Although prior studies have reported a link between autoimmunity and carcinogenesis, the roles of genetic factors and potential mediators involved in this process remain elusive. We constructed disease-specific and combined polygenic risk scores (PRSs) for 6 common autoimmune diseases (AIDs) (systemic lupus erythematosus [SLE], rheumatoid arthritis, multiple sclerosis, Crohn's disease, ulcerative colitis [UC], and type 1 diabetes mellitus [T1D]) in the UK Biobank cohort. Compared to those without AID, AID patients at baseline had increased risks of overall cancer, hematological, digestive, and urinary cancer. The combined AID-PRS was significantly associated with increased risks of hematological cancer (HR [95% CI] per SD increase: 1.06 [1.03-1.09]) and non-Hodgkin's lymphoma (HR [95% CI] per SD increase: 1.10 [1.05-1.14]). For individual AID-PRSs, we identified 21 significant associations between 5 PRSs and 11 types of cancer in the overall population, along with 15 additional associations in the sex-stratified analysis. For example, SLE-, UC-, and T1D-PRS showed complex cross-cancer effects on risks of up to 6 cancer types. These associations were generally independent of immunosuppressant drug use. Differential associations of SLE-PRS with prostate cancer risk were found by prostate cancer PRS status ( P interaction <0.05). Several peripheral biomarkers, including red or white blood cell counts, platelet counts, and CRP partly mediated the PRS associations (up to 16.96%). Our study provides important insights into the role of autoimmune diseases in carcinogenesis, which also highlights opportunities for target cancer screening and prevention in potentially vulnerable populations.

Background: Adolescents with inflammatory bowel disease (IBD) are faced with the complexities of acquiring self-management behaviours at a time when they are also navigating developmental challenges associated with adolescence. To date, limited treatment adherence interventions exist to support adolescents with IBD. Aim: To explore the experience and support needs of adolescents with IBD to facilitate optimum treatment adherence. Method: Thirty-three semi-structured interviews were conducted with adolescents with IBD (n = 12), parents of adolescents with IBD (n = 13) and healthcare professionals who support adolescents with IBD (n = 8). Adolescents and parents completed a creative task to prioritise adherence barriers and adherence intervention strategies. Results: The analysis generated three key themes: (1) striving for normality, (2) taking responsibility for IBD management and (3) seeking supportive environments. Living with IBD was often perceived as living a limited life, as adolescents had to manage their symptoms, which resulted in feelings of difference and stigmatisation. To manage their IBD, adolescents were required to develop treatment routines and communicate their health needs. Parents wanted to protect their child from the burden of living with IBD. Synthesis of findings with a creative mapping task generated seven priorities for intervention. Discussion: Adolescents discussed the complexity behind their adherence behaviours and the formation of treatment perceptions. The adherence barriers identified within this research can be utilised to develop a treatment adherence intervention that is effective for adolescents with IBD.

The travelling community in England and Scotland may consist of between 150,000 and 500,000 members. In Scotland ethnicity codings for hospital admissions includes: Gypsies, Roma, Irish travellers and show people. Few Trusts in England break down codings for "Other British" in such detail.

One hundred and thirty-two NHS Trusts were approached in England and 14 NHS Boards in Scotland through a Freedom of Information request to provide details of admission to hospital between 2016 and 2022 with ulcerative colitis and had undergone a panproctocolectomy and those with Crohn's disease and had undergone a hemicolectomy.

Of the 132 NHS Trusts approached in England only 7 were able to provide data on hospital admissions for inflammatory bowel disease from this community; whereas in Scotland 13 of 14 did so. There were 1012 admissions with ulcerative colitis and based on the number of admissions per patient in Somerset NHS Foundation Trust this would represent 138 patients. In contrast, there were 901 admissions with Crohn's disease and at least 9 patients underwent a hemicolectomy.

The inadequacy of data collection related to this community is discussed.

