bluuebunny/crossref_metadata_2025 huggingface dataset:
P1201 Association between Inflammatory Bowel Disease and Henoch-Schönlein purpura: A Bidirectional Two-Sample Mendelian Randomization Study
Authors: Yu Q , Luo J , Zhang Y , Chen J , Wang X , Lu X , lv M , Li S , Huang X , Hu W , Zhang M , Liu L , Hu Y , Xu J , Xu D , Zhang H , Chen M , Roozbahani A , Ghoushi E , Chen Y
Published: January 2024

Background

Henoch-Schönlein purpura (HSP) is a systemic small-vessel vasculitis, and its association with inflammatory bowel disease (IBD) has been the focus of considerable research. Despite numerous studies, it remains uncertain whether and in which direction causal relationships exist between HSP and IBD. To reveal the causal association between HSP and IBD, we conducted a bidirectional two-sample Mendelian randomization analysis using publicly available genome-wide association study (GWAS) summary statistics.

Methods

We obtained summarized data for IBD, Crohn's disease (CD), ulcerative colitis (UC), and HSP from various GWAS. To estimate causality, we used inverse-variance weighted approaches. Additionally, we conducted several sensitivity analyses. In our causality estimates, we present odds ratios (ORs) and 95% confidence intervals (CIs).

Results

We found that CD (OR: 1.12, 95% CI: 1.00 to 1. 25, P < 0.05), but not UC (OR: 1.04, 95% CI: 0. 909 to 1.19, P > 0.05), had significant positive causal effects on HSP risk. However, the overall result of the MR study demonstrated that there was no causal link between genetic predisposition to IBD and an increased risk of HSP (OR: 1.10, 95% CI: 0.989 to 1.23, P > 0.05). Regarding the reverse directions, no significant causal associations were discovered.

Conclusion

It appears that CD and HSP are causally related, which could influence clinical decisions regarding the management of CD in patients diagnosed with HSP. However, neither overall IBD nor UC has a causal effect on HSP.
P1218 Non-invasive point-of-care stool sample for detection of Cytomegalovirus infection in patients with Active or Refractory Ulcerative Colitis using multiplex polymerase chain reaction (mPCR): a pilot feasibility study
Authors: Peneva P , Lyutakov I , Valkov H , Vladimirov B , Penchev P
Published: January 2024

Background

Cytomegalovirus (CMV) infection is associated with more flare-ups and deteriorates the prognosis of active inflammatory bowel disease (IBD). Patients with refractory IBD should be tested for CMV colitis, especially if they are not responding to immunosuppressive therapy. The prevalence of CMV co-infection ranges from 10% to 30% in steroid-refractory acute colitis. Concurrent CMV-colitis is associated with an increased risk of worse therapeutic outcomes, resistance to corticosteroids, and need for salvage therapy. One of the two gold standards of diagnosis of CMV colitis in IBD patients with active disease requires the analysis of tissue biopsies using PCR. The aim of our pilot study was to evaluate the diagnostic accuracy of non-invasive point-of-care faecal samples using mPCR for detecting CMV in patients with ulcerative colitis compared to standard practice biopsies PCR.

Methods

We performed a prospective, observational, feasibility study including 62 consecutive patients with active ulcerative colitis (UC) requiring intravenous steroids or steroid-refractory UC in the Department of Gastroenterology of University Hospital „Tsaritsa Yoanna – ISUL", from April 2022 to October 2023. In all UC patients, colonic tissue biopsies were performed and analyzed by qualitative CMV PCR. Faecal sample mPCR CMV was performed on the positive patient cohort to compare the feasibility of (ME) Panel IVD using FilmArray mPCR (Biofire, bioMerieux, France). All the tested patients had undergone immunosuppressive therapy and initial stool specimen cultures were obtained to exclude infection with C. difficile and other pathogen flora.

Results

Out of 62 active UC patients with colonic tissue samples qualitative CMV PCR, n=5 (8%) were positive. Of these n=5 UC patients, n=4 (80%) were positive from the Fecal sample mPCR CMV, resulting in a compatibility of 80% for diagnosing CMV in these patients by the two DNA extraction methods. Calculated Sensitivity and diagnostic accuracy was 80% (95% CI) for the mPCR CMV. The patient cohort predominantly comprised males (75%) with a median age of 45 years (range: 30–72 years). Three patients (75%) out of this cohort group were treated with peroral antiviral agent Valganciclovir, one (25%) of them went into clinical and endoscopic remission after the treatment and two patients (50%) received colectomy. The median time performing the Faecal sample mPCR CMV was approx. 1 hour.

Conclusion

This novel faecal mPCR point-of-care test is a promising, fast and easy non-invasive tool for detection CMV in active or refractory UC patients, comparable with the colonic tissue CMV-DNA PCR.
P1231 7-ketositosterol in high-temperature heating oils aggravates colitis by gut microbiota dysbiosis induced-PDLIM3 activation
Authors: Yan J , Cao H
Published: January 2024

Background

Diet and gut microbiota alteration are considered as the most important environmental factors triggering inflammatory bowel disease. Phytosterols are rich in edible oils, and can be oxidized to oxyphytosterols during high-temperature cooking. Previous studies have indicated that oxyphytosterols exposure exerted potential adverse effects in cell and animal models. It remains unknown whether oxyphytosterols could promote colonic inflammation. 7-ketositosterol has the highest proportion in oxyphytosterols.

