bluuebunny/crossref_metadata_2025 huggingface dataset:
The distribution, habitat preference and population dynamics of the pale field-rat (
Authors: O’Neill Sally , Short Jeff , Calver Mike
Published: May 2021

Abstract Context The pale field-rat (Rattus tunneyi) is a small native rat that formerly had a wide distribution throughout Australia. It has suffered substantial range contraction since European settlement and is now largely absent from arid and semiarid Australia. In this biome, it was known to persist only at two Western Australian locations: Edel Land, on the south-western shore of Shark Bay, and islands off the Pilbara coast. Aims We aimed to establish the extent of the species range at Edel Land, its habitat preference, the temporal stability of its populations with respect to rainfall, and threats to its persistence. Methods We trapped at 54 sites to establish distribution and habitat preference, and re-trapped four of these sites at which R. tunneyi was present in each season for 2.5 years to establish trends in abundance. Key results Trapping resulted in the capture of 45 R. tunneyi individuals across 17 of 54 sites (4104 trap-nights; 1.1% capture success). Rattus tunneyi typically occupied localised areas of dense shrubland, often in habitats with free water or near-surface moisture from drainage from high dunes allowing denser and taller vegetation and, at some sites, year-round growth of grasses or rushes. Regular re-trapping of four sites in each season (2002 – 2004) suggested a declining population, probably owing to a sequence of dry years. Key conclusions Rattus tunneyi at Shark Bay occurred only in localised mesic refuges, apparently dependent on seepage from high dunes generated by major inputs of rainfall from infrequent cyclones or sequences of high-rainfall years. Implications This isolated population is likely to be threatened by browsing by feral goats, opening up otherwise densely vegetated habitats of refuge areas, and their trampling of R. tunneyi burrows; by the depletion of grasses from herbivory by European rabbits; and by the long-term impact of a drying climate. It is unlikely to persist without effective on-going management, particularly of the goat population.
Enhanced two-dimensional nematic order in slit-like pores
Authors: Gurin Péter , Odriozola Gerardo , Varga Szabolcs
Published: May 2021

The effect of out-of-plane positional freedom is examined on the stability of two-dimensional (2D) nematic order of hard non-spherical particles using the second virial density-functional theory. The particles are allowed to move and rotate freely in the plane of confining walls and can move between the two parallel walls. The wall-to-wall distance (H) is varied between the strictly 2D and the two-layer forming cases, i.e. σ < H < 2σ, where σ is the particle’s shortest length. As expected, we observe that more and more particles are required for the formation of 2D nematics with increasing H when the rod-like particles are hard ellipsoids. Surprisingly, we found that the opposite tendency is observed in the case of hard cylinders, i.e. fewer and fewer particles are needed to stabilize the nematic order with increasing H. This paradox can be understood by projecting the three-dimensional system into a 2D mixture of particles having position-dependent aspect ratios and molecular areas. However, the complex phase behaviour found for plate-like cylindrical particles with increasing H cannot be explained in terms of the same simple geometrical arguments.
Preparation of paper-based conductive pattern for 3D printing
Authors: Zhao Chenfei , Wang Jun , Qian Bo , Zhang Zhuoqing
Published: May 2021

With the development of printed electronics technology, the demand for printed conductive inks had also put forward higher standards. The shortcomings of traditional printed circuit boards, such as complex technology, consumables, and pollution, had also been resolved with the development of 3D printing technology. In this paper, low-content silver nanoparticles were blended with graphene alcohol slurry and dissolved in a non-polluting solvent such as absolute ethanol. The synergistic effect of the composite of the hexagonal structure of the graphene sheet and the silver nanoparticles improved the ink’s performance of electrical conductivity, adding water-based polyurethane/acrylic resin system to improve the adhesion between ink and paper. The conductive ink can be used to 3D print circuit circuits on paper. After drying, the resistance was measured. After the battery, diode, and switch were connected, a circuit diagram was made. After pressing the diode emits was lighted. This work is expected to be applied to flexible circuit boards to provide basic research.
Global Cytopathology-Hematopathology Practice Trends
Authors: Zadeh Sara L , Balassanian Ronald , Cheung Matthew C , Falchi Lorenzo , Hasserjian Robert , Lin Oscar , Long Steven R , Ly Amy , Menke Joshua R , Mou Eric , Natkunam Yasodha , Ruiz-Cordero Roberto , Volaric Ashley K , Wang Linlin , Wen Kwun Wah , Gratzinger Dita
Published: May 2021

Objectives

Small-volume biopsy—fine-needle aspiration biopsy (FNAB) with or without core biopsy—is in increasing use in diagnosis and management of lymphoma patients. Our objective was to survey the current practice in small-volume biopsy diagnosis of lymphoma, focusing on the interaction among hematopathologists and cytopathologists and the integration of FNAB, core biopsy, and flow cytometry studies at sign-out.

Methods

This study used a cross-sectional survey design employing the RedCap database distributed via nine pathology professional society email listservs. The survey consisted of 25 multiple-choice questions and several free text fields. In total, 128 pathologists participated.

Results

Most respondents indicated that FNAB specimens in which lymphoma is a diagnostic consideration (FNAB-L) are seen daily or weekly (68/116; 58.6%). However, most institutions have separate hematopathology and cytopathology services (72/116; 62.1%) with inconsistent communication. When communication occurred, respondents were frequently inclined to reconsider their original diagnoses. Barriers identified included lack of communication, inadequate access to diagnostic studies, no formal subspecialty training, and various opinions regarding FNAB in diagnosing lymphoma.

