bluuebunny/crossref_metadata_2025_split huggingface dataset:
P454 Treatment with biologics improves disability from Inflammatory Bowel Disease in therapy responders
Authors: Castillo G , Sultan K , Kwah J , Chen L A , Axelrad J 
Published: May 2021

Abstract

Background
The IBD-Disability Index (IBD-DI) is a quantitative measure of disease impact on physical activity and social participation, with higher sores indicating greater disability. Prior studies have been cross-sectional, but few studies have longitudinally measured disability with IBD treatment.

Methods
Patients with Crohn’s disease (CD) and ulcerative colitis (UC) starting a new biologic or small molecule therapy were surveyed using the IBD-DI at induction, and 2- and 6-months. Surveys also included the Harvey Bradshaw Index (HBI), Simple Clinical Colitis Activity Index (SCCAI), partial Mayo score (pMayo), depression index (PHQ-9), quality of life index [Short IBD Questionnaire (SIBDQ)], and illness perception scale [Brief Illness Perception Questionnaire (BIPQ)]. Clinical data included endoscopic scores, biomarkers (ESR, CRP, calprotectin), comorbidities, and IBD history. Therapy response was defined as a reduction in HBI, pMayo, SCCAI ≥3 or total HBI ≤ 4, pMayo &lt; 2, SCCAI ≤2 at survey 3.

Results
111 patients (65 males and 46 females) completed survey 1, 79 completed survey 2, and 63 completed survey 3. There were no significant differences in baseline demographic, disease activity, or psychosocial scores between participants who completed only survey 1, and those who completed all 3 surveys. The median age was 31 years, 58% had CD, 42% had UC, and 32% were non-white (Table 1). At induction, the median IBD-DI score was 34.0 out of 100. IBD-DI scores did not correlate with age, race, sex, comorbidities, IBD-type, or surgery, but there was a weak correlation with prior biologic use, specifically anti-TNF therapy (Table 1). There was a moderate correlation between clinical disease activity scales and the IBD-DI [HBI, pMayo, and SCCAI (r=0.63, r= 0.56, r=0.55; p &lt;0.001)] (Table 2). Endoscopic scores and biomarkers did not correlate with the IBD-DI. Psychosocial scales correlated strongly with the IBD-DI: SIBDQ, PHQ-9, and the wellbeing and emotional domains of the BIPQ (r=-0.83, r=0.78, r= 0.60, p &lt;0.0001, respectively). Among therapy responders, there was a significant improvement in IBD-DI scores from survey 1 to 3 [median 32 (IQR, 20–43) to 24 (IQR, 14–38), p =0.04] (Table 3). This difference was not observed in treatment non-responders.

Conclusion
Disability is not commonly measured in clinical studies, but it plays a large role in patients’ overall wellbeing. In this longitudinal cohort, there was a strong correlation between IBD-DI, clinical disease activity, depression, and quality of life indices. Among therapy responders, there was a significant improvement in IBD-DI from a moderate to mild degree of disability. These findings further clarify the relationship between disability, disease activity, and therapeutic response in IBD.
P506 The Impact of Anxiety in Patients With Inflammatory Bowel Diseases Treated With Biologics during COVID Lockdown. A Comparative Study between Hospitalized and non-hospitalized patients
Authors: Bertani L , Barberio B , Zanzi F , Maniero D , Ceccarelli L , Marsilio I , Minciotti M , Coppini F , Lorenzon G , Mumolo M G , Zingone F , Costa F , Savarino E V 
Published: May 2021

Abstract

Background
The first wave of COVID-19 pandemic management implied to remain at home in order to reduce the spread of the infection. Several patients with inflammatory bowel diseases (IBD) treated with biologics had to go to the hospital to perform intravenous (i.v.) therapies, whereas patients treated with subcutaneous (s.c.) ones could remain at home. Since immumodulatory therapies as well as the access to high-risk places like hopitals have been associated to an increased risk of infections, we have investigated whether patients hospitalized or treated at home showed similar levels of anxiety related to the pandemic situation.

Methods
We conducted a survey including consecutive IBD patients treated with biologics at three Italian referral centers referring to the first lockdown period. We included consecutive adult patients in clinical and biochemical remission treated with biologics, administered i.v. or s.c. Patients experiencing a disease flare during these months were excluded from the study, in order to avoid potential biases related to disease activity. Patients underwent the normally scheduled clinical visits, performed at home by using phone or video calls for patients treated with s.c. drugs and only in specific cases (i.e. suspected COVID symptoms) for patients treated with i.v. ones. We administered to all patients the Hospital Anxiety and Depression Scale (HADS) questionnaire and other 11 questions, specifically related to COVID and its implications. Group differences in continuous and nominal variables were tested by Kruskal–Wallis test and Fisher exact test, respectively.

