bluuebunny/crossref_metadata_2025_split huggingface dataset:
P621 Combination treatment of biologics with immunomodulator increases risk of infection after discharge in biologics naive steroid refractory acute severe ulcerative colitis patient: A KASID multicenter study
Authors: Kim S J , Lee J , Kim D H , Park S H , Kim E S , Kim K O , Lee Y J , Song E M , Kim D S ,   IBD Research Group in Korean Association for the Study of the Intestinal Diseases (KASID)
Published: January 2023

Abstract

Background
Biologics such as infliximab is the main treatment for steroid refractory acute severe ulcerative colitis (ASUC), However, there are only a few studies on the effectiveness and safety of biologics in steroid refractory ASUC. In this study, we evaluated the effectiveness and safety of biologics as a rescue therapy for biologics naïve steroid refractory ASUC patient in Korea.

Methods
We retrospectively included patients who were hospitalized at seven tertiary medical centers for ASUC management between January 2015 to December 2020, and data on the demographic and clinical variables, disease activity, treatment method, treatment response, adverse event, readmission due to any reasons were checked

Results
A total of 230 ASUC patients were included, of which 220 were biologic naïve patient. The response rate of steroid in these patients was 74%, and infliximab was administered as rescue therapy to 53 patients who failed initial steroid treatment. The response rate to infliximab as rescue therapy was 96%, and 2 patients who did not respond received colectomy. One of the two patients who underwent colectomy died of sepsis. There was no infliximab-related adverse event during hospitalization. Although infliximab itself was not a factor associated with infection after discharge (10% vs. 16%, p=0.355), combination therapy with thiopurine was a risk factor for infection after discharge. (Odd ratio 7.302, 95% CI 2.101-25.372, p=0.002). A total of 12 infections occurred in patients treated with infliximab after discharge (3 pneumonia, 1 skin infection, 3 cytomegalovirus colitis, 4 Clostridium difficile infection) and were associated with readmission. (40.1% vs. 75%, p=0.031)

Conclusion
As a rescue therapy in biologics naive steroid refractory ASUC, infliximab showed a 96% therapeutic response. Although infliximab itself did not increase the risk of infection after discharge, the combination with thiopurine increased the risk of infection after discharge
P693 Italian real-life study evaluating the long-term effectiveness of vedolizumab for the treatment of Inflammatory Bowel Disease- An IG-IBD study
Authors: Pugliese D , Privitera G , Armuzzi A ,   IG-IBD LIVE Studygroup
Published: January 2023

Abstract

Background
Real-world studies on vedolizumab (VDZ) are often limited by small sample size and short follow-up and there is still lack of knowledge regarding predictors of response. Our study aims to evaluate the long-term effectiveness and safety of VDZ in a large cohort, and to identify clinical features for precision medicine.

Methods
The Long-term Italian VDZ Effectiveness (LIVE) study included CD and UC patients started on VDZ from 04/2016 to 06/2017 at 47 Italian centers and prospectively followed-up until 06/2019. The primary endpoint was steroid-free clinical remission (SFCR) at 12 months (mo), defined as clinical remission + no steroid therapy in the previous 3 mo. Secondary endpoints included treatment persistence and safety. An eXplainable Artificial Intelligence (XAI) model (XGBoost) was used to predict 12 mo-SFCR. To assess the model performances, F1-score was adopted.

Results
We enrolled 1111 patients (564 CD, 547 UC). At baseline, mean age and disease duration were 47.7(±16) and 11.8(±9) years; 256 (23%) patients were bionaïve. SFCR was reported in 193 (34.3%) and 178 (31.6%) CD patients, and in 205 (41.9%) and 215 (42.6%) UC patients, at 12 and 24 mo (p=ns for all). Cumulative treatment persistence at 12 and 24 mo was 73.3% and 67.3%, respectively. A significantly longer persistence was observed among bionaïve compared to bioexperienced CD patients (p=0.04), but not in UC. At least 1 adverse event (AE) was experienced by 230 patients (20.8%), causing VDZ withdrawal in 58 (5.2%) of them; the most common AEs were infections. The trained machine learning (ML) algorithm was used to predict 12 mo-SFCR. To minimize the bias introduced by the imbalanced dataset, a data augmentation technique (Synthetic Minority Over-sampling Technique, SMOTE) was introduced. The predictive model’s accuracy (F1 score) was 0.85. To explore the relations among the variables for the predicted outcome, Shapley Additive exPlanations (SHAP) was adopted. Figure 1 presents the 8 best features, hierarchically listed, with their average impact on the outcome. Figure 2 shows how the value taken by each feature contributes to predicting 12 mo-SFCR (dots close to the 0 line predict SFCR). The most important variables. correlating with 12 mo-SFCR were No exposure to anti-TNF, male sex and no baseline steroid therapy.