Conclusions

This survey showed that FNAB-L specimens are common, with a lack of uniformity in how complementary fine-needle aspiration and core biopsy specimens or flow immunophenotyping results are shared across hematopathology and cytopathology services.
DOP04 Single cell RNA sequencing identifies distinct intestinal inflammation patterns between primary sclerosing cholangitis-associated colitis and Ulcerative Colitis
Authors: Uniken Venema W , Bangma A , Van der Wijst M , Kats-Ugurlu G , Bjork J , Vich Vila A , Weersma R , Festen E
Published: May 2021

Background

Primary sclerosing cholangitis (PSC) is an inflammatory disorder of the bile ducts. The etiology of PSC is unknown, but it is hypothesized that intestinal barrier dysfunction, as seen in inflammatory bowel disease (IBD), plays a role. Roughly 75% of PSC patients have concomitant IBD (PSC-IBD). PSC-IBD is phenotypically different from ulcerative colitis (UC) with predominantly right-sided disease and a higher risk for colorectal cancer. In this study we aim aim to find probable distinct pathomechanisms for PSC-IBD, by comparing gut mucosal biopsies between PSC-IBD and UC using single-cell RNA sequencing.

Methods

47 gut mucosal samples from the colon of subjects with either PSC-IBD (n=24), UC (n=18) or non-IBD control (n=5) were collected, from which 28 were paired inflamed and non-inflamed. Whole biopsies were cryopreserved and dissociated into single cells using collagenase digestion. Library preparation was done using the 10x Genomics system and subsequent sequencing was performed on an MGI2000 sequencer. The ‘Seurat’ R package was used for analysis.

Results

A total of 75.078 high quality cells identified 38 distinct cell types. No differences in cell type composition were observed between PSC-IBD and UC. We did see different cell type composition and gene expression between inflamed and non-inflamed samples. For example, in PSC-IBD specifically, an enterocyte subtype defined by DUOX2-expression showed inflammatory pathways upon inflammation. UC inflammation, on the other hand, was characterized by involvement of BEST4+ enterocytes and inflammatory fibroblasts. In addition, activated B cells and IgA plasma cells expressed stress-related genes in PSC, but not in UC inflammation.

Conclusion

We show that intestinal inflammation in PSC-IBD is characterized by distinct, cell-specific gene expression patterns as compared to UC. This highlights differential cell types mediating inflammation between these IBDs. Our study provides insight in cellular mechanisms underlying intestinal disease in PSC, and may serve as a starting point for further studies, for example on the functions of DUOX2+ enterocytes.
DOP89 Effects of ferric derisomaltose and ferric carboxymaltose on hypophosphatemia in iron-deficiency anaemia due to Inflammatory Bowel Disease: A Phase IV randomised clinical trial
Authors: Zoller H , Wolf M , Blumenstein I , Primas C , Lindgren S , Thomsen L L , Reinisch W , Iqbal T
Published: May 2021

Background

Intravenous iron can correct iron deficiency anaemia (IDA) in inflammatory bowel disease (IBD). Certain formulations are associated with hypophosphatemia, but this has not previously been investigated in a randomised clinical trial in IBD. The aim of this randomised, double-blind trial was to compare the risk of hypophosphatemia with ferric derisomaltose/iron isomaltoside 1000 (FDI) vs ferric carboxymaltose (FCM) in patients with IDA due to IBD.

Methods

Adults with IBD and IDA (haemoglobin [Hb] <13g/dL; s-ferritin ≤100ng/mL) who were unsuitable for oral iron treatment were recruited at outpatient clinics in 5 European countries. Patients were randomised 1:1 to FDI or FCM (1000mg at baseline and 500 or 1000mg at Week 5 based on weight and iron need at baseline). The primary endpoint was the incidence of hypophosphatemia (s-phosphate <2.0mg/dL) from baseline to Week 5. Additional endpoints included biomarkers of bone and mineral metabolism, Hb concentrations, fatigue score, and adverse events (AEs).

Results

Of 97 patients enrolled (mean age 42.1 years; 52.6% female; 39.2% Crohn’s disease; 60.8% ulcerative colitis), 48 received FDI and 49 FCM. The incidence of hypophosphatemia was significantly lower for FDI than FCM (8.3% vs. 51.0%; p<0.0001). After the first dose, biomarker responses (least squares mean change from baseline) were significantly less pronounced after FDI than FCM: s-phosphate decreased less with FDI than FCM, with a nadir at Week 1 (FDI, -0.49mg/dL; FCM, -1.33mg/dL; p<0.0001); urinary fractional excretion of phosphate increased less at Week 1 (FDI, 2.58%; FCM, 9.22%; p=0.0021); intact fibroblast growth factor 23 increased markedly over the first day only with FCM (FDI, -8.54pg/mL; FCM, 149.31pg/mL; p<0.0001); 1,25-dihydroxyvitamin D decreased less with FDI than FCM, with a nadir at Week 1 (FDI, -16.39pg/mL; FCM, -30.83pg/mL; p<0.0001); parathyroid hormone increased only in the FCM group, with a peak at Week 2 (FDI, -2.22pg/mL; FCM, 14.28pg/mL; p=0.011). Bone-specific alkaline phosphatase increased more with FCM than FDI at Week 2 (p=0.0025), with the difference persisting at Week 10 (p=0.0041). Hb increased in both groups and were comparable at all time points. Improvements from baseline in fatigue score were greater for FDI than FCM at Weeks 5 and 7 (both p<0.01). Incidence of AEs were comparable (FDI, 91.7%; FCM, 89.8%).