Results
A total of 189 IBD patients were recruited, 112 (59.3%) treated with i.v. drugs and 77 (40.7%) with s.c. ones. The two groups of patients had similar scores in the 14 single items of the HADS questionnaire (p&gt;0.10 for all). The total HADS score obtained by the sum of all items was also almost identical between groups (37.1 ± 2.8 vs 37.2 ± 2.8; p=0.98). In patients treated with i.v. drugs receiving a televisit (n=17), the rates of satisfaction about telemedicine (58.8%) and the lack of in-person care (33.3%) were significantly lower compared with those treated with s.c. drugs (94.8% and 92.2%, respectively; both p&lt;0.0005).

Conclusion
Our results suggest that there is no need to convert patients from i.v. to s.c. therapy, since the risk of infection as well as of disease relapse due to stressful events are similar in both groups. Moreover, the hospitalization for drug administration does not affect the the psychological status of the patients. Interestingly, patients used to coming to the hospital have more need for in-person contact than patients used to be treated at home, suggesting that the choice of telemedicine should be personalized.
P532 Delay of maintenance infliximab increases the risk of relapse in Crohn’s disease during the COVID-19 pandemic
Authors: Guo H , Tang J , Huang Z , Li B , Yang Q , Chao K , Gao X 
Published: May 2021

Abstract

Background
Scheduled maintenance infliximab (IFX) therapies were frequently delayed during the COVID-19 pandemic. The unusual situation allowed us to study the influence of decreased treatment adherence on Crohn’s disease (CD). This retrospective study aimed to evaluate the effect of IFX delay on relapse in Crohn’s disease (CD) patients.

Methods
166 CD patients with maintenance IFX between January 25, 2020, and April 25, 2020, were retrospectively enrolled. Demographic and clinical characteristics were recorded. Relapse was defined as clinical disease relapse or biochemical disease relapse (C-reactive protein (CRP) level ≥5 mg/L without other, non-IBD related explanation). Associations between relapse and IFX delay were analyzed.

Results
A retrospective cohort study was conducted, including 166 CD patients receiving maintenance IFX infusion during the COVID-19 pandemic. Of all, 135 (81.3%) had delayed their IFX infusion. Only 31 (18.7%) followed the schedule infusion during the COVID-19 pandemic. The median time of the IFX delay was 18.6±17.1 days. The relapse rate in the IFX-delay group was significantly higher than the group without delay (25.9% versus 5.5%, P＜0.02). During a median IFX delay interval of 46 days (95% CI 20.9–71.1), the ratio of relapse increased with the increase of IFX delay intervals. Delay interval had a cumulative effect on disease recurrence. We proposed interval prolongation resulted in a
significant IFX trough concentration reduction.

Conclusion
Our study provided real-world evidence of influence on relapse of IFX delay in CD patients undergone maintenance therapy. It might help the IBD specialists arrange reasonable IFX treatment intervals for patients.
P590 Which biomarkers have an effect on therapeutic vedolizumab drug levels? A retrospective analysis from a London Tertiary Centre
Authors: Bancil A , Stevens M , Kok K 
Published: May 2021

Abstract

Background
Vedolizumab is a humanised monoclonal antibody that binds to the α 4β 7 integrin and is an established treatment for both Crohn’s Disease (CD) and Ulcerative Colitis (UC). Drug levels for anti-tumour necrosis factor-α inhibitors such as infliximab and adalimumab have been used routinely for therapeutic drug monitoring (TDM). Target therapeutic levels for vedolizumab are yet to be established. Correlations with vedolizumab levels have been found in prospective and retrospective studies with a number of biomarkers such as C-Reactive Protein (CRP), albumin and Body Mass Index (BMI). However, these have failed to replicate consistently among studies of vedolizumab drug levels.

Methods
Trough serum vedolizumab drug levels were taken for 81 patients through a period of 3 months. These were analysed using a drug tolerant assay (IDKMonitor Drug level ELISA and IDKMonitor vedolizumab Free anti-drug antibody ELISA) run on a Dynex DS2 ELISA processor. These were collected from 33 CD patients, 46 UC patients and 2 patients with unclassified Inflammatory Bowel Disease (IBD-U). Faecal calprotectin (FCP) was collected in a subset of patients. Serum CRP, albumin, and haemoglobin (Hb) levels were also taken alongside levels. BMI was recorded at our infusion unit before receiving the infusion.