Patients with inflammatory bowel disease (IBD) remain at increased risk for colorectal cancer and death from colorectal cancer compared with the general population despite improvements in inflammation control with advanced therapies, colonoscopic surveillance and reductions in environmental risk factors. This guideline update from 2010 for colorectal surveillance of patients over 16 years with colonic inflammatory bowel disease was developed by stakeholders representing UK physicians, endoscopists, surgeons, specialist nurses and patients with GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodological support.An a priori protocol was published describing the approach to three levels of statement: GRADE recommendations, good practice statements or expert opinion statements. A systematic review of 7599 publications, with appraisal and GRADE analysis of trials and network meta-analysis, where appropriate, was performed. Risk thresholding guided GRADE judgements.We made 73 statements for the delivery of an IBD colorectal surveillance service, including outcome standards for service and endoscopist audit, and the importance of shared decision-making with patients.Core areas include: risk of colorectal cancer, IBD-related post-colonoscopy colorectal cancer; service organisation and supporting patient concordance; starting and stopping surveillance, who should or should not receive surveillance; risk stratification, including web-based multivariate risk calculation of surveillance intervals; colonoscopic modalities, bowel preparation, biomarkers and artificial intelligence aided detection; chemoprevention; the role of non-conventional dysplasia, serrated lesions and non-targeted biopsies; management of dysplasia, both endoscopic and surgical, and the structure and role of the multidisciplinary team in IBD dysplasia management; training in IBD colonoscopic surveillance, sustainability (green endoscopy), cost-effectiveness and patient experience. Sixteen research priorities are suggested.

To understand trends in the risk of all-cause hospitalization for individuals with inflammatory bowel disease, we explored age, period, and cohort effects in Canada.

Repeated cross-sectional survey data from the 2005-2014 Canadian Community Health Survey linked to the Discharge Abstract Database to capture the all-cause hospitalization within 3 years of entry into the study for eligible individuals. Random-effects 2-level models estimated fixed effects for age and random effects for time periods and birth cohorts on the risk of all-cause hospitalization within 3 years entry into the study.

An estimated 197,000 individuals were eligible for study inclusion. From this, an estimated 70,140 all-cause hospitalizations occurred within 3 years postentry into the study. The risk of hospitalization within 3 years increased with age and across birth cohorts, with older cohorts experiencing greater risks of hospitalization. A small temporal effect was identified for both inflammatory bowel disease groups. Within birth cohorts, the risk of hospitalization increased across ages for Crohn's disease, but in individuals with ulcerative colitis, the risk decreased across ages, except for the 2 oldest birth cohorts.

These data support the hypothesis that age effects are primarily responsible for increased risk of hospitalizations. As the prevalence of IBD continues to rise and age distribution of Canadians shifts toward an older-aged population, increasing the allocation of healthcare resources to prevent age-related risks of hospitalizations would be beneficial to reduce hospital burdens.

Paediatric inflammatory bowel disease (IBD) is often complicated by bone loss resulting in an increased risk of fractures and impaired quality of life. Underlying inflammation, nutritional deficiencies and glucocorticoid therapy are some of the factors contributing to secondary osteoporosis in IBD. Optimising nutrition, dietary supplementation and timely screening are essential in preventing bone loss. Bisphosphonate therapy remains the cornerstone of medical management of osteoporosis. This review explores the various mechanisms contributing towards poor bone health in IBD and the recent advances in diagnostic and preventive approaches along with updates in management strategies.