Conclusion

In IDA due to IBD, FDI resulted in significantly lower incidence of hypophosphatemia than FCM. FDI and FCM lead to similar increases in Hb concentration. In contrast to FDI, FCM treatment led to persistent changes in bone biomarkers, suggesting possible long-term adverse effects on bone health. ClinicalTrials.gov Identifier: NCT03466983. Supported by Pharmacosmos A/S (Holbæk, Denmark).
OP25 Efficacy of filgotinib in patients with Ulcerative Colitis by line of therapy in the phase 2b/3 SELECTION trial
Authors: Peyrin-Biroulet L , Dotan I , Hibi T , Taliadouros V , Oortwijn A , Zhao S , Zhang J , Hsieh J , Feagan B
Published: May 2021

Background

Patients with ulcerative colitis (UC) often do not respond to treatment or lose response over time, and thus switch between therapies with various mechanisms of action (MoAs).1 Filgotinib (FIL) is a once-daily, oral, Janus kinase 1 preferential inhibitor in development as a UC treatment. We assessed the efficacy of FIL in biologic (bio)-naïve and bio-experienced patients with UC, and in bio-experienced patients with failure of 1 or ≥2 biologics or 1 or 2 MoAs.

Methods

SELECTION (NCT02914522) was a phase 2b/3 double-blind, randomised, placebo-controlled trial comprising two induction studies and a maintenance study. Adults (18–75 years) with moderately to severely active UC were randomised 2:2:1 to FIL 200 mg, FIL 100 mg or placebo (PBO) once daily for 11 weeks in Induction Study A (bio-naïve) and B (bio-experienced). Patients in either clinical remission or Mayo Clinic Score (MCS) response at week 10 (responders) could enter the Maintenance Study. Responders who received induction FIL were re-randomised 2:1 to continue their induction regimen or PBO through week 58. Responders who received induction PBO continued PBO. We assessed clinical remission and MCS response at weeks 10 and 58 in bio-naïve patients and bio-experienced patients with failure of 1 or ≥2 biologics and 1 or 2 MoAs (TNF antagonists and vedolizumab). All p values for subgroup analyses are nominal.

Results

At week 10, clinical remission was achieved by a significantly higher proportion of bio-naïve and -experienced patients treated with FIL 200 mg than PBO (Figure 1a). A higher proportion of bio-experienced patients with 1 biologic or MoA failure treated with FIL 200 mg than PBO achieved clinical remission at week 10 (p<0.05); a smaller treatment effect was seen in patients with ≥2 biologic or 2 MoA failures (Figure 1b). None of these comparisons reached p<0.05 for FIL 100 mg. Higher proportions of patients treated with either dose of FIL than PBO achieved MCS response at week 10 in all (sub)groups (Figure 2). At week 58, higher proportions of bio-naïve and -experienced responders, and bio-experienced responders with ≥2 biologic or 2 MoA failures treated with maintenance FIL 200 mg than PBO achieved clinical remission (p<0.05) (Table 1). Higher proportions of responders treated with maintenance FIL 200 mg than PBO achieved MCS response at week 58 in all (sub)groups.

Conclusion

FIL 200 mg was effective in inducing and maintaining clinical remission in bio-naïve and -experienced patients. Induction results suggest FIL 200 mg is most effective in bio-naïve patients, and those who switch after failure of 1 biologic or MoA. Interpretation of week 58 data is limited by low patient numbers.

Reference
P012 Low frequencies of circulating inhibitory TIGIT+CD38+ effector T cells identify an immunologically distinct subgroup of pediatric patients with severe Crohn’s disease
Authors: Heredia M , Costes L , Tindemans I , Aardoom M , Klomberg R , Kemos P , Joosse M , van Haaften D , Tuk B , Ruemmele F , Croft N , Escher J , de Ridder L , Samsom J
Published: May 2021

Background

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a T cell driven intestinal inflammation. Current T cell suppressive therapeutic regimens are moderately successful due to a large clinical heterogeneity amongst patients. Detailed understanding of aberrant inflammatory and inhibitory T-cell responses in individual patients is lacking. Previously, we have shown that, in healthy individuals, 40% of peripheral blood CD38+ (CD62LnegCD4+) effector T cells, which are enriched for intestinal antigen specificity, express the inhibitory molecule T cell immunoglobulin and ITIM domain (TIGIT). TIGIT+CD38+ effector T cells have a regulatory function, produce IL-10 and express multiple co-inhibitory receptors. Conversely, TIGITnegCD38+ effector T cells are enriched in inflammatory IFN-γ producing cells. In a small cohort of pediatric-onset IBD patients, low frequencies of TIGIT+CD38+ effector T cells were associated with a reduced duration of clinical remission. We hypothesize that a subgroup of IBD patients has reduced frequencies of circulating inhibitory TIGIT+CD38+ effector T cells, reflecting a distinct pathogenesis associated with a more severe disease course.

Methods

In the Rotterdam PIBD-SETQuality cohort of newly diagnosed pediatric IBD patients (CD: n=37; UC: n=16), patients with suspicion of IBD but negative diagnosis (n=12) and age-matched healthy controls (n=22), we monitored TIGIT+ and TIGITnegCD38+ effector T cells in peripheral blood and collected plasma at diagnosis and during immunosuppressive therapy.

