bluuebunny/crossref_metadata_2025 huggingface dataset:
N32 Providing sexual well-being support to patients with Inflammatory Bowel Disease: analyzing the practices of international nurses
Authors: Wakai S , Tanaka M , Fourie S , Nozawa M , Kawakami A
Published: January 2025

Background

Inflammatory bowel disease (IBD) is often diagnosed in early adulthood and affects individuals’ sex life. People living with IBD report sexual dysfunction and reduced sexual satisfaction. While previous studies have demonstrated patients’ need for information about sexual health from healthcare providers, nurses’ practices for individuals’ sexual well-being (SWB) remain unclear. This study aimed to identify international nurses’ SWB support practices for patients with IBD.

Methods

This is an international qualitative study. Nurses with substantial experience in IBD nursing were recruited between May 2023 and October 2024 using a snowball sampling method, and online semi-structured and focus group interviews were conducted. After completing data coding, the results for each country were merged and analyzed as one dataset. Thematic analysis was used to analyze the data.

Results

A total of 29 nurses (male: 5; female: 24) from Japan, the UK, Ireland, Australia, and Canada were interviewed, and the focus group interviews were conducted at two sites in Japan. The mean years of experience in IBD nursing were 13 years. The thematic analysis led to the overarching theme of ‘Careful exploration in real life practice’ with the identification of the following primary themes: ‘Building the foundation for SWB care’, ‘Addressing SWB issues as a team’, ‘Identifying SWB needs’, and ‘Providing personalized nursing support’. These themes reflected the lack of SWB education in the foundation of nursing training, resulting in nurses being unprepared and lacking confidence in providing support, and the ways that support is provided in practice in the absence of formal education to address SWB as a tailored practice. Nurses strive to support SWB among individuals with IBD despite the challenges they encounter and the reticence to initiate the conversation.

Conclusion

All nurses reported that SWB support for patients with IBD was provided after establishing trust and working together as a team to support them. In addition, as sexual concerns are highly individualized, the nurses assessed each person’s life events and situations of need and engaged in practices tailored to their concerns. This was done by creating an environment that encouraged individuals to share their thoughts. Cultural aspects that make discussing SWB difficult stem from a general view of sex as taboo; this was observed regardless of the participants’ geographical provenience. Finally, nurses’ training needs for SWB education are similar, regardless of the participants’ demographics.
N36 Inflammatory bowel disease helpline use amongst individuals who are culturally and linguistically diverse, Crohn’s Colitis Cure Data Insight’s Programme
Authors: Cabaero A G , Su W K , Wilson W , Rivas C , Antoniades S , Ng W , Forbes A , Arnold K , Grafton R , Andrews J M , Connor S J
Published: January 2025

Background

Effective management of inflammatory bowel disease (IBD) requires sustained patient engagement in healthcare, with nurse-led IBD helplines proven to improve access to care and reduce healthcare costs. However, individuals who are culturally and linguistically diverse (CALD) face challenges, including impaired access to health information, communication barriers, and interpreter shortages. This study examined how individuals from CALD backgrounds use IBD helplines compared to the English as a first language (EFL) population in Australia and New Zealand.

Methods

Crohn’s Colitis Care (CCCare) is a cloud-based IBD-specific electronic medical record (EMR) used in Australasia. Deidentified data prospectively entered by clinicians and consumers during routine clinical practice from September 2023 to September 2024 were retrospectively analysed. Individuals with IBD who had an assessment within the past 14 months with their language background documented were included.

Results

Of 7506 eligible people, only 892 (11.9%) had their language background documented, with 231 (25.9%) from a CALD background. When compared to the EFL cohort, a higher percentage of CALD individuals reside in metropolitan vs non-metro areas (92.2% vs 86.2%, p<0.05) with a lower proportion attaining tertiary or high school education (40.7% vs 45.4% and 44.3% vs 48.2%, respectively; both p=0.01). See table for details.

The majority of helpline contacts from people of CALD backgrounds were via e-mail (n=379, 83.3%), a significantly higher proportion compared to the EFL cohort (n=987, 77.4%, p<0.001). The reasons for helpline contact were similar between CALD and EFL groups, mainly concerning medication or investigation queries (26.1% vs 24.3% and 24.3% vs 22.6%, respectively; both p>0.5). See table for patterns of helpline use. Multivariate analysis, considering age, gender, diagnosis, disease duration, education, language, and location, did not identify any factors that significantly influenced helpline use.

Conclusion

Individuals with a CALD background show preference for email over phone communication when using helplines. The current documentation of language preference is limited, and these findings highlight a need to enhance data collection practices. With more robust data, we can better understand and address the needs of these populations, ensuring equitable access to healthcare and improved outcomes.
N40 Efficacy and safety of Risankizumab in moderate to severe paediatric Crohn’s disease in a tertiary Paediatric IBD (PIBD) centre – A case series
Authors: Chadokufa S N , Gaynor E , El-Khouly S , Buckingham R , Jones K , Kukoyi B , Kiparissi F
Published: January 2025

Background

Risankizumab (Risa) is a humanized monoclonal antibody designed to target interleukin 23A (IL-23A). In UK approved in 2023 for moderate to severe Crohn’s disease (CD). There is limited data on its use in PIBD patients. The aim of the study was to assess efficacy and safety of Risa in pIBD after treatment failure on previous biologic agents.

