bluuebunny/crossref_metadata_2025 huggingface dataset:
Inference of taxonomic relationships betweenRhododendron ferrugineumandR.myrtifolium(Ericaceae) from leaf and fruit morphologies
Authors: Lewandowska Amelia , Marcysiak Katarzyna , Gómez Daniel , Jasińska Anna K , Romo Angel , Didukh Yakiv , Sękiewicz Katarzyna , Boratyńska Krystyna , Boratyński Adam
Published: January 2023

Rhododendron myrtifolium and R. ferrugineum are small, shrubby plant species that are morphologically similar to each other. They both grow on siliceous substrates in the subalpine belt of European mountains. In the present study, leaves and capsules from 11 populations of R. myrtifolium from the Carpathians were compared with those from 13 populations of R. ferrugineum from the Alps, Pyrenees and Sudetes. Fourteen leaf characteristics and 12 capsule characteristics of were analysed using ANOVA, discrimination analysis, principal component analysis and cluster analysis with agglomeration and the K-means method. All of the tested characteristics differed significantly between species, with the highest level of discrimination from the measured leaf traits. Less discriminatory were the proportions of the measured leaf features. According to the analyses, the populations of the two species were clearly separated, but individuals were partially intermixed. The similarities of the species may indicate a late divergence event, probably no earlier than the Pliocene. During the glacial cycles of the Pleistocene, populations of the two species may have mixed again. This may explain the presence of single individuals with R. myrtifolium morphology in some alpine R. ferrugineum populations and vice versa. The two species can be treated as another example of Carpathian–Alpine vicariance.
Molecular phylogenetics, biogeography and character evolution inSesamum(Pedaliaceae)
Authors: Zhigila Daniel A , Muasya A Muthama
Published: January 2023

As recently circumscribed, Sesamum was rendered monophyletic by including the three segregate genera Ceratotheca, Dicerocaryum and Josephinia. Here, the monophyly of Sesamum and the currently accepted infrageneric taxa was tested using expanded phylogenetic analyses. In addition, nine taxonomically useful morphological characters were optimized on the resulting phylogenetic tree to assess their evolutionary pattern. The phylogenetic analyses support the expanded circumscription of Sesamum and the monophyly of Sesamum section Sesamum relative to Sesamum sections Aptera, Ceratotheca, Chamaesesamum, Dicerocaryum, Josephinia and Sesamoptera. Most sections were retrieved as monophyletic, except Sesamum section Ceratotheca which was shown to be paraphyletic. Character reconstruction infers the ancestor of Sesamum to have had an erect growth habit, simple leaves with entire margins, ovaries with incompletely divided locules, indehiscent capsules that are oblong-quadrangular in lateral view with a beaked apex and winged seeds. Relative to the ancestral states, Sesamum has dehiscent fruits and fully divided locules as synapomorphies, with reversals to the ancestral state (indehiscence, undivided locules) in Sesamum sections Josephinia and Dicerocaryum. The absence of trichomes on mature vegetative parts and the development of lobed leaves are synapomorphies for Sesamum section Sesamopteris. Characters such as dentate and lobulate leaf margins and discoid fruit with horn-like protrusions are homoplastic in Sesamum. Dated phylogeny and ancestral range estimation suggest a southern African origin for the genus with subsequent diversification to tropical Africa, India and Australia. Sesamum has an estimated crown age of 38.1 ± 5.2 Myr with subsequent dispersal scenarios into tropical Africa, Asia and Australia during the Miocene from 24.5 Mya. Dispersal, rather than continental vicariance, is the probable explanation for the pantropical distribution of Sesamum.
Behavioural and physiological responses to salinization and air exposure during the ontogeny of a freshwater South American snail
Authors: Barrios-Figueroa R , Urbina M A
Published: January 2023

Salinization is of global concern, threatening freshwater biodiversity. Salinity tolerance is highly variable and therefore needs to be evaluated on a species-specific basis. An estuarine population of Chilina dombeiana, a freshwater gastropod endemic to Chile and classified as vulnerable, has been recently found in the Biobío River’s mouth, suggesting some degree of tolerance to brackish waters. This study evaluated the survival, behaviour (medium preference) and physiology of C. dombeiana when exposed to salinities higher than freshwater, thus elucidating the potential mechanisms used to survive salinization. Chilina dombeiana belongs to the Pulmonate group;, so we evaluated oxygen uptake in air and water, aiming to evaluate emersion as a potential avoidance response to a progressive salinity increase. Complete embryo development was observed for salinities ≤ 16 PSU (practical salinity units) but hatching rates above 50% were only achieved in freshwater (0 PSU). It was also found that salinity had stage-specific effects during embryonic development. In adults, acute exposure to brackish water (12 PSU) caused a decrease in oxygen consumption (compared to freshwater), in the ammonium excretion rates and in the percentage of muscular water content. Although C. dombeiana was able to take up oxygen in both mediums, survival in air decreased over time (days), which correlates with the behavioural preference to remain submerged, even at elevated salinities. Considering the survival of adults and embryos decreased as salinity increased and the lack of an avoidance behaviour or a physiological ability to maintain homeostasis at salinities higher than freshwater, our results suggest this snail could be adversely affected by salinization in the long term. Furthermore, given the ability of C. dombeiana to uptake oxygen in both mediums, it should be considered as a facultative air breather snail, rather than a strictly aquatic species.
Heart–gut microbiota communication determines the severity of cardiac injury after myocardial ischaemia/reperfusion
Authors: Zhao Jinxuan , Zhang Qi , Cheng Wei , Dai Qing , Wei Zhonghai , Guo Meng , Chen Fu , Qiao Shuaihua , Hu Jiaxin , Wang Junzhuo , Chen Haiting , Bao Xue , Mu Dan , Sun Xuan , Xu Biao , Xie Jun
Published: January 2023

Aims

Recent studies have suggested a key role of intestinal microbiota in pathological progress of multiple organs via immune modulation. However, the interactions between heart and gut microbiota remain to be fully elucidated. The aim of the study is to investigate the role of gut microbiota in the post-ischaemia/reperfusion (I/R) inflammatory microenvironment.

