bluuebunny/crossref_metadata_2025 huggingface dataset:
P650 IBD care from the patient perspective: The patient’s turn
Authors: Creemers R , van der Horst D , Raats I , Romberg-Camps M , Scherpenzeel M , van Bodegraven A
Published: January 2022

Background

There is an increased focus on patient reported outcomes and patient reported experiences as means to optimize provided care. Both are considered essential in improving quality and service. Zuyderland Medical Centre (ZMC) is transforming its inflammatory bowel disease (IBD) care into a patient oriented IBD Centre (PGC IBD) as a way to provide modern patient centred care.

The project ‘Patient aan zet’ is an initiative of Crohn & Colitis NL (CCNL) and takes place in several hospitals. The aim of the project is to optimize quality of care for adult patients with IBD by ensuring that the patient is properly and unambiguously informed and the patients involvement increases in treatment.

Methods

A cross-sectional survey using a questionnaire was performed to map out expectations and experiences of patients with the IBD outpatient clinic of ZMC. This questionnaire (part of the project ‘Patient aan zet’) was developed by CCNL as an online self-completion instrument. The results of this questionnaire were assessed in a subsequent discussion group.

All IBD-patients presenting for an outpatient appointment at ZMC in March 2021, received an e-mail with a link to the questionnaire. In total, 500 e-mails were sent. After completing the questionnaire, patients were given the opportunity to sign up for a discussion group.

Results

In total, 198 participants completed the questionnaire fully or partially (40%) (Table 1). We found patients were satisfied with health care in general and with the information supply concerning IBD specifically. Use of the online monitoring tool MyIBDCoach and response time in the online monitoring tool contributed to positive judgment.

In the discussion group emerged that continued attention must be paid to the impact of endoscopic procedures from the patient perspective as endoscopic procedures (as part of the mucosal healing concept) may induce lasting and major impact on patients disease experience. In line with the ongoing corona pandemic developments, patient prefer a combination of check-up appointments by phone and at the outpatient clinic depending on (burden of) disease activity. Finally, specific attention is necessary for patients with a longstanding disease history. Needs concerning dietary advice and psychosocial support appear to vary over time.

Conclusion

ZMC is transforming its IBD care into a PGC IBD as a way to provide optimal and patient centred care. Involving patient in this process has given direction to optimizing patient information and patient involvement. The experiences gained from this process will be used to evaluate the PGC IBD after implementation and, together with the patient association, to develop a PREM that can be used to optimize IBD care.
P654 Clinical outcomes in familial versus sporadic inflammatory bowel disease diagnosed in the era of biological therapies. Prospective data from the ENEIDA registry
Authors: González Muñoza C , Calafat M , Gisbert J P , Iglesias E , Minguez M , Sicilia B , Esteve M , Gomollon F , Calvet X , Ricart E , Carpio D , Rivero M , Lopez-Sanroman A , Marquez L , Nos P , Cabriada J L , Guardiola J , Garcia-Sepulcre M F , Garcia-Lopez S , Lorente Poyatos R , Taxonera C , Barrio Andres J , Vera I , Domenech E , Garcia-Planella E
Published: January 2022

Background

It has been reported that familial aggregation occurs in 10–20% of inflammatory bowel disease (IBD) patients1. Familial IBD has been associated with disease anticipation2 and with an increased need for immunosuppressants3 and surgery4. However, most studies were performed before the widespread use of biological agents and this may impact on the need for surgery.

We aimed to compare the clinical outcomes of IBD (by means of the need for biological therapy and abdominal surgery) between familial and sporadic forms of IBD in the era of biological therapies.

Methods

Data were extracted from the ENEIDA registry by GETECCU, a Spanish, prospectively-maintained, IBD database in which more than 80 centers are participating.

Only adult patients diagnosed with IBD since 2005 and prospectively followed in the registry since diagnosis were included.

Familial IBD was defined as those cases with at least one first-degree relative diagnosed with IBD. Sporadic IBD was defined as those cases with no familial relative (of any degree) with IBD.

Kaplan-Meier survival curves were performed to evaluate the cumulative probabilities of remaining biologic-free and surgery-free. Log-rank test was performed to compare them between familial and sporadic IBD forms. Chi-square test was performed for the rest of variables.

Results

A total of 5,263 patients (2,627 Crohn’s disease [CD]; 2,636 ulcerative colitis [UC]) were included. Of them, 507 (10%) were familial cases (274 CD, 233 UC; P=0.05). The median follow-up was 38,4 and 35.5 months, respectively (P=0.086).

Familial cases were younger (P=0.022) and had a higher proportion of females among UC cases (P=0.048).

No differences were observed in the need for biological therapy in both CD and UC between familial and sporadic IBD. Regarding surgery, no differences were observed in the cumulative probabilities of a first intestinal resection for CD and colectomy for UC. Similar results were obtained when all the analyses were restricted to those subgroups at high-risk for surgery (i.e. CD with ileal involvement and extensive UC).