Results

At diagnosis, approximately 50% of CD patients had strongly reduced frequencies of inhibitory TIGIT+CD38+ effector T cells compared to UC patients and age-matched controls. CD patients with low frequencies of TIGIT+CD38+ effector T cells at diagnosis needed earlier anti-TNF treatment with 73% of patients receiving anti-TNF treatment within 1 year versus 38% for patients with normal frequencies of TIGIT+CD38+ effector T cells. Inflammatory TIGITnegCD38+ effector T cells were enriched in Ki67, reflecting recent proliferation, and expressed chemokine receptors associated with inflammatory non-classical T-helper-1 IFN-γ hiIL-17lo producing cells. High frequencies of TIGITnegCD38+ effector T cells correlated with high plasma IFN-γ concentrations.

Conclusion

These results demonstrate that reduced frequencies of circulating inhibitory TIGIT+CD38+ effector T cells discriminate a subgroup of pediatric CD patients with high frequencies of inflammatory IFN-γ hiIL-17lo producing cells, high plasma IFN-γ concentrations, and in need of early anti-TNF treatment, possibly indicative of a distinct pathogenesis with a more severe disease course.
P017 Small bowel transcriptomics define similarities and divergent pathways between Crohn, environmental enteric dysfunction (EED), and celiac diseases, implicating role for the microbiome in the pathogenesis
Authors: Haberman Ziv Y , Iqbal N T , Braun T , Dexheimer P J , Hadar R , Rahman N , Syed S , Moskaluk C , Moore S R , Ali S A , Denson L A
Published: May 2021

Background

Crohn disease (CD), environmental enteric dysfunction (EED) and celiac disease are prevalent enteropathies linked to chronic gut inflammation. However, unlike celiac and Crohn that are prevalent in westernized countries, EED is seen in only in low- and middle-income countries of the developing world. Recent work has defined specific EED duodenal microbiota associated with stunting, and transmission of EED histologic changes and weight loss by microbial transfer to germ free mice.

Methods

We performed high throughput transcriptomics of 94 duodenal samples from the SEEM cohort:52 undernourished EED participants, 17 celiac and 25 healthy North American controls. We compared those to our previously reported transcriptomics of 248 newly diagnosed ileal CD from RISK. Comparison were performed between cases and controls within each cohort.

Results

Above 90% of the expressed protein coding genes are shared between duodenum samples within SEEM, and Crohn ileal within RISK enabling the anticipated comparison. A substantial number of the down-regulated genes in undernourished EED participants overlapped with celiac (212/481, 44%) and with Crohn Disease (249/481, 52%). Shared reduced signatures and functions included decrease in epithelial lipid metabolism, vitamins, and brush border transport signatures. Relative to celiac disease, suppression of antioxidant and detoxification genes were EED- and Crohn-specific, which include the reduction of metallothioneins (MT family) that buffer against toxic metals, and aldo-keto NADPH- genes (AKR1C family) involved in detoxification of environmental compounds. A smaller proportion of the EED up-regulated signal overlapped with celiac (85/781), and we noted a more significant overlap with Crohn disease (248/781, Chi squares p<0.05). Relative to celiac disease, up-regulation of an innate anti-microbial DUOX2 and LCN2 gene, and of myeloid response signals, several CCL chemokines, and extracellular matrix signature were EED- and Crohn-specific. Consistent with this, greater level of DUOX2 protein was detected in duodenal biopsies from EED subjects vs. celiac and controls and in ileal CD vs. ileal controls. As opposed to the robust dysbiosis previously characterized in Crohn disease, we were unable to identify significant microbial signal in celiac patients in comparison to controls, while recent studies identified microbial patterns linked with EED.

Conclusion

We highlight important biologic signals widely overlapping between Crohn Disease (CD) and EED transcriptome in the small intestine, suggesting mechanisms involving altered gut microbiota. Inhibiting innate immune activation or reverting Crohn dysbiosis may be beneficial future therapy for Crohn Disease and EED.
P032 MiR-511 deficiency aggravates T cell transfer colitis in mice
Authors: Rahman S , Elfiky A , van Hamersveld P  H P , Verseijden C , Welting O , Meijer S L , Hakvoort T B M , de Jonge W J , Heinsbroek S E M
Published: May 2021

Background

MiR-511 is embedded in intron region 5 of the CD206/MRC1 gene, expressed by macrophage and dendritic cell populations. In this study, we aimed to investigate the effect of MiR-511 deficiency on intestinal inflammation in a murine T cell transfer colitis model.

Methods

A double MiR-511- and Rag-1 (knockout) KO mouse was generated and a T cell transfer colitis was induced by intraperitoneal injection of naïve T cells from donor WT mice. Since these mice lack mature T and B cells, first signs of inflammation appeared at week 3 after T cell injection. An endoscopy score was obtained to determine inflammation at week 3 and 5, respectively. The experiment was terminated at week 5 and severity of inflammation was assessed on the basis of weight loss, colon weight/length ratio, histology score, spleen weight and disease activity index. In addition, flow cytometry was performed for analysing immune cell populations (monocyte, macrophages, dendritic cells, neutrophils) in the colons of both control and colitis groups and T cells in the spleens of colitis group, respectively.

Results

Following the induction of T cell transfer colitis, colon weight/length ratio, spleen weight and endoscopic score were significantly increased in the double KO mice compared to Rag-1 KO control mice. A higher histology score and disease activity index in the double KO with no change in weight loss compared to Rag-1 KO control mice was observed. A significant increase in monocyte population in the colons of double KO was seen and increased numbers of monocytes was also observed in the double KO control group with no inflammation. Also, a higher influx of T cells in the double KO mice with a significant increase in Foxp3 and IL4 population was observed in the group with colitis.