Methods and results

Here, we conducted a case-control study to explore the association of gut bacteria translocation products with inflammation biomarkers and I/R injury severity in ST-elevation myocardial infarction patients. Then, we used a mouse model to determine the effects of myocardial I/R injury on gut microbiota dysbiosis and translocation. Blooming of Proteobacteria was identified as a hallmark of post-I/R dysbiosis, which was associated with gut bacteria translocation. Abrogation of gut bacteria translocation by antibiotic cocktail alleviated myocardial I/R injury via mitigating excessive inflammation and attenuating myeloid cells mobilization, indicating the bidirectional heart–gut–microbiome–immune axis in myocardial I/R injury. Glucagon-like peptide 2 (GLP-2), an endocrine peptide produced by intestinal L-cells, was used in the experimental myocardial I/R model. GLP-2 administration restored gut microbiota disorder and prevented bacteria translocation, eventually attenuated myocardial I/R injury through alleviating systemic inflammation.

Conclusion

Our work identifies a bidirectional communication along the heart–gut–microbiome–immune axis in myocardial I/R injury and demonstrates gut bacteria translocation as a key regulator in amplifying inflammatory injury. Furthermore, our study sheds new light on the application of GLP-2 as a promising therapy targeting gut bacteria translocation in myocardial I/R injury.
DOP30 Identifying dietary factors and metabolites that may promote healthier Crohn Disease microbiome and mucosal transcriptomics signals as future targets using Diet-Omics
Authors: Haberman Ziv Y , Braun T , Amir A , Levhar N , Toren I , Malik A , Neuman S , Hadar R , Efroni G , Ben-Horin S ,   The Leona M. and Harry B. Helmsley Charitable Trust SOURCE consortium investigators
Published: January 2023

Background

The increase in prevalence of Crohn Disease (CD) worldwide together with suboptimal results with current therapies mandate identification of new targets. We aimed to identify dietary components and metabolites linked with host and microbial factors to support targeting beneficial exposures.

Methods

Analyses of the SOURCE Israeli sub-cohort included clinical, biomarkers, computerized food frequency questionnaire (FFQ), fecal metabolomics, mucosal terminal ileum (TI) transcriptomics, and microbiome.

Results

25 newly-diagnosed CD and 32 controls (median age 28 years, 53% males) were studied. MaAsLin multivariate analyses identified 13 increased and 74 decreased fecal metabolite in CD after controlling for age and gender (FDR<0.25) including the induction of N-Acetyl-putrescine, Cholate, and Tyramine, and reduction in Melatonin, Cytosine, Lipoic and Linolenic acid (Fig. 1). Using weighted gene co-expression network analysis together with functional annotation enrichments of the TI transcriptomics, we identified 7 gene co-expression modules that were significantly linked with CD. These modules showed no significant association with gender, age, BMI, or smoking but had strong associations with CRP and calprotectin (Fig. 2). Using a predefined gut microbial health index to summarize the microbial signals along the health-disease scale, we noted negative associations specifically with transcriptomics modules enriched for immune genes and functions. We then explored the directionality of the relationship with dietary and metabolomic features, which can rationalize decreasing their exposure if they correlate with disease, or increasing it if they correlate with control signals. Consumption of sugar, saturated fat, iodine, and selenium showed similar directionality as seen with disease; sugar and fat showed strongest associations with the epithelial innate defense module including DUOX2 and CEACAM5, and iodine and selenium were linked with the immune module that included OSM and CXCL8/9. In contrast, manganese and vitamin D consumption positively correlated with modules associated with controls and enriched in epithelial lipid processing and mitochondrial functions. Associations between fecal metabolites and host transcriptomics showed a robust signal identifying 237 significant associations (FDR<0.25). Most showed correlation with control-associated signals and an opposite direction to that seen with disease, which may justify testing them as beneficial interventions.

Conclusion

Detailed Diet-Omics dataset can quantify dietary constituents and fecal metabolites directional impact on host TI transcriptome and on the microbiome, which can prioritize interventions for testing in preclinical models
DOP43 Extended induction in the True North OLE study: ozanimod efficacy in biologic-naive and biologic-experienced patients
Authors: Dignass A , Regueiro M , Colombel J F , Jain A , Canavan J B , Wu H , Lawlor G , Osterman M T , Vermeire S , Rubin D T
Published: January 2023

Background

Prior exposure to biologics can influence response to subsequent lines of advanced therapies. Previous analyses showed that patients who did not achieve clinical response following 10 weeks of ozanimod treatment in the phase 3 True North (TN) study benefited from extended induction with open-label ozanimod in the TN open-label extension (OLE) study. As the impact of prior biologic exposure on outcomes with extended induction is unknown, the aim of this analysis was to evaluate that question.