Conclusion

In patients diagnosed with IBD in the era of biological therapies, familial forms have the same requirements for biological agents and resectional surgery as sporadic forms. Therefore, familial aggregation does not seem to be a factor for a more aggressive disease.
P659 No decrease in number of new Inflammatory Bowel Disease diagnoses in children in the Netherlands during the Covid-19 pandemic: a nationwide retrospective cohort study
Authors: Klomberg R , Joling A R , te Groen M , Kuijpers C , Escher H , Nagtegaal I , de Ridder L
Published: January 2022

Background

The COVID-19 pandemic has had a large impact on regular healthcare provision in the Netherlands. During the first wave, healthcare in children was strongly reduced due to safety regulations and reduced hospital capacity for non-COVID care. This, and fear of COVID-19 could have led to delayed inflammatory bowel disease (IBD) healthcare, and delayed or even missed diagnoses. This has already been demonstrated in adult IBD patients in the Netherlands1, but not yet in the paediatric population. This is of importance, as in children, diagnostic delay is associated with higher rates of strictures, fistulising complications, and growth delay2. Therefore, this study aims to determine the impact of COVID-19 on IBD-related procedures and new IBD diagnoses in children in the Netherlands.

Methods

In this nationwide retrospective cohort study, a search was conducted in the nationwide pseudonymized pathology registry of the Netherlands (PALGA), with complete national coverage. Using retrieval terms for ulcerative colitis, Crohn’s disease, IBD unclassified and corresponding synonyms, all IBD related pathology reports (resection specimens or intestinal biopsies) from January 2018 to December 2020 in children age 1–18 were selected. Patients with a recognized diagnosis of IBD were eligible for inclusion, which was scored independently by two authors based on all reports. All IBD-related procedures (endoscopies and intestinal resections) were identified. Monthly frequencies of procedures and new IBD diagnoses during the COVID-19 pandemic in the Netherlands (March 11, 2020 – December 31, 2020) were compared to the average monthly frequencies of 2018–2019.

Results

After exclusion of non-IBD related reports, 2161 IBD-related procedures were identified between January 2018 and December 2020. The average number of monthly IBD procedures in 2018–2019 was 59.8, whereas in 2020 this was 60.6 procedures per month, reflecting a 0.8% increase (Figure 1). In 2020, the number of new IBD diagnoses was 456, similar to the 458 new IBD diagnoses in 2018–2019. During the COVID-19 pandemic the weekly number of new diagnoses was 8.8, while between January 2018 and March 2020 this was 8.5 (Figure 2). A slight reduction in monthly IBD-related resections was observed (2.7 vs. 3.5).

Conclusion

Despite the reduction in regular healthcare in children in the Netherlands due to the COVID-19 pandemic, no reduction was observed in IBD-related endoscopies and surgeries during the pandemic in the Netherlands. This reassuring evidence demonstrates that pediatric IBD healthcare remained unchanged, thus not delaying diagnosis of new IBD patients or treatment of severe disease flares.

References

1. Groen M.T., et al. Gastroenterology, 2020.

2. Ricciuto, A., et al. J Crohns Colitis, 2021.
P679 Inflammatory Bowel Disease and cancer risk in the IBSEN study after 30 years of follow-up
Authors: Follin-Arbelet B , Småstuen Cvancarova M , Hovde Ø , Jelsness-Jørgensen L P , Moum B
Published: January 2022

Background

Inflammatory Bowel Diseases (IBD) are chronic diseases with a heterogeneous clinical course, which often cause serious complications. Previously our group has reported that male ulcerative colitis (UC) patients have an increased risk for developing colorectal cancer 20 years after diagnosis, compared to the general Norwegian population. This study aims to estimate the risk of cancer after 30 years.

Methods

Data from the Inflammatory Bowel disease in South-Eastern Norway (IBSEN) study, in which all patients diagnosed from 1990 to 1994 were included, as well as data on all cancer cases from the Norwegian Cancer Registry and mortality from the Norwegian Cause of Death Registry, were used. All IBD patients were age- and gender-matched with five controls and followed up from the date of IBD diagnosis to the date of first cancer diagnosis, death or end of follow-up (31.12.2020) whichever came first. We computed hazard ratios (HR) for all cancers combined and for cancers of digestive organs using conditional Cox regression model stratified by gender and IBD diagnosis.

Results

In total, 756 IBD patients were included, 519 with UC and 237 with Crohn’s disease (CD). Of these, 82 UC and 35 CD patients were diagnosed with cancer during the follow-up. The most frequent cancer diagnoses were intestinal, breast and prostate cancers (Table 1). For all cancers combined, males with UC and females with CD had slightly higher risk of developing cancer compared to matched controls, however, the increased risks were not statistically significant. The same pattern was observed for cancers of digestive organs (Table 2).

Table1.

Table 2.

Conclusion

Our data did not reveal significant differences in risk of developing cancer 30 years after diagnosis between IBD patients and age-and gender-matched controls.
P702 Faecal Microbiota Transplantation Sculpts the faecal and mucosal microbial and metabolomic profiles in patients with Ulcerative Colitis
Authors: Bajaj A , Markandey M , Singh M , Virmani S , Vuyyuru S K , Kante B , Thirunavukkarasu R , Verma M , Kumar P , Kshetrapal P , Makharia G , Gupta D , Kedia S , Ahuja V
Published: January 2022

Background

Gut microbiota modulation via faecal microbiota transplantation (FMT)is known to induce long lasting clinical as well as endoscopic remission in patients with UC. The present study aims to identify microbial and metabolomic changes in the faecal as well mucosal niches, in response to FMT in patients with UC.

