 ×109/L, and 18 were in IBD clinical remission.

Conclusion

Most ITP cases in this case series occurred after the IBD diagnosis and responded well to regular ITP treatment. The course of the ITP in the IBD patients follows a regular course, including response to medical therapy and low rates of splenectomy.
P648 Prevalence and Impact of Alcohol Consumption and Cannabis Use on Inflammatory Bowel Diseases
Authors: Martinho-Grueber M , Kapoglou I , Bravo F , Sarraj R , Benz E , Restellini S , Biedermann L , Rogler G , Vavricka S R , Schoepfer A , Maillard M , Michetti P , Brunner F , Clair C , Barry M P , Von Kaenel R , Juillerat P
Published: January 2022

Background

There is little guidance regarding the impact of alcohol and cannabis on the clinical course of inflammatory bowel disease. The aim of this study was to assess the prevalence, sociodemographic characteristics and impact of alcohol and cannabis use on the clinical course of the disease.

Methods

We performed a retrospective analysis of prospectively collected data within the Swiss Inflammatory Bowel Disease Cohort Study with yearly follow-ups and substance specific questionnaires. We analyzed the prevalence of use, profile of users at risk for addiction and the impact of alcohol and cannabis on the course of disease.

Results

We collected data of 2828 patients included between 2006 and 2018, and analyzed it according to their completion of specific surveys on alcohol and cannabis use. The prevalence of patient-reported active use was 41.3 % for alcohol and 6% for cannabis. Heavy drinkers were over-represented among retired, married smokers receiving mostly aminosalicylates and less immunosuppression. In ulcerative colitis patients, low-to-moderate drinking was associated with less extensive disease. Cannabis users were often students with ileal Crohn’s disease. A logistic regression analysis confirmed a risk of alcohol consumption in male workers > 50 years, whereas cannabis use was only associated with nicotine consumption. Female gender, retirement and being married were protective factors regarding cannabis consumption.

Conclusion

A significant proportion of patients with inflammatory bowel disease consume alcohol or cannabis. Heavy alcohol consumption is most likely in male smokers > 50 years, whereas young men with ileal disease rather use cannabis.
P655 Early life mebendazole exposure increases the risk of adult-onset ulcerative colitis: a population-based cohort study
Authors: Agrawal M , Allin K , Iversen A , Mehandru S , Colombel J F , Jess T
Published: January 2022

Background

According to the hygiene hypothesis, exposure to parasites may promote immune tolerance and protect against inflammatory bowel disease (IBD). The early life period, considered to extend from prenatal life to up to 5 years of age, is important towards immune maturation; exposures during this period are especially relevant towards IBD risk. We examined the impact of exposure to mebendazole, a broad-spectrum anthelminthic agent, during childhood and adolescence, on the risk of IBD, ulcerative colitis (UC) and Crohn’s disease (CD).

Methods

We used prospectively collected historical data of all individuals born in Denmark between 1995 and 2018 from national registers to conduct a population-based cohort study. Using the National Prescription Register, we identified mebendazole exposure at <18 years of age, as well as at <5 years of age. Using ICD8/10 codes in the cross-linked National Patient Register, we identified individuals who were subsequently diagnosed with UC or CD at <16 or ≥16 years of age. We performed adjusted Cox proportional hazards regression analyses to determine the risk of IBD, UC and CD with mebendazole exposure after adjusting for potential confounders, which included calendar period, number of siblings and half-siblings, antibiotic prescription, sex, socio-economic status, degree of urbanization and parental IBD status.

Results

Of 1,520,290 individuals in the cohort, 615,794 had childhood mebendazole exposure. 1,555 and 1,499 individuals were subsequently diagnosed with pediatric- and adult-onset IBD, respectively. On multivariable analysis, mebendazole exposure at <18 years of age did not impact pediatric- or adult-onset IBD risk (aHR 0.97, 95% CI 0.87, 1.07 and 1.08, 95% CI 0.97, 1.19, respectively) (Table). On limiting mebendazole exposure to age <5 years, while there was no association with pediatric-onset IBD (aHR 0.98, 95% CI 0.87, 1.11), adult-onset IBD risk was increased (aHR 1.17, 95% CI 1.04, 1.31). This increase in risk was driven by UC (aHR 1.32, 95% CI 1.12, 1.55), but not CD (1.03, 95% CI 0.87,1.22) (Figure)

Table: Crude and adjusted estimates for outcome with exposure to mebendazole in early life (<5 years of age)