Methods

Clinical nonresponders to ozanimod at TN Week (W) 10 entered the OLE (data cutoff: January 10, 2022, at which point the disposition was available until OLE W94 for all patients). Data were analysed in patients with and without prior biologic exposure at baseline. Disease activity was assessed at TN W0 (baseline) and at W10 (OLE entry). Symptomatic clinical response and remission were evaluated through OLE W94, and multiple clinical, endoscopic, and histologic endpoints were evaluated at OLE W46 and W94 using observed case (OC) and nonresponder imputation (NRI) analyses.

Results

A total of 220 patients with prior biologic information entered the OLE after not achieving clinical response at TN W10 (biologic-naive, n=122; biologic-experienced, n=98). Disease activity at baseline was generally consistent between biologic-naive and experienced patients. About half of the ozanimod W10 nonresponders in both groups achieved symptomatic clinical response by OLE W5, with a higher proportion of biologic-naive patients maintaining response until OLE W94 in both OC and NRI analyses (Figure 1). Higher proportions of biologic-naive patients also sustained symptomatic clinical remission until OLE W94 in both OC and NRI analyses. In OC analysis, a higher proportion of biologic-naive patients achieved all clinical, endoscopic, and histologic endpoints at OLE W46 compared with biologic-experienced patients; by OLE W94, however, the proportions of patients who achieved all clinical, endoscopic, and histologic endpoints were generally consistent, regardless of prior biologic exposure (Figure 2). As expected, a smaller proportion of patients achieved the efficacy endpoints in the NRI analysis, with proportions being higher in biologic-naive patients; response rates were sustained between OLE W46 and W94 in each group.

Conclusion

Both biologic-naive and -experienced clinical nonresponders to ozanimod at the end of induction demonstrated response to extended induction with ozanimod. Delayed response was durable for up to 2 years of continuous ozanimod treatment in both groups, with higher proportions achieved in biologic-naive patients.
P006 Engineered propionate-producing bacteria attenuates murine colitis by modulating the immune function of resident macrophages via histone deacetylase
Authors: Feng Z , Wang X , Kang G , Zhao J , Ye Y , Liu L , Huang H , Cao X
Published: January 2023

Background

Most inflammatory bowel disease (IBD) patients are unable to maintain long-term remission by current treatment. Propionate has been proven to be able to exert anti-inflammatory effects in intestinal inflammation, but direct supplement of propionate has actual disadvantages including low bioavailability and poor sustained effect, et. al.

Methods

In this study, the genes related to acetate synthesis and metabolism were knocked out through the double plasmid CRISPR/cas9 gene editing system to increase the yield of propionate to ultimately form the engineered propionate-producing bacteria (EPB). The dextran sulfate sodium（DSS）-induced colitis model was used to explore the protective effect of EPB in vivo. Flow cytometry was used to evaluate the ratio of resident macrophage. Peritoneal macrophage and RAW264.7 cell lines were used to explore the effect and mechanism of EPB on the immune function of macrophages in vitro. Real-time polymerase chain reaction (RT-PCR) was performed to detect the expression of several cytokines in colon tissue and cells. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of cytokines in the cell supernatant. Western bolt was used to detect the levels of histone deacetylase protein and transcription factor GATA6.

Results

EPB exhibited enhanced propionic acid production. In vivo results showed that EPB group had less barrier damage and less inflammatory infiltration than control groups indicating it could prominently ameliorate DSS-induced colitis. EPB promoted the production of anti-inflammatory cytokine IL-10 and reduced the production of IL-2、IL-5 and IL-6 in DSS-induced mice. In the further exploration of the effects of EPB, we found that EPB increased the proportion of resident macrophages (F4/80hiCD11bhi) in the peritoneal cavity, And the transcription factor GATA6, which is specific express in peritoneal macrophages, was detected in the intestinal tissue. Moreover, we investigated the effects of EPB on peritoneal macrophages in vitro and found EPB not only affected the cytokine production ability of resident macrophages but also reduced cell apoptosis. Further analysis showed the regulatory effect of EPB on macrophages is associated with G protein-coupled receptors 41/43 and histone deacetylase 2 (HDAC2), which is closely related to propionate. GPR41/43 inhibitor weakened the effects of EPB on macrophages, while HDAC inhibitor trichostatin A (TSA) exerted a similar effect to EPB.

Conclusion

The engineered propionate-producing bacteria (EPB) could attenuate DSS-induced colitis in the mouse by modulating the immune ability of resident macrophage and the production of classic inflammation-related cytokines, which indicates an effective and safe treatment strategy for ulcerative colitis.
P062 Antibody responses to SARS-CoV-2 vaccination outperform responses induced by natural infection in patients with IBD receiving immunosuppressive medications: a report from the ICARUS-IBD consortium.
Authors: González Cueto E , Matthew E , Wellens J , Martinez Pazos V , Thompson C , Klenerman P , Cadwell K , Colombel J F , Satsangi J , Wong S Y ,   ICARUS-IBD consortium
Published: January 2023

Background

The effects of immunosuppressive medications on immune responses to COVID-19 vaccination in patients with inflammatory bowel diseases (IBD) have been reported. However there is little data on immune responses in naturally infected SARS-CoV-2 patients compared with vaccination. We compared in a longitudinal study SARS-CoV-2 antibody and T cell responses in naturally-infected vs. vaccinated IBD patients.