Methods

28 patients with mild-moderate UC and 16 non-IBD controls were enrolled. Patients were given a weekly infusion of pooled-multidonor-FMT, for 8 weeks, while maintaining a uniform dietary pattern. We collected paired stool and recto-sigmoidal biopsysamples from patients with UC pre-FMT (n=28), post-FMT (n=10) and controls (n=16). 16S (V3-V4) rRNA sequencing and LC-MS based untargeted metabolomics was performed. α and β diversity analysis and differential abundance (DA) analysis of microbiota was performed using DeSeq2 R package. Differential metabolite peaks between the three groups were identified via volcano plot and annotated using LipidMaps, HMDB, Kegg and Metlin databases. (Fig.1)

Results

α-diversity of patients with UC was not significantly different from that of controls, in both sample matrices. Post-FMT α-diversity of faecal samples differed significantly from the Pre-FMT group, however in mucosal tissue, the difference was non-significant. β-diversity indices were significant in UC pre-FMT vs post-FMT populations for both matrices (Fig.2A and B). DA analysis identified faecal and mucosal controls and UC post-FMT samples to be significantly similar [ANOSIM R=0.07; p=0.1 (faecal) and R=0.02; p=0.315 (mucosal)]. Analysis of core microbiota revealed diminished faecal microbial core in UC, with no major UC-associated loss of mucosal core members, showing relatively conserved nature of mucosal microbiota. FMT restored microbial core along both niches.

UC pre-FMT samples displayed increased abundance of Firmicutes (Limosilactobacillus, Lactobacillus, Streptococcus, Veilonella and Sphingomonas) and Proteobacteria (Methylobacterium) in faecal samples, while mucosa-associated microbiota displayed increased abundances of Firmicutes (Streptococcus, Limosilactobacillus, Ligilactobacillus, Eubacterium, Enterococcus, etc), Bacteroidetes (Parabacteroides and Alistipes) and Proteobacteria (Burkholderia)(Fig.3). Distinct functional classes of metabolites, including bacterial cell wall and QS molecules, membrane lipids, metabolism of vitamins, long and medium chain fatty acids, bile acids, and tryptophan etc, were also found to be altered between the three groups in both sample matrices(Fig.4)

Conclusion

FMT efficiently restores beneficial bacterial populations and related metabolic pathways in faecal as well the relatively reserved mucosal microbial niches, which may pave way for induction of remission in patients with UC.
P706 A distinct subset of tissue-resident Th17 cells expands in the inflamed intestines of Crohn’s Disease patients and responds to colitogenic bacteria
Authors: Paroni M , Leccese G , Ranzani V , Pagani M , Landini P , Vecchi M , Abrignani S , Facciotti F , Caprioli F , Geginat J
Published: January 2022

Background

Inflammatory bowel diseases (IBDs) are characterized by excessive inflammatory T-cell responses to intestinal microbes. Th17-derived Th1 cells (“Th1/17”) are pathogenic in mice, and might also drive inflammation in IBDs.Here, we characterized the role of a novel subset of human intestinal-resident Th17 cells, which produced very high levels of IL-17, together with IFN-γ, in intestinal inflammation in Crohn’s Disease.

Methods

CD4+T-cell subsets from IBD patients and controls were analysed by RNA sequencing and flow cytometry. They were monitored pre/post-therapies in different tissues, and analysed for antigen specificities.

Results

CCR6+CCR5+CXCR3-T-helper cells co-expressed RORC and T-bet, and co-produced IL-17 and IFN-γ. These CCR5+Th17-cells were associated with intestinal inflammation in Crohn’s Disease (CD), but not in ulcerative colitis, and contracted upon Infliximab-induced mucosal healing. Conversely, CXCR3+CCR6+Th1/17 cells, which also co-produced IL-17 and IFN-γ, were unaltered. Intestinal CCR5+Th17-cells had up-regulated genes of pro-inflammatory Th17-effector cells, and down-regulated genes involved in recirculation. Consistently, CCR5+Th17-cells were rare in peripheral blood and lymph nodes, displayed a tissue-resident phenotype in the gut and were enriched in the intra-epithelial compartment of CD patients. Conversely, CCR5-Th17-cells were abundant in the circulation, had an increased gut-homing potential in IBDs, and decreased post-Vedolizumab treatment in the intestine. Moreover, they up-regulated CCR5 with IL-23, which was abundant in the guts of CD patients. Importantly, intestinal CCR5+Th17 cells were selectively activated by adherent-invasive Escherichia coli (AIEC), but not by a commensal/probiotic strain. Th1/17-cells responded instead to Cytomegalovirus. Notably, AIEC induced also IL-23 and the CCR5 ligand RANTES from dendritic cells (DCs).

Conclusion

We identified a gut-resident Th17-cell subset that was activated by CD-associated bacteria, suggesting a key role in pathogenesis. They could differentiate from conventional, circulating Th17-cells that are recruited to the gut and activated by AIEC-infected DCs. Conversely, intestinal Th1/17-cells may protect CD patients from CMV-induced colitis.
P710 Evaluation of helminth extracellular vesicles as a novel therapeutic for inflammatory bowel disease in murine models of colitis
Authors: Bray G , Giacomin P
Published: January 2022

Background

With the increasing complexity of inflammatory bowel disease (IBD) new therapies are clearly required. Recent evidence is coming to light demonstrating beneficial effects of helminth proteins. We aim to assess the prophylactic and therapeutic effects of extracellular vesicles (EVs) from the nematode N. brasiliensis, which serves as a model organism for human hookworm infections, in an acute and chronic model of colitis.

