bluuebunny/crossref_metadata_2025_split huggingface dataset:
P185 Psychosocial impact of the COVID-19 pandemic on patients with inflammatory bowel disease in Spain
Authors: Hernandez Camba A , Ramos L , Madrid Álvarez M B , Pérez-Méndez L , Nos P , Hernández V , Guerra I , Jimenez N , Lorente R , Sierra-Ausín M , Ginard D , Varela P , Arranz L , Cabello Tapia M J , Zabana Y , Barreiro M 
Published: May 2021

Abstract

Background
Few studies have examined the effects of COVID-19 on the mental health of patients with inflammatory bowel disease (IBD), who are already at higher risk of depression, anxiety and stress than the general population. This cross-sectional study was conducted to assess the psychosocial impact of COVID-19 on patients with IBD in Spain during lockdown and the first wave of the pandemic.

Methods
A self-report questionnaire that integrated the Spanish version of the Depression, Anxiety and Stress Scale–21 items (DASS-21) and the Perceived Stress Questionnaire (PSS) was designed to gather sociodemographic data and information related to the effects of COVID-19 on the lives of IBD patients. Twelve IBD units invited their patients to answer the anonymous online survey via email or by using a QR code displayed at the unit. A link to the survey was also published on the GETECCU (Spanish IBD group) website and social media account. The survey was conducted between the 1st July and the 25th August 2020.

Results
Of the 693 survey participants with IBD, 67% were female, mean age 43 (12y SD). 61% had ulcerative colitis, 36% Crohn’s disease 3% indeterminate colitis. Only 15 participants were diagnosed with COVID-19: 3 of them required hospital admission and none required ICU admission. Physical activity levels and sleep habits were adversely affected for 79% and 67% of respondents, respectively. In addition, 39% reported a decrease in income due to the pandemic. 95% report having complied with IBD treatment during the COVID-19 pandemic, despite over 50% of them feeling that they were more at risk of infection due to their medication. DASS-21 scores indicate that during the lockdown the estimated prevalence of depression was 10.5% [95% CI 8.2–13%], anxiety 20% [95% CI –17–23%] and stress 18% [95% CI 8.2–13%]. Multivariate analysis is described in table 1.

Conclusion
In the short-term, lockdown during the COVID-19 pandemic seemed to have an impact on the mental health of our IBD patients in Spain. Further follow-up studies should be carried out to determine the real long-term impact, as it’s known that the wellbeing of this population might be affected because of IBD itself.
P188 Artificial Intelligence and Colon Capsule Endoscopy: Automatic detection of colonic mucosal lesions and blood using a convolutional neural network
Authors: Afonso J , Mascarenhas M , Ribeiro T , Cardoso H , Ferreira J , Andrade P , Jorge R , Lopes S , Macedo G 
Published: May 2021

Abstract

Background
Conventional colonoscopy is the standard criterion for the diagnosis and staging of colonic disease, including inflammatory bowel disease (IBD). However, it has the risk of complications, including bleeding and perforation. Colon capsule endoscopy (CCE) is a minimally invasive alternative for patients refusing conventional colonoscopy or for whom the latter is contraindicated. However, reading CCE images is a time-consuming task and prone to diagnostic error. Detection of colonic blood is relevant for the diagnosis and assessment of the activity of IBD, particularly ulcerative colitis. An accurate and early diagnosis is essential as it directs subsequent treatment.
Our aim was to develop an Artificial Intelligence (AI) algorithm, based on a multilayer Convolutional Neural Network (CNN), for automatic detection of blood and other significant lesions in the colonic lumen in CCE exams:

Methods
A total of 24 CCE exams (PillCam COLON 2®) from a single centre, performed between 2010–2020, were analysed. From these exams 7640 images (2915 normal mucosa, 3065 blood and 1660 mucosal lesions) were ultimately extracted. Two image datasets were created for CNN training and testing. These images were inserted in a CNN model with transfer of learning. The output provided by the CNN was compared to the classification provided by a consensus of specialists (Figure 1). Performance marks included sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), accuracy and area under the receiving operator characteristics curve (AUROC).

Results
Blood was detected with a sensitivity and specificity of 97.2% and 99.9%, respectively. The AUROC for detection of blood was 1.00 (Figure 2). Detection of other findings had a sensitivity and specificity of 83.7% and 96.7%, respectively. The overall accuracy of the CNN was of 95.4%.