Methods

110 IBD patients enrolled at the Icahn School of Medicine at Mount Sinai were prospectively followed with serial blood collection between May 2020, and February 2022. Samples were screened by ELISA to determine seropositivity, and stratified by infection, vaccination status, and IBD medications. Subsequently, ELISA-based inhibition assay and pseudotyped SARS-CoV-2 microneutralization assays were used to determine the inhibition and neutralization capacity of the seropositive individuals for wild type (WT) delta variant (Dv) and Omicron. Cellular responses were measured by IFN-γ ELIspot using nucleocapsid and spike peptide libraries.

Results

Overall, 64 patients had Crohn’s Disease and 46 had Ulcerative Colitis (UC), 69 were naturally infected. Only Anti-TNF (N=52), Ustekinumab (N=16), and Vedolizumab (VDZ) (N=33) treatment groups were considered. Only US-available vaccinations were included. Double-vaccinated IBD patients showed greater neutralizing responses to SARS-CoV-2 WT and Dv than naturally-infected individuals (p=0.0003, p=0.0025). Moreover, double-vaccinated individuals had greater neutralizing reactions against WT than DV (p 0.017) and Omicron (p 0.001) variants. Following natural infection, there were no differences between treatment groups in neutralization response, however those double-vaccinated on anti-TNF had lower neutralization than VDZ (p=0.008). Neutralization responses were maintained for a period of 8 months following natural infection and double vaccination. SARS-CoV-2 spike T cell responses were significantly higher in naturally infected (p=0.009) and double vaccinated individuals (p=0.005), with no significant differences between treatment groups (p<0.999).

Conclusion

After a second vaccine dose, IBD patients showed stronger neutralizing antibody titers than naturally infected patients. Those on anti-TNF exhibited lower neutralizing responses than VDZ. T-cell responses were similar in infected and double-vaccinated subjects after vaccination or infection. These data imply COVID-19 immunization provides additional serological protection over natural infection.
P079 Attenuation of inflammation and histologic production-dependent improvement by engineered high acetate producing Saccharomyces boulardii in DSS-induced colitis
Authors: Deleu S , Trindade de Carvalho B , Jacobs I , Arnauts K , Deprez L , Vissers E , Lenfant M , De Hertogh G , Huys G , Thevelein J , Raes J , Vermeire S ,   MIMOSA
Published: January 2023

Background

It has been hypothesized that the probiotic potential of the yeast Saccharomyces boulardii (Sb) is associated with its acetate production. This SCFA is of interest in IBD due to its cross-feeding potential with beneficial butyrate-producing bacteria and low toxicity to epithelial cells . Our previous in vitro work supports this hypothesis (Deleu et al, 2022) but still requires in vivo validation. Therefore, we evaluated the effect of different engineered Sb strains producing variable amounts of acetate in DSS-induced colitis in mice.

Methods

Nine week old female C57/Bl6 mice (N=120) were allocated to 12 treatment groups receiving drinking water or 2.75% DSS in combination with PBS (control), Baker’s yeast (non-probiotic control), SDH1 (non-acetate producing Sb), ENT (transient acetate producing Enterol strain-probiotic control), SbP (high acetate producing Sb) and ENT3 (extra high acetate producing Sb). Disease activity including weight loss, diarrhoea and the presence of occult blood was scored daily. On day 7, the DSS groups were transferred to regular drinking water and on day 14 mice were sacrificed. Colonic tissue and blood were collected for resp. histologic and cytokine analysis.

Results

Disease activity, determined by the area under the curve, in DSS subgroups was lower for SbP compared to PBS and Baker’s yeast (both p<0.05). Remarkably, Sb SDH1 showed even higher disease activity compared to the Sb strains ENT, SbP and ENT3 (all p<0.05). At sacrifice, macroscopic damage score in DSS subgroups was lower for SbP and ENT3 (both p<0.05) compared to Sb SDH1 and the colon weight/length-ratio was decreased for ENT and SbP compared to Sb SDH1 (resp. p=0.06 and p=0.08). Higher histologic inflammation was noted in the non- or only transient-acetate producing strains on DSS compared to healthy PBS control (all p<0.05), whereas this increase was not observed for both high-acetate producing strains SbP and ENT3 on DSS (p=NS). Lower IL1β, IL2 and IL4 concentrations for DSS groups on SbP and ENT3 compared to DSS groups on Sb SDH1 and ENT were observed (all p<0.05). In contrast, IL10, TNFα and KC/GRO were lower for the DSS groups on Sb SDH1 and ENT compared to DSS groups on SbP, ENT3, and even PBS for IL2 and 4 (all p<0.05).

Conclusion

Engineered high acetate producing Sb strains show a significant trend towards improved attenuation of DSS-induced colitis compared to the parent Sb strain on disease activity, macroscopic damage score and show production-dependent response on histology. Mixed pro-inflammatory serum profiles were observed potentially pointing in the direction of other effects of acetate accumulation. Together with our previous in vitro work, these data indicate a role for Sb-produced acetate in attenuating inflammation.
P095 Newly discovered gut matrikines from Crohn’s disease intestinal tissue induce cell proliferation, activation and inflammatory response in intestinal myofibroblasts in vitro
Authors: Papatheodoridi M , Giuffrida P , Canetti D , Yutaka Y , Hodgetts H , Di Sabatino A , Johnston H , Verona G , Rendell N , Al-Akkad W , Frenguelli L , Hall A , Luong T , Sampietro G , Pinzani M , Rombouts K , Belloti V , Mazza G
Published: January 2023

Background

The interaction between intestinal myofibroblasts (iMFBs) and extracellular matrix (ECM) changes contributes to Crohn’s disease (CD) fibrosis, but the exact mechanisms are not yet clear. Our group recently discovered a selection of matrix-derived peptides (matrikines) that specifically appear in the intestinal tissue of patients with CD fibrostenosis.1 Here, we evaluate the in vitro effect of 19 matrikines (with various bioactivity likelihood) on primary human intestinal myofibroblasts (IMFBs), key cells in CD fibrosis.