This study aimed to detect the causal effect of ulcerative colitis (UC) on heart failure. A bidirectional two-sample Mendelian randomization (MR) analysis was performed. The causal impact of UC on heart failure was determined via MR by performing a genome-wide association study in which 4 UCs descending from European ancestors were set as individual exposures. The inverse-variance weighted (IVW) method was used as the main method, and 4 other methods were set as assistant parameters. Susbequently, the MR results were combined with meta-analysis results. The MR Egger method was employed to investigate pleiotropy. The leave-one-out method was utilized for sensitivity analysis. Furthermore, a reverse-directional study was conducted. There was evidence of the causal effect of UC on heart failure in MR estimates using 4 UC datasets. The IVW method revealed that the odds ratio (OR) = 1.03, 95% confidence interval (CI) = 1.01-1.06, P = 0.0441 when the first UC dataset was used; OR = 1.03, 95% CI = 1.01-1.05, P = 0.0445 when the second UC dataset was used; OR = 2046, 95% CI = 1.37-3.05E + 06, P = 0.0409 when the third UC dataset was used; and OR = 8.12E + 04, 95% CI = 29.09-2.27E + 08, P = 0.0052 when the fourth UC dataset was used. A meta-analysis of 4 MR studies revealed that UC had a statistically significant causal effect on heart failure (OR = 1.03, 95% CI = 1.01-1.05; P = 0.0074). Reverse MR analysis revealed that heart failure did not have a causal effect on UC. There was no pleiotropy. This MR study demonstrated that UC had a causal effect on heart failure and that there was no reverse causal effect.

The risk of developing colorectal cancer (CRC) is increased in ulcerative colitis patients compared to the general population. This increased risk results from the state of chronic inflammation, a well-known tumour-promoting condition. This review explores the pathologic and molecular characteristics of colitis-associated colon cancer (CAC), emphasizing the distinct features from sporadic CRC. We focus on the key signalling pathways involved in the transition to CAC, highlighting the emerging role of alternative splicing in these processes, namely on how inflammation-induced alternative splicing can significantly contribute to the increased CRC risk observed among UC patients. This review calls for more transcriptomic studies to elucidate the molecular mechanisms through which inflammation-induced alternative splicing drives CAC pathogenesis. A better understanding of these splicing events is crucial as they may reveal novel biomarkers for disease progression and have the potential to target changes in alternative splicing as a therapeutic strategy.

With 20-40% of patients who have inflammatory bowel disease (IBD) not responding to therapy, resource use and costs can be high. We performed a descriptive analysis of health-care data for IBD management in the National Health Service to explore potential areas for improvement.

In this exploratory study, we analysed real-world data from the Discover dataset for adults with a diagnosis of incident IBD recorded in northwest London, UK, between 31 March, 2016, and 31 March, 2020. We compared mean visit numbers and primary and secondary care costs per patient to examine resource use and costs for active disease versus remission.

We included 7,733 patients (5,872 with ulcerative colitis [UC], 1,427 with Crohn's disease [CD], and 434 with codes for both [termed IBD-undefined in this study]). Remission was recorded in 19,218 (82%) of 23,488 observations for UC, 4,686 (82%) of 5,708 for CD, and 1,122 (65%) for IBD-undefined observations. Health-care resource use was significantly higher with active disease in all settings except primary care for UC. Total health-care costs were greater with active disease than remission for all diagnoses (all p < 0.0001). The main driver of costs was inpatient hospital care among those with active disease; elective inpatient costs were high among patients with UC and IBD-undefined in remission.

Higher health-care resource use and costs were observed with active disease, which underscores the importance of early induction and maintenance of remission in UC and CD. Updated strategies that incorporate treat to target may offer cost benefits by the offsetting of biologic drug costs with a reduction in costly inpatient hospital stays.

This trial was not registered as it used pseudonymised retrospective data.

While corticosteroids have led to significant reduction in ASUC mortality over the last few decades, they are associated with significant side effects and up to 30% of patients have steroid refractory ASUC, which means we require safer and better therapies for patients with ASUC. Several salvage therapies have been proposed in guidelines; however, we lack high quality head-to-head randomised controlled trials to assess effectiveness and safety of these agents. Furthermore, the role of newer novel agents in ASUC management is unclear. We aim to present an up to date review and envisage future treatment of ASUC without steroids based on current trials and data. In summary, we conclude that ASUC treatment still heavily relies on corticosteroids despite the side effect profile. While infliximab and cyclosporine have extensive data, there are no prospective studies comparing them with corticosteroids as initial therapy. Novel therapies open up the possibility of oral options but require prospective data before any conclusion can be made.