Methods

Prophylactic and therapeutic effects of EVs were assessed in an acute model of colitis by the administration of 20µg intraperitoneally (i.p) of Nb EVs or grape EVs. Mice were sacrificed after 5 days. The therapeutic effects of Nb EVs were also assessed in a chronic model of colitis. Here, Rag1 knockout mice were treated twice weekly for three weeks with 20µg of either Nb EV, grape EV or aIL-12. Outcomes assessed for both experiments included weight loss, clinical disease, as well as macroscopic and histologic disease scores. Groups were statistically compared for significant differences.

Results

The prophylactic administration of Nb EVs significantly reduced weight loss, clinical disease, and histologic pathology compared to grape EV-treated negative controls. Therapeutic administration of Nb EVs significantly reduced weight loss and histologic pathology in the colon.

Conclusion

The current study provides important evidence that the anti-inflammatory effects of helminth EVs can be harnessed to prevent and reverse inflammation in an acute and chronic mouse model of colitis. With further characterization of helminth EVs, these compounds have the potential to generate much needed new anti-inflammatory therapies for IBD.
P711 Stool microbiome communities predict remission in pediatric Crohn’s disease patients even after start of treatment
Authors: Verburgt C , Dunn K A , Bielawski J P , Otley A R , Heyman M B , Sunseri W , Shouval D , Levine A , de Meij T , Hyams J S , Denson L A , Kugathasan S , Benninga M A , de Jonge W J , Van Limbergen J E
Published: January 2022

Background

Early relapse in children with Crohn’s Disease (CD) after reaching remission is associated with a more severe disease course that significantly impairs quality of life. We have previously shown that a Bayesian approach predicted clinical course in children with CD following the first year after diagnosis with high accuracy when ensuring samples were truly treatment-naïve. Here, we aimed to assess the impact on the accuracy when taking a broader timeframe of stool collection to baseline, in order to facilitate use in clinical trials and eventually daily practice.

Methods

We selected de novo paediatric CD patients with PCDAI>10 from the RISK cohort with baseline stool samples within 14 days after start of induction treatment. We assessed if they sustained remission at 12 months (PCDAI≤10). Using QIIME2 sequences were demultiplexed, joined, and denoised (deblur) to obtain amplicon sequence variants (ASVs). The ASVs were classified (classify-sklearn) using a pre-trained SILVA database. We used hierarchical Bayesian model for microbial community structure (BioMiCo), previously trained on treatment-naïve stool samples to predict treatment outcomes at 6 months according to baseline gut microbiome differences.

Results

Patient metadata and 16S rRNA amplicon data were available from 197 stool samples of newly diagnosed paediatric CD patients as part of the RISK cohort. Previous analysis of 42 truly treatment-naïve samples lead to prediction of samples in patients maintaining remission without early treatment escalation and those that did not in 81% and 75% (AUC=0.79). In this analysis, we selected 13 samples of children with PCDAI that were taken within 14 days after start of induction therapy. PCDAI varied from 15–47.5 at baseline. Therapy regimens started within the first 14 days were EEN, 5ASA, corticosteroids, immunomodulators and antibiotics. The Bayesian model predicted 12-month outcome of patients that maintained remission with a positive predictive value of 75% and negative predictive value of 60% (AUC 0.76).

Conclusion

Using treatment-naïve faecal samples only, a Bayesian approach predicted clinical course in treatment-naïve children with CD over the first year after diagnosis with high accuracy. When taking a broader timeframe of stool collection after start of treatment, the accuracy of the model decreased only slightly. Further exploration of microbiome signatures and potential use in practice should therefore emphasize the importance of treatment naivety of samples, but not necessarily rule them out for prediction of treatment outcome.
P712 Fungal microbiota composition in Inflammatory Bowel Disease patients in a Norwegian cohort: characterization of disease phenotypes and correlation with clinical activity and disease course
Authors: Catalàn-Serra x I , Thorsvik S , Beisvag V , Bruland T , Underhill D , Sandvik A K , Van Beelen Granlund A
Published: January 2022

Background

There is growing evidence of the role of the fungal microbiota in the pathogenesis of IBD, but a definite pattern defining the mycobiome in IBD is currently lacking.

In addition, the variations within the different phenotypes as well as the correlation between fungal composition and disease outcomes has been poorly characterized.

Our aim is to evaluate the fungal composition within the different IBD phenotypes, the changes with disease activity and the association with disease outcomes.

Methods

This prospective study presents sequencing of the faecal fungi of 111 individuals: 89 IBD (52 UC/37 CD) and 22 HC. Demographics,medication,Montreal Classification and disease history was collected. A fCalpro>100 was considered active disease.

A subset of IBD patients was followed clinically (6±2 y) and classified as either “Complicated” or “Uncomplicated” based on the need of intensified medication and/or surgery.

Sequencing was done on amplicons targeting the ITS1 region of fungal DNA on a Illumina MiSeq sequencer. Chosen OTUs were compiled taxonomically.Data analysis was performed in R(phyloseq and deSeq2-packages).

Results

We found significant variations in the fungal microbiota composition in the different IBD phenotypes(Fig1)

In UC, Saccharomyces was predominant in pancolitis (E3), while Penicillium was more abundant in proctitis(E1) and Galactomyces in left-side UC (E2)(Pan.A). At species level, Rhodotorula mucilaginosa was significantly depleted in E3 (p≤0.05)(Pan.B)

In CD, Aspergillus was predominant in ileal affection(L1) while Candida and Rhodotorula genus were more abundant in L2-L3.Patients with structuring phenotype(B2) were depleted of Apergillus and Rodhotorula (Pan.A). At species level, ileal (L1) patients were depleted of Candida tropicalis and Penicillium kudriavzevii. B1 patients had a marked predominance of Candida albicans vs B2(p≤0.01)(Pan.B)

The mycobiome correlation with disease activity is depicted (Pan.C). Candida dublinensis was overrepresented in activity, while Saccharomyces pastorianus was depleted(p≤0.01)

The correlation of the mycobiome with disease outcomes is represented in Pan.D. Penicillium glabrum was significantly overrepresented in patients with a complicated course. The abundance of Candida tropicalis and D. nepalensis was correlated with the need for surgery.