Methods

Primary human iMFBS (500K/mL, Passage 4, Novabiosis) were cultured in serum-free medium (SFM) (DMEM high glucose, 1% sodium pyruvate, 1% non-essential aminoacids, 1% Antibiotics-Antimycotics and 3mg Gentamicin), complete medium (SFM with 10% fetal bovine serum), PDGF-bb 10ng/mL or treated with each of the matrikines at 10, 50, 100 μg/mL for 24hours. The effect of each matrikine on cell proliferation, gene expression and migration was assessed by BrdU, qPCR and Transwell assays, respectively. RNA sequencing data was analysed using the GSEA software.

Results

The effect on iMFBs proliferation and viability was tested with each of the 19 matrikines at 3 different doses (Table 1).

Among 9 most likely-bioactive matrikines (M1-M9) (Figure 1), M1, M4, M7, M8 and M9 induced the highest effect in cell proliferation and were selected for further experiments. Gene expression assays showed upregulation of ACTA2 with M1 or M7 and upregulation of COL1A1 with M1, M7 or M8, indicating activation of the iMFBs (Figure 2).

Transwell assays also showed that M1, M4 and M8 induce iMFB cell migration.

A total of 1948, 1024, 460, 570, and 2749 differentially expressed genes (DEGs) were identified in iMBFs treated with M1, M4, M7, M8 and M9 vs no treatment, showing enrichment in pathways related to “smooth muscle contraction”, “fibroblast growth factor”, “cell migration”, “collagen formation”, “elastin formation” and “ECM organization”; most of which were also enriched by complete medium and/or PDGFbb that served as positive controls. However, pathways related to “proinflammatory and profibrotic mediators” or “vascular permeability” were only enriched in iMFBs treated with M1, M4, M8 and M9 or M1 and M9, respectively (Figure 3).

Conclusion

A selection of newly discovered CD-specific matrikines induce activation of iMFBs as well as inflammatory response and endothelial changes, suggesting an important role and therefore their potential value as biomarkers in the progression of intestinal fibrostenosis.
P119 Perianal Crohn’s disease and the development of colorectal and anal cancer: A systematic review and meta-analysis
Authors: Johansen M P ,   Martha Pollen Johansen Mads Damsgaard Wewer Andreas Nordholm-Carstensen Johan Burisch
Published: January 2023

Background

Over the course of their disease, 15-30% of patients with Crohn's disease(CD) develop Perianal Crohn's disease (pCD). In approximately 5% of patients, perianal fistula is the only manifestation of their CD. Previous studies have found that perianal involvement results in an 11-fold increased risk for anal cancer. The aim of this systematic review was to assess the literature on the incidence and risk factors for colorectal cancer and anal cancer in patients with perianal Crohn’s disease.

Methods

A systematic review of the literature was performed using PubMed, Embase and Google Scholar. A meta-analysis was then conducted using a random-effect model.

Results

Five studies were included in the systematic review. Of the total patients, 26.5% had perianal Crohn’s disease. The median follow-up was 6 years. In total, 127 cases of colorectal cancer were found [0.43% of the included Crohn’s disease patients]. Perianal involvement was present in 50% of colorectal cancer patients [0.89% of the population]. Three of the studies specified the cancer to be rectal or anal, which were present in 68 and 24 cases [0.3% and 0.1% of patients], respectively. In a subgroup analysis of rectal and anal cancer, perianal involvement was most frequent in anal cancer, accounting for 46% of the cases. In the rectal cancer group, 37% had perianal involvement. The higher incidence of colorectal cancer in patients with perianal Crohn’s disease was confirmed in a meta-analysis.

Conclusion

Half of the patients with colorectal cancer and anal cancer were found to have perianal Crohn’s disease. In patients with perianal involvement, there was a higher percentage of anal cancer compared with rectal cancer. These results support the theory that patients with perianal Crohn’s disease are at increased risk for developing colorectal and anal cancer. Studies collecting more detailed data regarding patients and their cancers are needed to further specify the disease course.
P126 Ask twice: The importance of repeated faecal calprotectin testing prior diagnostic colonoscopy in an adult inception cohort
Authors: Rimmer P , Cheesbrough J , Quraishi M N , Sharma N , Cooney R , Love M , Iqbal T
Published: January 2023

Background

Elevated Faecal Calprotectin (FCP) is established as a valuable tool in differentiating Inflammatory Bowel Disease (IBD) from Irritable bowel syndrome (IBS) and monitoring IBD activity. Initial implementation studies in the UK demonstrated benefit from repeat testing to exclude false positives. This is not currently mandated by IBD consensus guidelines. Growing waiting times are increasing pressure to include a single result in straight to test pathways. No one level for significant elevation is defined with levels between 100-250ug/g used. We present our experience of the real-world utility of FCP used in a primary care referral pathway.