Figure: Cumulative incidence curves for (a) ulcerative colitis and (b) Crohn’s disease

Conclusion

Early life, but not later in childhood or adolescence, mebendazole exposure is associated with increase in the risk of adult-onset UC. Mebendazole exposure does not impact pediatric-onset IBD risk or CD risk. These findings emphasize the importance of early-life exposures in shaping the risk of IBD later in life, may indicate differences between UC and CD risk factors and pathways, and may call for re-evaluation of risks and benefits of large-scale helminth eradication programs.
P674 Predictors of response to biologics in Crohn’s Diseases: A population-based study from the epi-IIRN
Authors: Atia O , Lujan R , Greenfeld S , Kariv R , Matz E , Dotan I , Nevo D , Turner D
Published: January 2022

Background

Approximately one third of patients with inflammatory bowel disease (IBD) fail to response to anti TNF drugs, and another 25–50% loses response within one year. Identifying prognostic factors of therapeutic failure, may facilitate balancing the risks and benefits of this therapy. In this population-based study, we aimed to explore predictors of therapeutic failure of biologics in Crohn’s disease (CD).

Methods

We retrieved data from two of four Health Maintenance Organizations in Israel, covering 38% of the population as part of the validated epi-IIRN IBD cohort. We included an inception cohort of CD patients, diagnosed since 2005 who were commenced on biologics. Those who underwent CD-related surgery within 90 days from diagnosis were excluded. The primary outcome was therapeutic failure (i.e. discontinuation of treatment or need for surgery or >1 short steroid courses). The secondary outcome was primary non-response (PNR; i.e. therapeutic failure within 4 months of initiation). Predictors were sought through Cox proportional hazard model.

Results

A total of 2,805 patients were included (923 [33%] pediatric-onset, 1,882 [67%] adults) with a median follow-up of 7.5 years (IQR 4.4–11.5). The probability of of PNR was 11% and of therapeutic failure 29%, 52% and 62%, after one, three and five years after commencing biologics, respectively. Female sex (HR 1.2 [95%CI 1.1–1.4]), intestinal surgery prior to biologic treatment (HR 1.5 [95%CI 1.1–1.8]) and number of flares prior to biologic treatment (HR 1.1 [95%CI 1.1–1.2]) were associated with therapeutic failure. PNR was associated with intestinal surgery (HR 2.0 [95%CI 1.3–2.9]) and steroid use (HR 1.7 [95%CI 1.3–2.2]). Laboratory blood work, including CRP, ESR, albumin, hemoglobin, leukocytes and platelets, at diagnosis (HR 0.8 [95%CI 0.4–1.5]) and at initiation of biologics (HR 1.1 [95%CI 0.6–1.9]) did not predict therapeutic failure in the multivariable model.

Conclusion

Half of CD patients failed to response to biologic treatment within three years. Disease severity prior to biologic treatment, reflected by intestinal surgeries, number of flares and steroid use, predicted therapeutic failure. These results emphasize the importance of timely introduction of intensified treatment in patients at risk.
P677 Patients with Inflammatory Bowel Diseases on anti-TNF treatment have impaired antibody production after Anti-SARS-CoV-2 vaccination: Results from a Panhellenic registry
Authors: Zacharopoulou E , Orfanoudaki E , Kitsou V , Tzouvala M , Tribonias G , Mantzaris G J , Viazis N , Christidou A , Almpani F , Karmiris K , Theodoropoulou A , Tsafaridou M , Michopoulos S , Zampeli E , Papathanasiou E , Michalopoulos G , Tigkas S , Karatzas P , Laoudi E , Liatsos C , Kyriakos N , Mylonas I , Theocharis G , Koutroubakis I E , Bamias G
Published: January 2022

Background

The novel corona virus (SARS-CoV-2) outbreak was declared as a pandemic in March 2020; this prompted the need for rapid vaccine development. Currently four EMA approved vaccines exist but their efficacy and safety data on patients with Inflammatory Bowel diseases are limited.

Methods

Greek IBD patients, from 10 tertiary referral centres, who had completed the initial vaccination protocol with the available anti-COVID-19 vaccines at least two weeks before enrolment, were prospectively studied. Demographic and safety data were collected and blood samples were drawn for serum Anti-S1 IgG measurement [Euroimmun Anti-SARS-CoV-2 QuantiVac ELISA (IgG)].

