bluuebunny/crossref_metadata_2025_split huggingface dataset:
P103 Identifying CES-1 positive myeloid cells with mass cytometry as a potential therapeutic target for Crohn’s disease
Authors: Hageman MD I , Elfiky A , Becker M , Joustra V , Buskens C , Li Yim A , Hakvoort T , Verhoeff J , Garcia Vallejo J , D’Haens G , Wildenberg M , De Jonge W 
Published: January 2022

Abstract

Background
Myeloid cells are key players in the sustained inflammatory process in Crohn’s disease (CD), and are therefore therapeutic targets. Human mononuclear myeloid cells express the cell selective expression of carboxylesterase 1 (CES-1). Esterase-sensitive motif (ESM) technology has been developed to specifically target ESM tagged small molecules on human mononuclear myeloid cells, based on their CES-1 expression, creating a larger therapeutic window with less side effects. This study investigates the presence of CES-1 expressing cells in PBMCs, intestinal biopsies and fistula cells of CD patients, highlighting the potential of ESM-technology in CD. This could benefit CD treatment in non-responsive patients or patients with a fistulizing phenotype.

Methods
Intestinal biopsies were collected from CD patients who underwent endoscopy. PBMCs were collected from CD patients who were receiving Vedolizumab (VDZ) treatment and categorized as responders or non-responders. Criteria for response was based on clinical (HBI ≤4) and biochemical (fecal calprotectine ≤250 µg/g) and/or endoscopic assessment (≥50% reduction in SES-CD score). Fistula tissue was of CD patients was obtained during surgery. CES1-positive cells were phenotyped by mass cytometry with a panel of 32-markers, including the myeloid markers CES-1, CD14, CD16, HLA-DR, CD11c, CD206.

Results
We demonstrated the presence of CD14+HLADR+CD11a+CD44+CD11b+ myeloid cells exclusively expressing CES-1 in intestinal biopsies of CD patients (n=7). CES-1 expression did not differ between inflamed and uninflamed tissue. In PBMCs of VDZ responders (n=5) and non-responders (n=6), we were able to identify different subsets of myeloid cells such as classical (CD14++CD16-), intermediate(CD14+CD16+) and non-classical (CD14-CD16++) monocytes, DCs and CD2+ DC precursors all demonstrating CES-1 expression. Percentage of CES-1 positive cells in inflamed PBMCs (or non-responders) was higher than in uninflamed PBMCs (responders) in all of the above-mentioned subsets. Furthermore, we demonstrated different myeloid populations within fistula cells (n=13) such as pDCs (CD123+CD68+HLA-DR+), DCs (CD11c+CD11b+HLA-DR+ CD44+), CD141+DCs (CD141+CD49d+HLA-DR+),Macrophage (CD14+CD11c+CD11b+HLA-DR+CD44+) and M2 Macrophages (CD14+CD163+CD206+CD11c+CD11b+HLA-DR+CD44+), all expressing CES-1.

Conclusion
We demonstrated specific CES-1 positive myeloid cells within intestinal biopsies, PBMCs of non-responsive patients, and fistulae samples of CD patients. Targeting CES-1+ with ESM-technology could provide new therapeutic targets for CD.
P119 Hereditary Colorectal Cancer Syndromes and Inflammatory Bowel Diseases: an ECCO CONFER Multicenter Case Series
Authors: Barberio B , Savarino E , Verstockt B , Fumery M , Pugliese D , Bertani L , Buda A , Dragoni G , Goren I , Laish I , Spinelli A , Teich N , Truyens M , Ellul P 
Published: January 2022

Abstract

Background
Hereditary colorectal cancer syndromes (HCCS) are rare polyposis or nonpolyposis syndromes with a higher risk of developing colorectal cancer (CRC). Coexisting inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), with HCCS is exceedingly rare and presumably increases the risk of early-onset colorectal cancer.

Methods
This was a multicenter case series performed as a part of the European Crohn’s and Colitis Organisation (ECCO) Collaborative Network of Exceptionally Rare case reports (CONFER) project.