Methods

The fried and baked foods intake was collected and compared in IBD patients and healthy individuals. 7-ketositosterol was synthesized from β-sitosterol and impacts of 7-ketositosterol on intestinal inflammation was evaluated in colitis mice models. 16S rRNA and transcriptome sequencing were carried out. Furthermore, fecal microbiota transplantation was carried out to evaluate the effect of gut microbiota. Protein interaction of Staphylococcus lentus and PDLIM3 was explored by co-immunoprecipitation.

Results

The fried and baked foods intake in IBD patients was much more than that of healthy individuals, with higher exposure to oxyphytosterols. 7-ketositosterol (KS) aggravated mice colitis. KS increased the abundance of Actinobacteria (p=0.023). Meanwhile, the abundance of potential pathogens such as Staphylococcus (p=0.004) and Corynebacterium_1 (p=0.003) were increased in KS group, while the abundance of short chain fatty acids producing bacteria were decreased. Transcriptome data showed KS increased the expression of PDLIM3 (p=0.004). PDLIM3 expression was demonstrated to increase in intestinal epithelial cells, and the expression tendency of p-p38 and p-p65 was consistent with PDLIM3. In addition, KS did not exacerbate DSS induced colitis after antibiotic cocktails treatment, and PDLIM3 expression decreased in parallel. The gut microbiota from KS also aggravated DSS induced colitis in antibiotic treated mice. Proteins from Staphylococcus lentus could interact with PDZ domain and promote PDLIM3 expression.

Conclusion

7-ketositosterol in high temperature heating oils such as fried foods could aggravate colitis by modulation of gut microbiota. Gut microbiota interacted with PDZ domain, promoted PDLIM3 expression and then activated p38MAPK/NF-κB signaling pathway.
P1234 The gut microbiome as a reporter of health, and its associations with different exposures
Authors: Braun T , Hadar R , Efroni G , Haaronian O , Leshem R , Amit S , Abbas-Egbariya H , Truma K , Segev S , Amir A , Haberman Ziv Y
Published: January 2024

Background

The prevalence of metabolic and immune-mediated diseases has increased in the last century, with many of these diseases showing alterations in the gut microbial composition. We previously reported (PMID:35197084) that a large group of bacteria shows constant differential abundance (increase and decrease) across multiple diseases and can therefore provide a general indication of the host's health. We aimed to utilize a “health index” based on these bacteria to compare how different exposures are associated with this index as potential contributors to general health.

Methods

The gut microbial composition was derived using fecal 16S sequencing (V4), and the per-participant microbial health index was calculated. Exposures, diseases, and laboratory results were recorded at sample collection.

Results

372 participants (62% males, median age 57y, Table 1) were included (the study is ongoing). Median BMI was 25 (IQR 23-28), with 9% smokers. Participants are relatively fit: only 22% reported performing physical activity less than once weekly, and the median average steps (for the 55% that reported their daily average) is 6000 steps/day (IQR 4500-8000). Subjects performing more frequent physical activity (>3 times/week) had a higher gut microbial health index (p=0.009) in comparison to less than once weekly. Subjects having no documented disease (22%) had higher indexes, and the number of diseases negatively correlated with the health index (rho=-0.19, p=0.004). A higher microbial health index (Figure 1) was found in subjects drinking >=4 coffee cups/day vs. less or no coffee (p=0.002). Interestingly, a higher percentage of eosinophils was positively correlated with a higher index (p=0.002). Lower health index was recorded in subjects who reported dietary supplements intake (p=0.01), those with above-normal levels of uric acid (p=0.02), with primary hypertension or fatty liver (p=0.02), and those taking beta-blockers (p=0.009) or glucose-lowering medications (p=0.003). The microbial health index positively correlated with Faith alpha diversity (rho=0.47). Still, in some cases, each factor was linked with different features suggesting that these microbial-based factors (diversity and health index) captured a complementary epiphenomenon of the microbiome. For example, only higher alpha diversity (but not health index) was linked with the daily bowel movement frequency (p=0.0008).

Conclusion

Using the gut microbial health index, we developed a methodology to assess correlations between different lifestyles, diets, and health. This approach may highlight personal modifiable factors that can be translated into risk prevention strategies for improving general health reported by microbial composition.
P1242 Pediatric IBD microbiome and microbial profiles formed within the family
Authors: Dovrolis N , Moschoviti A , Karamanolis G , Fessatou S , Kolios G , Gazouli M
Published: January 2024

Background

The rise of microbiome-focused research, reveals that the intrafamilial microbiome can be linked to specific genetic traits and be studied for its behavior during dysbiosis. It has been reported that microbiota composition is shared between cohabitating individualsand displays patterns of similarity that differ between families. Based on these observations, this study focuses on treatment-naïve pediatric IBD patients and their immediate families to identify the role of the microbiome in disease onset.

Methods

Families with pediatric IBD were recruited,comprising seven drug-naïve Crohn’s disease (CD) patients and two drug-naïve ulcerative colitis (UC) patients, as well as healthy siblings/parents. Fecal samples were collected for 16S ribosomal RNA gene sequencing and bioinformatics analysis.

Results

Our results elucidate the fact that even though family members share lifestyle and dietary habits, the patients exhibit unique microbiome patterns which could only be attributed to the disease. In addition, we studiedthe impact of the disease on specific microbial taxa and how these could serve as potential biomarkers for early detection.