Results

In total 403 IBD patients (59% Crohn’s disease, median age 45 years, 53% male) and 124 healthy controls (HC) were included (Table 1). Antibody testing was conducted after a median of 31 (IQR, 23–46) days post-vaccination. Following a full vaccination regimen, 98% of IBD patients seroconverted (anti-S1 IgG≥11 RU/ml). Administration of mRNA vaccines resulted in higher seroconversion rates and higher antibody titers than viral vector ones (98.6% vs 93.6%, P=0.02 and 111.2 RU/ml vs 76 RU/ml, P<0.0001, respectively). In total, IBD patients had lower anti-S1 levels than HC (RU/ml 108 vs 133 RU/ml, P=0.00009). IBD patients without immunosuppression had higher antibody titers than immunocompromised patients (P=0.012). In univariable analysis, older age, longer time since vaccination, and treatment with corticosteroids, immunomodulators, anti-TNFα or combination therapy were associated with lower anti-S1 titers. In contrast, higher anti-S1 levels were detected in patients on vedolizumab monotherapy or non-immunosuppressive treatment. In multivariable analysis, only age, time since vaccination, and anti-TNFα therapy remained significant (P=0.011, P=0.002, and P=0.013 respectively). Treatment with vedolizumab monotherapy was associated with higher antibody levels than anti-TNFα or ustekinumab monotherapy (P=0.023 and P=0.032). Patients with prior COVID-19 infection showed numerically higher levels of Abs. All vaccines were safe in IBD patients.

Conclusion

Patients with IBD have high seroconversion rates to anti-SARS-CoV-2 vaccines, with mRNA vaccines being more efficacious. However, IBD patients have impaired response to vaccination comparing to HC. Lower antibody responses were observed in patients who received viral vector vaccines, in older patients, and in those on anti-TNFα treatment. It is important to consider booster vaccination in those low-response groups.
P683 Discontinuation of infliximab treatment: a comparison between IBD patients who retransitioned to originator and those who remained on biosimilar
Authors: Meijboom R , Gardarsdottir H , Becker M , Movig K , Egberts T , Giezen T
Published: January 2022

Background

Since the introduction of infliximab biosimilars, many patients with inflammatory bowel disease (IBD) transitioned from originator (Remicade) to an infliximab biosimilar, mainly for cost containment. Studies showed that, despite proven biosimilarity, 2 to 16.5% of patients who transition to biosimilar, retransition to infliximab originator (stopped biosimilar and re-initiated originator), mainly due to increased disease activity or (subjective) adverse events. It is unclear whether this unsatisfactory treatment response is related to the product or to the patient and his/her disease.

This study aimed to compare the risk of infliximab treatment discontinuation between patients who retransitioned from infliximab biosimilar to originator and patients who remained on infliximab biosimilar.

Methods

IBD patients treated at the Medisch Spectrum Twente or Spaarne Gasthuis who transitioned from Remicade to an infliximab biosimilar between January 2015 and September 2019 were eligible for inclusion. Patients who retransitioned to Remicade were included in the retransitioning cohort and matched with up to 3 patients who remained on biosimilar (biosimilar cohort). Patients were matched on: hospital, calendar date of biosimilar transitioning and duration of biosimilar treatment.

Patients were followed until discontinuation of infliximab (>16 weeks no administration, or switch to another biological). Risk of infliximab discontinuation (overall discontinuation and stratified into switching to another biological or discontinuation without switching) was compared using a (adjusted) conditional Cox proportional hazards model.

Results

The retransitioning cohort comprised 42 patients and the biosimilar cohort comprised 120 patients. Baseline characteristics of the cohorts were similar, but dosing interval was shorter in the retransitioning cohort (44 versus 56 days). Infliximab treatment discontinuation was 24.6% in the retransitioning cohort compared to 6.7% in the biosimilar cohort at 12 months (p<0.01) (Figure 1). Patients in the retransitioning cohort had a more than twofold risk (HR 2.5, 95%CI 1.3–5.1) for discontinuing infliximab treatment compared to patients in the biosimilar cohort. When analyzing the type of discontinuation, patients in the retransitioned cohort had a fivefold risk for switching to another biological (HR 4.8, 95%CI 0.6–37.0) and over a twofold risk for discontinuing without switching (HR 2.4, 95%CI 1.1–5.5) (Table 1).