Conclusion

MiR-511 deficiency aggravates intestinal inflammation compared to Rag-1 KO control mice. Also, a higher presence of monocyte as well as T cell populations were observed in these mice. Together these data show that MiR-511 is involved in the regulation of intestinal health. Future research will focus on underlying mechanisms.
P047 The ATG16L1 T300A polymorphism in Crohn’s Disease patients leads to abnormal autophagy flux in dendritic cells
Authors: Quiniou G , Dinet O , Cervantes O , Verdet M , Boschetti G , Viret C , Nancey S , Faure M , Rozieres A
Published: May 2021

Background

Crohn’s disease is a chronic inflammatory bowel disease, whose pathogenesis is largely determined by an inappropriate immune response towards luminal microbiota in genetically susceptible hosts, affecting in particular genes involved in the autophagy process. The autophagy-related ATG16L1 T300A variant is one of the most frequently associated polymorphisms with susceptibility to Crohn’s disease, but the functional consequences of this polymorphism on the dynamic properties of the autophagy flux remains unknown.

Methods

Using dynamic monitoring of LC3 lipidation, a key protein marker of autophagy, we have quantitatively analysed the autophagic flux of human primary dendritic cells, which are very potent antigen-presenting cells whose function is critical in Crohn’s disease.

Results

The detailed analysis of the dynamic properties of the autophagic flux reveal that the maturation process in dendritic cells from healthy subjects is associated with a decrease of the velocity and the intensity on the autophagy flux although the turnover of autophagosome formation was maintained, demonstrating the capacity of resilience of the autophagy flux for a maintenance of functional autophagy during maturation process. Strikingly, the expression of the ATG16L1 T300A variant, but not NOD2 R702W variant, in dendritic cells from patients with Crohn’s disease is associated with a disorder of the autophagic flux dynamics in immature dendritic cells, that was not modulated upon maturation. The lack of adaptation of the autophagy flux in ATG16L1 T300A expressing dendritic cells of Crohn’s disease patients, during their maturation was not associated with altered phenotypic acquisition of maturation markers but highlighted a very specific autophagic flux signature.

Conclusion

Dendritic cells of Crohn’s patients expressing the autophagy-related ATG16L1 T300A have an altered autophagy flux, that could affect their function and contribute to the pathogenesis of Crohn’s disease.
P078 Proteomics and Lipidomics Analysis Revealed Alterations of Complement Activation and Lipid Metabolism in peripheral blood mononuclear cells of Inflammatory Bowel Disease Patients
Authors: Notararigo S , Bravo S , Martin-Pastor M , Baston-Rey I , Quiroga-Castiñeira A , Dominguez-Munoz J E , Domínguez Medina E , Barreiro-de Acosta M
Published: May 2021

Background

The lack of interaction between immune system cells and microbiota is considered a key driver of the pathogenesis of inflammatory bowel disease (IBD). The association of age-associated B cells (ABC) from antigen-experienced B cells and autoimmunity is now well established. The increased demands in lipid metabolism during immune response and cell activation upon autoimmune signals leads to lipid tag modifications of proteins. In IBD patients, we observed an impairment of B cell development, identifying a transitional B cell subset expressing CD38Hi, CD24Hi and CD19+. We hypothesize that metabolic alterations of proteins and lipids during immune cell activation might be a relevant mechanism of autoimmune disease.

Methods

An IBD cohort of patients in clinical remission under anti-TNF treatment was included in order to test metabolic and proteomic changes in peripheral blood mononuclear cells (PBMCs). Proteomic analysis was performed by Mass Spectrometry using a label free quantitative method (SWATH-MS analysis) and lead to identify a number of proteins underregulated (< 0.6) and overexpressed (> 1.5) fold change respect to control. Lipidomics of serum samples analyzed by proton Nuclear Magnetic Resonance spectroscopy (NMR)2 and multivariant statistics.

Results

Serum samples were obtained in Crohn disease (CD) n = 18, ulcerative colitis (UC) n = 9, before biological infusion and healthy controls (CTRL) n = 10. Proteins related with lipid metabolism like APOC2 for CD and APOB, APOA1 for UC, were differentially modulated. Significant differences in non-polar metabolites and lipids that phenotypically define CD and UC groups respect to CTRL were observed (Fig. 1)

Fig. 1 Orthogonal-Partial Least Square-Discriminant Analysis (OPLS-DA) of the global NMR data of the serum samples of groups CD and CTRL.

Indeed, proteins associated with complement activation like Complement Factor 1 and Complement C1q subcomponent subunit B were differentially expressed in CD group. These results were confirmed by lipidomic analysis, in which palmitic (Fig. 2) as well as other candidate lipids were more abundant in IBD groups than CTRL.

Fig 2. Differences of palmitic acid concentration in CD and UC patients vs CTRL (Bonferroni test showed statistical difference between CTRL vs. CD and CTRL vs. UC with p = 0.02 and p = 0.004 respectively).

Conclusion

Our study detected high levels of proteins regulating lipid metabolism and palmitic in IBD patients. This observation can be interpreted as part of deleterious alterations of proteins through palmitoylation during B-cell activation and might be a relevant mechanism of disease. Further exploration of palmitate catabolism might shed light to the mechanisms that result in immunometabolic disorders.
P083 High prevalence of ulcerative appendicitis in UC patients without colonic disease activity
Authors: Heuthorst L , Mookhoek A , Wildenberg M , D’Haens G , Bemelman W , Buskens C
Published: May 2021

Background

The aim of the current study was to assess histological features of appendices from patients with UC and its clinical relevance.