Methods

All children initiated on Risa between March and November 2023 were identified in our database in a retrospective review, including patients’ characteristics, treatment response and safety. All patients received 3 intravenous doses at 4 weekly intervals then went on to subcut doses. Clinical activity at initiation was assessed by the 4 point ‘Improve Care Now’ Physician Global Assessment (PGA) based on severity of symptoms (1=asymptomatic; 2=mild; 3=moderate, and 4=severe). Primary outcome was clinical reduction of PGA between week 12-16. Clinical remission was defined as a PGA of 1.Data on faecal calprotectin (FC), radiologic and endoscopic response between week 12-16 were collected. Adverse events were recorded to date

Results

13 patients were identified (11 male) 6 had perianal Crohn’s. 11/13 have had follow up for at least 12 weeks. 2 were excluded for not meeting follow up at the time of the study. Age range from 13 years to 17 years old, median age 16 years. Prior to commencing Risa, 81% (9/11) had moderate to severe disease activity on PGA. Although the remaining 2 patients had mild or asymptomatic PGA for the GI tract, switched for metastatic penile Crohn’s disease and severe joint issues. At re-assessment between week 12 and 16 weeks, 92% (10/11) had a PGA of 1 indicating clinical remission. 1/11 patient had a PGA of 4. Faecal calprotectin available in 63.6% (7/11) showed a dramatic drop in 86% (6/7). Radiological assessment either MRI or SBUS at week 12 or 16 was performed in 37% (4/11) with 2 showing improvement of small bowel disease when compared to radiology assessment prior to Risa, 1 showed no response and 1 showed worsening of disease. 1 patient who had Risa for joint issues showed improvement in inflammatory joint symptoms and the other for penile CD awaits assessment. Endoscopy assessment performed in 1/11 showing persistent disease resulting in a laparotomy and resection of proximal ileal segment and anastomosis. No serious adverse events were reported

Conclusion

Risankizumab induces sustained clinical response in this heterogenous, refractory group of pIBD patients with no significant side effects reported. However, mucosal healing reflected by FC, radiologic and endoscopic findings remains challenging. Further longer term follow up studies and the use as a 1st or 2nd line bilogic treatment on effectiveness and safety of Risankizumab in pIBD patients are required
N41 eHealth management in Inflammatory Bowel Disease: a survey of the views of people with IBD and their healthcare professionals: preliminary results from a questionnaire survey
Authors: Avery P , Kemp K , Lesley D , Green S
Published: January 2025

Background

In a previous qualitative study, interviews were conducted with people with inflammatory bowel disease (IBD) using NHS services and healthcare professionals (HCPs1). Themes arising from the findings of this research included “Human matters” and “Accessibility matters”. Participants described generally accepting eHealth solutions, but some concerns were expressed about accessibility and challenges to effective eHealth. This study aimed to gain a broader understanding of the themes identified.

Methods

A 32-item online questionnaire was developed with items relating to demographic characteristics, level of agreement with statements based on the themes identified in the previous study, experiences of using eHealth, and opinions on the future use of eHealth in IBD care. People with IBD and their HCPS were invited to participate via professional networks, patient groups, and charities. The online survey was available between June and October 2024. Descriptive statistics were used to summarise the data.

Results

Two hundred and thirty respondents completed the survey; 103 (45%) reported being healthcare professionals (HCPs), and 127 (55%) participants had IBD. HCP respondents reported to be medical doctors (n=17, 17%), nurses (n=73, 71%), dietitians (n=5, 5%), surgeons (n=2, 2%), pharmacists (n=4, 4%), an Advanced Clinical Practitioner (n=1, 1%), and psychologist (n=1, 1%). Participants with IBD reported a diagnosis of Ulcerative Colitis (n=52, 41%), Crohn’s Disease (n=57, 45%) or IBD of unknown origin (n=18, 14%). Only 5 (4%) participants with IBD and 5 (5%) HCPs reported not using eHealth to support condition management. Most HCPs (n=97, 86%) and participants with IBD (n=116, 91%) reported valuing in-person care, with 94 (91%) HCPs emphasising its relevance for eHealth effectiveness. 45 (32%) HCPs and 33 (36%) participants with IBD reported technology in the NHS supports IBD care effectively. However, some participants (n=75, 37%) responded "yes" or "not sure" when asked if there were negative impacts of eHealth on IBD management.

Conclusion

Preliminary results of this study indicate that people with IBD and HCPs value eHealth and face-to-face contact. Some participants expressed that the use of eHealth could negatively impact their experience during healthcare delivery. Further data analysis, including free text responses in the survey, aims to explore further participants’ views on e-health to manage IBD.

References

1.Avery P, Kemp K, Dibley L, Green S. N03 Flexibility & Accessibility, e-Literacy, Resourcing and The Human Factor: Early Lessons from EIBD, a UK Qualitative Interview Study. Journal of Crohn's and Colitis. 2024;18(Supplement_1):i2201-i2201.
N45 The Words of Bowels: Exploring Crohn's Disease through Metaphors
Authors: Sözeri Öztürk E , Kırca K , Uçan Ş
Published: January 2025

Background

Crohn’s disease causes patients to cope with many symptoms and conditions during the course of illness, treatment and therapy. Patients experience psychosocial symptoms as well as physical symptoms. The metaphors with which patients describe their illnesses are important in terms of the disease process and compliance with treatment. This study was conducted to explore the meanings patients attribute to Crohn's disease through metaphors.