Results
This report includes 26 patients with IBD (10 UC, 15 CD, and one with IBD unclassified (IBD-U)) and concomitant HCCS. Among these 26 patients (median age 33 years, IQR 20–44), 15 (57.7%) were males, 24 (92.3%) Caucasians and 2 (7.7%) of Arab origin. Among patients with UC, 4 (40%) had proctitis, 3 (30%) left-sided colitis and 3 (30%) an extensive disease; while, among patients with CD, 8 (53.3%) had ileal, 5 (33.3%) ileocolonic, 2 (13.3%) colonic disease. One of these patients had ileocolonic disease associated with upper disease location and six (40%) had an associated perianal disease. Many of patients with CD had a non-stricturing non-penetrating phenotype (53.3%, n=8), while 20.0% (n=3) and 26.7% (n=4) had a stricturing or penetrating phenotype, respectively. HCCS was diagnosed before the IBD diagnosis in 11 patients (42.3%), after diagnosis of IBD in 11 patients (42.3%) and concurrently in 4 patients (15.4%). Sixteen patients had Lynch syndrome, 7 had FAP, 2 had AFAP and one had MAP. The most frequent genetic mutations were those of APC (n=7) and MLH1 (n= 7). Thirteen patients were treated with immunomodulatory (IMM) therapy. During IMM therapy, only 5 patients developed drug-induced side-effects which did not require drug interruption. One patient treated with vedolizumab developed CRC, despite yearly colonoscopy surveillance, after 4 years of treatment. Overall, CRC developed in 38.5% of patients (n=10): in 5 patients (50%) after IBD diagnosis, in 4 (40%) patients before IBD diagnosis, and in 1 patient the 2 conditions were diagnosed simultaneously. Eighteen (69.2%) patients underwent colectomy or abdominal surgery: 9 patients due to CRC diagnosis, 7 patients preventively due to the underlying HCCS and 2 patients because of active IBD disease. On follow-up, one patient died due to CRC.

Conclusion
This case series describes the largest series to date of patients with IBD patients and HCCS, with special emphasis on the use of IMM in this population. The most frequent diagnosis of HCCS associated with IBD was Lynch syndrome. These data demonstrate the high malignancy rate and surgical intervention rate in this IBD cohort. The optimal medical approach still needs to be addressed.
P120 First year remission rates among patients with newly diagnosed Crohn’s disease: data from a real-world prospective inception cohort
Authors: Yanai H , Sharar Fischler T , Goren I , Ollech J , Snir Y , Broitman Y , Barkan R , Peffer-Gik T , Raykhel B , Kutukov L , Friedeberg A , Pauker M , Eran-Banai H , Avni-Biron I , Dotan I 
Published: January 2022

Abstract

Background
There are sparse data regarding the effectiveness of novel treatment strategies for newly diagnosed patients with Crohn’s disease (CD). Data from clinical trials demonstrate 30–40% remission rates after 1-year. We aim to assess remission rates among newly diagnosed patients with CD in a referral center.

Methods
A prospective observational cohort study of patients with newly diagnosed CD between 03/2018- 01/2021. Patients were scheduled for semi-annual visits for assessment, data collection, and education by an IBD-oriented gastroenterologist who determined a treatment plan, IBD nurse, and dietitian. Disease activity was determined by Crohn’s disease activity index (CDAI). Clinical remission (CR) at 1-year-period (9–18 months) was defined as: CDAI &lt; 150, no active perianal disease, and steroid-free&gt; 3 months. Biochemical remission: C-reactive protein (CRP)&lt;1mg/dl, fecal calprotectin (FC)&lt;150 ug/g and normal albumin levels. Endoscopic remission: SES-CD&lt;3. Deep remission: composite of clinical, biochemical, and endoscopic remission. Predictors for clinical remission were assessed by multivariable logistic regression.