Methods

Patients with UC in remission and active UC (therapy refractory) that underwent an appendectomy in the frame of clinical trials between 2012–2019 were included. Histological features of UC appendices were compared to those of patients with acute appendicitis and colon carcinoma. The Robarts Histopathology Index score (RHI) was used to assess appendiceal inflammation. In patients with active UC, clinical and histological characteristics were compared between patients with and without endoscopic response after appendectomy.

Results

In total, 140 appendix specimens were assessed (n=35 UC remission, n=35 active UC, n=35 acute appendicitis, n=35 colon carcinoma). Histological features of appendices from UC patients looked like UC rather than acute appendicitis. The incidence of active appendiceal inflammation was not different between UC patients in remission versus active disease (53.7% versus 46.3%, p=0.45) and limited versus extensive disease (58.5% versus 41.5%, p=0.50). Endoscopic response, assessed in 28 therapy refractory patients, was more frequently seen in patients with higher RHI scores (RHI>9 81.8% versus RHI≤9 9.1%, p=0.004) and limited disease (proctitis/left sided 63.6% versus pancolitis 36.4%, p=0.02).

Conclusion

The presence of active appendiceal inflammation is common in UC and not related to disease activity in the colon. More than 50% of UC patients in remission show active histological disease in the appendix. Favorable response to appendectomy for refractory UC was seen in cases with ulcerative appendicitis. These findings might support the role of the appendix as a driving force in UC.
P125 Could gut microbiota metagenomic analysis improve diagnosis in paediatric Inflammatory Bowel Disease population?
Authors: Pujol Muncunill G , Monleon-Getino A , Méndez-Viera J , Álvarez-Carnero L , Martin de Carpi J
Published: May 2021

Background

Gut microbiota plays an important role in maintaining intestinal homeostasis. Recent studies postulate that dysbiosis may be involved in the pathogenesis of Inflammatory Bowel Disease (IBD). The aim of the study was to characterize the metagenomic biodiversity of the gut microbiota in Paediatric Inflammatory Bowel Disease patients (PIBD) and whether microbiome data could be used as diagnostic tool.

Methods

A prospective, longitudinal observational pilot clinical trial with consecutive inclusion of PIBD patients matched with healthy controls by age and sex was performed. A total of 36 children were planned to be included: 12 Crohn’s Disease (CD), 12 Ulcerative Colitis (UC) and 12 healthy controls (HC). Demographic, clinical and analytical data were recorded and stool and saliva samples were collected at onset, 3 and 6 months for DNA sequencing and bioinformatics analysis.

Results

Twenty-three patients (12CD, 11UC) and 9 HC were included (at the time of data analysis). Fifty-six percent were male; mean age: 11.7 years (IQR: 8–15). CD patients at onset had a mean Paediatric Crohn’s Disease Activity Index (PCDAI) of 22.5 (IQR: 10–55), a mean Faecal Calprotectin (FC) of 2384 mg/kg (IQR: 159–6000) and 83% of them had inflammatory markers elevation (Erythrocyte Sedimentation Rate (ESR) and/or C-reactive protein (CRP)). Patients with UC presented a mean Paediatric Ulcerative Colitis Activity Index (PUCAI) of 43.6 (IQR: 10–80) at onset, mean CF of 3381 mg/kg and 18% presented an increase of inflammatory markers (ESR and/or CRP). To date, Next Generation Sequencing (NGS) metagenomic study (saliva and stools) has been performed from 15 subjects (9 CD, 2 UC and 4 HC) at onset and 9 subjects (7 CD and 2 UC) at 3 months. A differential microbiota pattern was observed in both, saliva and stools, for CD at onset and at 3 months. In the stools, three differential taxa were found at onset of the disease and at 3 months and in saliva, another three differential taxa were observed compared to HC. In UC, 6 differential taxa (> 3 % diff. HC-UC, p-value=0) were selected in stools and 7 in saliva at onset compared to HC. Globally, a higher microbial biodiversity was observed for HC compared to CD at onset, but it was not statistically significant.

Conclusion

Provisional results showed a possible differential signature in both saliva and stools of patients with paediatric CD. These results must be validated with all the samples in process, and probably using larger paediatric cohorts before the development of these techniques as a diagnostic tool in the clinical practice.
P137 Preliminary validation of a multi-stage machine learning algorithm to assess histological inflammation in inflammatory bowel disease
Authors: Hagendorn E , Karsen S , Pai R , Jairath V , Knight H , Schwartz A , Laroux S , Butler J , Dunstan R
Published: May 2021

Background

The histologic assessment of inflammatory bowel disease (IBD) relies on qualitative grading methods. Although widely accepted, these instruments are time consuming, require specialized training, and suffer from inter-rater disagreement. For these reasons there is a need for more consistent and less biased methods to assess IBD histology.

Methods

The algorithm was initially developed using hematoxylin and eosin (H&E) stained whole slide images of colon biopsies (238 ulcerative colitis [UC], 30 Crohn’s Disease [CD], and 28 endoscopically normal adjacent [ENA]). The first two stages implement convolutional neural networks (CNN) which segment 11 key anatomical features (Figure 1). The third stage extracts the features and models them for prediction.