Conclusion

We found a potential role of maternal factors in the establishment and modulation of the early life microbiome, consistent with the current literature, which may have implications for understanding the etiology and progression of IBD.
N05 Are we meeting the sexual wellbeing concerns of patients with IBD and a stoma? A survey on current practice in addressing sexual wellbeing
Authors: Fourie S , Czuber-Dochan W , Norton C
Published: January 2024

Background

People with inflammatory bowel disease have a high incidence of stoma formation, either temporary or permanent. Although a stoma can be a life saver, for some it can negatively impact body image and psycho-emotional wellbeing. Sexual function can also be affected by a poor body image. Therefore, intimacy and sexuality should be addressed in clinical settings during stoma care. We aimed to explore the experiences of sexual wellbeing concerns of people living with IBD and a stoma, and how these were addressed by healthcare professionals.

Methods

This was Stage 1 of an international mixed method study. Data were collected via an anonymous online survey advertised on social media platforms and charity webpages.

Results

These are the quantitative results. 134 participants with IBD responded: 11 had colostomy and 123 had ileostomy. Time from stoma formation to survey response was between 2 weeks to 32 years. Peristomal hernia was reported by 27.6% (n=37) participants. Only 30.5 % (n=41) reported that sexual wellbeing was discussed around the time of their stoma formation, mainly with their surgeon or stoma nurse. Some 33.5% (n=45) reported having had no intimacy and sexuality concerns at all at the time of stoma formation. The patient perspective on barriers for asking healthcare professionals (HCPs) questions about sexual wellbeing despite having concerns, were reported as being ashamed to ask, afraid of being judged by their HCPS, and not knowing what to ask as being overwhelmed with technical information related to stoma care. Around 66% (n=89) reported having concerns related to their intimacy and sexuality following stoma formation, with the top three reported concerns being appearance/body image, fear of rejection from partner, and bag leakages. All participants reported wanting sexual wellbeing discussed routinely at any point of care, and the majority wanted partners involved in these discussions.

Conclusion

Patients expect to be informed about intimacy and sexuality aspects as an integral part of stoma care. Current practice does not meet the patient’s care needs, with potential for having a negative impact on their overall quality of life, since a significant number of ostomates report sexual wellbeing concerns after the stoma formation.Sexual wellbeing conversations should be an integral part of perioperative and stoma care to prevent persistent concerns within this patient group. Not providing adequate information during stoma care about sexual wellbeing can negatively impact their quality of life. The results will form the basis of an interview guide for the second (interview) stage of the study, to understand better the reasons behind these findings.
N22 Compliance with Anti-TNF Alpha Treatment and Quality of Life of Inflammatory Bowel Patients: A Descriptive and Correlational Study
Authors: Sözeri Öztürk E , Uçan Ş , Karakan T
Published: January 2024

Background

Today, anti-TNF agents are often preferred in the treatment of inflammatory bowel diseases. During this long-term treatment, patients' compliance with the treatment is very important. This study aims to determine the relationship between compliance with anti-TNF alpha treatment and quality of life in inflammatory bowel patients.

Methods

This study is currently being carried out at Gazi Hospital Gastroenterology Department, Inflammatory Bowel Diseases Outpatient Clinic. The study will be carried out between November and February 2024. Data are collected using the "Patient Information Form", "Inflammatory Bowel Diseases Quality of Life Scale", "Anti-TNF Alpha Treatment Compliance Scale". Whether the variables were suitable for normal distribution was determined by the Kolmogorov-Smirnov test. Since parametric test assumptions were not met, Mann-Whitney U test, Kruskal Wallis test and Sperman correlation analysis were used in the analysis of scale scores. Statistical significance value was accepted as p<0.05.

Results

In this section, the pilot results of the study are presented and its implementation is ongoing (Number of patients reached: 117). The mean age of the patients participating in the study was determined to be 38.99±13.73 (minimum=18, maximum=68). It was determined that 53.7% of the patients were male, 57.3% were married and 42.7 of them had no children. The diagnosis of 65% of patients is Crohn's disease. The rate of patients being diagnosed with inflammatory bowel disease for 3-5 years was found to be 29.9%. The total score of the Inflammatory Bowel Diseases Quality of Life Scale was found to be 160.04±32.24 (minimum=88.00, maximum=224.00). The total score of the Anti-TNF Alpha Treatment Compliance Scale was found to be 2.36±0.72 (minimum=1.00, maximum=4.58). It was determined that there was a strong negative relationship between the total scores of the scales (p= <0.001).

Conclusion

It can be said that the treatment compliance of the patients is at a moderate level and their quality of life is at a good level. The relationship between patients' treatment compliance and their quality of life is also negative.
N36 Inflammatory Bowel Disease Dysplasia Surveillance Pathway (IBD DSP)
Authors: Joseph B , Misra R
Published: January 2024

Background

UK-wide concerns have arisen regarding patients with Inflammatory Bowel Disease (IBD) on surveillance lists being missed or dropped off waiting lists due to the COVID-19 pandemic's impact on waiting times and lists.

An IBD surveillance link nurse role was developed involving clinical sessions with a gastroenterology consultant. The IBD Dysplasia Surveillance pathway (DSP) was created to improve education and counselling for high-risk patients, alleviate concerns, and facilitate shared decision-making in IBD care.