Pediatric inflammatory bowel disease (pIBD) incidence has increased over the last 25 years. We aim to report contemporaneous trends across the South West United Kingdom.

Data were provided from centers covering the South West United Kingdom (Bristol, Oxford, Cardiff, Exeter, and Southampton), with a total area at-risk population (<18 years of age) of 2 947 534. Cases were retrieved from 2013 to 2022. Incident rates were reported per 100 000 at-risk population, with temporal trends analyzed through correlation. Subgroup analysis was undertaken for age groups (0-6, 6-11, and 12-17 years of age), sex, and disease subtype. Choropleth maps were created for local districts.

In total, 2497 pIBD cases were diagnosed between 2013 and 2022, with a mean age of 12.6 years (38.7% female). Diagnosis numbers increased from 187 to 376, with corresponding incidence rates of 6.0 per 100 000 population per year (2013) to 12.4 per 100 000 population per year (2022) (b = 0.918, P < .01). Female rates increased from 5.1 per 100 000 population per year in 2013 to 11.0 per 100 000 population per year in 2022 (b = 0.865, P = .01). Male rates increased from 5.7 per 100 000 population per year to 14.4 per 100 000 population per year (b = 0.832, P = .03). Crohn's disease incidence increased from 3.1 per 100 000 population per year to 6.3 per 100 000 population per year (b = 0.897, P < .01). Ulcerative colitis increased from 2.3 per 100 000 population per year to 4.3 per 100 000 population per year (b = 0.813, P = .04). Inflammatory bowel disease unclassified also increased, from 0.6 per 100 000 population per year to 1.8 per 100 000 population per year (b = 0.851, P = .02). Statistically significant increases were seen in those ≥12 to 17 years of age, from 11.2 per 100 000 population per year to 24.6 per 100 000 population per year (b = 0.912, P < .01), and the 7- to 11-year-old age group, with incidence rising from 4.4 per 100 000 population per year to 7.6 per 100 000 population per year (b = 0.878, P = .01). There was no statistically significant increase in very early onset inflammatory bowel disease (≤6 years of age) (b = 0.417, P = .231).

We demonstrate significant increases in pIBD incidence across a large geographical area including multiple referral centers. Increasing incidence has implications for service provision for services managing pIBD.

Treatment of ulcerative colitis (UC) aims to reduce symptoms and complications by decreasing intestinal inflammation. A proportion of patients do not respond to, do not tolerate, or are inappropriate candidates for current therapies. Interleukin (IL)-23 is a therapeutic target and mirikizumabis the first p19-targeted IL-23 antibody approved for the treatment of moderately to severely active UC.

This review summarizes the pro-inflammatory effects of IL-23 and outlines the pharmacokinetics of mirikizumab. It provides a synopsis of the available phase II and phase III evidence for the efficacy and safety of mirikizumab in UC.

The mirikizumab clinical development program demonstrated its superiority over placebo and its favorable safety profile in the treatment of UC. Its positioning in therapeutic algorithms remains to be fully understood but mirikizumab has proven efficacy in both advanced therapy (AT)-naïve and AT-experienced patients. The inclusion in the license of extended induction for non-responders as well as rescue intravenous dosing allows for flexibility in patient with limited primary response and secondary loss of response.

Huge advances in the medical treatment of ileocaecal Crohn's disease have occurred in the last 20 years. Consequently, surgery has become synonymous with treatment failure and is often only implemented when multiple medical interventions have been trialled. However, evidence that patients avoid surgery in the long term is questionable. When surgery occurs, the disease progresses. Surgery is more complex and outcomes such as complications and stoma formation are more common. Many studies suggest that, in terms of longer-term quality of life, earlier surgery may be superior. Specific clinical scenarios exist where this benefit is more obvious (fibrostenotic or fistulating disease) but even with disease limited to the lumen, benefits can be realised. Significant barriers exist to this mindset of earlier surgery. Such barriers can only be overcome with a vigorous multidisciplinary approach. This editorial describes the debate surrounding the concept of early bowel resection in these patients.