Methods

From Jan 2021-Nov 2022, new referrals were streamed into a rapid access ‘Inception IBD’ clinic on the basis of symptoms and raised FCP. A repeat FCP (kit sent in advance) was brought to the first appointment, with same day processing using the Buhlmann fCAL Turbo Test. Results and accompanying diagnosis and outcome data was collected prospectively. There was no standardised testing interval but median time from referral to review was 34 days.

Results

A single FCP was available for 425 patients with a final diagnosis. Two pre-treatment FCPs were available in 185. Median initial FCP was 949ug/g in those subsequently diagnosed with IBD (Ulcerative colitis 1162ug/g, Crohn’s 893ug/g) vs 353ug/g in those without IBD. This difference heightened on retesting, with median FCP in IBD 749ug/g vs 34ug/g in non-IBD (Fig 1). FCP fell between 1st and 2nd measurement in 88.6% of patients who had IBD excluded.

In IBD, baseline FCP showed strong correlation with established disease activity markers (Fig 2).

Baseline FCP levels were significantly higher in IBD patients who went on to require biologic treatment (Mann-Whitney U 2763, p<0.001).

A variety of FCP cut-off values were assessed (Fig 4). A two sample >200ug/g cut off performed best as assessed by Area Under the Curve (AUC). However, sensitivity fell to 81.5% at this level.

Of 15 IBD patients who didn’t have two FCPs >200ug/g, 7 had an increase between the 1st and 2nd FCP (median 147 vs 487ug/g). The remaining 8 comprised 4 ileal Crohn’s, 3 mild proctitis and 1 stricturing colonic Crohn’s in whom FCP failed to correlate with disease activity. Overall, 83% (48/58) of patients with increasing 1st to 2nd FCP were diagnosed with IBD.

Conclusion

Our data supports repeat testing of FCP to avoid unnecessary investigations adding to post COVID endoscopy backlogs. A cut off of two values >200ug/g had the best overall performance but can miss a small number of IBD cases, particularly those with isolated ileal disease or a more indolent disease course. This cut off should not be used in those with a marked increase between 1st and 2nd result, where IBD is likely.
P162 Earlier (luminal) surgery is associated to reduced postoperative morbidity in ileocaecal Crohn’s disease: results from SURGICROHN – LATAM study
Authors: IBD Latam Consortium S , Avellaneda N L , Saddy Rodrigues Coy C , Sarubbi Fillmann H , Saad-Hossne R , Muñoz J P , García-Duperly R , Bellolio F , Rotholtz N , Rossi G , Marquez V J R , Cillo M , Lacerda-Filho A , Carrie A , Yuki Maruyama B , Sarubbi Fillmann L , Ferro E , Londoño-Schimmer E , Iglesias A , Bras Harriott C , Campana J P , Londoño Estrada D , Kotze P G ,   SURGICAL IBD LATAM CONSORTIUM
Published: January 2023

Background

Early surgical resection is an emerging concept for patients with ileocaecal Crohn’s disease (CD). The aim of this study was to compare postoperative outcomes after ileocaecal resections between patients with luminal and complicated CD.

Methods

A retrospective analysis of patients operated for ileocaecal CD during an 8-year period in ten tertiary referral academic centres from Latin America was performed. Patients were allocated into 2 groups: those operated for early (luminal) disease (Early Crohn’s Disease -ECD-) and for complications of CD (Complicated Crohn’s disease -CCD-). A comparative analysis was performed regarding short-term outcomes of surgery, considering overall postoperative complications as main outcome.

Results

337 patients were included in the analysis, 60 (17.80%) in the ECD group. Smoking and exposure to perioperative biologic drugs were more prevalent in CCD group. CCD patients had increased requirement of urgent surgery (26.71 vs. 15%, p=0.056), longer operative time (164.25 vs. 90.53 minutes, p< 0.01), lower rates of primary anastomosis (90.23 vs. 100%, p=0.012), increased rate of overall postoperative complications (33.21 vs. 16.67%, p=0.013), more reoperations (13.36 vs. 3.33%, p=0.026), and higher rates of major anastomotic fistulas and hospital stay. On multivariable analysis, smoking (p= 0.001,95%CI: 2.59-32.11), operative time (p=0.022,95%CI:1-1.02), associated procedures (p=0.036,95%CI:1.09-15.72) and intraoperative complications (p=0.021,95%CI:1.45-92.31) were independently related to presenting postoperative complications.

Conclusion

Early (luminal) ileocaecal resections were associated to lower rates of overall postoperative complications. Proper timing for surgery, avoiding delays in surgical indication can impact postoperative outcomes.
P184 Identification of the PAI-1, as a potential non-invasive, fecal biomarker in the Inflammatory Bowel Diseases
Authors: Jójárt B , Molnár T , Diána K , Szabó V , Varga Á , Resál T , Bacsúr P , Szántó K , Földesi I , Molnár T , Maléth J , Farkas K ,   HAS-USz Momentum Epithelial Cell Signaling and Secretion Research Group
Published: January 2023

Background

Inflammatory bowel diseases (IBD) are defined by unregulated immune response leading to intestinal inflammation. Monitoring of the intestinal inflammation are mostly invasive, time-consuming and expensive. Therefore, a simple, rapid and non-invasive test, with ability to differentiate IBD from other gastrointestinal conditions and to monitor disease activity and therapeutic response, will have important clinical implications. Our previous cytokine profiling identified that plasminogen activator inhibitor 1 (PAI-1) is expressed in IBD patients with active disease, but not in control. Therefore, our aim was to assess the utility of PAI-1 in monitoring disease activity and therapeutic response of IBD patients in different biological samples.