Figure 1 - Output obtained from the application of the convolutional neural network. N: normal mucosa; B - blood or hematic residues; ML – mucosal lesions.

Figure 2 – Receiver operating characteristic analyses of the network’s performance in the detection of normal mucosa, blood and colon mucosal lesions. AUROC – are under the receiver operating characteristic curve; N – normal colonic mucosa; B – blood; ML – mucosal lesions.

Conclusion
We developed a pioneer CNN for CCE which demonstrated high levels of efficiency for the automatic detection of blood and lesions with high clinical significance. The development of tools for automatic detection of these lesions may allow for minimization of diagnostic error and the time spent evaluating these exams.
P243 Elevated presepsin levels are a marker of sepsis risk in patients with inflammatory bowel diseases receiving therapy of TNF-α blockers
Authors: Knyazev O , Kagramanova A , Lishchinskaya A , Li I , Noskova K , Fadeeva N , Subbotin V , Demchenko A , Babayan A , Zvyaglova M , Kulakov D 
Published: May 2021

Abstract

Background
Sepsis is a severe disease characterized by a systemic inflammatory response syndrome (SARS) associated with infection. Sepsis is registered in 1–2% of all hospitalized patients. IBD patients receiving immunosuppressive therapy have a high risk of developing sepsis. Diagnosis of sepsis is based on internationally agreed criteria. Predicting the course and outcomes of sepsis is evaluated on the MEDS (Mortality in Emergency Department Sepsis) scale. Clinical studies of a new biomarker called presepsin have shown that it is a promising early and predictive marker of sepsis

Aim
to establish the role of presepsin as a marker of sepsis development in patients with inflammatory bowel diseases (IBD) receiving therapy with genetically of TNF-α blockers.

Methods
The clinical status of 128 IBD patients receiving of TNF-α blockers therapy (without immunosuppressive drugs) was evaluated in the Department of IBD. 68 patients with ulcerative colitis (UC) and 60 patients with Crohn’s disease (CD). Presepsin level (PSP) was determined in all IBD patients (100.0%). To stratify patients, the following criteria were used for baseline PSP levels (pg/ml): &lt; 200 – very low risk of sepsis; - 200 - 300– low risk of sepsis; - 300 - 500– moderate risk of sepsis; - 500 - 1000 – sepsis; - ≥ 1000-severe sepsis, septic shock

Results
The distribution among 128 IBD patients receiving of TNF-α blockers by presepsin level was as follows: &lt; 200 -75 (58,6%); - 200 – 300 – 34 (26,6%); - 300 – 500 – 19 (14,8%); - 500 - 1000 – 0 (0%); ≥ 1000 – 0 (0%).
Of the 75 IBD patients receiving gibp and having a very low risk, none of the patients developed sepsis; of the 34 IBD patients with a low risk, one patient developed septicemia (2.9%). Among 19 patients with IBD with a moderate risk, the development of a septic condition occurred in 4 (21.0%) patients (HR-0.140, 95% CI 0.017 - 1.162; x2-2,800; p= 0.04997).

Conclusion
IBD patients receiving of TNF-α therapy, it is advisable to determine the level of presepsin in order to identify risk groups for the development of sepsis. Patients with IBD who receive of TNF-α therapy and have presepsin values in the range of 300–500 pg/ml have a significantly higher risk of developing sepsis.
P270 Mesenchymal stromal cells contribute to the recovery of secondary loss of response to infliximab in patients with ulcerative colitis
Authors: Knyazev O , Kagramanova A V , Lishchinskaya A , Li I , Shkurko T , Kulakov D , Babayan A , Zvyaglova M , Zhulina E , Parfenov A 
Published: May 2021

Abstract

Background
Long-term experience with infliximab (IFХ) shows that within a year, 20–30% of patients with ulcerative colitis (UC) develop acquired drug resistance (secondary inefficiency).

Aim
To establish the possibility of overcoming the secondary inefficiency of IFX in UC patients using mesenchymal stromal cells (MSC).