Results
Out of 110 enrollees, 77 completed 1-year period: 50.6% female, median age 27 years (22–38), median BMI 22 kg/m2 (20–25), 16.9% smokers. At diagnosis 72.7% had an inflammatory phenotype (B1), and 26% had complex perianal disease, 55.8% had moderate-severe CD (CDAI&gt;220). During the first year after diagnosis 59.7% were treated with a biologic (58.5% anti-TNF, 1.3% ustekinumab, 3.9%&gt;1 biologic), diagnosis-biologic interval 4.3 months (IQR:2.6–7.3), and 9.1% required surgery. At 1-year-period 63.6% achieved CR (comparable CR rates in patients recruited with mild-moderate vs moderate-severe CD:61.8% vs 65.1%, p= 0.814). Biochemical, endoscopic and deep remission rates: 51.9% (40/77), 44.4% (24/54), and 25.9% (14/54), respectively. Significant decrease in clinical and biochemical activity during follow up: median CDAI 233 (IQR:143–286) to 83 (IQR:29–150); median CRP 1.8 mg/dl (IQR:0.4–4.1) to 0.2 (IQR:0.1–1); median FC 714 ug/g (IQR:128–1538) to 114 (IQR:18–355); all p&lt;0.001. Paired endoscopic data, available for 54 patients, demonstrated decrease in median SES-CD from 8 (IQR:5–11) to 3 (IQR:0–5), p&lt;0.001. Short IBDQ score increased from a median of 43 (IQR:36–55) to 56 (IQR:42–61). B1/P0 phenotype and lower BMI at diagnosis were associated with higher probability to achieve CR (OR 3.37, 95% CI, 1.08–10.46; p=0.036, and 1.2, 95% CI, 1.37-1.05; p=0.06, respectively).

Conclusion
In a cohort of patients with newly diagnosed CD treated by a multidisciplinary team, there were favorable 1-year outcomes; specifically, CR demonstrated in &gt;60%.
P122 Low Risk of new dysplastic lesions during inflammatory bowel disease surveillance with dye-cromoendoscopy: a multicenter population-based retrospective study
Authors: Saiz Chumillas R M , Alba L , Gonzalez-Lama Y , Velayos B , Suarez P , Maroto-Martin C , Nuñez A , Hernandez L , Relea L , Fernandez-Salazar L , Sierra-Ausin M , Barrio J , Muñoz F , Arias L , Sicilia B 
Published: January 2022

Abstract

Background
The 21st century has witnessed advances in endoscopic surveillance technology such as high-definition imaging and virtual or dye-based chromoendoscopy, which have led to increased detection of dysplasia. It is unknown the rates of new dysplastic lesions or cancer progression with these techniques though it seems lower than previously described.

Methods
We developed a multicenter, population-based and retrospective cohort from 7 Spanish hospitals from the Group of Inflammatory bowel disease of Castilla Y Leon (GEICYL) including sequentially all patients with inflammatory bowel disease and colonic dysplastic lesions completely resected (R0) in surveillance with dye-based indigo carmine chromoendoscopy between January 2013 and December 2019, with a minimum endoscopic follow-up of 12 months. The aim was to evaluate the risk of developing more advanced metachronous neoplasia during follow-up, analysing possible associated risk factors.

Results
A total of 99 patients and 148 index lesions (145 low-grade dysplasias [LGD] and 3 high-grade dysplasias [HGD]) with a medium follow-up of 48.76 months (IQR: 36.34 – 67.15) were included. Patients and IBD baseline characteristics are reflected in table 1. During follow-up, 37 patients developed 97 new dysplastic lesions (92 LGD, 4 HGD and 1 CRC) and 1 patient developed multifocal invisible dysplasia (3 HGD). The overall incidence rate for new dysplastic lesions was 0.23 per 100 patient-year, 1.15 per 100 patients at 5 years and 2.29 per 100 patients at 10 years (Figure 1). Personal history of dysplasia was associated with higher risk of developing any grade of dysplasia during follow-up (p 0.025), meanwhile, left colon lesions was associated with a lower risk (p 0.043). 6 patients developed more advanced lesions (5 patients HGD and 1 CCR) with an incidence rate at year and 10 years of 1% and 14% respectively; LGD lesion &gt;1cm was a risk factor for developing HGD or CRC (p 0.041), meanwhile LGD lesion &lt; 1 cm was a protective factor (p 0.013) (table 2,3). 1/8 patients (13%) with HGD lesions developed CRC during follow-up. 3 patients were colectomized (2 by HGD and 1 by CRC). Neither mesalamine treatment or immunosuppressive or biological treatment were associated with a lower risk of dysplasia development.