Despite distinct sex- and gender-related differences in the presentation and manifestation of Crohn's disease (CD), little research to date has considered men's particular experiences. Whilst hegemonic masculine ideals have been reported to negatively impact men's mental and physical health, increasingly research has emphasized that men engage in a diverse range of practices, including those beneficial to health. One such practice is posting about their illness experiences on social media. The interactive nature of posting online means that a dialogical approach, based on a relational epistemology, is particularly useful. This study therefore asked: "How do men who post publicly on social media author themselves and their experiences of CD?" Three participants were recruited, all of whom had a diagnosis of CD, wrote a blog, and posted on other social networking sites (SNSs) about CD. Two resided in Canada and one in the United Kingdom. All were white. For each participant, 2 years of multimodal social media data was downloaded. After screening, in-depth analysis was conducted using a dialogical approach focusing on three key dialogical concepts: genre, chronotope, and forms of authorship. The key findings emphasized the participants' different responses to the lack of predictability caused by CD and the different ways they used social media to gain a greater sense of control over their illness stories and identities, providing important insights into the interaction between masculine identities and illness. Finally, the potential deployment of such methods in future research and within therapeutic contexts was considered.

Treatment non-adherence is common in young people with inflammatory bowel disease (IBD), yet support is lacking. A self-led self-management intervention supporting teens with IBD (ASSIST-IBD) is a new theory-based digital treatment adherence intervention, co-developed by young people living with IBD. ASSIST-IBD includes 10 short modules supporting adolescents to feel confident to follow their treatment plan, develop skills to overcome adherence obstacles, feel confident when talking to others about IBD and feel positive about the future. This research aims to determine the feasibility of implementing and measuring the effectiveness of ASSIST-IBD, using a single-arm mixed-methods feasibility trial.

24 young people (aged 13-17) with IBD identified as being ≤80% adherent, and their parents, will use ASSIST-IBD for 6-12 weeks. For the primary endpoint of progression to randomised controlled trial, qualitative and quantitative data will be collected on; number of eligible members of the target population; number of recruited participants; reasons for non-participation and ineligibility; retention and follow-up rates; reasons for early withdrawal; completeness and utility of outcome measures; as well as further data on intervention acceptability, user experiences and user engagement. Secondary outcomes of preliminary effectiveness will include pre-intervention and post-intervention measures of treatment adherence (MARS-5), quality-of-life (IMPACT-III) and well-being (WEMWBS), and self-reported behaviour change success. Quantitative data will be analysed using descriptive statistics; qualitative data will be analysed thematically. An active patient and public involvement and engagement group will advise on the research throughout, including the development of the protocol.

The study has been granted ethical approval by Aston University's Health and Life Sciences Research Ethics Committee (ref:#HLS2112) and NHS Research Ethics Committee, Nottingham 1 Board (IRAS:#344918). Findings will be disseminated via peer-reviewed publications and lay summaries.

This protocol is registered on the Open Science Framework (https://doi.org/10.17605/OSF.IO/KC649).

Estimated to affect 3 million individuals in Europe alone, Crohn's disease is an inflammatory bowel disease causing transmural inflammation throughout the gastrointestinal tract. We describe the case of a patient with a known background of Crohn's disease who presented with abdominal pain following blunt abdominal trauma after a hit and run where initial diagnosis of perforation was missed on pan-computed tomography, however, diagnosis was made early due to high clinical suspicion of perforation. This suggests that current diagnostic imaging can be inaccurate, leading to delays where urgent surgery is otherwise indicated which is a cause for concern. Herein, we emphasize the importance of a high index of suspicion for perforation in patients with blunt abdominal trauma, especially where there is underlying bowel disease.