Methods

Biopsy, serum and fecal samples were collected from more than 150 active IBD patients and controls without IBD. Inclusion criteria included change of therapy or initiation of new treatment for IBD patients. Immunofluorescence (IF) staining was used to observe the presence and localisation of cytokines. Total protein and mRNA were isolated from biopsies and fecal samples. Protein levels were measured by ELISA and gene expression by qRT-PCR.

Results

The IF staining of the biopsy samples revealed a significantly higher percentage of PAI-1 positive cells in the inflamed mucosa compared to the control. The relative mRNA expression of PAI-1 was significant higher in non-responders and untreated, inflamed IBD patients compared to controls and responders. On the other hand, we were not able to detect significant changes between responders and non-responders in gene expression of TNF-α, IL-1β and IL-6. Serum, mucosal and fecal PAI-1 protein levels were significantly higher in IBD patients compared to controls. Whereas no significant difference was observed between Crohn’s disease and ulcerative colitis patients. The PAI-1 level was significant increased in endoscopically and clinically active disease compared to inactive patients and controls. In responders, PAI-1 concentration significantly decreased after initiation of therapy compared to non-responders. Significantly upregulated fecal PAI-1 level was found in active IBD compared to patients with inactive IBD, tumor, adenoma, diverticulosis and control. In addition, the stability analysis of fecal PAI-1 showed that the protein was detectable up to one week at room temperature and 4ºC.

Conclusion

Our findings suggest that serum, mucosal and fecal PAI-1 expression correlates with disease activity in IBD patients, suggesting that it could be utilized to monitor disease activity and possibly therapy response as a non-invasive biomarker in IBD.
P204 Preoperative optimization of patients with inflammatory bowel disease: a multicentre study of EIGA Group
Authors: Molina Arriero G , Mauriz Barreiro M V , Echarri Piudo A , Fraga Iriso R , González Furelos T , López de Ullibarri I , Vázquez Rey M T , Calviño Suárez C , Carmona Campos A , Tejido Sandoval C , García Morales N ,   Inflammatory Bowel Disease Group of Galicia [EIGA]
Published: January 2023

Background

A significant percentage of patients with inflammatory bowel disease (IBD) will require surgical treatment at some point in their disease. Preoperative optimization (PO) intends to ensure that the patient arrives in optimal condition to surgery and to minimize the risk of complications. The aim of this study was to assess whether optimization criteria were met in patients with IBD undergoing elective surgery and to describe the percentage of post-surgical complications based on exposure to any of these risk factors.

Methods

IBD patients undergoing intra-abdominal surgery between 1st January 2013 and 30st September of 2021 were retrospectively selected. Data collection included clinical characteristic of IBD, nutritional biochemical parameters and surgical aspects. In addition, risk factors associated with a worse prognosis were collected. Among them, anemia, risk of malnutrition (using the Malnutrition Universal Screening Tool, MUST), smoking, presence of intra-abdominal sepsis and treatment received for IBD in the 30 days prior to surgery, especially the use of corticosteroids. Postsurgical complications were defined as those occurring within 30 days after surgery.

Results

A total of 212 surgeries performed in 5 centres from northwest of Spain were included: 87% in Crohn’s disease, 11% in ulcerative colitis and 2% in unclassified-IBD patients. Patients' clinical and demographic characteristics are summarized in Table 1. Postoperative complications were reported in 20.1% (n=62) of the patients, including suture dehiscence, infection, obstruction, bleeding and thrombosis. The most frequent complication was surgical site infection (10.8% of all the cases). Up to 35.6% of the patients were at risk of malnutrition at the time of surgery (MUST>=1), only half of these patients received some type of nutritional therapy. 20% of patients received at least 20 mg daily of prednisone or equivalent four weeks prior to surgery. Risk factors of post-surgical complications are presented in Table 2. Corticosteroid therapy (> 20 mg daily prednisone or equivalent) (OR 3.52 [95% CI: 1.05–12.6] (p=0.042) and the absence of nutritional support (OR 2.34 [95% CI:1.17-4.65] (p=0.016) were associated with postoperative complications. Multivariate and univariate analysis for postoperative complications are shown in Table 3 and Table 4.

Conclusion

The absence of a PO model increases the risk of postoperative complications. Inadequate preoperative nutritional care and corticosteroid therapy are risk factors for complications in our study. Protocols of PO in IBD patients are recommended.
P223 The usefulness of tissue calprotectin in pediatric Crohn’s disease – a pilot study.
Authors: Szymanska E , Szymanska S , Karkucinka-Wieckowska A , Aldona W , Kierkus J , Dadalski M ,   Biomarkers inflammatory bowel disesae elafin
Published: January 2023

Background

Fecal calprotectin (FCP) is a highly sensitive biomarker of intestinal inflammation widely used in diagnostics and monitoring of inflammatory bowel disease (IBD). However, it cannot be used to localize the disease activity and its levels may be false negative or false positive in some cases. The aim of this study was to evaluate tissue calprotectin (TCP) in pediatric patients with Crohn’s disease (CD) and correlate it with FCP and clinical activity of the disease.