Conclusion
Risk of dysplasia progression to advanced neoplasia and specifically risk of new neoplastic lesions after endoscopic resection of colitis-associated dysplasia are very low in our cohort with dye-chromoendoscopy. Personal history of dysplasia, as risk factor, and left colon location, as protective factor, were associated with new dysplastic lesions. Finally, size above 1 cm was the only risk factor for progression to advanced lesions.
P124 Views of patients with Inflammatory Bowel Disease on their care during COVID-19 pandemic
Authors: Klimova K , Ajaz I , Padilla Suarez C 
Published: January 2022

Abstract

Background
Patients with inflammatory bowel disease (IBD) have experienced changes to their usual management during the COVID-19 pandemic. We organised an anonymous survey to obtain their perspective on what impact COVID-19 had on their disease and care.

Methods
115 patients with IBD followed up in our clinics between August and October 2021 were sent a questionnaire with multiple choice questions as well as free comment sections which enabled patients to develop their answers in more detail. 53 patients returned the questionnaire until now.

Results
There were no statistically significant differences in descriptive characteristics – 52.8% patients were men, mean age was 53.1 years (range 18–85). 52.8% patients had Crohn’s disease. Overall, 38/53 were satisfied with services provided during the pandemic and similarly, 39/53 patients reported that they were happy or very happy with the use of virtual clinics. Overall, it was surprising that 56.6% patients felt that the pandemic had no impact on their disease. Nevertheless, 20.8% experienced delay in clinic appointments, 18.9% felt uncertainty about their diagnosis and 15.1% felt programmed investigations were postponed. 41 patients had a flare and 24/41 used our Helpline to obtain advice. Only one patient reported negative experience. In the free comment section, most messages were appraising the IBD team and Helpline as a useful way of keeping in touch and receiving advice. Patient 45 wrote: “I contact the team via email and am always responded to quickly.”
Most patients had positive views about virtual clinics, finding them easy and straightforward (31/53), with the advantage of not having to commute to hospital (28/53) and receiving good communication (26/53). 7/53 described virtual clinics as negative, rushed (8/53) and found it difficult to communicate (2/53). In the free comment section, many patients felt that “… there is no real substitute for a face-to-face consultation.” (patient 34) Nevertheless, in the future, 28.3% patients would like to continue with face-to-face appointments, 17.0% would be happy to continue with virtual clinics. The rest was happy with both options.
27/53 patients were able to have regular blood tests with their GP, the rest used hospital or associated services. 26/53 obtained their new medications directly from hospital, 7/53 were able to contact their GP. 18 patients did not require any new medications and continued with their regular prescription.
All patients have received vaccination against COVID-19.

Conclusion
Most of our patients were happy with the services provided during COVID-19 pandemic and felt that the pandemic had not had a significant impact on their disease.
(Note: this project is ongoing and will continue in November 21).
P126 The predictive value of the modified Rutgeerts score at index endoscopy after primary ileocolic resection in patients with Crohn’s disease for the risk of re-resection and severe endoscopic inflammation after long-term follow-up
Authors: Bak M , van Ruler O , Bodelier A , Dijkstra G , Romberg-Camps M , de Boer N , Hoentjen F , Stassen L , van der Meulen – de Jong A , West R , van der Woude C J , de Vries A 
Published: January 2022

Abstract

Background
The modified Rutgeerts score (mRS) differentiates i2 into lesions confined to the anastomosis (i2a) vs. ileal lesions (i2b), and is considered appropriate to assess postoperative recurrence in Crohn’s disease (CD) patients. This study aimed to assess the predictive value of mRS at index endoscopy after primary ileocolic resection for the risk of re-resection and severe endoscopic inflammation after long-term follow-up. In addition, we aimed to predict the association of i2a and i2b for both outcomes.