Conclusion

Retransitioned patients have an increased risk for infliximab discontinuation, including both switching to another biological or discontinuing without switching. Our results indicate that retransitioning is mainly patient or disease related and less likely to be product related.
P698 Mapping field cancerisation and clonal evolution in IBD colons with dysplasia and colorectal cancer
Authors: Yalchin M , Curtius K , Nowinski S , Moorghen M , Kimberley C , Smith K , Baker A M , Al-Bakir I , Mossner M , Nadhamuni V , Hart A , Graham T
Published: January 2022

Background

In Inflammatory Bowel Disease (IBD), clonal evolution and field cancerisation precedes the development of colitis-associated colorectal cancer (CA-CRC), however the extent and spread of pre-cancerous clones in the IBD colon remains incompletely determined and consequently clinical practice is poorly informed of how best to detect these clones by endoscopy and accurately predict future cancer risk. This study aims to quantify the number and size of mutant clones arising across the length of the colitic bowel, reveal the mechanism of how they arise and spread, and through this gain a detailed molecular understanding of the evolutionary dynamics of progression to CA-CRC.

Methods

Three IBD patients undergoing a total panproctocolectomy for multifocal dysplasia or CA-CRC were recruited prospectively. Fresh-frozen biopsies were taken at regularly spaced intervals (~2cm) across the entire colon (rectum to caecum, comprising 118, 108 and 25 biopsies respectively). Epithelial tissue was isolated from each biopsy using laser capture microdissection and DNA was extracted. Low pass whole genome sequencing (lpWGS) was performed to generate genome-wide copy number alteration (CNA) profiles.

Results

Analysis from the first 45 samples from colon 1 show; 1) Multiple CNA events occur in macroscopically ‘normal’ parts of the colon. 2) Recurrent CNAs were shared between biopsies, revealing clonal expansions in multiple areas of the colon, both proximal and distal to the cancer, and comprising in normal, inflammed, dysplastic and cancer-adjacent tissue. 3) Clonal expansions ranged from 4-18cm in size, and were separated by distances of 2-20cm. 4) Certain CNA events occur more commonly across the colon, both independently and from within different clonal patches, such as a gain on chromosome 7 and 20, and losses on chromosomes 5, 8 and 17. 5) Whole genome doubling events within clonal clades.

Conclusion

These data show that across the IBD bowel, CNAs occur and expand in ostensibly ‘normal’ cells, demonstrating evidence of field cancerisation. Moreover, similar CNAs are seen occurring independently throughout the whole colon, suggesting patterns of convergent evolution. Further work is needed to more precisely quantify the clonal and sub-clonal distribution across the IBD colon, in addition to deriving measures of intra-colon, intra-lesion and intra-clade genomic diversity to complement the above measures of evolvability. This data, along with the genomic-phenotypic mapping (from pending RNA analysis) and analysis of the stromal microenvironment will help demonstrate the mechanisms of CA-CRC progression and therefore help guide clinical practice through endoscopic sampling, to best predict future cancer risk.
P699 Machine Learning-based Prediction for Early Progression in Korean Crohn’s disease: Results from the IMPACT Study
Authors: Chun J , Suji K , Kwang Sung A , Soo Kyung P , Sangsoo K , Dong Il P
Published: January 2022

Background

Transcriptome-wide association studies (TWAS) improve to detect functionally relevant loci by leveraging expression quantitative trait loci (eQTLs) from reference panels in relevant tissues. Herein, we developed machine learning-based prediction models using a novel Korean TWAS model for early progression to stricturing or penetrating phenotypes in Korean patients with Crohn’s disease (CD).

Methods

A total of 431 patients diagnosed with CD were retrospectively enrolled from 15 referral hospitals in Korea. Single-nucleotide polymorphism genotype was analyzed using the Korea Biobank Array. Using the GTEx genotype and Korean chip genotype database from the terminal ileum, a novel Korean TWAS model was developed and compared with a European TWAS model. Predictive models for early progression were trained and cross-validated using logistic regression models and leave-one-out cross validation. Early progression was defined as transition to stricturing or penetrating phenotypes within 2 years from the diagnosis of CD.

Results

Among the study population, early progression to stricturing and penetrating phenotype was detected in 60 (13.9%) and 73 patients (16.9%), respectively. Combined clinical-gene expression prediction models predicted early progression to stricturing (AUROC, 0.816) and penetrating phenotypes (AUROC, 0.801) more accurately than the models using clinical parameters alone. The following gene expression was significantly associated with early progression: CCDC154, FAM189A2, TAS2R19, FCSK, SP1, and KCNIP1 for stricturing phenotype and PUS7, CCDC146, MLXIP, LRGUK, UROS, and TAFA1 for penetrating phenotype.