Methods
In the IBD treatment Department, the clinical status of 84 UC patients receiving IFX therapy was evaluated. Secondary loss of response was registered in 28 UC patients, which required optimization of IFX therapy. 12 patients (group 1), in order to overcome the secondary loss of response, were administered MSCS three times every 4 weeks, 16 patients with UC (group 2) received standard optimized IFX therapy. The effectiveness of therapy was evaluated after 12 weeks of therapy (reduction of the Mayo score) and normalization of laboratory parameters (ESR, C-reactive protein (CRP), hemoglobin, fecal calprotectin (FCP). The comparative analysis was carried out using the method of four-field tables using nonparametric statistical criteria.

Results
In 10 (83.3%) of 12 patients of group 1, a significant positive dynamics was observed after 12 weeks: a decrease in the Mayo index and normalization of laboratory parameters (ESR, CRP, hemoglobin, FCP). In 4 (25.0%) patients with UC from group 2, against the background of optimized IFX therapy, a significant positive dynamics was also observed with a decrease in the meio index and an improvement in ESR, CRP, hemoglobin and FCP levels. However, 12 patients from group 2 were transferred to therapy with other anti-TNF-α drugs and drugs with a different mechanism of action (RR-0.222, 95% CI 0.061–0.812; x2 - 7.146; p=0.00334).

Conclusion
The use of mesenchymal stromal cells of the bone marrow helps to overcome the secondary loss of response to infliximab in patients with ulcerative colitis.
P283 Decrease in bowel wall thickness at intestinal ultrasound accurately detects early endoscopic remission and improvement in ulcerative colitis patients on tofacitinib: a longitudinal prospective cohort study
Authors: de Voogd F , Van Wassenaer E , Mookhoek A , Bots S , Van Gennep S , Duijvestein M , Ponsioen C , Löwenberg M , D’Haens G , Gecse K 
Published: May 2021

Abstract

Background
To assess disease activity in ulcerative colitis (UC) intestinal ultrasound (IUS) highly correlates with endoscopic outcomes. However, data on treatment response evaluated with IUS is limited. In this study we aim to evaluate bowel wall thickness (BWT) at follow-up to determine treatment effectiveness in moderate-severe UC patients treated with tofacitinib according to central read endoscopy and histology.

Methods
Patients with moderate-severe UC (endoscopic Mayo score (EMS)≥2) starting tofacitinib 10 mg bid were included. Disease activity was evaluated by recorded IUS cine-loops and video-taped endoscopies with biopsies from the sigmoid (SC) and descending colon (DC) at baseline and at 8 weeks. BWT and EMS were assessed per segment (SC and DC). Histology was scored for the SC with the Robarts Histology Index (RHI). BWT, EMS and RHI were centrally read and for IUS there was a second reader. Endoscopic remission (ERem) was defined as EMS=0, endoscopic improvement (EI) as EMS≤1 and endoscopic response (ERes) as a decrease of EMS≥1. For statistical analysis a Wilcoxon signed-rank and Spearman’s test were used. Area under the ROC was used to determine optimal cut-off values. Inter-observer agreement was analyzed by intra-class correlation coefficient (ICC).

Results
29 patients were included and started tofacitinib. 10% reached complete ERem after 8 weeks, respectively. Per-segment analysis for EMS showed 22% and 53% reaching ER and 40% and 60% having EI in the SC and DC, respectively. BWT in SC and DC correlated highly with the EMS (rho=0.68, rho=0.75, both p&lt;0.0001) and moderately with RHI (rho=0.49, p=0.002). Patients with EMS≥2 after 8 weeks had an increased BWT (SC: 4.32 ± 1.57 mm, DC: 4.38 ± 1.58 mm) when compared to ERem (SC: 2.10 ± 0.67 mm, DC: mean: 2.00 ± 1.18 mm, both p&lt;0.0001) and EI (SC: 2.29 ± 0.76 mm, DC: 2.56 ± 1.38 mm, both p&lt;0.0001) in the similar segment (Figure 1 and 2). BWT decreased after 8 weeks when there was ERes (SC: mean: -2.59 ± 1.44 mm, DC: -1.82 ± 1.01 mm, both p=0.007) and did not when there was no ERes (Figure 3). BWT cut-off values for ERem are reported in Figure 4. Furthermore, agreement for BWT in the SC and DC was excellent (ICC: 0.92 and ICC: 0.89), respectively.