Conclusion

This study shows important differences in the fungal microbiota composition in the different IBD phenotypes.

Some species are clearly correlated with the activity of the disease and worse clinical outcomes suggesting a potential deleterious role.Candida tropicalis was associated with the need of surgery in CD.

This in-depth characterization of the mycobiome serves as a significant addition to the understanding of the role of fungi in IBD.
P715 Selective enhancement of immune cell response to opportunistic microorganisms: An innovative proposal for Inflammatory Bowel Disease from an ancient grain
Authors: Pumarola Segura S
Published: January 2022

Background

Inflammatory Bowel Disease (IBD) results from an unbalanced immune response to the gut microbiome. There is a lack of proposals that integrate and may balance the multiple factors that together condition the onset and evolution of the disease: immunity, microbiome and diet.

D-fagomine is a small molecule, naturally present in buckwheat grain. It Is a monosaccharide mimetic showing glycosidase enzyme inhibition properties. Clinical studies have shown its efficacy to control postprandial glycemic response. Subsequent research “in vitro” had also shown D-fagomine to inhibit the fimbriae adhesion and biofilm formation of some proteobacteria, including ie E. coli or Salmonella.

The original aim of the study was to confirm the effects of D-fagomine on the adhesion to human gut mucosa using adherent-invasive E coli (AIEC) that is a microorganism usually linked to IBD.

Methods

A) Ex vivo human resected colonic mucosa was cultured (4 h) with AIEC inoculum and D-fagomine at different range of doses (0-5000 ppm). The amount of E. coli in tissue and supernatant was quantified, measuring also TNF-alfa and LDH.

B) Ex vivo human blood was cultured with D-fagomine (50 ppm) and the correspondent inoculum of different microorganism models able to evade the human immune system: bacteria = E. coli (AIEC) and fungus = Blastomyces sp. TNF-alfa was quantified.

Results

It was confirmed the inhibition of AIEC adhesion to the colonic mucosa in a direct dose-response relationship. Totally unexpected, D-fagomine was found to modulate TNF-alfa in an apparent double sigmoid curve with the max activity in the range of 50 ppm (Fig 1). This curve corresponds to an activator of the innate immune cells with mechanism related to complement activation, (ie mannose, betaglucan). Finally D-fagomine was helping the mucosa to detect and overcome the evasion mechanism of AIEC at the range of 50 ppm.

Additional studies (method B) were carried out with the result that D-fagomine, at 50 ppm, stimulates TNF-alfa response of human immune cells against AIEC and also Blastomyces (Fig 2). Both models give coherent results, and confirm that D-fagomine at the range of 50 ppm improves the capacity of the innate immune cells to detect human opportunistic microorganisms.

Conclusion

Our results have shown for the first time D-fagomine helping human immune cells to develop a more efficient immune response to better control the presence of opportunistic microorganisms. This is of great interest in IBD and is also synergistic with the other known properties of D-fagomine, which overall could finally help reduce some of the negative effects of the Western diet on humans and also their microbiome.
P716 Exclusive Enteral Nutrition refurbishes beneficial gut microbiota in patients with Acute Severe Ulcerative Colitis
Authors: Bajaj A , Markandey M , Sahu P , Vuyyuru S K , Kante B , Kumar P , Singh N , Gupta A , Singh M , Verma M , Makharia G , Kedia S , Ahuja V
Published: January 2022

Background

Exclusive enteral nutrition (EEN) acts as an adjunctive therapy to intravenous corticosteroids in patients with ASUC. Recently reported by Sahu et.al., patients with ASUC undergoing EEN showed reduced corticosteroid failure rates compared with standard-of-care (SOC) group1. While the mechanism of action of EEN is unclear, EEN is known to cause marked alterations in the gut microbiome. The present study extending the findings of Sahu et.al., aims to decipher the compositional changes in gut microbiome accompanying the EEN-augmented steroid responsiveness

Methods

In an open-label RCT, patients with ASUC were randomized 1:1 to EEN and SOC groups. Patients on EEN received a semi-elemental formula for 7 days along with SOC. The primary outcome was steroid failure, defined by the need for salvage medical intervention. Faecal microbial analysis was performed on day-0 and day-7 by 16S-rRNA gene sequencing. Processing of raw reads, ASV tables, diversity, and core microbiome analysis was done using QIIME2-2021.4. Differential abundance analysis (DAA) was performed using Deseq2.

Results

The α and β diversity indices showed deviation neither in EEN nor in SOC groups. EEN caused a shift in core microbiota of patients with ASUC, adding Streptococcus and Faecalibacterium prausnitzii, while SOC could not change the core microbiota. DAA on the pre- and post-treatment samples showed that EEN resulted in diminished Ruminococcus gnavus, Escherichia sp., Bifidobacterium longum and Enterococcus sp., while the SOC led to reduction in beneficial F. prausnitziiand enhanced Escherichia.