Methods
Data of CD patients who underwent a ICR, between 2000 – 2019, were retrospectively collected from a national, multicenter database. Patients were eligible for inclusion if ≥1 postoperative endoscopy assessed with the mRS was available. Primary outcome was re-resection per mRS (i0-i4) at index (i.e. first postoperative) endoscopy. Secondary outcome was severe endoscopic inflammation (defined as i3-i4) for a subset of patients (mRS i0-i2b). Rates for both outcomes were compared in subgroups (i0-i1, i2a-i2b, i3-i4) by Kaplan-Meier analyses. Multivariable analysis was conducted to identify risk factors for both outcomes.

Results
In total, 638 patients were included. Index endoscopy was performed at median 8.5 months (IQR: 5.9 – 22.8) after ICR(Table 1), with a mRS of i0(30.4%), i1(17.7%), i2a(15.8%), i2b(19.6%), i3(9.6%) and i4(6.9%). After a mean follow up of 6.5 years (SD: 4.7), re-resection rate (Figure 1) was 7.2% for patients with a mRS of i0, 6.2%(i1), 14.9%(i2a), 18.4%(i2b), 22.9%(i3) and 47.7%(i4). Re-resection rates in the subgroups were significantly higher in the group with a mRS i2a-i2b (16.8%) vs. i0-i1 (6.8%) (log-rank test, p&lt;0.001) and in i3-i4 (33.3%) vs. i2a-i2b (16.8%)(log-rank test, p=0.006). Follow-up endoscopy was performed in 54.0% of the patients with mRS i0-i2b at median interval of 20.4 months (IQR: 10.9 – 37.7). Progression to severe endoscopic recurrence was observed in 19.8% of patients with i0, 33.9%(i1), 25.4%(i2a) and 33.8%(i2b) (Figure 2), but no significant difference was observed between subgroups i0-i1 vs. i2a-i2b (respectively 24.7% vs. 30.2%)(log-rank test, p=0.134). In multivariable analysis, anastomotic lesions (i2a) are not statistically significant associated with re-resection and progression to i3-i4 (Table 2).

Conclusion
After primary ICR, the ascending order of the mRS corresponds with an increasing long-term risk of re-resection. In multivariable analysis, anastomotic lesions (i2a) are not significantly associated with the risk of re-resection and progression to severe endoscopic inflammation, in contrast to i2b lesions. The influence of therapeutic decisions on these associations requires further investigation.
P138 Psychometric validation and interpretation of a patient-reported outcomes instrument to assess bowel urgency among adults with moderate to severe Ulcerative Colitis
Authors: Dubinsky M C , Delbecque L , Lewis J , Hunter T , Shan M 
Published: January 2022

Abstract

Background
Urgency, the sudden or immediate need for a bowel movement, is one of the most bothersome symptoms experienced by Ulcerative Colitis (UC) patients. We aimed to evaluate the psychometric properties of the Urgency Numeric Rating Scale (UNRS), inform the clinically meaningful within-patient change (MWPC) threshold and determine the UNRS threshold associated with clinical, endoscopic and histologic remission.

Methods
In this study, the UNRS was collected daily through an electronic diary that measures the severity of the urgency to have a bowel movement in the past 24 hours using an 11-point NRS ranging from 0 (no urgency) to 10 (worst possible urgency). A weekly score was calculated for a 7-day period by averaging the observed entries if 4 or more observations are available. Item performance, reliability, validity, responsiveness, and score interpretation were assessed at baseline (BL) and week 12 in moderate-severe patients with UC enrolled in a multicenter, randomized, placebo-controlled Phase 3 study.