Conclusion
BWT reduction showed early endoscopic remission, improvement and response after 8 weeks of tofacitinib treatment and correlated with histology in this central read cohort. Furthermore, accurate and reliable cut-off values for BWT in SC and DC were found for endoscopic remission and improvement. Therefore, IUS should be incorporated in the standard follow-up and close monitoring of UC patients.
P291 Pharmacokinetics, safety, and tolerability of etrasimod (APD334) in subjects with mild, moderate, or severe hepatic impairment: a single-dose, open-label, parallel-group study
Authors: Lee C , Tang Y , Schroeder C , Zhang J , Nguyen-Cleary T , Mullin S , Ma M , Lyon N , Grundy J 
Published: May 2021

Abstract

Background
Etrasimod is an oral, selective sphingosine 1-phosphate receptor modulator in clinical development for immune-mediated inflammatory disorders, including ulcerative colitis, Crohn’s disease, and eosinophilic esophagitis. The objective of this study was to evaluate the effect of hepatic impairment on the pharmacokinetics (PK), safety, and tolerability of etrasimod.

Methods
This single-dose, open-label, parallel-group study included 36 adult subjects (aged 18-80 years; body mass index ≥18 kg/m2) with hepatic impairment, based on Child-Pugh score at screening (mild=5 to 6 [n=8], moderate=7 to 9 [n=8], severe=10 to 14 [n=6]), and their demographically matched control subjects with normal hepatic function (n=14 total). The first subject with severe hepatic impairment was enrolled after ≥2 subjects with mild and ≥2 subjects with moderate hepatic impairment had been enrolled and followed for ≥48 hours after dosing to ensure no observed significant safety signals. On Day 1, subjects received a single oral dose of etrasimod 2 mg after a ≥10 hour fast. PK and safety data were collected over a 21-day follow-up period.

Results
Thirty-six subjects were enrolled and dosed; 35 subjects completed the study. When compared with their respective demographically matched normal control groups, single dose etrasimod peak exposure (Cmax) was comparable for all hepatic impairment groups, whereas etrasimod total exposure (AUC) measures were progressively higher (up to 57.3% higher) in the mild, moderate, and severe hepatic impairment groups (Table 1). Unbound etrasimod Cmax values were progressively lower (up to 42.0% lower) in the mild, moderate, and severe hepatic impairment groups, whereas unbound etrasimod AUC values were typically comparable for all hepatic impairment groups, when compared with their respective demographically matched normal control groups (Table 2). Etrasimod t1/2 only moderately increased as hepatic function decreased, with mean values ranging from 43.9 to 59.5 hours in the demographically matched normal control groups and mean values of 55.7, 69.7, and 76.5 hours in the mild, moderate, and severe hepatic impairment groups, respectively. A single oral dose of etrasimod 2 mg was well tolerated; there were no clinically significant safety findings when administered to subjects with normal hepatic function or subjects with mild, moderate, or severe hepatic impairment.

Conclusion
A single oral dose of etrasimod 2 mg was well tolerated, with relatively modest changes in etrasimod exposure observed in subjects with mild, moderate, or severe hepatic impairment. These results suggest that etrasimod dose adjustment may not be warranted in subjects with hepatic impairment.
P330 Long-term outcomes following a switch from originator adalimumab to the biosimilar SB5 (Imraldi) in IBD
Authors: Derikx L , Dolby H , Plevris N , Lucaciu L , Rees C , Lyons M , Siakavellas S , Constantine-Cooke N , Noble C , O’Hare C , Merchant L , Arnott I , Jones G R , Lees C 
Published: May 2021

Abstract

Background
Multiple adalimumab (ADA) biosimilars, including SB5 (Imraldi) and ABP 501 (Amgevita), are now approved for use in IBD. Data about biosimilar ADA in IBD remain scarce. We therefore aimed to investigate long-term outcomes of the biosimilar SB5 in IBD patients following a switch from the ADA originator (Humira) or after start of SB5 as their first ADA-therapy.

Methods
We performed a retrospective cohort study in a tertiary IBD referral centre. All IBD patients treated with Humira underwent an elective switch to SB5 regardless of IBD phenotype, disease activity and ADA dosing. All patients were reviewed regularly in the virtual biologics clinic with protocol driven collection of clinical disease activity, blood tests, TDM and faecal calprotectin. We identified all patients on SB5 in a biologic prescription database that prospectively registered all ADA by brand name and start and stop dates.