Methods

This study employed a phenomenological design and a qualitative research approach. It was conducted with 102 patients who consented to participate in research at the inflammatory bowel diseases clinic of a university hospital from January 15 to March 30, 2024. Data were collected through socio-demographic information, the Harvey-Bradshaw Index, and the completion of the sentence "Crohn's disease is like/because..." Participants produced metaphors that were categorized and presented with supporting examples. Demographic data were analyzed using frequency, percentage, mean, and standard deviation, calculated using IBM SPSS Statistics v26.0. Qualitative data were evaluated using content analysis.

Results

Participants with a mean age of 39.68±3.71 years created 80 metaphors about Crohn's disease. These metaphors were analyzed in 8 categories: loss of control, uncertainty, destruction/exhaustion, long process, suffering, transformation/change, care and support needs, and hope. The most frequently used metaphors are nightmare, flower, child, enemy, darkness, and snake.

Conclusion

The most common metaphors used by Crohn's disease patients are nightmare, flower, child, enemy, darkness, and snake. How patients make sense of their illnesses should be evaluated throughout the process by healthcare professionals and the care and treatment process should be planned.
N52 Transition care does not end at transfer of treatment
Authors: Crook K P , Arebi N , Hart A , Hyer W , Adio J
Published: January 2025

Background

Whilst there are many documents telling us how to ‘do’ transition of care from paediatrics to adults i.e. ‘The Inbetweeners’ (NCEPOD) (2023) we report on a constantly evolving Adolescent and Young people’s IBD (AYP) service to meet the patient needs in an inflammatory bowel disease (IBD) setting.

The paediatric IBD advanced nurse practitioner (ANP) as the transition lead, and Adult IBD link nurse are co-located within the same nursing team. The transition process starts at first contact in paediatrics – where the AYP and family are made aware that we aim to transfer care to adult services in the year following their 16th birthday and exams have been completed, enabling 2 years within the AYP service with paediatric and adult nursing support.

Transfer of care occurs in a multidisciplinary clinic with adult and paediatric Consultants and Nurses. This initial appointment determines the need for more ‘joint’ clinics and is tailored to the AYP needs. Subsequent AYP clinics are led by the Adult IBD Link nurse until the AYP naturally moves into a regular clinic. We wanted to review the current process and identify any barriers to young people accessing timely support.

Methods

We identified the cohort from a variety of routes that AYP have entered the adult IBD service. The structured transition patients formed the spine of our current AYP database. Patients lost to follow up were identified and challenges and barriers to engagement with services were identified to inform service improvement projects.

Results

286 AYP were identified using a variety of means – Adviceline calls, clinics, transition lists. Some ‘well’ patients may not have been identified. Initial audit shows that 3 out of 143 patients had been lost to follow-up and not seen/had contact in the last 12 months.

Table 1: Changes to AYP clinics

Conclusion

After reviewing the current structure of AYP clinics we made several changes, some changes have been more successful than others.

Due to the numbers of AYP identified, Paediatric nursing support is planned for the clinic (upto 18 years), but adapting Adult clinic style i.e. the patient is in the lead of the consultation.

The use of the LUSCII app meets 4 of the top 10 most important questions from James Lind Alliance Digital Technology for Adolescents and Young persons with IBD. Although only recently launched, initial interaction indicates that it may reduce need for routine monitoring, for which the AYP has no perceived benefit and AYP engagement appears to be increasing.

Ongoing audit of the changes continues along with monitoring the DNA rate of contact with the young adult group.
The role of SMooth muscle cell minerAlocorticoid Receptor in inTestinal fibrosis (SMART)
Authors: Marion-Letellier R , Jaisser F , Ghosh S , Jaisser F
Published: January 2025

Background and aims

Intestinal fibrosis is a common complication in inflammatory bowel diseases (IBD) with no specific therapy1. Because mineralocorticoid receptor (MR) antagonism prevented inflammation and fibrosis in extra-intestinal organs but also in intestine and since we showed that smooth muscle cell (SMC)-MR deletion prevented colon fibrosis development in mice, we now aim to understand the underlying mechanisms of these benefits.

Methods

Fibrosis will be assessed in male and female mice with conditioned smooth muscle MR overexpression. We previously demonstrated that NGAL (Lipocalin-2) is a MR target in murine SMC and is involved in MR-mediated fibrosis and inflammation. We therefore will study the impact of MR or NGAL agonism/antagonism in murine SMC upon TGF-beta stimulation. To understand the potential inducers of MR or NGAL in murine SMC, we will screen the ability of microbial factors to induce fibrosis or MR signalling in intestinal fibroblasts or SMC. To assess the role of MR/NGAL signaling in macrophages/SMC interaction, we will also investigate the impact of myeloid MR or NGAL invalidation on SMC activation in co-culture experiments of murine macrophages and SMC. For translational approaches, conditioned medium of intestinal biopsies from Crohn’s disease (CD) patients or isolated monocytes derived macrophages from CD patients will be incubated with SMC to study their impact of MR/NGAL signalling and/or fibrosis development.

Anticipated impact

SMART may open new therapeutic avenues in IBD by the repositioning of MR antagonists already available in other medical applications. As SMC represent the main cell component of the increased wall thickness in intestinal fibrosis, a better understanding of the crosstalk between SMC, macrophages and gut microbiota will provide novel insights to develop potentially more effective therapies targeting stromal cells.
Inhibition of the gut sulfidogenic bacteria targeting the production of toxic and inflammatory sulfide
Authors: Pímenta A
Published: January 2025

Background and aims

This project seeks to develop novel strategies to modulate the human gut microbiota and mitigate the production of pathogenic sulphide strongly associated with inflammatory bowel diseases (IBD). Our focus lies in inhibiting a key respiratory complex present in majority of the gut sulfidogenic bacteria to curb excessive sulphide production.