Conclusion

The clinical-genetic machine learning models predicted progression to stricturing or penetrating phenotypes in the early stage of CD. Use of the comprehensive prediction models might enable clinicians to select patients requiring early aggressive therapeutic strategy to prevent disease-related complications.
P719 Identification of differentially expressed genes between AIEC and non-AIEC clinical isolates during in vitro cell infection
Authors: Bonet Rossinyol Q , Camprubí-Font C , Lopez-Siles M , Martinez-Medina M
Published: January 2022

Background

Adherent invasive Escherichia coli (AIEC) have been related to Crohn’s disease. Phenotypic assays of adhesion and invasion of intestinal epithelial cells and intra-macrophage replication are used to identify AIEC. No molecular tools are still available for AIEC identification. We hypothesise that differential gene expression may drive to the AIEC phenotype. To test this hypothesis we sequenced the genes expressed by AIEC and non-AIEC strains during infection, and we investigated differential expressed genes (DEGs) suitability as molecular markers.

Methods

Comparative transcriptomics was performed between two AIEC/non-AIEC strain pairs, belonging to the phylogroups B1 and D, during Intestine-407 cells infection. Each strain pair displayed identical pulsotypes and similar genomes. Supernatant fractions of the infected cell cultures (SN) and eukaryotic cells containing adhered and/or intracellular bacteria (A/I) were considered separately. DEGs obtained were quantified by RT-qPCR in the same samples to confirm the results, and in a strain collection of 13 AIEC and 23 non-AIEC to investigate their suitability as molecular markers. Binary logistical regression was performed to identify DEGs whose quantification could be used as AIEC biomarker.

Results

Comparative transcriptomics revealed 67 DEGs between the two phenotypes in the strain pairs (19 over-expressed in AIEC, and 48 under-expressed), 51 of which (82.26%) were corroborated by RT-qPCR. When explored in the whole strain collection, 29 DEGs were found to be differentially expressed between AIEC and non-AIEC phenotypes (p < 0.042), and 42 genes between SN and A/I fractions (p < 0.049). Notably, six DEGs detected in the strain collection were implicated in a metabolic pathway that could be involved in acid resistance, and eight in the synthesis of two virulence determinants. Finally, binary logistical regression revealed three DEGs able to predict the AIEC phenotype with an accuracy of ≥ 85%.

Conclusion

No previous comparative transcriptomic studies have been performed using AIEC-infected cell cultures. Our research revealed three genes, whose quantification presents higher sensitivities and specificities than other molecular markers previously suggested. Moreover, we have identified functionally related genes that can be involved in AIEC pathogenicity. These results open the door to further research to confirm the suitability of these genes as AIEC biomarkers and to investigate new therapeutic targets against AIEC colonisation.
N10 The impact of an educational and networking event on nurses caring for Inflammatory Bowel Disease (IBD) paediatric patients receiving biologic therapy
Authors: Gil Zaragozano E , Wiskin A , Williams J
Published: January 2022

Background

Biologic therapies usage is increasing across the United Kingdom. Gastroenterology departments and all stakeholders need to continuously update their knowledge and practice to the safe use of this therapy (IBD Standards, 2013). Paediatric gastroenterology services in tertiary hospitals often cover a wide geographical region and deliver care in collaboration with district general hospitals closer to the child’s home. A virtual educational and networking event was developed in order to deliver interprofessional education (IPE) and facilitate networking for nurses caring for IBD paediatric patients receiving biologic therapy in two large regions of the United Kingdom (South West of England and South Wales).

The aim of this study was to establish the level of self-reported competencies of nurses involved in the administration of biologic therapy in paediatric IBD patients and to evaluate the impact that the event had on the self-reported competency of the participants and their practice.

Methods

The event compromised a range of relevant topics and it was delivered by experts in the field in a virtual platform and using a range of participant interacting virtual tools. Participants were requested to complete an online questionnaire before and after the event. It was open to registered nurses working in paediatric community and/or day care settings, and caring for paediatric IBD patients receiving biologic therapy.

Results

There were 21 participants registered to attend the event that completed a pre –event questionnaire. 55% (11) of the participants had more than 5 years’ experience in post. 81% (17) reported no previous formal training on paediatric IBD and biologic therapy. 19.9% did not feel competent in the administration of biologic therapy and monitoring of the patient; and 28.6% did not feel competent to meet the holistic needs of the patient and their family.