Methods

All patients with dysplasia with a background of IBD are referred to the IBD MDT. After discussion the patients are referred to the DSP clinic. The clinic maintains a dysplasia database capturing all high-risk patients with dysplasia, demographic data, co-morbidities, grade of dysplasia and scheduled endoscopy are collated. Outcome measures of did not attend (DNA) and missed cancers were analysed.

Results

Since April 2022, 170 patients have been referred to the DSP, with 52 reviewed in the surveillance Clinic and 16 referred to joint surgical clinics, with 15 invisible, 34 visible, three high-grade dysplasia and 25 low-grade dysplasia cases. Four patients underwent surgery, and two patients declined surgery. Sixteen patients underwent yearly colonoscopies. Two patients DNA for their colonoscopy. There were no missed cancers.

Conclusion

The IBD Dysplasia Surveillance Pathway is a systematic approach for IBD surveillance. It improves communication between IBD and endoscopy teams. The clinic's hybrid approach improves accessibility and engagement with surveillance, reducing cancellations/DNA of surveillance colonoscopies in the IBD patient population, and facilitating the BSG guidelines for cancer surveillance.
N39 Exploring the impact of an Inflammatory Bowel Disease Biologics Nurse on the management of a biologics service
Authors: Scott G
Published: January 2024

Background

Biologics nurses play a critical role in the management of patients receiving treatment for Inflammatory Bowel Disease (IBD).Their impact spans various facets of patient care and service management. Prior to December 2021 all patients who required biological therapy were reviewed by any member of the IBD nursing team. This review would entail a comprehensive history taken, screening bloods ordered and explained and a thorough ex[planation of the risks and benefits of the medication including a detailed explanation of the use of the drug. The nurses were also responsible for the preparation of biologic prescriptions and checking of bloods. With a number of nurses undertaking this can lead to duplication of work or patients not receiving medication timely.

Methods

A business was written to secure funding for extra nurses and was unsuccessful. At the time of the Covid pandemic workload escalated to an extent that the current IBD Helpline and nurse led clinics could not continue in their present form. Resulting in a suspension of nurse clinics which led to a backlog of reviewing patients who required biological therapy, thus delaying their treatment. A meeting was convened with the senior management team and staffing numbers were increased resulting in the development of a biologics nurse.

Results

A band 6 biologics nurse was employed who completely transformed the biologics service. One person completing a role independently assumes total responsibility for all of the tasks annexed to the role. This involved patients education and support, monitoring and assessment of patients, coordination and communication with patients and relevant departments. It also included quality improvement, patient advocacy, emotional support to patients and patient empowerment/ One person responsible for this role has now led to a reduction in complaints, more timely treatment, less missed treatment appointments and a single point of contact for patients and departments. Our biologics nurse has not only achieved all of these roles but has been fundamental in the biologic switch to more coast effective biological therapies.

Conclusion

The impact of a dedicated biologics nurse in an IBD service is significant. They enhance the overall quality of care, improve patient outcomes, and contribute to the efficient functioning of the service by ensuring proper management, patient education, and support throughout the treatment journey. The team have had an increased number of praise and favourable comments from patients, families and departments that interact with our service such as the Medical Day Unit. The introduction of this role has been invaluable to our service has increased to such an amount that the team could do with a second nurse in post.
N45 Nurse intervention in patients with Inflammatory bowel disease: impact in their quality of life
Authors: Diaz Rodriguez D , Bernarte M J , Granados-Martín M
Published: January 2024

Background

Physical inactivity is considered as a modifiable risk factor in chronic diseases1 and IBD. Regular physical activity could help patients with IBD by reducing some IBD complications, such as improving immune response, increasing muscle mass and strength, and improving bone density.

The aim of this study is to determine the impact of a Nurse intervention, on Physical Activity, in quality of life of IBD patients.

Methods

Quasi-experimental study before and after. 20 patients, both sex, with IBD from Hospital Universitario del Henares, 18-65 years old, in clinical remission or mild activity; IBD ≥ 6 months. Exclusion: physical impairment for daily activities (cardiac, orthopedic or cognitive impairment); pregnancy; surgery < 3 months.

Nurse intervention on physical exercise: 4 group sessions of 60 minutes, 10 months follow-up. Training on strength and endurance exercises by a physiotherapist adapted to each patient’s special needs.

Data were collected in Inflammatory Bowel Disease Questionnaire 32 (IBDQ-32), Rapid Assessment of Physical Activity (RAPA), Hospital Anxiety and Depression Scale (HADS). Variables: quality of life, physical activity, IBD activity, socio-demographic, health status and lifestyle. A descriptive analysis was carried out with qualitative and quantitative variables. Four dimensions of quality of life index and impact of exercise on quality of life were calculated, before and after intervention with Students-T.

Results

Quasi-experimental study before and after. 20 patients, both sex, with IBD from Hospital Universitario del Henares, 18-65 years old, in clinical remission or mild activity; IBD ≥ 6 months. Exclusion: physical impairment for daily activities (cardiac, orthopedic or cognitive impairment); pregnancy; surgery < 3 months.

Nurse intervention on physical exercise: 4 group sessions of 60 minutes, 10 months follow-up. Training on strength and endurance exercises by a physiotherapist adapted to each patient’s special needs.

Data were collected in Inflammatory Bowel Disease Questionnaire 32 (IBDQ-32), Rapid Assessment of Physical Activity (RAPA), Hospital Anxiety and Depression Scale (HADS). Variables: quality of life, physical activity, IBD activity, socio-demographic, health status and lifestyle. A descriptive analysis was carried out with qualitative and quantitative variables. Four dimensions of quality of life index and impact of exercise on quality of life were calculated, before and after intervention with Students-T.

