bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 (&gt;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&lt;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

Abstract

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

Abstract

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

Abstract

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 &lt; 0.042), and 42 genes between SN and A/I fractions (p &lt; 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

Abstract

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

ABSTRACT
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 &lt; 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.

Summary
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.