Results

The first stage of the algorithm was validated on an independent test dataset by calculating the intersection-over-union (IoU) for the ground truth and prediction masks, resulting in a value of 0.97. A preliminary validation for stage 2 was performed by randomly selecting 30 unique biopsy sections from the test dataset and applying a 150um x 150um counting frame. An expert gastrointestinal pathologist confirmed correct cell identification by the algorithm for three of the primary inflammatory cell types: plasma cells, eosinophils, and neutrophils which resulted in a sensitivity/specificity of 0.76/0.99, 0.78/1.00, and 1.00/0.98 respectively. The final stage predicts RHI grades which could be directly compared to pathologist reads (Figure 2, 3, and 4).

Conclusion

This is the first study to demonstrate the value of machine learning to assess histologic activity in IBD. These methods lay the foundations for future work, and we believe stages 1 and 2 can be explored independently to statistically characterize the histologic changes of IBD, enabling the improvement of preexisting grading systems.
P164 Celiac Disease among a large cohort of inflammatory bowel disease patients: epidemiology and outcome implications
Authors: Vernero M , Ribaldone D G , Giudici G , Stalla F M , Dutto C , Bugianesi E , Saracco G M , Caviglia G P , Astegiano M
Published: May 2021

Background

Inflammatory bowel disease (IBD), including Crohn’s disease (CD), ulcerative colitis (UC) and undetermined IBD (IBD-U), are autoimmune chronic remittent diseases affecting the gut. On the other hand celiac disease (CeD) is a gluten related disorder leading to duodenal villous atrophy. Lately, the link between CeD and IBD has become of growing interest. Indeed, CeD prevalence among IBD population has been widely investigated, as well as IBD prevalence in CeD population. Particularly, IBD seems to have a significantly higher prevalence among CeD population than in general population and CeD seems to be more prevalent in IBD population. However, there is still lack of data on whether CeD can influence IBD outcome. So, primary outcome of our study is to measure prevalence of CeD among IBD population and secondary outcome is to evaluate possible influence of CeD on IBD outcome.

Methods

Data were collected from march 2020 to September 2020 from IBD internal registry in San Giovanni Antica Sede Hospital in Turin. To detect CeD patients, all patients were screened and the ones with a reported duodenal lesion were selected. From those, the ones with defined diagnosis of CeD (presence of serum IgA antitransglutaminase and or IgA anti endomisial antibodies) were finally selected. Prevalence of CeD among IBD was compared to that of general population basing on literature. Then 76 patients were randomly selected as control group, in roder to investigate secondary outcome. To define IBD as complicated Siegel’s score was used (1 out of five item needed to define complicated disease).

Results

Among 5732 IBD patients we detected 80 patients with duodenal lesions, of whom 27 were diagnosed with CeD. So, prevalence of CeD among our population is about 0,49% whiich is similar to that of general population (0,48%, P=0.98). No differences were found in CeD prevalence among CD, UC and IBD-U subgroups. As regards secondary outcome, in case group complicated IBD was 44,4% while among control group 26,3% (p=0.08). In a mean follow up time of 133,93 months, mean time from diagnosis to complication of IBD was 58,2 months in case group and 102,7 months in control group. As shown in figure 1, Kaplan-Maier curve for event free survival comparing the two groups shows a significant difference between CeD + IBD patients and IBD only patients (p=0,002).

Conclusion

Even though the retrospective nature of the study could lead to underestimate CeD diagnosis, among our cohort of IBD patients CeD prevalence seems not to be significantly higher than among general population. Despite of that, when associated to CeD, IBD seems to have earlier complications, so these patients may deserve a top down therapeutical approach and/ or a more strict follow up.
P179 Treatment decisions and biologic adoption rates in newly diagnosed Crohn’s disease in Japan
Authors: Hisamatsu T , Yoon A
Published: May 2021

Background

Biologic therapy in Crohn’s disease (CD) has significantly improved treatment outcomes. Still, providing an optimal care for individual patient in real-world is complex. We report the real-world treatment decisions between biologics and systemic corticosteroids (SCS) and associated factors in newly diagnosed CD in Japan.

Methods

Patients with CD diagnosis (Index) and at least one CD therapeutic agent prescribed between 2006 and 2019 were screened from the JMDC database. JMDC is a health claims database where various sized (small to very large) companies’ employees and their dependents are enrolled. Subjects with a minimum 12-month CD-diagnosis-free enrolment period up to the Index, and a minimum 12-month observational period after the Index were included in the analysis. Subjects were categorised into 2 groups (A: without biologics, B: with biologics) based on their first-year treatment, and then further into 4 groups: SCS without biologics (A1), No SCS nor biologics (A2), Biologics with no prior SCS (B1), Biologics with prior SCS (B2).

Results

859 subjects were included. 38.4% (B: n=330/859) initiated biologics within a year since diagnosis (Table 1). Among them, 73.3% (B2: n=242/330) initiated biologics without prior SCS, so-called a top-down approach. Among the rest who were not treated with biologics within the first year, 27.2% (A1: n=114/529) received SCS. B were 7.5 years younger on average and had a higher rate of perianal symptoms (43.0%) compared to A (22.9%). Trend analyses showed that the rates of biologic adoption in the first year have been relatively stable over a decade since 2008 to 2019 (Table 2).