After the event, a total of 13 completed evaluations were received. All participants (13) reported feeling more competent in caring for paediatric IBD patients receiving biologic therapy and their families; and 84.7% felt more competent in administering and monitoring biologic therapy.

All comments relating to the event were very positive and 10 participants could identify changes to make to their own clinical practice directly related from attending this event.

Conclusion

This study highlighted the need for IPE for nurses caring for paediatric IBD patients, particularly where care is delivered in district general hospitals. Feedback demonstrated that virtual educational events are effective in raising self-reported nursing competencies and in ensuring high standards of practice related to biologic therapy.
Sexual and urinary function post-surgical treatment of femoroacetabular impingement: experience from the FIRST trial and embedded cohort study
Authors: Jean Pierre-Olivier , Simunovic Nicole , Duong Andrew , Heels-Ansdell Diane , Ayeni Olufemi R
Published: January 2022

The goal of this study was to investigate the sexual and urinary function and any related complications in patients post-hip arthroscopy for the treatment of femoroacetabular impingement (FAI). Data from 214 patients enrolled in the FIRST trial and 110 patients enrolled in the trial’s embedded prospective cohort study (EPIC) were analyzed. EPIC patients either refused to participate in the trial or did not meet the FIRST eligibility criteria. Outcomes included the International Consultation on Continence Questionnaire (ICIQ) for males (ICIQ-MLUTS) and females (ICIQ-FLUTS) and the Female Sexual Function Index (FSFI) and International Index of Erectile Function (IIEF) administered before surgery and at 6 weeks and 12 months. Urinary and sexual function adverse events were recorded up to 24 months. Linear regression analyses were conducted to compare the osteochondroplasty and lavage groups in the FIRST trial and to evaluate age and traction time as prognostic factors among all patients. Longer traction time was associated with a small but statistically significant improvement in urinary voiding function in males at 6 weeks and 12 months (MD (95% CI) = 0.25 (0.12, 0.39), P < 0.001 and 0.21 (0.07, 0.35), P = 0.004), respectively. Mean traction time was 43.7 (± 23.2) min for FIRST trial and 52.8 (± 15.2) min for EPIC cohort patients. Increasing age in male patients was associated with a decrease in urinary continence at 6 weeks (MD (95% CI) = 0.25 (−0.42, −0.09), P = 0.003). FIRST male patients who received osteochondroplasty improved significantly in sexual function at 12 months compared to males in the EPIC cohort (MD (95% CI) = 2.02 (0.31, 3.72), P = 0.020). There was an overall complication rate of 1.2% at 24 months [one urinary infection, two instances of erectile dysfunction (one transient and one ongoing at 24 months) and one reported transient numbness of tip of the penis]. Hip arthroscopy for the treatment of FAI has a low rate of sexual and urinary dysfunction and adverse events.
Serum or Plasma for Quantification of Direct Oral Anticoagulants?
Authors: Aakerøy Rachel , Stokes Charlotte L. , Tomić Marija , Hegstad Solfrid , Kristoffersen Ann Helen , Ellekjær Hanne , Schjøtt Jan , Spigset Olav , Helland Arne
Published: January 2022

Background:

Direct oral anticoagulants are increasingly replacing vitamin K antagonists for prevention of stroke in patients with atrial fibrillation, partly owing to the lack of a need for routine monitoring. Therapeutic drug monitoring may still be warranted under certain circumstances. It is generally assumed that serum and plasma can be interchangeably used for this purpose. The aim of this study was to investigate possible differences between the serum, citrate-plasma, and ethylenediaminetetraacetic acid (EDTA)-plasma concentrations of apixaban and rivaroxaban in a larger patient group and their relation to factor X measurements.

Methods:

Plasma and serum samples were drawn during the same venipuncture from patients treated with apixaban or rivaroxaban. Drug levels were measured using ultrahigh-performance liquid chromatography combined with tandem mass spectrometry. Three sample matrices were obtained from 8 healthy volunteers for measurement of factor X antigen and activity.

Results:

Mean concentrations of apixaban and rivaroxaban were 16.8% and 36.6% higher in serum than in citrate-plasma, respectively (both P < 0.001). The corresponding differences in serum versus EDTA-plasma were 4.5% for apixaban and 13.1% for rivaroxaban (both P < 0.001). Factor X antigen measurements in citrate-plasma, EDTA-plasma, serum with clot activator, and serum without additives yielded comparable results, and factor X activity was significantly higher in serum than in plasma.