Results
81 patients had drug levels taken: CD patients (mean drug level Q8w - 7.8 mcg/ml, Q4w - 18.6 mcg/ml, 9 patients with concomitant immunomodulators (CIM)), UC patients (mean drug level Q8w - 9.4 mcg/ml, Q4w – 22.0 mcg/ml, 5 patients with CIM), IBD-U (mean drug level Q8w - 15.2 mcg/ml, no patients with CIM). One patient developed anti-drug antibodies. Correlation was analysed using simple linear regression. A positive correlation was found with vedolizumab levels and albumin (correlation coefficient (r) = 0.11; p=0.03) but not with CRP (p=0.49), Hb (p=0.56), BMI (p=0.33) or FCP (p=0.08).

Conclusion
Our results indicate that albumin positively correlates with a higher vedolizumab drug level, which suggests that drug levels will be lower and perhaps less effective in patients with a low albumin level. Further studies should look at larger numbers of patients to identify whether the correlations identified with other biomarkers are significant and identify therapeutic target levels for vedolizumab. These will help guide TDM for patients and inform clinicians of when to switch as well as recognising likely non-responders and thus provide a personalised approach to biologic choice.
P638 Changes in the management of IBD patients since the onset of COVID-19 pandemic. A path towards the implementation of telemedicine in Spain?
Authors: Del Hoyo Francisco J , Millán M , Garrido-Marín A , Nos P , Barreiro-de Acosta M , Bujanda L , de la Portilla F , Aguas M 
Published: May 2021

Abstract

Background
COVID-19 pandemic increased medical services demand aside from interrupting daily clinical practice for other diseases such as Inflammatory Bowel Disease (IBD). Here we present the results of a survey to gain the perception of IBD specialists in their patient-management using telemedicine in their daily practice.

Methods
This was an observational survey study among physicians focused on IBD (gastroenterologist, surgeons, and pediatricians) members of the Spanish Working Group on Crohn’s Disease and Ulcerative Colitis (GETECCU), the Spanish Association of Gastroenterology (AEG), and the Spanish Association of Coloproctology (AECP), regarding changes of management of IBD patients.

Results
We received a total of 269 responses to the survey (from May to June 2020). Before the pandemic, nearly all the respondents reported performing very frequently their visits face-to-face (n=251, 93.3%) while, during the pandemic, the telephone visits were the most frequent visits performed (n=138, 51,3%). Regarding communication difficulties, 157 (58.4%) respondents reported the impossibility of performing a proper examination as the most relevant issue. Also, 114 (42.4%) respondents considered remote visits more time-consuming than face-to-face visits. Most gastroenterologists (n=188, 83.2%) considered patients with active perianal disease in special need of face-to-face consultation and more than half of the surgeons (n=35, 50.7%) reported having performed an immediate postoperative follow-up remotely.

Conclusion
Most IBD units have implemented remote visits during the pandemic, but most professionals found them more time-consuming and unsuitable for some disease profiles. Therefore, there is a need for the development of better telemedicine systems that can meet professionals’ and patients′ requirements.
P667 Characterization of a large Hispanic cohort with Inflammatory Bowel Disease across a 25-year span
Authors: Torres E A , Ramos L , Sanchez A , Amaya C , Perez-Gilbe A 
Published: May 2021

Abstract

Background
Inflammatory Bowel Disease (IBD) in Hispanics has increased, but characterization of this population is limited. We describe the demographic and clinical characteristics of a large Hispanic population with IBD and compare it among two periods, 1995- 2009 and 2010–2019.

Methods
The Registry of IBD has been recruiting patients with IBD continuously since 1995. Data is obtained from the subject and the medical record. This study includes 1365 Hispanics recruited between 1995 and 2019. Variables include age, gender, age at onset and diagnosis, IBD type, family history, smoking, extraintestinal manifestations (EIM), medications, and surgery for IBD. Descriptive statistics included frequency, median, mean, and standard deviation. SPSS software was used for comparison analysis utilizing Chi square and Fisher′s test. The protocol is approved by the IRB.