Conclusion

There are non-significative differences in quality of life before and after intervention. Patients increased their physical activity after intervention. Regular physical activity is a useful tool for improving quality of life in patients with IBD.
ECCO Global Grant Genetic risk factors for IBD in its emergent phase in sub-Saharan Africa
Authors: Croft N M , Hodges P , Kelly P , Alatise O , Boateng K G A , Katsidzira L , Duduyemi B , Adeniyi F , Watermeyer G , Musa Y , Opio C , McGovern D P B
Published: January 2024

Background and Aims

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is an idiopathic, chronic, and frequently disabling inflammatory disorder of the intestines characterized by a dysregulated mucosal immune response. The pathophysiology of the disease remains incompletely understood. Genetic factors affecting disease are under investigation, however, genetic studies in non-European populations are scarce and it is an urgent scientific, social, and ethical requirement that research in under-studied populations is prioritized. The objective of this study is to understand the genetics of IBD in sub-Saharan African ancestry populations and to identify genetic factors that affect pathogenesis of IBD in this region.

Methodology

A case-control study will be conducted from January 2024 to December 2025. Consecutive eligible subjects with IBD and controls will be invited to take part in the study. Data will be collected through chart review, structured interviews, and collection of saliva samples for genotyping using the H3Africa chip in the first instance. Genome-wide imputation and replication analysis will be done. Single-marker association analyses will be performed using the Cochran Armitage trend and logistic regression test after correction for population structure. We will look at known European ancestry and African American (AA) IBD-associated variants as well as variants that are unique to our populations (we will be able to look at local admixture in the AA population to see if these variants are replicated).

Anticipated Impact

This study will contribute significantly to knowledge of genetic risk factors for IBD in sub-Saharan Africa. It may also help to identify potential complications of treatments such as thiopurines which have been commonly used in European populations but where experience of use in sub-Saharan Africa is lacking.
ECCO Grant Dissecting the intestinal mucosa-associated HUMoral immune response in ileal Crohn’s Disease: the HUM-CD study
Authors: Uzzan Mathieu
Published: January 2024

Background and Aims

The pathophysiology of Crohn's disease (CD) is complex and not fully understood. While CD can affect the entire gastrointestinal tract, it primarily affects the terminal ileum. The underlying mechanistic reasons for this preferential location are unknown. Patients with isolated ileal CD have higher levels of circulating IgG antibodies targeting flagellins. These antibodies are associated with the ileal location of CD as well as with a complicated phenotype (intestinal stenosis and fistulae). Cellular determinants of this humoral response in ileal CD are yet to be unraveled. Techniques to study B cells at the single-cell levels have tremendously evolved these recent years and our laboratory has developed expertise in most of these techniques. The objectives of our study are to comprehensively characterize the humoral B cell response in patients with ileal CD.

Methods

To fulfill our aim, we will use different approaches:

1. Extensive characterization of the B cell cellular and molecular landscape of the intestinal ileum in CD as compared to homeostasis states at the single-cell level

2. Dissection of the intestinal B cell antigen-specific response in CD and assess differences between inflamed and non-inflamed, and ileal and colonic mucosa and the cross-reactivity of the flagellin-specific response

3. Identification of the antigenic reactivity and clonal dynamics of memory B cells extracted from the terminal ileum of patients with CD.

We will work from human samples, collected from ileal, colonic biopsies, and blood of patients with CD and healthy controls using

Anticipated Impact

Using advanced B-cell-focused single-cell techniques, we will unravel the humoral response at the ileal level and its association with clinical outcomes. By doing so, we aim to identify the main antigenic drivers and putative therapeutic targets of ileal CD.
ECCO Grant Ablating perianal fistulizing Crohn’s disease through genetically engineered patient specific induced pluripotent stem cells (iPSC)-derived stromal cells
Authors: Molendijk I , Peppelenbosch M P , Fuhler G , de Vries A C , van Ruler O
Published: January 2024

Background and Aims

Despite the wide range of available therapies treatment of perianal fistulizing Crohn’s disease (pCD) remains challenging. Therefore, exploring new effective therapies is of crucial importance. Local injection of allogeneic mesenchymal stromal cells has been reported to be effective, however, application of these cells is hindered by their limited expandability and differences in therapeutic effect due to donor variations. To overcome these problems, induced pluripotent stem cells (iPSC) can be used to create stromal cells as iPSC can be propagated indefinitely in their undifferentiated state. Therefore, the aim of our study is to generate patient specific iPSC-derived stromal cells of patients with pCD. Furthermore, we will engineer programmed death-ligand 1 (PD-L1)-expressing cultures to enhance the immunomodulatory capacity of these stromal cells. Last, preclinical testing of these cells will be performed in experimental colitis models.

Methods

Ten patients with pCD will be included at the outpatient clinic in the Erasmus Medical Center (EMC). Patient specific iPSC will be generated from peripheral blood in the iPSC core facility of the EMC. iPSC cultures will be exposed to a low dose of retinoic acid creating stromal cells. The variety of stromal cells will be sorted using a FACS and a stromal specific sorting panel. In parallel, cultures will be engineered, using CRISPR-Cas technology, to express PD-L1. Mixed lymphocyte reactions will be performed to assess the ability of both transduced and non-transduced cultures to provoke the proliferation of non-MHC matched T-lymphocytes. Next, cultures will be generated to express murine PD-L1 to assess their immunomodulatory capacity in established experimental colitis models to provide essential knowledge for a future clinical trial.