Ulcerative colitis (UC) is associated with changed dietary habits and mainly linked with the gut microbiota dysbiosis, necroptosis of epithelial cells, and mucosal ulcerations. Liver dysfunction and abnormal level of liver metabolism indices were identified in UC patients, suggesting a close interaction between gut and liver disorders. Methionine-choline deficient diet (MCD) has been shown to induce persistent alterations of gut microbiota and metabolome during hepatitis. In this study we further explored the disease phenotypes in UC patients and investigated whether MCD functioned as a trigger for UC susceptibility. After assessing 88 serum specimens from UC patients, we found significant liver dysfunction and dyslipidemia including abnormal ALT, AST, TG, TC, LDL-c and HDL-c. Liver dysfunction and dyslipidemia were confirmed in DSS-induced colitis mice. We fed mice with MCD for 14 days to cause mild liver damage, and then treated with DSS for 7 days. We found that MCD intake significantly exacerbated the pathogenesis of mucosal inflammation in DSS-induced acute, progressive, and chronic colitis, referring to promotion of mucosal ulcers, colon shortening, diarrhea, inflammatory immune cell infiltration, cytokines release, and abnormal activation of inflammatory macrophages in colon and liver specimens. Intraperitoneal injection of clodronate liposomes to globally delete macrophages dramatically compromised the pathogenesis of MCD-triggering colitis. In addition, MCD intake markedly changed the production pattern of short-chain fatty acids (SCFAs) in murine stools, colons, and livers. We demonstrated that MCD-induced colitis pathogenesis largely depended on the gut microbes and the disease phenotypes could be transmissible through fecal microbiota transplantation (FMT). In conclusion, this study supports the concept that intake of MCD predisposes to experimental colitis and enhances its pathogenesis via modulating gut microbes and macrophages in mice.

Biologics have been widely used as injectables in the treatment of inflammatory bowel disease (IBD). Different local treatment attempts have been developed in recent years. However, maintaining systemic levels of biologics is still crucial for achieving colitis remission. An equilibrium between systemic and local concentrations of biologics is therefore essential for treatment of colitis. Current formulations struggle to create optimal balance between drug concentrations in plasma and the colonic wall. Addressing this challenge, we developed a rectally delivered in situ foam that generates CO2via a reaction between potassium bicarbonate (PB) and citric acid (CA) without the aid of an external device. An anti-TNF-α antibody fragment (Fab) was loaded into the foam formulation, which promoted prolonged colon retention and improved Fab distribution up to proximal colon following rectal administration to mice. In addition, we observed increased plasma Fab concentrations in mice receiving the rectal Fab foam compared to a Fab solution. In a non-everted rat gut ex vivo model, a single exposure to the CO2-containing foam improved macromolecule transepithelial flux across colonic tissue by over ten-fold. Foam efficacy for Fab was investigated in a range of colitis mouse models, from acute to chronic. This non-invasive formulation platform demonstrates potential to overcome existing limitations in delivering biologics to inflamed colonic tissue.

The incidence and prevalence of inflammatory bowel diseases (IBD) are increasing around the world, especially in Western countries. The objective of this study was to evaluate the health habits of healthy controls and individuals with IBDs to identify possible risk factors for IBD development.

A case-control study was conducted among Spanish participants over 18 years of age. A self-administered questionnaire was completed by subjects to collect information on several sociodemographic variables and habits, such as the consumption of tobacco, alcohol, antibiotics, nonsteroidal anti-inflammatory agents and macronutrients; anxiety and depression; and quality of life.

The main risk factors identified were age; living in an urban environment; anxiety; and excessive consumption of proteins, carbohydrates and fats. In addition, the consumption of fibre had a preventive effect against IBD development.