DAA between steroid responders and steroid non-responders in the EEN group, showed significant enhancement of Veillonella, Ligilactobacillus, Limosilactobacillus, Gamella, Enterococcus and Eggerthella in the SR group, while Schaalia, R.gnavus, Lactobacillus, Bifidobacterium, Haemophilus were elevated in SNR group.

Conclusion

ASUC accompanies gut dysbiosis. EEN refurbishes certain beneficial gut microbial genera, which may account for its augmentation of the steroid responsiveness in patients with ASUC.

Reference

1. Sahu P, Kedia S, Vuyyuru SK, Bajaj A, Markandey M, Singh N, Singh M, Kante B, Kumar P, Ranjan M, et al. Randomised clinical trial: exclusive enteral nutrition versus standard of care for acute severe ulcerative colitis. Aliment Pharmacol Ther 2021.
P718 Characterization of microbiota and metabolomic profile in human colonic surgical resections of UC patients
Authors: Bauset C , Carda-Diéguez M , Buetas E , Lis-López L , Navarro F , Ortiz-Masiá D , Calatayud S , Barrachina M D , Mira Á , Cosín-Roger J
Published: January 2022

Background

Ulcerative colitis (UC) is characterized by a diffuse, continuous, and chronic inflammation of mucosa and submucosa layers in the colon whose etiology is still unknown. Intestinal microbiota dysbiosis and alterations in the metabolomic profile have been reported in mucosal biopsies from Inflammatory Bowel Disease (IBD) patients. We aim to characterize the microbiota composition and metabolomic profile in colonic resections of UC patients.

Methods

Colonic resections from UC (n=18) and non-IBD (n=20) patients were obtained. Microbiota identification, composition and classification was performed by 16S rRNA gene Illumina Miseq sequencing. The bioinformatic analysis of sequencing data was performed using constrained correspondence analysis (CCA) and non-parametric Wilcoxon test to compare species and genera proportions. Bacterial load was estimated by qPCR. Metabolomic analysis was performed using Nuclear Magnetic Resonance (NMR) to study polar metabolites and Gas-Chromatography or Liquid-Chromatography Mass-Spectrometry to study non-polar metabolites.

Results

Microbiota analysis revealed differences at genus and species level between UC and non-IBD patients. Cellulosimicrobium was found at 10-fold higher levels in UC samples while Escherichia genus was 3.88 times more abundant in controls. A reduction in bacterial load was seen in UC samples. Levels of short-chain fatty acids (FA), medium-chain FA, long-chain FA, carboxylic acids and amino acids were obtained from the metabolomics analysis and a positive correlation between propionic, aspartic and hydroxybutyric acids and Cellulosimicrobium and Pseudomonas was found (Fig1B). Gut commensals such as unclassified Agathobacter, Blautia faecis, Oscillospiraceae or Faecalibacterium prausnitzii positively correlated with the abundance of butyric acid, acetic acid and succinic acid; meanwhile Subdoligranulum, Lachnospireace or unclassified Blautia negatively correlated with some medium or long chain fatty acids (Fig1B).

Fig1. Correlations between bacterial species and metabolites in (A) controls and (B) UC patients. Performed with mixOmics library in R.

Conclusion

Significant differences in microbiota composition and abundance are found in UC patients, which undergo a clear gut dysbiosis in colonic tissue. Correlation analysis suggests Cellulosimicrobium and Pseudomonas as sources of propionic, aspartic and hydroxybutyric acid. These results point at Cellulosimicrobium as a potential candidate in UC pathology.
N13 Clinical service delivery implications of the Covid-19 pandemic on people with inflammatory bowel disease: a qualitative study
Authors: Kemp K , Avery P , Bryant R , Cross A , Danter K , Kneebone A , Morris D , Walker A , Whitley L , Dibley L
Published: January 2022

Background

As part of a qualitative study exploring the experiences of IBD patients during three UK lockdowns, we identified specific clinical service implications of the pandemic on IBD care.

Methods

Participants aged 18 years+ with a confirmed diagnosis of Crohn’s disease, Ulcerative Colitis or IBD-Unclassified, who had shielded or not during any lockdown period were recruited from Crohn’s and Colitis UK. Semi-structured online or phone interviews (captured February-May 2021) were audio-recorded, transcribed professionally, and analysed using thematic analysis.

Results

Forty-three people took part; median age 38 years (19–63 years); 27 (62.7%) females; diagnosed with Crohn’s Colitis (n=2), Crohn’s disease (n=21), Ulcerative colitis (n=18) and IBD-Unclassified (n=2). Median disease duration 13 years (0.6–36 years). Four clinically focussed themes emerged: The Risk of Attending Hospital; Missing Routine Monitoring; Accessing Care as Needed and Remote Access and The Future.

The Risk of Attending Hospital

Against the prevailing media messages to avoid going to hospital, staying at home to avoid burdening the healthcare system and the rising numbers of Covid patients in hospitals, participants felt anxious about the dilemma of needing treatment for their IBD but putting themselves at risk to receive it.

Missing Routine Monitoring

Routine appointments and monitoring, which participants relied on for ‘keeping on top of’ their condition, stopped for some. Many could not access their IBD team or GP services at all, so routine blood tests for therapeutic levels were missed; in some cases, disease activity increased.

Accessing Care as Needed

Many were able to get clinical help as needed, even if the method of contact, and source of help, was different to usual. For others, the pandemic had caused considerable delay in getting diagnosed, and they felt overwhelmed and unsupported. Most understood the disruption to services due to staff redeployment, but some coped with the changes better than others.