Methods

We will use an array of genetic, microbiological, and biochemical techniques to perform both in vitro and in vivo experiments. Our primary target is the membrane complex DsrMKJOP, involved in the essential Dsr pathway in sulfidogenic bacteria, which is pivotal for sulphur respiration. To achieve this, we will evaluate the efficacy of inhibitors, specifically quinone analogues, which compete for binding sites in the DsrMKJOP complex. Our comprehensive work plan comprises two main components:

(1) expression and production of the DsrMKJOP complex from a major sulfidogenic bacterium and investigation of its inhibition profile through in vitro enzymatic assays; and

(2) assessment of the efficacy and toxicity of DsrMKJOP inhibitors in vivo. This includes determining minimal inhibitory and bactericidal concentrations for the two bacteria, evaluating cytotoxicity in human colonic cells, assessing toxicity in a non-vertebrate animal model, and determining the antimicrobial properties of the inhibitory drugs to modulate bacterial growth during infection and colonization.

Anticipated impact

The outcomes of this research will contribute to identifying new therapeutic agents against sulfidogenic bacteria, acting as metabolic modulators to inhibit the production of pathogenic inflammatory sulphide. We aim to not only identify novel DsrMKJOP inhibitors but also to characterize their in vivo efficacy and toxicity profiles. Successful outcomes hold the potential to significantly advance human health, offering promising avenues for preventing IBD, enhancing the quality of life for IBD patients, and alleviating the burden on healthcare systems.
Diagnostic Markers of Primary Sclerosing Cholangitis in Newly Diagnosed Patients with Inflammatory Bowel Disease - a Copenhagen IBD Inception Cohort Sub-study
Authors: Honoré T V , Attauabi M , Madsen G , Bendtsen F , Ytting H , Seidelin J B , Burisch J
Published: January 2025

Background and aims

Between 5-10% of patients with inflammatory bowel disease (IBD) will eventually be diagnosed with primary sclerosing cholangitis (PSC) [1,2]. Studies suggest that a significant number of IBD patients may have PSC despite lacking biochemical or clinical signs, leading to delayed diagnosis. Sometimes, the liver disease is identified only after severe liver complications or malignancy have developed. This highlights the need for improved diagnostic markers to identify individuals at a high risk of developing PSC [3]. The primary objective of this study is to identify new biomarkers that can detect patients at risk of developing PSC among newly diagnosed IBD patients, enabling early diagnosis of PSC.

Methods

Since May 2021, a prospective population-based inception cohort study (Copenhagen IBD Inception Cohort) has been conducted, including newly diagnosed IBD patients within the uptake area of Hvidovre and Herlev University Hospital, Denmark (approx. 1.1 million inhabitants) [4]. Blood samples have been collected from the cohort at the time of diagnosis. These samples, now stored in a biobank at our disposal, will be utilized for this study.

In this study, we will investigate diagnostic markers in blood samples by comparing proteomic and genetic profiles between data from newly diagnosed PSC-IBD patients (n=15) and IBD patients without PSC (n=30). Plasma will be analysed using the Olink Explore 3072 panel (Olink Proteomics, Uppsala, Sweden). RNA will be extracted from the blood samples and analysed by bulk RNA sequencing.

Anticipated impact

To our knowledge, no studies have yet investigated biomarkers in newly diagnosed PSC-IBD patients who are naive to any prior treatment for both IBD and PSC. This study presents a unique opportunity to discover biological markers in PSC-IBD patients at early stages of the disease.

References

1.Karlsen TH, Folseraas T, Thorburn D, Vesterhus M. Primary sclerosing cholangitis – a comprehensive review. Vol. 67, Journal of Hepatology. Elsevier B.V.; 2017. p. 1298–323.

2.Dyson JK, Beuers U, Jones DEJ, Lohse AW, Hudson M. Primary sclerosing cholangitis. Vol. 391, The Lancet. Lancet Publishing Group; 2018. p. 2547–59.

3.Lunder AK, Hov JR, Borthne A, Gleditsch J, Johannesen G, Tveit K, et al. Prevalence of Sclerosing Cholangitis Detected by Magnetic Resonance Cholangiography in Patients With Long-term Inflammatory Bowel Disease. Gastroenterology. 2016 Oct 1;151(4):660-669.e4.

4.Attauabi M, Madsen GR, Bendtsen F, Wewer AV, Wilkens R, Ilvemark J, et al. Influence of Genetics, Immunity and the Microbiome on the Prognosis of Inflammatory Bowel Disease (IBD Prognosis Study): The protocol for a Copenhagen IBD Inception Cohort Study. BMJ Open. 2022 Jun 1;12(6).
Role of indole derivatives in neutrophil functions in homeostasis and inflammation
Authors: Danne C
Published: January 2025