Conclusions:

Apixaban and rivaroxaban concentrations were significantly higher in serum than in plasma. The difference was more pronounced with rivaroxaban and was larger between serum and citrate-plasma than between serum and EDTA-plasma. Higher factor X activity in serum may explain the observed concentration differences. The choice of matrix is, thus, important when interpreting therapeutic drug monitoring results and in research involving analyses of direct oral anticoagulants. The authors recommend citrate-plasma as the preferred matrix.
Intestinal failure-associated liver disease in the neonatal ICU: what we know and where we’re going
Authors: Khalaf Racha T. , Ford Steven L.
Published: January 2022

Purpose of review

Parenteral nutrition is an integral part of the care of infants in the neonatal ICU. However, prolonged use of parenteral nutrition can be associated with adverse outcomes, most notably parenteral nutrition-associated liver disease, now known as intestinal failure-associated liver disease (IFALD). This review highlights pertinent developments in the epidemiology of IFALD as it pertains to neonates and showcases recent advances in the pathophysiology, treatment, and outcomes of neonates with IFALD.

Recent findings

The role of intravenous lipid emulsions in the pathogenesis, prevention, and treatment of IFALD remains a target for investigative studies. Recent data continues to support the use of fish-oil based intravenous lipids, but its use is limited due to concerns for essential fatty acid deficiency. Use of soy-based lipids and mixed lipids is not wrought with such concerns as these are often used at greater doses but their use is limited due to higher proinflammatory fatty acid content, increased phytosterols and decreased antioxidants, risk factors for the development of IFALD.

Hepatic complications may limit the use of parenteral nutrition in the neonatal ICU. However, the pathophysiology of IFALD is continuing to be further elucidated and novel targets are being developed for the treatment of IFALD. As noninvasive disease monitoring strategies continue to be developed, early enteral nutrition ameliorates the risk of IFALD and should be considered when possible.
Comparison of Intracorporeal Trapezoidal-shaped Gastroduodenostomy and Delta-shaped Anastomosis After Laparoscopic Distal Gastrectomy for Gastric Cancer: A Single-center Retrospective Study
Authors: Iwasaki Kenichi , Cho Haruhiko , Ogawa Rei , Ishida Hiroyuki , Oguri Yohei , Maezawa Yukio , Tsuchida Kazuhito , Nagakawa Yuichi , Katsumata Kenji , Tsuchida Akihiko
Published: January 2022

Background:

Laparoscopic/robotic distal gastrectomy (LDG/RDG) as a treatment for early gastric cancer has become increasingly and widely accepted for its minimal invasiveness and proportionate outcomes. Over the years, in addition to the LDG/RDG technique and the lymphadenectomy and gastrectomy procedures, various reconstruction methods have been developed and further improved upon. In particular, the number of minimally invasive intracorporeal anastomosis reconstruction techniques has been increasing.

Materials and Methods:

The medical records of 445 patients with gastric cancer who underwent reconstruction following LDG/RDG via either trapezoidal-shaped gastroduodenostomy (TAPESTRY; n=126) or delta-shaped anastomosis (DSA; n=319) at our hospital between April 2012 and May 2021 were retrospectively reviewed. Short-term surgical outcomes, including the operation time, blood loss, length of hospital stay, and complications, were compared between the 2 groups. Anastomosis-related complications, namely leakage, bleeding, stricture, and delayed gastric emptying, were monitored and graded using the Clavien-Dindo classification.

Results:

All operations were either performed or supervised by qualified surgeons. Patients’ characteristics in the TAPESTRY group and the DSA group were biased in terms of the surgical approach, but they were well-balanced after propensity score matching. Overall anastomosis-related complications (Clavien-Dindo grade II or above) within 30 days after surgery in the TAPESTRY group were comparable with those in the DSA group, either all patients (1.5% vs. 5.0%, P=0.115) or after propensity score–matching analysis (2.1% vs. 6.5%, P=0.134). There were no records of reoperation or mortality during hospitalization in either group.