Remote Access and The Future

the shifting focus away from face to face and towards remote appointments received mixed opinions. Many were happy with remote (phone, email) contact during the pandemic, out of necessity, but there were concerns from others that this would become normal in the future. It was suggested that first appointments should always be face to face.

Conclusion

Maintenance of IBD services in some form is essential throughout crisis periods; newly diagnosed patients needed additional support; dependence on IBD services could be reduced in the future through use of treatment/self-management plans. Mode of appointment needs to suit the patient.
N17 Co Design of young person’s IBD clinic for 16–24 year olds
Authors: Hamzawi M , Brannick S , Hickey Y , Cullen G , Sheridan J
Published: January 2022

Background

In Ireland,young people with Inflammatory Bowel Disease (IBD), diagnosed in a paediatric hospital transition to adult services at 16 years of age. Transition is an essential milestone for adolescents with IBD as critical functioning skills necessary for self-management are not fully developed and adolescents often find it difficult to engage with health care professionals about their disease. To date an ideal transition model has not been defined. The aim of this pilot study was to seek input from a transition group to aid the development of future transition and young person clinics.

Methods

During 2019, 8 patients transitioning into our adult IBD service were assigned to the pilot structured multidisciplinary (MDT) pathway for 12 months. This involved meeting with Consultant, CNS, psychologist and dietitian at each clinic appointment. Patient experience measures were given after each visit and on completion of the pathway participants rated their experience on Likert scales and free text responses. Findings would be useful to steer service development.

Results

At the end of 1 year excellent satisfaction rates were reported by those attending clinics with MDT input. Nonetheless 50% preferred consultant only clinics. 37.5% opted for full MDT review and 12.5% requested psychology input plus consultant at clinic.

Conclusion

The project highlights the importance of patient focused studies when designing young patient’s transition clinics. 50% of young IBD patients did not request full MDT on a regular basis. This study is being expanded to review patient experiences from a larger cohort aged 18–24 years and a Randomised Control Trial will be conducted to guide future a transition pathway
The Frequency of Focal Cortical Dysplasia-Like Histologic Features Near Adult-Type Diffuse Gliomas
Authors: Bitar Mireille , Chornenkyy Yevgen , Flanagan Margaret E , Steffens Alicia , McCortney Kathleen , Horbinski Craig
Published: January 2022

While the coexistence of focal cortical dysplasia (FCD) and grade 1 noninfiltrative gliomas has been described, to date, only rare case reports have described FCD adjacent to infiltrating gliomas. We therefore sought to determine how often FCD-like findings occur near adult-type diffuse gliomas. This was a retrospective survey of 186 consecutive, newly diagnosed, en bloc glioma resections. Fifty-nine (31.7%) had sufficient adjacent cortex to evaluate for FCD-like features. Among IDH mutant (“IDHmut”) gliomas, 40/77 (52%) had adjacent evaluable cortex, whereas only 19/109 (17%) of IDH wild-type (“IDHwt”) gliomas did (p < 0.0001). Among cases with evaluable cortex, 15 (25.4%) contained features suggestive of FCD, including radial/tangential dyslamination and/or maloriented neurons. In a multivariable analysis, increasing glioma grade (OR = 4.0, 95% CI = 1.2–13.5, p = 0.027) and IDHmut (OR = 6.5, 95% CI = 1.3–32.2, p = 0.022) emerged as independently positive correlates with the appearance of FCD-like findings. However, FCD-like features were also found in 13/32 (40.6%) cortical samples from adult brains without any neoplastic disease or seizure histories (p = 0.16). Together, these data suggest that, while FCD-like histologic features can be incidentally found in at least a subset of diffusely infiltrative gliomas, the frequencies are not significantly different from that seen in otherwise non-neoplastic brains, and are therefore most likely nonpathologic.
Feasibility and Acceptability of Home-Collected Samples for Human Immunodeficiency Virus Preexposure Prophylaxis and Severe Acute Respiratory Syndrome Coronavirus 2 Laboratory Tests in San Francisco Primary Care Clinics
Authors: Saberi Parya , Ming Kristin , Shrestha Isha , Scott Hyman , Thorson Brad , Liu Albert
Published: January 2022

Background

Due to the difficulty of conducting laboratory testing during the pandemic shelter-in-place orders, the objective of this study was to examine the feasibility and acceptability of conducting home-collected samples for preexposure prophylaxis (PrEP) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) laboratory tests.

Methods

We conducted a pilot study among patients on PrEP in San Francisco primary care clinics. Individuals on PrEP provided home-collected laboratory samples using dried blood spot for fourth-generation human immunodeficiency virus antigen/antibody test, serum creatinine, syphilis antibody, and hepatitis C antibody, as needed; 3-site (oropharyngeal, rectal, and urine) swabbing for sexually transmitted infections; and nasopharyngeal swabbing for SARS-CoV-2 polymerase chain reaction. We examined feasibility and acceptability of collecting these laboratory samples using predefined benchmarks to determine feasibility or acceptability.

Results

Of 92 individuals who consented to participate, 73 (79.3%) mailed back their home-collected kit. Nearly 87.7% noted being extremely to moderately satisfied with the ability to complete the laboratory tests without having to come into a clinic. Approximately 49.3% of participants chose this home-collection method as their first choice for providing laboratory samples. Mean time from collection of samples by the participant to receipt of test results was reduced from the first quarter of the study (17 days) to the last quarter of the study (5 days).