Conclusion

Real-world treatment decisions in newly diagnosed CD were investigated, and perianal symptoms were strongly associated with biologic therapy. Biologic adoption rates in CD seemed higher and faster in Japan compared to Europe. According to a Danish study reported by Alulis et al. (2020), 28.5% of CD patients received biologics at some point during the whole study period, of which 46.2% received within a year. These figures suggest that 13.2% of newly diagnosed CD were treated with biologics within the first year in the Danish study compared to 38.4% in our study.
P180 Endoscopic scoring systems for Crohn’s Disease and Ulcerative Colitis and their correlation with histological and clinical outcomes
Authors: Gibbons E , Hayes T , Shahzad C K , Hussain A , Hall B , Smyth C , Farrell R , Kelly O
Published: May 2021

Background

Endoscopy and histopathology are vital for evaluating disease activity and treatment response in inflammatory bowel disease. Correlation between endoscopic and histological indices has not been fully examined. The primary aim of this study was to examine the correlation of endoscopic scores with histological assessment and association with flare/hospitalisation in the ensuing 12 months.

Methods

We selected 100 random colonoscopies performed for IBD surveillance/assessment in 2019. Adult patients with a complete colonoscopy were included. All reports were blindly scored by 2 expert endoscopists using SES CD or Mayo score as appropriate. Histology was retrieved from HistoLab database and classified as normal, mild, moderate and severe. Clinical demographics, CRP, fecal calprotectin levels, flare episodes and hospitalisations were recorded. Correlation between endoscopic and histologic activity was tested. Comparisons were made between patients in histologic and endoscopic remission v those with endoscopic and histologic activity regarding association with flare/hospitalisation.

Results

100 IBD patients (median age 49 IQR 22; 54% female; 50% Crohn’s disease) were included. A wide range of SES-CD scores were noted (median score 2 and IQR 6). 48% were in remission (0–2), 34% mild with score 3–6, 18% moderate with score 7–15 and 4% severe disease activity scoring > 16. Of those in endoscopic remission, 87.5% had normal histology. Of the 9 with moderate endoscopic disease all ranges of histological status were described. All levels of the Mayo scale (median score 1) were represented. Similar to the Crohn’s group, 87.5% of those in endoscopic remission also had normal histology. In total 42 patients were in both endoscopic and histological remission, and only 7% experienced a flare of disease activity in the following 12 months, with no hospitalisations. In total 40 patients had both endoscopically and histologically active disease, and 45% of these had a flare in the ensuing 12 months with two hospitalisations.The ROC curve for SES-CD score and histological remission is 0.73 +/- 0.07 95%CI 0.59 -0.87 and for the Mayo score and histological remission 0.87 +/- 0.05 95%CI 0.78- 0.97.

Conclusion

Accurate assessment of disease activity guides therapy choices and helps assess response to treatment in our IBD cohort. In this study the SES-CD and Mayo endoscopic scores showed good correlation with histological assessment. Those with active endoscopic and histologic disease experienced more flares and had higher rates of hospitalisation than those in remission. Further investigation with higher study numbers and incorporation of a standardised histological grading system are required.
P191 Non-specific terminal ileitis: prevalence, clinical course and association with later diagnosis of Crohn’s disease
Authors: Koureta E , Tampaki M , Voulgaris T , Laoudi E , Karatzas P , Papatheodoridis G
Published: May 2021

Background

The existing literature does not provide adequate guidance on the diagnosis and management of patients with non-specific terminal ileitis, while the data regarding the percentage of patients that finally develop Crohn’s disease are scarce.

Methods

The aim of this study was to evaluate the prevalence and natural course of non-specific terminal ileitis in patients who underwent colonoscopy in our department during the last decade. All patients with endoscopic findings of terminal ileitis and non-specific histological findings between 2008 and 2018 were included in the study. Patient characteristics, initial symptoms, biopsy findings, and the patients’ clinical and endoscopic course were recorded. Patients with a history of Crohn’s disease or histological findings related to specific diseases were excluded.

Results

Out of 5.353 colonoscopies in total, 92 patients (mean age: 50 years, men: 56.5%, asymptomatic: 72.5%) with non-specific terminal ileitis were identified (prevalence: 1.7%). Among 92 patients, 56 (61%) had available follow-up information for at least 6 months after initial endoscopy. In these patients, the reasons for performing endoscopy were chronic diarrhea (21/56, 37.5%), screening (16/56, 28.6%), abdominal pain (12/56, 21.4%), iron deficiency (5/56, 9%) and visible blood in stool (2/56, 3.5%). Endoscopic findings included erosions/ulcerations (62.5%), mucosal edema (23.2%), mucosal erythema (10.7%) and ileal valve stenosis (3.6%). Among 56 patients, 16 (28.6%) received medical treatment that included aminosalicylates (25%), budesonide (62.5%) and antibiotics (12.5%). Recession of symptoms was recorded in 20 out of 40 symptomatic patients (50%). Interestingly, symptomatic relief was more frequent in patients who did not receive any treatment (75%) comparing to those who received medications (26.3%), (p=0.02). In total, 23/56 (41%) patients underwent 2nd endoscopy with persisting endoscopic findings in 15/23 (65.2%). Eleven out of 56 (19.6%) patients were eventually diagnosed with Crohn’s disease. The probability of Crohn’s disease diagnosis was significantly higher in symptomatic patients (27.5%) comparing to asymptomatic (0%) (p=0.019). The majority of patients with Crohn’s disease (9/11, 81.8%) remained symptomatic after initial endoscopy (p= 0.002), while 90% of them had persisting endoscopic findings in follow-up endoscopy (p=0.019).

Conclusion

Non-specific terminal ileitis has a generally benign clinical course regardless of the administered treatment. However, patients with persisting symptoms and endoscopic findings should be followed closely to monitor later development of Crohn’s disease.