Conclusion
In this preliminary analysis, about 1/3 of VDZ-treated patietns achieved 12 mo-SFCR. With ML, we identified the most important predictors of SFCR and estimated their impact on it. XAI is a promising tool in precision medicine, as it helps reconciling sophisticated models with the biological explainability of data.
P773 Extended induction in the True North open-label extension study: clinical outcomes of ~2 years of ozanimod treatment
Authors: Vermeire S , Colombel J F , Chiorean M V , Ghosh S , Jain A , Lawlor G , Osterman M T , Wu H , Canavan J B , Rubin D T 
Published: January 2023

Abstract

Background
Ozanimod is approved in the EU, US, and other countries for the treatment of moderately to severely active ulcerative colitis in adults. In the phase 3, 52-week, double-blind True North (TN) study, Week 10 clinical nonresponders to ozanimod could enter the open-label extension (OLE) to continue treatment. Previous analysis showed that approximately 50% of Week 10 nonresponders achieved symptomatic clinical response with extended induction during the OLE in as early as 5 weeks. The current analysis evaluated long-term clinical and symptomatic endpoints up to 2 years in this delayed responder subgroup.

Methods
Efficacy data were analysed for TN Week 10 ozanimod nonresponders who subsequently received open-label ozanimod in the OLE, both by whole subgroup and original study arms (double-blind [Cohort 1] and open-label ozanimod [Cohort 2]) (data cutoff: January 10, 2022). Endpoints included symptomatic clinical response, symptomatic clinical remission, total Mayo score, clinical response, clinical remission, and corticosteroid (CS)-free remission up to OLE Week 94 (104 weeks of continuous ozanimod treatment). Data were evaluated using observed case (OC) and nonresponder imputation (NRI) analyses.

Results
A total of 226 nonresponders at TN Week 10 entered the OLE (Cohort 1, n=150; Cohort 2, n=76). Males comprised 67% of this subgroup, and mean (SD) age was 39.6 (13.6) years. Symptomatic clinical response (Figure 1), symptomatic clinical remission, and reduction in partial Mayo scores were observed as early as OLE Week 5 and were maintained through OLE Week 94. Minimal change in total Mayo score was observed from TN Week 0 (baseline) to TN Week 10 (OLE Week 0), but significant reductions from baseline occurred by OLE Week 46 (–4.2 [2.7]) and OLE Week 94 (–5.3 [2.6]). Overall, 62% of patients achieved clinical response, 26% achieved clinical remission, and 24% achieved CS-free remission at OLE Week 46; these increased to 74%, 35%, and 33%, respectively, by OLE Week 94 in the OC analysis (Figure 2). Data were similar between Cohorts 1 and 2.

Conclusion
Symptomatic response in ozanimod nonresponders was observed as early as 5 weeks after extended induction with ozanimod. Delayed response to ozanimod was maintained for up to 2 years as demonstrated by both symptomatic and objective endpoints. Even in those with delayed initial response, efficacy of ozanimod was durable.
P805 Selnoflast, a potent NLRP3 inhibitor - results from a phase 1b experimental medicine study in patients with Ulcerative Colitis
Authors: Klughammer B , Piali L , Nica A C , Nagel S , Bailey L , Jochum C , Ignatenko S , Bläuer A , Danilin S , Gulati P , Hayward J , Scepanovic P , Retout S , Zhang J D , Bhosale S , Sue-Ling K , Chong C F , Christ A 
Published: January 2023

Abstract

Background
The Nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) inflammasome is a driver of caspase 1-dependent release of IL-1β and IL-18 and has been identified as a potential drug target for ulcerative colitis (UC) (Tourkochristou et al. 2019). Selnoflast (RO7486967) is an orally active, potent, selective, and reversible small molecule NLRP3 inhibitor. To assess whether NLRP3 is a driver of inflammation and more specifically of IL-1β production and signaling in UC, we performed a Phase 1b study (BP43099) with selnoflast in patients with UC.