Anticipated Impact

With this study, we are taking the first steps towards improved remission rates of perianal fistulas in the future. On the long-term, this will result in reduction of health care costs.
D-ECCO Grant Personalizing the dietetic strategy in children with IBD: exploring an antioxidant approach
Authors: Gatti S , Quattrini S , Galeazzi T , Monachesi C
Published: January 2024

Background and Aims

Diet is a key element in the pathogenesis and treatment of Inflammatory Bowel Disease (IBD). Also, oxidative stress (OS) is involved in IBD onset and evolution. Our group is conducting a multicenter trial (the OxIBDiet study, NCT0451301) to explore the OS imbalance in both children and adults with IBD, compared to matched controls, the genetic variants of genes implicated in OS and the effects of an Antioxidant diet (AoD) on these patients. Preliminary results have shown a great imbalance in the total antioxidant capacity in IBD compared to healthy matched controls, particularly in IBD children, and a clear improvement of the antioxidant capacity and oxidant parameters after 3 months of AoD. Aims of this study are: 1. To identify IBD subjects’ responders to a specific dietetic treatment (on the basis of clinical, biochemical and genetic characteristics); 2. To evaluate the effect of antioxidant compounds on stem cell derived 3D models of the intestinal epithelium by organ-on-a-chip technology; 3. To characterize the effect of AoD and Mediterranean diet in terms of inflammatory pattern.

Methods

A machine-learning algorithm that integrates clinical parameters, anthropometrics, blood parameters and genetic data measured in OxIBDiet cohort will be generated and validated in a new cohort of 30 IBD children (15 CD and 15 UC). Human intestinal organoids will be generated from 10 patients, in which an endoscopy is planned for disease reassessment, and levels of interleukins and TNF-alfa will be measured, after stimulation with antioxidant compounds. Thirdly, cytokine analysis in serum from OxIBDiet cohort who performed dietetic sub-study will be evaluated.

Anticipated Impact

Results of this study will provide useful indications on factors that influence redox imbalance in IBD and will permit to identify patients who may benefit from a personalized dietetic approach, especially an AoD.
IIS Registry Grant Risk of relapse and retreatment success after vedolizumab discontinuation in IBD patients in long-standing remission
Authors: Dragoni Dr Gabriele
Published: January 2024

Background and Aims

Treatment withdrawal and “cycling” of anti-TNFs has been extensively investigated in the recent years. To date, none or scarce data are available for biological agents other than anti-TNFs, such as vedolizumab (VDZ), which is the first non-anti-TNF agent approved for the treatment of inflammatory bowel disease (IBD). Our aim will be to investigate the risk of relapse and retreatment success in IBD patients that discontinue vedolizumab due to sustained steroid-free remission.

Methods

This will be a prospective observational study in which two groups of patients in sustained remission will be formed, i.e., patients stopping vedolizumab and patients continuing the treatment. Differences regarding rates of disease flares, IBD-related hospitalisations and surgeries will be analysed. The rate of retreatment success in patients presenting a flare after discontinuation will also be recorded. In addition, potential predictive factors of disease relapse will be investigated to provide future guidance on the patient profile that might benefit the most from intermittent VDZ treatment. The study will last 3 years in total, with the first year dedicated to patient inclusions.

Anticipated Impact

Only few data are currently available regarding intermittent treatment with vedolizumab. Therefore, this study may provide insights on when to interrupt this biologic with high probability of maintaining remission, while also showing high-risk features that would suggest against stopping the treatment. The use of treatment cycles may represent an impactful cost reduction for our healthcare systems as well as a decrease of potential side effects that are an inevitable consequence of years of immunosuppression.
IIS Registry Grant Modelling Inflammatory Bowel Diseases trajectories combining dynamic, multifactorial, Artificial Intelligence-based approaches
Authors: Comoretto R I , Tavazzi E , Martinato M , Azzolina D
Published: January 2024

Background and Aims

The aim of this project is to model Inflammatory Bowel Diseases (IBD) progression using an innovative approach that considers the manifestation of the disease from a dynamic and multifactorial point of view, with a focus on model explainability.

Methods

With the aim of modelling the course of IBD in the study population of the UR-CARE registry, an innovative approach will be applied consisting of the combined use of two different data-driven Artificial Intelligence techniques, namely dynamic Bayesian networks and Process Mining. Specifically, these two approaches will be jointly used to model IBD progression trajectories, providing a broader overview of the disease through the description of its patterns of progression (including clinical events, treatments and/or outcomes) and the interactions between clinical variables. The potential of the proposed methodology to address the predictive needs of chronic IBD progression, such as the forecasting of the next relapse, the effect of a therapy, or the impact of a risk factor, will also be explored.