Conclusions

We report high levels of feasibility and acceptability with the use of home-collected laboratory samples for patients on PrEP. Our results indicate that home-collected laboratory samples for patients on PrEP is a viable option that should be offered as an alternative to clinic-collected laboratory samples.
Contributions of Pubic Rami Fracture Morphology and Fixation to Pelvic Ring Stability in Type 1 Lateral Compression Injuries: A Biomechanical Cadaveric Study
Authors: Marenghi Natalie , Bang Katrina E. , Danelson Kerry , Hasty Eddie , Snoap Tyler , Taylor LaTarsha , Okundia Samantha , Kelly Erin , Teater Rachel , Halvorson Jason , Carroll Eben
Published: January 2022

Background:

Treatment of lateral compression type 1 (LC-1) injuries has historically been nonoperative with immediate weight-bearing. However, management of these injuries remains controversial, with reports of displacement at follow-up for nonoperatively managed LC-1 fractures. The goal of our study was to determine the effect of superior pubic ramus fracture morphology and fixation construct on pelvic stability.

Methods:

Ten fresh-frozen cadaveric were transected into hemi-pelvises. Incomplete Denis type 1 sacral fractures were made. Hemi-pelvises were randomized to receive a transverse-type or oblique-type superior pubic ramus fracture with the contralateral hemi-pelvis receiving the opposing morphology. A lateral load to 135N was applied with an Instron materials testing machine and lateral displacement of the hemi-pelvis was recorded. Deflection and stiffness were calculated. Statistical analysis was conducted using a t test assuming unequal variances with an alpha = 0.05.

Results:

Oblique-type superior pubic ramus fractures allowed more deflection compared with transverse-type fractures in the absence of fixation (P = 0.018). The posterior-only and combined anterior and posterior fixation configurations on average reduced deflection more than no fixation or anterior fixation only. In all fixation configuration cases, the average deflection for transverse-type fractures was less than that of the oblique-type fractures.

Conclusions:

Our findings suggest that displacement of LC-1 pelvic injuries may be related to pubic rami fracture morphology. When looking at initial injury imaging, oblique-type pubic rami fractures may suggest an increased potential for displacement over time. In such cases, we recommend an examination under anesthesia to evaluate for underlying instability and consideration for fixation.

Level of Evidence:

Therapeutic Level V.
Functionality of Scarce Healthcare Resource Triage Teams During the COVID-19 Pandemic: A Multi-Institutional Simulation Study
Authors: Butler Catherine R. , Webster Laura B. , Sakata Vicki L. , Tonelli Mark R. , Diekema Douglas S. , Gray Megan M.
Published: January 2022

Objectives:

Plans for allocating scarce healthcare resources during the COVID-19 pandemic commonly involve the activation of institutional triage teams. These teams would be responsible for selecting patients who are most likely to survive to be prioritized to receive scarce resources. However, there is little empirical support for this approach.

Design:

High-fidelity triage-team simulation study.

Setting:

Healthcare institutions in Washington state.

SUBJECTS:

Triage teams, consisting of at least two senior clinicians and a bioethicist.

INTERVENTIONS:

Participants reviewed a limited amount of deidentified information for a diverse sample of critically ill patients. Teams then assigned each patient to one of five prioritization categories defined by likelihood of survival to hospital discharge. The process was refined based on observation and participant feedback after which a second phase of simulations was conducted.

MEASUREMENTS AND MAIN RESULTS:

Feasibility was assessed by the time required for teams to perform their task. Prognostic accuracy was assessed by comparing teams’ prediction about likelihood of survival to hospital discharge with real-world discharge outcomes. Agreement between the teams on prognostic categorization was evaluated using kappa statistics. Eleven triage team simulations (eight in phase 1 and three in phase 2) were conducted from December 2020 to February 2021. Overall, teams reviewed a median of 23 patient cases in each session (interquartile range [IQR], 17–29) and spent a median of 102 seconds (IQR, 50–268) per case. The concordance between expected survival and real-world survival to discharge was 71% (IQR, 64–76%). The overall agreement between teams for placement of patients into prognostic categories was moderate (weighted kappa = 0.53).

Conclusions:

These findings support the potential feasibility, accuracy, and effectiveness of institutional triage teams informed by a limited set of patient information items as part of a strategy for allocating scarce resources in healthcare emergencies. Additional work is needed to refine the process and adapt it to local contexts.
Autologous Mandible Reconstruction in a Hypercoagulable Patient following Multiple Failed Free Flaps
Authors: Maier Mark A. , Guidry Richard F. , Palines Patrick A. , Stalder Mark W.
Published: January 2022

Coagulopathies affect 3% of free flap patients and are among the leading causes of free flap failure. This report describes the case of a head and neck cancer patient that experienced two remote free flap failures before successful autologous mandibular reconstruction. Following identification of an unrecognized thrombophilic state, a focused anticoagulation strategy was executed, including an intraoperative heparin drip, stringent postoperative maintenance of Factor Xa levels between 0.3 and 0.5 IU per mL, and transition to an outpatient enoxaparin regimen of 1 mg per kg twice daily for 1.5 months following surgery. Here, we demonstrate that free tissue transfer following multiple previous failed attempts in the setting of hypercoagulability remains a viable reconstructive option with close interdisciplinary collaboration, close clinical monitoring, and patient-specific antithrombotic protocols.