Background and aims

Inflammatory Bowel Disease (IBD) are chronic inflammatory conditions of the gastrointestinal tract with increasing prevalence. Current therapies are only partially efficient and associated with potentially severe side effects. New therapeutic strategies with innovative targets are thus urgently needed. Neutrophils are key players of innate immunity in IBD, but their roles in disease development are neglected compared to those of other immune cells. Essential to host defence, their overactivation can cause chronic inflammation and tissue damage. Converging evidence has highlighted interactions between neutrophils, gut inflammation and microbiota. Notably, numerous IBD susceptibility genes are involved in neutrophil functions related to defence against microbes; and IBD is associated with alterations of the intestinal microbiota. However, the influence of microbiota on neutrophil functions, and the consequences in terms of disease development remain largely unknown. Microbiota metabolites, including short-chain fatty acids, bile acids, and tryptophan (Trp)-derived metabolites, have shown regulatory effects on immune cell types, such as T cells and macrophages. However, their impact on neutrophils is underexplored, especially concerning indole derivatives, molecules derived from Trp degradation by the microbiota. Based on preliminary data, our objectives are to (i) explore the influence of two indole derivatives, indole and indoxyl-3-sulfate (I3S), on neutrophil functions in homeostasis, and (ii) decipher the effect of these microbiota metabolites on neutrophils in the context of intestinal inflammation.

Methods

Our project follows systematic approaches and takes advantage of up-to-date technologies (flow cytometry and Seahorse) and access to unique mouse and human samples (blood and intestinal tissue from the Saint-Antoine Hospital).

Anticipated impact

Based on both basic and translational research, it is essential to better understand the roles played by neutrophils in host-microbiota interactions in homeostasis and intestinal inflammation and to identify new therapeutic targets for IBD patients.
Deciphering the role of the intestinal microbiota in mediating the protective effect of Exclusive Enteral Nutrition on patients with Crohn’s disease
Authors: Stallbaum Bertram F , Huber S , Gerasimidis K
Published: January 2025

Background and aims

The intestinal microbiota, influenced by the host's diet, regulates the immune system. Exclusive enteral nutrition (EEN) effectively treats Crohn’s Disease (CD). Though likely involving the microbiome and its metabolites, the mechanism of action remains unclear. We aim to unravel the direct and indirect effects of microbiota from EEN-responsive patients (EENr) on the immune system and, by extension, CD.

Methods

We will generate patient-specific gnotobiotic mice of individuals with CD before and after EEN and assess IBD susceptibility using in vivo models. Supervised and unsupervised approaches will be combined to elucidate mechanism(s) underlying the effect of EEN on the immune system and the intestinal barrier. To identify active metabolites of the microbiota of EENr, we will stimulate intestinal organoids using cell-free filtrates from faecal samples, and single metabolites. We will describe the effect of total and single metabolites generated by the microbiota of EENr on the immune system

Anticipated impact

We propose a collaborative project establishing a long-lasting collaboration between the University of Glasgow, Scotland, and the University Medical Centre Hamburg. We anticipate deciphering the effects of EENr-microbiota and its metabolites. Our results will pave the way for the development of dietary and pharmaceutical approaches that emulate these effects and form a basis for the development of targeted microbiome-modifying treatments for patients with IBD.
Targeting hypoxia-induced signaling via HIF-2 inhibition, a promising treatment strategy for intestinal fibrosis?
Authors: Van Welden S
Published: January 2025

Background and aims

With this project, we aim to evaluate if targeting hypoxia-induced signalling via hypoxia inducible factor (HIF)-2 inhibition impacts experimental intestinal fibrosis and validate our findings in stenotic fibroblasts from CD patients.

Methods

Colonic fibroblasts will be sorted from mice with a fibroblast-specific deletion of the oxygen sensitive enzyme prolyl hydroxylase (PHD2) (i.e. PHD2ff- Col1a2-ERT2:Cre) and their wildtype littermate controls, followed by RNA sequencing and pathway analysis. Validation of key fibrotic mediators will be performed via qPCR or immunostainings. Intestinal fibrosis will be induced in PHD2ff Col1a2-ERT2:Cre mice wildtype littermate controls by chronic administration of dextran sodium sulphate in their drinking water, followed by treatment with the oral HIF-2 inhibitor, belzutifan. Translatability of preclinical findings will be confirmed in bio-banked fibrostenotic fibroblasts from CD patients.

Anticipated impact

Intestinal fibrosis is a debilitating complication of IBD which cannot be fully prevented by current anti-inflammatory therapies, highlighting the unmet clinical need for anti-fibrotic treatment strategies. Our preliminary data demonstrated that genetic deletion of Phd2 in fibroblasts aggravates experimental intestinal fibrosis without affecting inflammation and is most likely mediated via HIF-2. This suggests that signaling induced by this transcriptional modulator plays a crucial role in the fibrotic process. This proposal will identify the molecular mediators driving this fibrosis-promoting effect and validate if HIF-2 targeting could represent a promising novel anti-fibrotic treatment strategy. Data resulting from this project will therefore represent a final preclinical step and provide proof-of-concept data with the perspective to initiate a clinical trial in fibrostenotic IBD with belzutifan (awaiting EMA approval, but recently FDA-approved for advanced renal cell carcinoma).
Klebsiella pneumoniae T6SS impact in IBDs
Authors: Aschtgen M S
Published: January 2025

Background and aims

Our hypothesis is that Klebsiella pneumoniae (Kp) Type VI Secretion System (T6SS), normally used for bacteria competition during host colonization have a collateral impact on the host inflammatory pathway (Fig1). Our specific aims are to: (i) Characterize the impact of bacterial type VI Secretion System (T6SS) on host gut inflammation (ii) Develop a screen to identify T6SS inhibitors.