Anticipated Impact

On the one side, IBD patients experience constant uncertainty regarding disease progression, while clinicians, on the other hand, need tools that can support them in understanding the multidimensionality of disease progression. In this scenario, AI can be the key to successfully satisfy these needs, effectively investigating the disease processes, allowing to describe pathological evolution over time, handling and capturing patients’ inter-variability, and providing tools to forecast disease evolution. By adopting an ad-hoc developed analytic approach, this project can help in better understanding IBD mechanisms and best care strategies, defining the relationships among the patient characteristics and the sequence of experienced clinical events, evaluating the impact of key elements on disease’s prognosis. These results would be useful not only to better manage the disease from a clinical and care point of view, but also in economic terms.
Knockdown of Kmt2d leads to growth impairment by activating the Akt/β-catenin signaling pathway
Authors: Shangguan Huakun , Huang Xiaozhen , Lin Jinduan , Chen Ruimin
Published: January 2024

The KMT2D variant–caused Kabuki syndrome (KS) is characterized by short stature as a prominent clinical characteristic. The initiation and progression of body growth are fundamentally influenced by chondrocyte proliferation. Uncertainty persists regarding the possibility that KMT2D deficiency affects growth by impairing chondrocyte proliferation. In this study, we used the CRISPR/Cas13d technique to knockdown kmt2d in zebrafish embryos and lentivirus to create a stable Kmt2d gene knockdown cell line in chondrocytes (ATDC5 cells). We also used CCK8 and flow cytometric studies, respectively, to determine proliferation and cell cycle state. The relative concentrations of phosphorylated Akt (ser473), phosphorylated β-catenin (ser552), and cyclin D1 proteins in chondrocytes and zebrafish embryos were determined by using western blots. In addition, Akt inhibition was used to rescue the phenotypes caused by kmt2d deficiency in chondrocytes, as well as a zebrafish model that was generated. The results showed that a knockdown of kmt2d significantly decreased body length and resulted in aberrant cartilage development in zebrafish embryos. Furthermore, the knockdown of Kmt2d in ATDC5 cells markedly increased proliferation and accelerated the G1/S transition. In addition, the knockdown of Kmt2d resulted in the activation of the Akt/β-catenin signaling pathway in ATDC5 cells. Finally, Akt inhibition could partly rescue body length and chondrocyte development in the zebrafish model. Our study demonstrated that KMT2D modulates bone growth conceivably via regulation of the Akt/β-catenin pathway.
Longitudinal Studies of Aging in Sub-Saharan Africa: Review, Limitations, and Recommendations in Preparation of Projected Aging Population
Authors: Akinrolie Olayinka , Iwuagwu Anthony O , Kalu Michael E , Rayner Daniel , Oyinlola Oluwagbemiga , Ezulike Chigozie D , Okoh Augustine C , Makanju Adebayo O , Ugwuodo Ebere P , Ugwuja Immaculata A , John Makanjuola Osuolale , Adeleke Deborah , Egbumike Chukwuenyegom J , Anieto Ebuka Miracle , Anieto Ijeoma B , Alumona Chiedozie James , Onyeso Ogochukwu Kelechi , Ojembe Blessing , Omeje Chidinma A , Nwachukwu Ernest C , Ekediegwu Ezinne C , Onyeso Kelechi M , Adeboye Ademuyiwa , Ibekaku Michael , Akinrolie Omobolade , Onyekere Chukwuebuka P
Published: January 2024

Background and Objectives

The United Nations has projected a 218% increase in older people in Sub-Saharan Africa (SSA) between 2019 and 2050, underscoring the need to explore changes that would occur over this time. Longitudinal studies are ideal for studying and proffering solutions to these changes. This review aims to understand the breadth and use of longitudinal studies on aging in the SSA regions, proffering recommendations in preparation for the projected aging population.

Research Design and Methods

This paper is the third of a four-part series paper of a previous systematic mapping review of aging studies in SSA. We updated the search (between 2021 and 2023) and screened the titles/abstracts and full-text articles by a pair of independent reviewers. Data were extracted using a standardized data-charting form, identifying longitudinal studies in SSA.

Results

We identified 193 studies leveraging 24 longitudinal study data sets conducted at 28 unique sites. The World Health Organization’s Study on Global AGEing and Adult Health (WHO-SAGE) (n = 59, 30.5%) and Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) (n = 51, 26.4%) were the most used longitudinal data sets. Four studies used more than one longitudinal study data set. Eighteen of the longitudinal study data sets were used only in 1–4 studies. Most (n = 150, 77.7%) of the studies used a cross-sectional analytical approach.

Discussion and Implications

Longitudinal studies on aging are sparingly being utilized in SSA. Most analyses conducted across the longitudinal data set were cross-sectional, which hindered the understanding of aging changes that occurred over time that could better inform aging policy and interventions. We call for funding bodies, such as WHO-SAGE, to develop funding competitions that focus on conducting longitudinal analyses, such as structural equation modeling, highlighting changes occurring among the aging population in SSA.
Bounds for the Bergman Kernel and the Sup-Norm of Holomorphic Siegel Cusp Forms
Authors: Das Soumya , Krishna Hariram
Published: January 2024

We prove “polynomial in $k$” bounds on the size of the Bergman kernel for the space of holomorphic Siegel cusp forms of degree $n$ and weight $k$. When $n=1,2$ our bounds agree with the conjectural bounds, while the lower bounds match for all $n \ge 1$. For an $L^{2}$-normalized Siegel cusp form $F$ of degree $2$, our bound for its sup-norm is $O_{\epsilon } (k^{9/4+\epsilon })$. Further, we show that in any compact set $\Omega $ (which does not depend on $k$) contained in the Siegel fundamental domain of $\textrm {Sp}(2,\mathbb {Z})$ on the Siegel upper half space, the sup-norm of $F$ is $O_{\Omega }(k^{3/2 - \eta })$ for some $\eta>0$, going beyond the “generic” bound in this setting.
Blind spots of universal primers and specific FISH probes for functional microbe and community characterization in EBPR systems
Authors: Yuan Jing , Deng Xuhan , Xie Xiaojing , Chen Liping , Wei Chaohai , Feng Chunhua , Qiu Guanglei
Published: January 2024