Methods
A randomized, placebo-controlled, double blind study assessed safety, tolerability, PK and PD of selnoflast in patients with active, moderate to severe UC. 19 patients were recruited: 6 were treated with placebo and 13 were treated with 450 mg selnoflast QD for 7 days. Stool and blood samples were taken at baseline, during and at the end of treatment. Sigmoidal tissue samples were taken at baseline and at the end of treatment. Adverse events were assessed throughout the study. https://www.isrctn.com/ISRCTN16847938

Results
Selnoflast was well tolerated in all patients, with mainly mild AEs. No serious or severe AEs were reported. Plasma PK was in line with PK data from previous studies in healthy subjects. In addition, selnoflast demonstrated a good distribution in sigmoidal tissue in all treated patients.
The gene signature of 8 genes (i.e. CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CCL2, IL-6, TNFAIP6) downstream of IL-1β, known to be responsive to IL-1β stimulation across different cell types and differentially expressed in colonic biopsies (UC vs healthy), was assessed and showed on average a slight decrease from baseline after treatment with selnoflast compared to placebo (log2 fold change mean (sd) = -1.14 (1.8) and +0.38 (3.26) respectively, t-test p-value = 0.206) in sigmoidal tissue biopsies. Single-cell RNA sequencing showed minimal differences between the two treatment arms.

Conclusion
Selnoflast was well tolerated and achieved the plasma and tissue exposure predicted to inhibit NLRP3. Expression of IL-1β gene signature in sigmoidal tissue biopsies, single-cell RNA sequencing and additional biomarker analyses showed no robust differences between the two treatment arms, suggesting that targeting the NLRP3 inflammasome with selnoflast may be of limited therapeutic benefit to reduce inflammation in UC.
Tourkochristou E, Aggeletopoulou I, Konstantakis C, Triantos C. Role of NLRP3 inflammasome in inflammatory bowel diseases. World J Gastroenterol. 2019
P824 Sexual Dysfunction among young patients with Crohn′s disease. A Spanish case control study.
Authors: Gutiérrez Casbas A , Madero Velázquez L , Herreros B , Zapater P , Rodríguez A , Muñoz R , Bernal L , Orts B , Belen O , Sempere L , Moreno-Pérez O , Francés R 
Published: January 2023

Abstract

Background
Sexuality is a complex entity and a major determinant of quality of life in patients diagnosed with inflammatory bowel disease (IBD). It has been estimated that sexual dysfunction (SD) affects 30% of women and 5% of men in the general population as well as 50% in women and 25% in men with IBD.

Objectives
To compare the rates of SD between young female and male patients with Crohn’s disease (CD) and healthy controls matched by age and sex and to search for predictors of SD in CD patients.

Methods
Observational, case-control, prospective study including CD patients with CD, 18-40 years of age. Age and sex-matched (2:1) healthy controls (HC) were selected.
Demographic characteristics of all subjects and clinical features of CD were collected. The variables explored were SD in women (Index of Female Sexual Function (IFSF), SD in men (International Index of Erectile Function [IIFE-15]) and presence of anxiety-depression (Hospital Anxiety/Depression Scale [HADS]).

Results
A total of 163 subjects were included: 83 men (58 CD, median 28 years (RIQ 24-36) and 25 male HC, median 31 years (RIQ 26-37) and 80 women (50 female CD, median 26 years (RIQ 21-36) and 30 HC, median 28 (RIQ 26-32). 24% of women with CD and 8% of men had clinical activity (HBI &gt;4). Table 1 summarizes main clinical characteristics of overall study population. Demographic characteristics of men with CD and HC were not significantly different. Sedentary lifestyle was more common among women with CD vs HC (46% vs 3.3%, p&lt;0.001), as well as educational level (universitary studies 44% CD vs 83%, HC,p= 0.003) and employment status (unemployment CD 26% vs CS 3%, p=0.01) were significantly different between groups.
SD in men, measured by IIFE, was more common in CD patients than among HC, 14/58 (24%) vs 1/25 (4%), p=0.031. CD male patients scored significantly lower than HC regarding overall sexual satisfaction 8 (6-9) vs 9 (8-10), p=0,02. Erectile dysfunction occurred only in CD (7/46, 15%), p= 0.08. Female SD was, likewise more frequent in women with CD vs female HC, (18/50 (38%) CD vs 3/30 (12%) HC,p=0.017), and female CD patients scored significantly lower with regard sexual desire (5 vs 7, p=0.008), arousal (9.0 vs 11, p=0.06) and lubrication (10 vs 13, p=0.04) than female HC. Logistic regression analysis showed that only anxiety was associated with SD in women, finding no associated risk factors with SD in CD male patients.