Methods

In vivo experiments involve infecting mice with Kp wild type (WT) and T6SS mutants to evaluate gut inflammation and immune response. Metagenomic analysis of IBD and CRC patients' microbiota will be conducted to assess T6SS gene enrichment. The molecular mechanism of T6SS activity and LPS release will be explored using various imaging and biochemical techniques. High-throughput screening of small molecule inhibitors targeting T6SS assembly will be performed, followed by validation in cellular models. The role of bacteria in tumorigenesis is increasingly recognized, yet our understanding of the underlying mechanisms remains incomplete, hindering the identification of new therapeutic strategies. It is therefore critical to decipher the bacterial mechanisms and their impact on the host to identify pathways that can be targeted from both sides.

Anticipated impact

Our preliminary data have uncovered a novel role of Type VI Secretion System (T6SS) role in gut inflammation. Building on our extensive expertise of this specific system, we will employ a multidisciplinary approach to inhibit T6SS. Inhibiting the T6SS could prevent both gut inflammation and Enterobacteria competition advantage in the gut, therefore reducing dysbiosis. Moreover, inhibition of bacterial virulence factors is an attractive strategy to complement antibiotic and anti-inflammatory treatments already in use.
Self-care in patients affected with inflammatory bowel disease and Mutuality in nursing: A protocol for a longitudinal study
Authors: Napolitano D , Vellone E , Martella P , Monaci A , Radice S , Schiavoni E , Lusignani M , Cocchieri A , Ciluffo S
Published: January 2025

Background and aims

Inflammatory bowel diseases (IBD) pose a growing global health challenge, with prevalence expected to double in coming years. The chronic nature of IBD, marked by recurrent inflammatory episodes, significantly impacts patients' quality of life and increases healthcare costs. In this context, the IBD nurse plays a crucial role in building a supportive relationship with patients, promoting self-care, and encouraging active health management, ultimately reducing hospitalizations. This study examines self-care behaviours and nurse-patient mutuality among IBD patients in Italy. The aims are: describing levels of self-care, assessing mutuality between patients and nurses, and analysing the impact of these factors on clinical outcomes, quality of life, and resilience.

Methods

This multicentre, longitudinal study will enrol 400 IBD patients across 9 Italian centres. Guided by the Middle-Range Theory of Self-Care of Chronic Illness, which defines self-care as an active process for maintaining health in chronic conditions, data will be collected at baseline (T0), 6 months (T1), and 12 months (T2). Sociodemographic and clinical characteristics, disease severity, self-care practices, and mutuality levels will be gathered using standardized tools. Mutuality, based on the Nurse-Patient Mutuality conceptual framework, will be measured with the Nurse-Patient Mutuality in Chronic Illnesses Scale, assessing the quality of relationship, including shared understanding, collaboration, and emotional support. Clinical indicators include C-reactive protein levels, faecal calprotectin, endoscopic scores, QoL, and resilience.

Anticipated impact

The findings will provide valuable insights into self-care behaviours and nurse-patient mutuality in managing IBD, identifying predictors of effective self-care and the role of mutuality in enhancing clinical outcomes, QoL, and resilience. This project will further advance nursing research, fostering collaboration across centres and promoting a nationwide network of evidence-based, patient-centred care. These outcomes will lay a foundation for future research, strengthening the role of specialized IBD nurses and supporting an integrated, optimized approach to patient management.
Kissing balloon technique as rescue strategy to treat left ventricular outflow tract obstruction after transcatheter mitral valve replacement: a case report
Authors: Çatalkaya Sibel , Erkan Hakan
Published: January 2025

Background

Transcatheter mitral valve replacement (TMVR) has become a viable, minimally invasive treatment for inoperable patients with severe mitral valve disease, particularly among elderly individuals with significant comorbidities. A key complication of TMVR is left ventricular outflow tract (LVOT) obstruction, necessitating various preventive and therapeutic strategies. This report presents a case of severe LVOT obstruction following TMVR and highlights the effective application of the kissing balloon technique as a therapeutic intervention.

Case summary

A 79-year-old female with New York Heart Association Class IV dyspnoea due to severe mitral stenosis and a high operative risk, with a Society of Thoracic Surgeons Risk of Mortality (STS-PROM) score of 6.2%, underwent TMVR. Pre-procedural evaluations indicated significant mitral valve calcification and a mitral valve area of 0.9 cm². After successful TMVR deployment, post-implantation echocardiography revealed an LVOT pressure gradient of 53/85 mmHg, prompting the use of the kissing balloon technique, which reduced the gradient to 28 mmHg. Follow-up assessments showed normal mitral valve function and stable LVOT gradients during short-term follow-up throughout the patient’s hospital stay.

Discussion

Left ventricular outflow tract obstruction is a potentially life-threatening complication of TMVR, often associated with high mortality rates due to haemodynamic impairment. This complication can arise from various anatomical factors and valve positioning issues. Several strategies have been developed to address LVOT obstruction, including the laceration of the anterior mitral leaflet and alcohol septal ablation. The successful implementation of the kissing balloon technique in this case underscores its potential to improve outcomes in LVOT obstruction.
Evaluation of right ventricular pacing-induced coronary microvascular dysfunction using guide wire-based sensor technology: a case report
Authors: Mishina Takashi , Inoue Naoya , Morikawa Shuji
Published: January 2025

Background

The diagnosis of ischaemic non-obstructive coronary artery disease is crucial for the differential diagnosis of chest pain. However, the pathophysiology of chest pain and evaluation of coronary microcirculation in patients with right ventricular pacing (RVP) have not been sufficiently reported.