Age, anxiety and living in urban areas pose a risk of suffering from IBD, as does the excessive consumption of certain macronutrients. However, the consumption of fibre has a protective effect on the development of some IBD types.

This study aimed to investigate the trends in diseases of the digestive system hospital admissions (DDSHA) in England and Wales between (1999-2019). Secondary objectives were to investigate the type of admission and medication prescribing related to the digestive system in England. This is an ecological study using data from the Hospital Episode Statistics (HES) database and the Patient Episode Database between April 1999 and March 2019. The rate of hospital admissions with 95% confidence intervals (CIs) was calculated by dividing the number of DDSHA by the mid-year population. The trend in hospital admissions was assessed using a Poisson model. Overall, the rate of DDSHA rose by 84.2% (from 2231.27 [95% CI 2227.26-2235.28] in 1999 to 4109.33 [95% CI 4104.29-4114.38] in 2019 per 100,000 persons, trend test, P < .001). The most remarkable rise in hospital admission was seen in liver diseases, followed by other diseases of intestines with 1.85-fold, and 1.59-fold, respectively. Between 2004 and 2019, the overall prescribing rate for medications related to the gastrointestinal system increased by 74.6%, and stoma care related medications prescribing rate increased by 2.25-fold, followed by drugs affecting intestinal secretions and antisecretory drugs and mucosal protectants. There was an increase in hospital admission rate due to GI diseases in the United Kingdom (UK) by 84.2% from 1999 to 2019. The most remarkable rise in the rate of hospital admissions was seen in diseases of the liver and intestine.

Ulcerative colitis (UC) and Crohn's disease (CD) are two types of idiopathic inflammatory bowel disease (IBD) that are increasing in frequency and incidence worldwide, particularly in highly industrialized countries. Conventional tablets struggle to effectively deliver anti-inflammatory drugs since the inflammation is localized in different areas of the colon in each patient. The goal of 3D printing technology in pharmaceutics is to create personalized drug delivery systems (DDS) that are tailored to each individual's specific needs. This review provides an overview of existing 3D printing processes, with a focus on extrusion-based technologies, which have received the most attention. Personalized pharmaceutical products offer numerous benefits to patients worldwide, and 3D printing technology is becoming more affordable every day. Custom manufacturing of 3D printed tablets provides innovative ideas for developing a tailored colon DDS. In the future, 3D printing could be used to manufacture personalized tablets for UC patients based on the location of inflammation in the colon, resulting in improved therapeutic outcomes and a better quality of life.

Women's health encompasses life-course healthcare, and mounting evidence emphasizes the pivotal contribution of gut microbiota. Therefore, understanding the temporal dynamics of gut microbiota and how age influences disease-gut microbiota associations is essential for improving women's health. By analyzing metagenomic data from 3625 healthy women, we revealed significant effects of age on gut microbiota and age-dependent patterns in microbial features, such as relative abundance, Shannon index, and microbial network properties. Additionally, declining trends in the predictive accuracy of gut microbiota for age groups were shown using iterative sub-sampling based random forest (ISSRF) model. Age-specific species markers were also identified, many of which were shared across age groups. To investigate the influence of age on disease-gut microbiota associations, metagenomic data from 681 women with various disease conditions and 491 matched healthy controls were collected. A substantial proportion of species markers for inflammatory bowel disease (IBD), type 2 diabetes (T2D), atherosclerotic cardiovascular disease (ACVD), and impaired glucose tolerance (IGT) differed in relative abundance across age groups, and were also age-specific species markers. Besides, the microbiota-based probabilities of IBD and ACVD were positively correlated with age. Furthermore, the age specificity of disease-gut microbiota associations was explored using the ISSRF model. Associations between IBD and gut microbiota were age-specific, with reduced stability of disease species markers in childhood and adolescence, possibly due to decrease in the effect size between patients and controls. Our findings provided valuable insights into promoting healthy aging and developing personalized healthcare strategies for women.