Results
712 were males and 653 females. Crohn’s disease (CD) was more prevalent in males (479/836, 57.3%) and ulcerative colitis (UC) in females (288/517, 55.7%). The mean age at diagnosis was 34.1 + 15.4 for UC and 24.4 + 12 for CD (p&lt;.001). History of smoking was infrequent (24.3%). Interval between onset of symptoms and diagnosis was 1.8 + 4.7 yrs. for UC and 2.5 + 5.3 yrs. for CD (p=.012). At recruitment, duration of disease was 7.4 + 8.4 yrs. for UC and 5.6 + 7.3 yrs. for CD (p&lt;.001). Family history of IBD was present in 23% of CD and UC participants. The most frequent EIM was arthropathy in 37.9% and 25.9 % of UC and CD (p=.670), followed by skin manifestations in 13.2% and 18.9% respectively (p=.070). Aminosalicylates (94.9%) and corticosteroids (81.6%) were more frequent in UC, and immunomodulators (23%) and anti-TNF drugs (aTNF) (46.2%) in CD (p&lt;.001). At the time of recruitment, 54.5% of CD and 23.7% of UC patients had previous surgery for IBD.
Stratification of subjects into two groups by date of recruitment,1995–2009 and 2010–2019, showed similar ages at onset and diagnosis, but the time to diagnosis decreased for UC (2 vs 1.55 yrs.) and increased for CD (2.2 vs 2.6 yrs.) in the later interval. Medications varied between decades, with aTNF increasing markedly in CD and UC (p&lt;.001) and aminosalicylates decreasing in CD (p&lt;.001) in the later years. Surgery for UC decreased from 25.2% to 20.7%, whereas surgery for CD remained the same (52.2% vs 52.5%).

Conclusion
We describe a large cohort of Hispanics with IBD studied over two decades. Differences over time may reflect changes in disease phenotypes, environmental influences and the impact of physician awareness and new management guidelines and therapies. Further studies are needed to better characterize this population and explore outcomes.
P681 Higher in vitro mucin degradation, but no increased paracellular permeability by faecal water from Crohn’s disease patients
Authors: Becker H , Kameli N , Rustichelli A , Britt H , Stassen F , Penders J , Jonkers D 
Published: May 2021

Abstract

Background
Crohn’s disease (CD) is a chronic inflammatory gastro-intestinal condition with a variable disease course. Impaired intestinal integrity and microbial dysbiosis are associated with disease onset and exacerbations. We hypothesized that a perturbed microbial activity in CD patients may contribute to the impaired barrier function. Therefore, this study aimed to examine the impact of faecal bacterial products of active CD patients, CD patients in remission, and healthy controls (HC) on mucin degradation and intestinal epithelial barrier function in vitro.

Methods
Six HC and twelve CD patients were included. Faecal samples were obtained within one week prior to endoscopy processed within 6 hours after collection. Disease activity was determined by the short endoscopic score for CD (SES-CD). Faecal water (FW) and bacterial membrane vesicles (MVs) were applied on mucin agar to determine mucin degradation. Further, differentiated Caco-2 cell monolayers were exposed to FW and MVs to assess transepithelial electrical resistance (TEER) and paracellular junction stability using permeation of fluorescein isothiocyanate-labelled dextran of 4 kDa. Relative abundances of faecal bacterial genera were evaluated by 16S rRNA gene amplicon sequencing.

Results
FW-induced mucin degradation was higher in CD samples as compared to HC (p&lt;0.01), but was not linked to specific bacterial relative abundances. FW resulted in 78–87% decrease of TEER in three of the remissive (p&lt;0.001) but not the active CD or HC samples. The decrease of TEER was not linked to increased paracellular permeability. MVs did not induce mucin degradation or epithelial barrier disruption.

Conclusion
The higher mucin degradation capacity of CD patient-derived FW might indicate contributions of microbial products to CD pathophysiology and warrants further investigation. Moreover, the altered epithelial resistance in some individuals is not due to paracellular alterations.
P689 Aeromonas infection and Inflammatory Bowel Disease: a single tertiary center analysis
Authors: Alves Da Silva J , Pereira Guedes T , Falcão D , Neves S , Costa P , Lago P , Pedroto I , Salgado M 
Published: May 2021

Abstract

Background
Aeromonas genus consists of gram-negative rods known to cause a spectrum of diseases in humans. Inflammatory bowel disease (IBD) is an idiopathic complex condition where multiple factors contribute to its development and progression. The association of Aeromonas infection with IBD manifestation have been proposed by other authors and is still largely unknown. We aim to look for the significance of Aeromonas infection and for significant differences between IBD and non-IBD patients.