Case summary

The patient was a 53-year-old woman who underwent dual-chamber pacemaker implantation because of sinus node dysfunction. She experienced chest pain before pacemaker implantation; however, the frequency and severity of her chest pain increased after the implantation. She was referred for the evaluation of coronary microvascular dysfunction (CMD). Coronary angiography revealed no significant stenosis of the epicardial vessels. Subsequent evaluation of CMD showed that while the index of microcirculatory resistance [normalized index of microcirculatory resistance (IMR)] in the left anterior descending artery (LAD) was 19 U during the native rhythm, an increase in IMR (normalized IMR: 27 U) was observed during RVP.

Discussion

Right ventricular pacing may not only induce left ventricular dyssynchrony due to non-physiological excitation propagation but may also provoke CMD in the LAD territory, particularly in the septal branches, which could contribute to pacing-induced structural CMD and chest pain. However, RVP may well be a contributing but not exclusively a factor of CMD.
Thrombotic prosthetic valve dysfunction requiring valve re-replacement after mitral valve replacement for caseous calcification with hypereosinophilic syndrome: a case report
Authors: Miyazawa Keishi , Imai Eriya , Kodaira Ami , Ota Toshiki , Yokozuka Motoi
Published: January 2025

Background

Caseous calcification of the mitral annulus (CCMA) and hypereosinophilic syndrome (HES) are both associated with thrombotic tendencies. Caseous calcification of the mitral annulus may cause mitral valve regurgitation (MR), which may necessitate surgical intervention, depending on its severity. Given the absence of reported cases combining CCMA and HES, the optimal target range for anticoagulation therapy after mitral valve replacement remains to be established.

Case summary

A 64-year-old man with CCMA complicated by HES was admitted due to heart failure and severe MR. The patient underwent mitral valve replacement with a mechanical valve. Despite standard anticoagulation therapy, prosthetic valve dysfunction had developed because of thrombosis. Intraoperative transoesophageal echocardiography revealed a closed stuck valve, necessitating valve re-replacement. A bioprosthetic valve was selected.

Discussion

In cases of CCMA complicated by HES, the target of anticoagulation therapy is unclear. This case demonstrated that more intensive anticoagulation is required because of the thrombogenic risk of CCMA and HES. The mechanism of calcification due to eosinophilia has been suggested, and the relationship between eosinophilia and CCMA remains a subject for future research.
Expanded-access use of elamipretide in a newborn with Barth syndrome: a case report
Authors: Ortmann Laura , Velasco Danita , Cole Jason
Published: January 2025

Background

Barth syndrome (BTHS) is a rare genetic disease, with no approved curative therapies, characterized by abnormally developed cardiolipin, resulting in mitochondrial dysfunction. Cardiomyopathy, a common clinical manifestation of BTHS, often appears in infancy. Elamipretide, an investigational drug that binds to cardiolipin on the inner mitochondrial membrane, leads to improved membrane stability, enhanced adenosine triphosphate production, and reduced reactive oxygen species. This patient case aims to further support elamipretide’s role in treating BTHS infants.

Case summary

We present an infant diagnosed in utero with BTHS who demonstrated a moderately dilated left ventricle (LV) with an LV ejection fraction (LVEF) of 20% at birth. He was transferred to a tertiary children’s hospital where he was intubated and administered medications for haemodynamic support. After several weeks, the patient was extubated and his LVEF improved, although still below normal. On day of life (DOL) 34, therapy with daily IV elamipretide (0.25 mg/kg increased to 0.5 mg/kg on DOL39) began, followed by standard-of-care oral heart failure medications. Subsequent echocardiograms demonstrated improvement of LVEF to near-normal levels. He was weaned off oxygen completely on DOL49 and discharged home on DOL61 on daily subcutaneous elamipretide 0.5 mg/kg and oral heart failure medications. His most recent echocardiogram showed improvement of LVEF to 60%.

Discussion

Our case suggests that elamipretide may have contributed to the improvement of LV function in this BTHS infant, supporting elamipretide’s early use in BTHS. Our findings align with the previous studies in which elamipretide treatment demonstrated normalization of mitochondrial function and improvement in LV function.
Fibroblast growth factor 5: a novel biomarker for familial hypercholesterolaemia
Authors: Baragetti Andrea , Alieva Asiiat S , Grigore Liliana , Pellegatta Fabio , Lupi Andrea , Scrimali Chiara , Cefalù Angelo B , Hutten Barbara A , Wiegman Albert , Knaapen Paul , Bom Michiel J , Nurmohamed Nick S , Reutova Olga , Konradi Alexandra , Shlyakhto Evgeny , Stroes Erik S G , Averna Maurizio , Catapano Alberico L
Published: January 2025

Background and Aims

Identification of individuals affected by familial hypercholesterolaemia (FH) is suboptimal when genetic tests are unavailable. Relying only on low-density lipoprotein cholesterol (LDL-C) is challenging as it may not allow distinguishing individuals with FH from hypercholesterolaemic (HC) individuals from the general population. The aim of this study was to determine whether biomarkers associated with cardiovascular disease and/or inflammation identify FH individuals and distinguish them from HC individuals.

Methods

A panel of 264 proteins in plasma was measured and machine learning was used to search for those that can distinguish FH individuals, either genetically proven (genFH) or clinically diagnosed (clinFH) from HC and control individuals.