Conclusions:

TAPESTRY was performed safely, with a low rate of anastomosis-related complications. These findings suggest that trapezoidal-shaped gastroduodenostomy could be a feasible option for reconstruction in patients undergoing LDG/RDG.
Coordination chemistry of polynitriles. Part 9. Decacyanoferrocene revisited: crystal and molecular structure of cis-[{C5(CN)5}2(MeCN)4Fe]
Authors: Sünkel Karlheinz , Blockhaus Tobias
Published: January 2022

The reaction of Ag[C5(CN)5] with anhydrous FeCl2 in acetonitrile leads to colourless crystals of tetrakis(acetonitrile-κN)bis(pentacyanocyclopentadienido-κN)iron(II) acetonitrile 1.8-solvate, [Fe(C10N5)2(CH3CN)4]·1.8CH3CN or cis-[{C5(CN)5}2(MeCN)4Fe]·1.8MeCN. The compound crystallizes in the triclinic space group P\overline{1} as monomers, which exhibit weak C—H...N and π–π interactions. The crystals contain ca 20% solvent-accessible voids, which are nearly completely filled by two MeCN molecules.
Databases for intrinsically disordered proteins
Authors: Piovesan Damiano , Monzon Alexander Miguel , Quaglia Federica , Tosatto Silvio C. E.
Published: January 2022

Intrinsically disordered regions (IDRs) lacking a fixed three-dimensional protein structure are widespread and play a central role in cell regulation. Only a small fraction of IDRs have been functionally characterized, with heterogeneous experimental evidence that is largely buried in the literature. Predictions of IDRs are still difficult to estimate and are poorly characterized. Here, an overview of the publicly available knowledge about IDRs is reported, including manually curated resources, deposition databases and prediction repositories. The types, scopes and availability of the various resources are analyzed, and their complementarity and overlap are highlighted. The volume of information included and the relevance to the field of structural biology are compared.
Kiyaslio: a gamified mobile crowdsourcing application for tracking price dispersion in the grocery retail market
Authors: Macakoğlu Şevval Seray , Alakuş Çınar Burcu , Peker Serhat
Published: January 2022

Purpose

In the recent years, the rapid growth of the grocery retailing industry has created a great heterogeneity in prices across sellers in the market. Online price comparison agents which are key mechanisms to solve this problem by providing prices from different sellers. However, there are many sellers in the grocery industry do not offer online service, and so it is impossible to automatically retrieve price information from such grocery stores. In this manner, crowdsourcing can become an essential source of information by collecting current price data from shoppers. Therefore, this paper aims to propose Kiyaslio, a gamified mobile crowdsourcing application that provides price information of products from different grocery markets.

Design/methodology/approach

Kiyaslio has been developed through leveraging the power of crowdsourcing technology. Game elements have also been used to increase the willingness of users to contribute on price data entries. The proposed application is implemented using design science methodology, and it has been evaluated through usability testing by two well-known techniques which are the system usability scale and the net promoter score.

Findings

The results of the usability tests indicate that participants find Kiyaslio as functional, useful and easy to use. These findings prove its applicability and user acceptability.

Practical implications

The proposed platform supports crowd sourced data collection and could be effectively used as a tool to support shoppers to easily access current market product prices.

Originality/value

This paper presents a mobile application platform for tracking current prices in the grocery retail market whose strength is based on the crowdsourcing concept and incorporation of game elements.
To serve and protect: a typology of service robots and their role in physically safe services
Authors: Schepers Jeroen , Streukens Sandra
Published: January 2022

Purpose

Although consumers feel that the move toward service robots in the frontline so far was driven by firms' strive to replace human service agents and realize cost savings accordingly, the COVID-19 pandemic has led customers to appreciate frontline robots' ability to provide services in ways that keep them safe and protected from the virus. Still, research on this topic is scant. This article offers guidance by providing a theoretical backdrop for the safety perspective on service robots, as well as outlining a typology that researchers and practitioners can use to further advance this field.

Design/methodology/approach

A typology is developed based on a combination of a theory- and practice-driven approach. Departing from the type of behavior performed by the service robot, the typology synthesizes three different service robot roles from past literature and proposes three new safety-related role extensions. These safety-related roles are derived from a search for examples of how service robots are used in practice during the COVID-19 pandemic.

Findings

The typology's roles are corroborated by discussing relevant robot implementations around the globe. Jointly, the six roles give rise to several ideas that jointly constitute a future research agenda.

Originality/value

This manuscript is (one of) the first to provide in-depth attention to the phenomenon of service customers' physical safety needs in the age of service robots. In doing so, it discusses and ties together theories and concepts from different fields, such as hierarchy of needs theory, evolutionary human motives theory, perceived risk theory, regulatory focus theory, job demand–resources theory, and theory of artificial intelligence job replacement.