Fluorescence in situ hybridization (FISH) and 16S rRNA gene amplicon sequencing are commonly used for microbial ecological analyses in biological enhanced phosphorus removal (EBPR) systems, the successful application of which was governed by the oligonucleotides used. We performed a systemic evaluation of commonly used probes/primers for known polyphosphate-accumulating organisms (PAOs) and glycogen-accumulating organisms (GAOs). Most FISH probes showed blind spots and covered nontarget bacterial groups. Ca. Competibacter probes showed promising coverage and specificity. Those for Ca. Accumulibacter are desirable in coverage but targeted out-group bacteria, including Ca. Competibacter, Thauera, Dechlorosoma, and some polyphosphate-accumulating Cyanobacteria. Defluviicoccus probes are good in specificity but poor in coverage. Probes targeting Tetrasphaera or Dechloromonas showed low coverage and specificity. Specifically, DEMEF455, Bet135, and Dech453 for Dechloromonas covered Ca. Accumulibacter. Special attentions are needed when using these probes to resolve the PAO/GAO phenotype of Dechloromonas. Most species-specific probes for Ca. Accumulibacter, Ca. Lutibacillus, Ca. Phosphoribacter, and Tetrasphaera are highly specific. Overall, 1.4% Ca. Accumulibacter, 9.6% Ca. Competibacter, 43.3% Defluviicoccus, and 54.0% Dechloromonas in the MiDAS database were not covered by existing FISH probes. Different 16S rRNA amplicon primer sets showed distinct coverage of known PAOs and GAOs. None of them covered all members. Overall, 520F-802R and 515F-926R showed the most balanced coverage. All primers showed extremely low coverage of Microlunatus (<36.0%), implying their probably overlooked roles in EBPR systems. A clear understanding of the strength and weaknesses of each probe and primer set is a premise for rational evaluation and interpretation of obtained community results.
Partial body fat percentage as a predictor of fragility fractures in a large cohort: a cross-sectional study
Authors: Amin Hamzah , Syed Fauzaan Ali , Khan Muhammed Aqib , Sultan Zain , Bukhari Marwan
Published: January 2024

Objectives

BMI is a component of fracture risk calculators; however, it may be too simplistic to predict fracture risk. There is emerging evidence for the role that fat plays as a predictor of fracture. Partial body fat percentage (PBF%) may be a novel way to predict both hip and non-hip fractures. The aim of this study is to evaluate PBF% as a predictor of fragility fractures.

Methods

A multivariate logistic regression analysis was conducted looking at PBF% as a predicter of both non-hip and hip fractures in an observational cohort. Our results were adjusted for age, biological sex, gender, smoking status, excess alcohol consumption (>3 units/day), current steroid therapy and the T-scores in both femurs. To allow for comparison, the same model was used with BMI, height and weight as the primary predictor of fracture. A subgroup analysis was conducted stratified by fracture site. A sensitivity analysis using a negative binomial regression was conducted.

Results

A total of 31 447 patients were included in our analysis [mean age 64.9 years (s.d. 12.9)]. PBF% was shown to predict all non-hip fractures after adjustment [odds ratio (OR) 22.14 (95% CI 15.08, 32.50)]. Hip fractures were not predicted by our model [OR 4.19 (95% CI 0.43, 41.46)]. Sensitivity analysis demonstrated a lack of predictive capability for hip fracture but not non-hip fractures.

Conclusion

PBF% may be a suitable predictor for all non-hip fractures, independent of confounding variables. More research is needed on whether it can predict hip fractures.
The Expanded Application of the Acellular Dermal Matrix: Traumatic Nail Bed Defect of the Digits
Authors: Park Kwang Hyun , Woo Soo Jin , Woo Sang Hyun , Cheon Ho-jun
Published: January 2024

Reconstruction of traumatic nail bed defects in the digits is a frequently encountered procedure, yet often presents many challenges. In such scenarios, staged procedures may be required with significant limitations in shape and increased donor site morbidity, particularly when multiple defects are present. In this study, we introduce a simple method for the reconstruction of nail bed defects using an acellular dermal matrix (ADM). The study involved 19 digits with nail defects, which underwent reconstruction using an ADM graft. The surgical procedure was performed on all patients on the day of injury, after which they were promptly discharged. The dimensions of the defect ranged from 0.5 × 0.5 cm to a maximum of 2 × 3 cm (average, 0.9 × 1.4 cm). Final examinations were performed at postoperative 5–11 months (average, 6.6 months). All ADM grafts were successfully taken. Nail growth was observed at an average of 4 months after surgery in the treated finger. The surgical results were retrospectively evaluated using the Zook criteria. Outcomes were “excellent” in 11 patients (57.9%), “very good” in five patients (26.3%), “good” in two patients (10.5%), and “fair” in one patient (5.2%). The expanded application of ADM explored in this study illustrates a straightforward method for the reconstruction of traumatic nail bed defects, providing effective results in a single stage without incurring donor site morbidity.