Results
The full distribution of responses was provided by patients at BL and Week 12, with no floor or ceiling effects. Test-retest reliability was strong, with intra-class correlation coefficients ranging 0.76–0.89. As expected, moderate to high correlations were seen between the UNRS and health-related quality of life measures, patient ratings of UC severity, disease change, stool frequency and rectal bleeding (establishing convergent validity), while low correlations were seen with endoscopy and histology measures (establishing discriminant validity) (Table 1). As predicted, statistically higher UNRS scores were found in patients with more severe UC compared to those with less severe UC, providing evidence of known groups validity. Findings also indicated the UNRS is responsive to changes over time. Anchor-based analyses suggested that a 3-point score reduction from BL to week 12 constitutes a MWPC (Figure 1). A UNRS score of 0, 1, or 2 best reflected urgency severity level when patients were in clinical (YI=0.36), histologic (YI=0.27), or endoscopic remission (YI=0.27) (Table 2). A UNRS score of 0 or 1 may be a more conservative endpoint to define patients with no to minimal urgency.

Conclusion
The UNRS is a valid and reliable patient-reported measure of urgency in adults with UC. A 3-point improvement is a MWPC threshold. A UNRS score of 0 or 1 is a conservative threshold that reflects clinical, endoscopic and histologic remission. These findings provide strong evidence supporting that the UNRS is appropriate for inclusion as an endpoint in clinical trials to evaluate UC treatments efficacy.
P162 Prevalence and incidence of nonalcoholic fatty liver disease in Inflammatory Bowel Disease patients: risk factors for progression
Authors: Crispino F , Brinch D , Scrivo B , Celsa C , Di Grado G , Sapia A , Petta S , Cappello M 
Published: January 2022

Abstract

Background
Cross-sectional studies have assessed the prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with inflammatory bowel disease (IBD). However, longitudinal studies are more suitable to capture dynamic changes. Our aim was to investigate the prevalence and progression of NAFLD in a cohort of IBD patients using validated non-invasive tools. The role of metabolic, disease-related and genetic factors as predictors of NAFLD was also assessed.

Methods
IBD patients without known chronic liver disease were enrolled between 2019 and 2021. NAFLD was defined as Hepatic Steatosis Index (HSI) ≥ 36 or controlled attenuation parameter (CAP) ≥288 dB/m. Demographic data, traditional risk factors for NAFLD, biochemical tests and disease features were retrospectively collected in a dedicated database at the time of IBD diagnosis (defined as baseline) and at the last follow-up visit. PNPLA3 rs738409 C&gt;G and TM6F2 E167K C&gt;T polymorphisms were also investigated. Univariate and multivariate logistic regression analysis were performed to identify risk factors for NAFLD at baseline and at the end of follow-up.

Results
227 consecutive patients (mean age 46.1 ± 13.4 years, 48.7% males, 57% Crohn’s disease, mean disease duration 9.4 ±7.5 years) were enrolled. Laboratory data at the time of diagnosis were available for 64 patients. The mean HSI was 30.9 ± 4.9 and 8/64 eligible patients (12.5%) had NAFLD at baseline. Male sex (odds ratio [OR]: 5.6; 95% confidence interval [CI] 3.1–8.9; P = 0.02) and body mass index (BMI) (OR: 1.4, 95% CI 1.1–2.9; P = 0.0008) were significantly associated with NAFLD at baseline. 11/64 (17.1%) patients developed NAFLD, accounting for an incidence rate of 4.0/100 PY; this was predicted only by changes in BMI over time (OR: 13.6, 95% CI 4.8–19.5; P = 0.001). At the last follow-up visit, NAFLD was diagnosed in 31.2% (71/227) according to HSI and in 21.1% (48/227) according to CAP. Among 8 patients with NAFLD at baseline, HSI worsened in 6 patients (41.0 ± 3.3 vs 44.0 ± 5.2), while two patients had steatosis regression. At the end of follow-up, age (P = 0.01), BMI (P = 0.002) and previous surgery (P = 0.01) were independently associated with NAFLD.

Conclusion
Our study confirms that NAFLD is common in patients with IBD. Variables related to IBD were not associated with incident NAFLD. Age, BMI and previous surgery were independently associated with NAFLD progression, suggesting a pathogenetic role of gut microbiota and impairment in bile acids metabolism. Our results suggest the need for active surveillance for NAFLD in patients with IBD.