Conclusion
CD patients present a disease activity-independent higher risk of SD compared to the general population. Domain affected in male patients is impairment of satisfaction whereas lubrication, sexual desire and arousal, being associated with anxiety, are affected in female CD patients.
P904 Genetic Variants in IBD Chilean Patients are related to clinical outcomes
Authors: Pérez T , Bustamante M L , Travisany D , Magne F , Hernandez-Rocha C , Alvarez-Lobos M , Orellana M , Ascui G , Azocar L , Espino A , Aguilar N , Baez P , Zazueta A , Estela R , Silva V , Escobar S , De la Vega A , Arriagada E , Miquel J F , Alvares D 
Published: January 2023

Abstract

Background
IBD has emerged as a worldwide disease with an increased incidence in newly industrialized countries such as Chile. This population has been underrepresented in genome-wide association studies (GWAS) because IBD genetics studies have focused mainly on North America and European populations. In addition, specific IBD risk alleles have been related to different races and ethnicities. Aim: To investigate the association of IBD risk variants reported in previous GWAS studies with clinical outcomes in our Chilean patients.

Methods
192 Chilean individuals with IBD (145 UC and 47 CD) were genotyped using Illumina GSA Arrays. From IBD GWAS (Jostin et al. and Liu et al.), we selected gene variants with pGWAS value &lt; 5x10-8 and looked for them in our Chilean IBD group. Then, we built a Chilean dataset (clinical-genotype information). Using this dataset, we performed a Spearman correlation matrix to correlate clinical outcomes with IBD variants. Further, we built regression models to predict the clinical outcomes using the variants obtained from the correlation matrix (p &lt;0.05). Then, we selected the best models using significance testing (P values) or likelihood-based information criterion, such as the Akaike Information Criterion (AIC) and plotted the models using a Receiver Operating Characteristic Curve (ROC). Finally, to evaluate the association among variants in each model, we perform a Gene Ontology biological process enrichment analysis using PANTHER (Fisher, FDR).

Results

As shown in Figure 1 and Table 1, the best predictive regression models (more than 80%) for the clinical outcomes were surgery, Clinical/Endoscopy remission for more than five years, and Naïve anti-TNF. Association with genetic variants was observed significantly (p&lt;0.05) in the enrichment analysis for the model Clinical/endoscopy remission (Table 2).

Conclusion
Conclusion. Candidates’ genes related to clinical outcomes in our Chilean IBD cohort were related to epithelial, innate, and adaptative immune responses and host-microbial interactions. Future research is needed to validate these findings.
N21 Patient education is (sometimes) better than cure
Authors: Müskens B ,   P. (Petra) Waayenberg MSc K.H.N. (Nanne) De Boer MD PhDA S. (Sigrid) Müller-Schotte OD PhD FAAOB
Published: January 2023

Abstract

Background
About half of all patients with Inflammatory Bowel Disease (IBD) experience Extra Intestinal Manifestations (EIMs)1. One of these EIMs are non-inflammatory joint complaints. Preliminary research2 has shown that IBD patients treated by Amsterdam university medical centers (UMC) experience a lack in pre-symptomatic patient education regarding these complaints. The patients interviewed in this preliminary study were all unaware of the possible development of these joint complaints in addition to their IBD.

Methods
A practice-oriented study was set up. Both qualitative and quantitative research techniques were used. Literature research into innovations for patient education was performed. Questionnaires were distributed among IBD patients in Amsterdam UMC to identify wishes and needs regarding patient education about non-inflammatory joint complaints. To determine how this education is provided elsewhere, questionnaires were distributed among caregivers of IBD patients in other Dutch hospitals.