Results

Both genFH and clinFH had elevated plasma levels of fibroblast growth factor 5 (FGF-5) compared with controls (mean area under the curve [AUC] > .990 for both, P < .001) or HC individuals (mean AUC >.990, P < .001), even after matching for LDL-C levels. An immunoenzymatic assay confirmed that FGF-5 was elevated in genFH and clinFH in all cohorts analysed.

Conclusions

This analysis suggests that FGF-5 could be a biomarker to discriminate individuals living with FH from HC individuals.
Developmental and conditional regulation of DAF-2/INSR ubiquitination in Caenorhabditis elegans
Authors: Falsztyn Ivan B , Taylor Seth M , Baugh L Ryan
Published: January 2025

Insulin/IGF signaling (IIS) regulates developmental and metabolic plasticity. Conditional regulation of insulin-like peptide expression and secretion promotes different phenotypes in different environments. However, IIS can also be regulated by other, less understood mechanisms. For example, stability of the only known insulin/IGF receptor in Caenorhabditis elegans, DAF-2/INSR, is regulated by CHIP-dependent ubiquitination. Disruption of chn-1/CHIP reduces longevity in C. elegans by increasing DAF-2/INSR abundance and IIS activity in adults. Likewise, mutation of a ubiquitination site causes daf-2(gk390525) to display gain-of-function phenotypes in adults. However, we show that this allele displays loss-of-function phenotypes in larvae and that its effect on IIS activity transitions from negative to positive during development. In contrast, the allele acts like a gain-of-function in larvae cultured at high temperature, inhibiting temperature-dependent dauer formation. Disruption of chn-1/CHIP causes an increase in IIS activity in starved L1 larvae, unlike daf-2(gk390525). CHN-1/CHIP ubiquitinates DAF-2/INSR at multiple sites. These results suggest that the sites that are functionally relevant to negative regulation of IIS vary in larvae and adults, at different temperatures, and in nutrient-dependent fashion, revealing additional layers of IIS regulation.
High-quality phenotypic and genotypic dataset of barley genebank core collection to unlock untapped genetic diversity
Authors: Yuan Zhihui , Rembe Maximilian , Mascher Martin , Stein Nils , Himmelbach Axel , Jayakodi Murukarthick , Börner Andreas , Oldach Klaus , Jahoor Ahmed , Jensen Jens Due , Rudloff Julia , Dohrendorf Viktoria-Elisabeth , Kuhfus Luisa Pauline , Dyrszka Emmanuelle , Conte Matthieu , Hinz Frederik , Trouchaud Salim , Reif Jochen C , El Hanafi Samira
Published: January 2025

Background

Genebanks around the globe serve as valuable repositories of genetic diversity, offering not only access to a broad spectrum of plant material but also critical resources for enhancing crop resilience, advancing scientific research, and supporting global food security. To this end, traditional genebanks are evolving into biodigital resource centers where the integration of phenotypic and genotypic data for accessions can drive more informed decision-making, optimize resource allocation, and unlock new opportunities for plant breeding and research. However, the curation and availability of interoperable phenotypic and genotypic data for genebank accessions is still in its infancy and represents an obstacle to rapid scientific discoveries in this field. Therefore, effectively promoting FAIR (i.e., findable, accessible, interoperable, and reusable) access to these data is vital for maximizing the potential of genebanks and driving progress in agricultural innovation.

Findings

Here we provide whole genome sequencing data of 812 barley (Hordeum vulgare L.) plant genetic resources and 298 European elite materials released between 1949 and 2021, as well as the phenotypic data for 4 disease resistance traits and 3 agronomic traits. The robustness of the investigated traits and the interoperability of genomic and phenotypic data were assessed in the current publication, aiming to make this panel publicly available as a resource for future genetic research in barley.

Conclusions

The data showed broad phenotypic variability and high association mapping potential, offering a key resource for identifying genebank donors with untapped genes to advance barley breeding while safeguarding genetic diversity.
How do community pharmacists perceive practice-based research?
Authors: Kummer Ingrid , Šepetavc Martina , Šolić Ivana , Jurišić Grubešić Renata
Published: January 2025

Objectives

Practice-based research (PBR) is an integral part of community pharmacy practice. The results obtained from PBR allow community pharmacists to gain the knowledge necessary to develop new patient services and acquire strategies to strengthen their role in the health system. The study aimed to assess pharmacists’ attitudes and barriers towards PBR and investigate the factors that prevent or motivate community pharmacists from participating.

Methods

The cross-sectional study was conducted in May to Jun 2023 via an online structured pretested questionnaire. All licensed pharmacists registered in the Registry of Pharmacists of the Croatian Pharmaceutical Chamber, who listed community pharmacy as a place of work participated, i.e. 500 community pharmacists. The questionnaire consisted of two sections. Section A collected the respondents’ sociodemographic characteristics. Section B contained two groups of relevant statements on a 5-point Likert scale divided into two sections: pharmacists’ attitudes towards research in PBRs and barriers to participation in PBRs.

Key findings

The results showed that 97% of community pharmacists considered PBR important for developing new pharmacy services, and almost two-thirds considered participation in research to be part of pharmacy practice. The most often perceived barrier to research participation was the workload of daily tasks necessary for normal pharmacy functioning, recognized by 68% of community pharmacists.

Conclusion

This study revealed community pharmacists’ perception of the importance of PBR for the pharmacy profession. Involvement in PBR was important for the community pharmacists. The motivation for the PBR was present, despite the detected barriers. The results indicate the directions the community pharmacists should inspire.