Methods
A retrospective observational data retrieval and analysis was performed of all patients positive for Aeromonas in stool cultures, during a 10-year period, from a Portuguese tertiary and university setting hospital.

Results
Fifty patients, 56% of male sex and with a mean age of 42.1 years-old were included. Thirty-eight (76%) were non-IBD and 12 (24%) were IBD patients. IBD patients were more frequently under immunosuppressors. Two patients were asymptomatic and 44% develop mild, 44% moderate and 16.7% severe infection. The main Aeromonas strains isolated were Aeromonas hydrophila/caviae. Co-isolation with other bacteria was found in 4 non-IBD patients and histological findings compatible with Cytomegalovirus were found in 2 IBD patients. Non-IBD patients presented more frequently with fever and IBD patients with bloody diarrhea and abdominal pain. There was higher tendency for severe infection rate in IBD patients with higher antimicrobial therapy use. Steroids were exclusively used in IBD group. No significant differences were observed for isolation of Aeromonas resistant strains. From the IBD, 4 patients had the diagnosis of Ulcerative Colitis and 9 of Crohn’s Disease with colonic involvement. Of them 5 patients received the diagnosis after the acute episode of Aeromonas infection.

Conclusion
Clinical presentation of Aeromonas infection differ between IBD and non-IBD patients. Non-IBD patients had milder severity of infection with less use of antibiotics. Aeromonas infection seem to play an important role on the contribution of IBD manifestation.
Characterization of a Sex-Determining Region and Its Genomic Context via Statistical Estimates of Haplotype Frequencies in Daughters and Sons Sequenced in Pools
Authors: Cordaux Richard , Chebbi Mohamed Amine , Giraud Isabelle , Pleydell David Richard John , Peccoud Jean 
Published: May 2021

Abstract
Sex chromosomes are generally derived from a pair of autosomes that have acquired a locus controlling sex. Sex chromosomes may evolve reduced recombination around this locus and undergo a long process of molecular divergence. At that point, the original loci controlling sex may be difficult to pinpoint. This difficulty has affected many model species from mammals to birds to flies, which present highly diverged sex chromosomes. Identifying sex-controlling loci is easier in species with molecularly similar sex chromosomes. Here we aimed at pinpointing the sex-determining region (SDR) of Armadillidium vulgare, a terrestrial isopod with female heterogamety (ZW females and ZZ males) and whose sex chromosomes appear to show low genetic divergence. To locate the SDR, we assessed single-nucleotide polymorphism (SNP) allele frequencies in F1 daughters and sons sequenced in pools (pool-seq) in several families. We developed a Bayesian method that uses the SNP genotypes of individually sequenced parents and pool-seq data from F1 siblings to estimate the genetic distance between a given genomic region (contig) and the SDR. This allowed us to assign more than 43 Mb of contigs to sex chromosomes, and to demonstrate extensive recombination and very low divergence between these chromosomes. By taking advantage of multiple F1 families, we delineated a very short genomic region (∼65 kb) that presented no evidence of recombination with the SDR. In this short genomic region, the comparison of sequencing depths between sexes highlighted female-specific genes that have undergone recent duplication, and which may be involved in sex determination in A. vulgare.
The Axes of Life: A Roadmap for Understanding Dynamic Multiscale Systems
Authors: Chandrasekaran Sriram , Danos Nicole , George Uduak Z , Han Jin-Ping , Quon Gerald , Müller Rolf , Tsang Yinphan , Wolgemuth Charles 
Published: May 2021

Synopsis
The biological challenges facing humanity are complex, multi-factorial, and are intimately tied to the future of our health, welfare, and stewardship of the Earth. Tackling problems in diverse areas, such as agriculture, ecology, and health care require linking vast datasets that encompass numerous components and spatio-temporal scales. Here, we provide a new framework and a road map for using experiments and computation to understand dynamic biological systems that span multiple scales. We discuss theories that can help understand complex biological systems and highlight the limitations of existing methodologies and recommend data generation practices. The advent of new technologies such as big data analytics and artificial intelligence can help bridge different scales and data types. We recommend ways to make such models transparent, compatible with existing theories of biological function, and to make biological data sets readable by advanced machine learning algorithms. Overall, the barriers for tackling pressing biological challenges are not only technological, but also sociological. Hence, we also provide recommendations for promoting interdisciplinary interactions between scientists.