Results
According to literature research, verbal education, information leaflets, informational websites, group education and educational programs contribute to an increased knowledge of disease in IBD patients. Surveyed IBD patients from Amsterdam UMC wish to be informed about non-inflammatory joint complaints via verbal education or by information leaflets and/or internet. Of the surveyed caregivers in other Dutch hospitals, the majority do not have educational materials and/or methods about (non-inflammatory) joint complaints. Information is given verbally by most of them. The innovation is an information leaflet entitled 'Joint complaints in IBD'. This can be used to support verbal patient education and can be used as a reference work. The leaflet is also offered via internet.

Conclusion
Offering the information leaflet 'Joint complaints in IBD' is an appropriate innovation that meets the wishes of IBD patients in Amsterdam UMC with regard to patient education about non-inflammatory joint complaints. The leaflet is preferably used to support verbal patient education and is subsequently given to the IBD patient as a reference work or offered via the internet. Content optimization is recommended. Afterwards, a pilot implementation can be set up. After implementation, further research is recommended to investigate whether the innovation actually contributes to optimization of pre-symptomatic patient education about non-inflammatory joint complaints.
Sibling Cannibalism in Group-Living Larvae of the Solitary Wasp,Isodontia harmandi(Hymenoptera: Sphecidae): Effects of Prey Availability and Size Discrepancy
Authors: Imasaki Yui , Endo Tomoji 
Published: January 2023

AbstractSibling cannibalism has rarely been documented in the resource-based context of sibling rivalry. The solitary wasp Isodontia harmandi (Pérez) (Hymenoptera: Sphecidae) has an exceptional style of nursery ‘communal brood cells’, in which multiple larvae gregariously develop while relying on maternal prey provisioning. In this species there are several distinct features; e.g., cannibalism-driven brood reduction, single-sex broods, and mass provisioning. Rearing of the wasp larvae in artificial nest chambers provides the novel opportunity to study larval interactions under controlled conditions. To determine the factors that influence the occurrence of cannibalism and its timing, we conducted a rearing experiment using sib and non-sib pairs under two prey-availability treatments, and recorded the occurrence of cannibalism and the processes of larval growth and prey consumption over a 96-hr period. Cannibalism occurred more frequently in the low-prey treatment than in the high-prey treatment, and in female pairs than in male pairs. Cannibalism tended to occur earlier when the amount of prey remaining decreased rapidly. However, cannibalism did not occur only when all prey had been completely consumed, implying that it was not triggered directly by prey exhaustion. Cannibals were always larger than their victims, whose growth rates had often slowed before they were eaten. These results strongly imply that wasp larvae commit sibling cannibalism in the context of resource-based sibling rivalry, ensuring the double benefit of nutritional gains and reduced resource competition. We also investigated the possibility that wasp larvae monitor the size difference and/or body condition of brood-mates as an indicator of prey availability.
Long-term survival outcomes after lobe-specific nodal dissection in patients with early non-small-cell lung cancer
Authors: Kamigaichi Atsushi , Aokage Keiju , Ikeno Takashi , Wakabayashi Masashi , Miyoshi Tomohiro , Tane Kenta , Samejima Joji , Tsuboi Masahiro 
Published: January 2023

Abstract

OBJECTIVES
We investigated the long-term outcomes of lobe-specific nodal dissection (LSD) and systematic nodal dissection (SND) in patients with non-small-cell lung cancer (NSCLC).

METHODS
Patients with c-stage I and II NSCLC who underwent lobectomy with mediastinal nodal dissection were retrospectively analysed. After propensity score matching, we assessed the overall survival (OS), recurrence-free survival (RFS) and cumulative incidence of death (CID) from primary lung cancer and other diseases.

RESULTS
The median follow-up period was 8.4 years. Among 438 propensity score-matched pairs, OS and RFS were similar between the LSD and SND groups [hazard ratio (HR), 0.979; 95% confidence interval (CI), 0.799–1.199; and HR, 0.912; 95% CI, 0.762–1.092, respectively], but the LSD group showed a better prognosis after 5 years postoperatively. CID from primary lung cancer was similar between the 2 groups (HR, 1.239; 95% CI, 0.940–1.633). However, the CID from other diseases was lower in the LSD group than in the SND group (HR, 0.702; 95% CI, 0.525–0.938). According to c-stage, the LSD group tended towards worse OS and RFS, with higher CID from primary lung cancer than the SND group, in patients with c-stage II.

CONCLUSIONS
LSD provides acceptable long-term survival for patients with early-stage NSCLC. However, LSD may not be suitable for patients with c-stage II NSCLC due to the higher mortality risk from primary lung cancer.