Methods

Fifty-seven pediatric patients with CD at the median age of 10.5 (1-17) years (yrs) were examined for fecal and tissue calaprotectin. Values were correlated to disease activity and histopathological changes of the patients’ endoscopic biopsies. Disease activity was assessed using Pediatric Crohn’s Disease Activity Index (PCDAI), fecal calprotectin (FCP) was measured with ELISA test and the immunohistochemical (IHC) staining for calprotectin antigen was performed on bioptic samples from 6 bowel segments and the number of TCP cells was counted per high power field (HPF). Non-parametric statistical tests were used for data analysis.

Results

Patients’ median PCDAI score was 10 (0-63.5), while median FCP was 535 (30-600) ug/g. The only observed correlation was between FCP level and disease activity. There was no associated neither between FCP and TCP, nor TCP and PCDAI.

Conclusion

Tissue calprotectin unlike FCP does not seem to be a good predictor of disease activity in Polish pediatric patients with CD.
P248 The diagnostic accuracy of Intestinal ultrasound for assessing disease activity in the proximal ileum and jejunum in children with Crohn’s disease: Preliminary results of a prospective study
Authors: Vos H , van Wassenaer E , van Schuppen J , van Rijn R , D'Haens G , Benninga M , Koot B ,   RAINBOW group
Published: January 2023

Background

Crohn’s disease (CD) is an inflammatory bowel disease (IBD) involving mainly the small intestine and the colon. Current imaging modalities such as magnetic resonance enterography (MRE) to assess disease activity in the small bowel are expensive and are often poorly tolerated by children. Intestinal ultrasound (IUS) is a non-invasive and well tolerated monitoring tool for assessing disease activity in colon and terminal ileum. In children the diagnostic accuracy of IUS for proximal bowel has not been systematically studied. In this study we assess the diagnostic accuracy of IUS compared to MRE for the proximal ileum and jejunum in the paediatric population. Furthermore we aim to establish which IUS features are the best predictors for IBD activity in the proximal ileum and jejunum.

Methods

Paediatric CD patients were prospectively enrolled and underwent MRE and IUS within 7 days. MRE-images were scored using the segmental grading system by Tielbeek et al. The ultrasonographer was blinded for the MRE results and the paediatric radiologist who assessed the MRE images was blinded for IUS results.

Results

Forty-two paediatric CD patients underwent IUS paired with MRE until now. Eighty-four bowel segments were available for analyses. In total 24 bowel segments had mild (n=12) to moderate severe (n=12) disease activity based on MRE. The AUROC of BWT for moderate severe disease was 0.78 (95% CI 0.61-0.95). A cut-off value of BWT >2.5 mm showed had a specificity of 90%. A cut-off value of BWT <1.7 mm showed had a sensitivity of 91%. Of the affected segments 12 had increased Doppler signal and 13 showed mesenteric fat proliferation. No regression analysis was performed since the number of inflamed segments was too low.

Conclusion

IUS is an promising tool to non-invasively assess disease activity in the proximal ileum and jejunum. Our preliminary results suggest that a cut-off for BWT < 2,5mm IUS can be used to demonstrate disease activity. A lager sample size to perform regression analysis and to assess other IUS features for disease activity is currently being collected.
P291 Long term outcomes of children with ulcerative colitis after acute severe colitis: a multicenter study from the GETAID pédiatrique group
Authors: Pigneur B , Cochet M , Delphine L , Coopman S , Raphael E , Thierry L , Claire D , Stéphanie W , Rémi D L , Georges D , Valérie B , Anne B , Christine M , Jerome V , Frank R , Julie L ,   GETAID pédiatrique
Published: January 2023

Background

Acute Severe Colitis (ASC) is a frequent and severe complication of ulcerative colitis (UC) that can occur at any time during the disease. Its prognosis can be severe with a high risk of colectomy. The use of immunosuppressants and more recently biotherapies seem to reduce the risk of colectomy. We wished to study the long-term evolution of paediatric-onset UC patients after ASC.

Methods

This retrospective study was conducted in 12 centres of the GETAID paediatric in France. Data on patients with UC aged < 18 years admitted with ASC (defined as paediatric ulcerative colitis activity index [PUCAI] score ≥ 65) between January 2010 and January 2021 were collected at discharge and at 1, 3 and 5 years after admission. The primary outcome of our study was colectomy-free rates at one year. A univariate analysis comparing the profile at diagnosis and at ASC of patients who underwent colectomy, and others was performed to look for prognostic factors associated with the risk of surgery.

Results

Of the 102 patients admitted with ASC, 95 [93%] were treated with corticosteroids. Forty-six [48%] patients were escalated to second-line therapy, mainly to infliximab. Nine patients [8.8%] underwent colectomy before discharge. Long-term follow-up showed colectomy-free rates were 83%, 76% and 72% at 1, 3 and 5 years after initial ASC admission, respectively. In a multivariate analysis, active disease, and use of methotrexate were significantly associated with a higher risk of colectomy. A short delay between diagnosis and ASC, rapid steroid use for ASC and second line therapy with azathioprine and Infliximab were significantly associated with a lower risk of colectomy.

Conclusion

The rate of colostomy remains high after an episode of acute colitis despite the earlier use of biotherapies. But long-term outcome of paediatric-onset UC patients is good with sustained clinical and biological remission.