Results
441 patients were treated with SB5, including 234 who switched from Humira to SB5 (CD=209, 89.3%; median IBD duration 10 years, IQR 6-16) and 207 who started on SB5 as their first ADA-therapy (CD=162, 78.3%; median IBD duration 6 years, IQR 1-16.8).
107/234 (45.7%) patients who switched to SB5 used infliximab before ADA. These patients were treated for a median of 32 months (IQR 17-57) with Humira prior to switching. At Humira – SB5 switch, 60.1% (140/234) received 40mg ADA every other week and 39.1% (91/234) once weekly. The median duration of follow up was 13 months (IQR 8-14). At week 26 and week 52, 194/231 (84.1%) and 148/215 (70.3%) patients remained on SB5, respectively (Figure 1). 81/234 patients (35.0%) discontinued SB5, mostly due to adverse events (n=40/81) or secondary loss of response (n=35/81). Pain at the injection site was the most frequently reported adverse event (n=31); all these patients switched to Amgevita. 30/31 patients with a double biosimilar continued Amgevita until the end of follow up (median 30 months), resulting in 172/215 (81.3%) patients that remained on ADA at week 52 (Figure 1).
Proportions of patients in biochemical remission and clinical remission were similar at baseline, week 26 and week 52 following switch (Figure 2). Median ADA trough levels were similar before (10.2 ug/ml, IQR 7.4-13.5) and after switch 10.3 (IQR 7.4-13.1). 17/234 (7.3%) patients developed antibodies during SB5 treatment.

Conclusion
Switching from Humira to SB5 appeared effective and safe in this study with over 12 months of follow up. The most common adverse event was injection site pain; these patients were successfully moved on to Amgevita providing the first data about a double biosimilar switch. Over the 24 months of this biosimilar ADA program substantial cost savings were effected.
P333 Endoscopic severity and CRP predict failure of medical rescue therapy in patients with acute severe ulcerative colitis
Authors: Kakkadasam Ramaswamy P , Subhaharan D , Willmann L , Edwards J , Shukla D , Bhullar M , Moattar H , Dorrington A , Ishaq N , McIvor C , Mohsen W 
Published: May 2021

Abstract

Background
The efficacy of Infliximab and Cyclosporin A as medical rescue therapy in patients with corticosteroid refractory acute severe ulcerative colitis (ASUC) is well established. We aimed to identify predictors of failure of medical rescue therapy and colectomy during the same admission in this population.

Methods
Patients hospitalized with ASUC who received infliximab or cyclosporin A after failing intravenous corticosteroid therapy between 1st January 2013 to 31stJuly, 2020 at two Australian tertiary IBD centres were retrospectively analysed. Patients who underwent colectomy during the same admission after medical rescue therapy were defined as non-responders. Logistic regression analysis was performed to identify predictors of colectomy during same admission.

Results
226 episodes of ASUC [110 (48.7%) female, median disease duration 2 years] were analysed. 104 (46%) episodes required rescue therapy [94 episodes received medical rescue (16 cyclosporine/78 Infliximab) and 10 underwent direct colectomy]. In patients receiving medical rescue therapy, 16 (17%) underwent colectomy during same admission and 28 (29.8%) underwent colectomy by 12 months. On multivariable analysis, UCEIS score at admission [Coef 0.100 (0.02-0.17), p 0.011] and CRP on Day 3 post-rescue therapy [Coef 0.004 (0.0007-0.007), p 0.018] were significant for predicting colectomy during the same admission. A score with 1 point for each variable (UCEIS score ≥ 7 and CRP value of ≥ 22 mg/L on day 3 post medical rescue therapy) was developed. A score of 2 points had sensitivity 57%, specificity 97%, PPV 80%, NPV 91%, accuracy 89% for predicting colectomy during the same admission and sensitivity 33%, specificity 94%, PPV 80%, NPV 67%, accuracy 69% for predicting colectomy at 12 months.

Conclusion
UCEIS and CRP on day 3 after rescue therapy are predictors of non-response to medical rescue therapy and need for colectomy during the admission for the ASUC episode. Combination of UCEIS ≥ 7 and CRP ≥ 22mg/L on day 3 post medical rescue therapy has a PPV of 80% for colectomy during same admission and at 12 months. The score can be used to make decisions about colectomy or further medical rescue therapy.