Maintenance treatment with 5-aminosalicylic acid (5-ASA) is recommended in ulcerative colitis (UC), but accurate estimates of discontinuation and adherence in adolescents transitioning to young adulthood are lacking.

To determine rates and risk factors for discontinuation and adherence to oral 5-ASA in adolescents and young adults 1 year following diagnosis of UC.

Observational cohort study using the UK Clinical Practice Research Datalink among adolescents and young adults (aged 10-24 years) diagnosed with UC between 1 January 1998 and 1 May 2016.

Time to oral 5-ASA discontinuation (days) and adherence rates (proportion of days covered) were calculated during the first year of treatment using Kaplan-Meier survival analysis. Cox regression models were built to estimate the impact of sociodemographic and health-related risk factors.

Among 607 adolescents and young adults starting oral 5-ASA maintenance treatment, one-quarter (n = 152) discontinued within 1 month and two- thirds (n = 419) within 1 year. Discontinuation was higher among those aged 18-24 years (74%) than younger age groups (61% and 56% in those aged 10-14 and 15-17 years, respectively). Adherence was lower among young adults than adolescents (69% in those aged 18-24 years versus 80% in those aged 10-14 years). Residents in deprived versus affluent postcodes were more likely to discontinue treatment (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] = 1.10 to 1.92). Early corticosteroid use for an acute flare lowered the likelihood of oral 5-ASA discontinuation (aHR 0.68, 95% CI = 0.51 to 0.90).

The first year of starting long-term therapies in adolescents and young adults diagnosed with UC is a critical window for active follow-up of maintenance treatment, particularly in those aged 18-24 years and those living in deprived postcodes.

Data on the association between atopic dermatitis (AD) and inflammatory bowel disease (IBD) are inconsistent. Few studies have examined the association of AD or AD severity with risk of ulcerative colitis (UC) and Crohn disease (CD) separately.

To examine the risk of new-onset IBD, UC, and CD in children and adults with AD.

This population-based cohort study assessed patients with AD matched with up to 5 controls on age, practice, and index date. Treatment exposure was used as a proxy for AD severity. Data were retrieved from The Health Improvement Network, a UK electronic medical record database, for January 1, 1994, to February 28, 2015. Data analysis was performed from January 8, 2020, to June 30, 2023.

Outcomes of interest were incident IBD, UC, and CD. Logistic regression was used to examine the risk for each outcome in children and adults with AD compared with controls.

A total of 1 809 029 pediatric controls were matched to 409 431 children with AD (93.2% mild, 5.5% moderate, and 1.3% severe). The pediatric cohort ranged in median age from 4 to 5 years (overall range, 1-10 years), was predominantly male (936 750 [51.8%] controls, 196 996 [51.6%] with mild AD, 11 379 [50.7%] with moderate AD, and 2985 [56.1%] with severe AD), and with similar socioeconomic status. A total of 2 678 888 adult controls were matched to 625 083 adults with AD (65.7% mild, 31.4% moderate, and 2.9% severe). The adult cohort ranged in median age from 45 to 50 years (overall range, 30-68 years) and was predominantly female (1 445 589 [54.0%] controls, 256 071 [62.3%] with mild AD, 109 404 [55.8%] with moderate AD, and 10 736 [59.3%] with severe AD). In fully adjusted models, children with AD had a 44% increased risk of IBD (hazard ratio [HR], 1.44; 95% CI, 1.31-1.58) and a 74% increased risk of CD (HR, 1.74; 95% CI, 1.54-1.97), which increased with worsening AD; however, they did not have increased risk of UC (HR, 1.09; 95% CI, 0.94-1.27) except for those with severe AD (HR, 1.65; 95% CI, 1.02-2.67). Adults with AD had a 34% (HR, 1.34; 95% CI, 1.27-1.40) increased risk of IBD, a 36% (HR, 1.36; 95% CI, 1.26-1.47) increased risk of CB, and a 32% (HR, 1.32; 95% CI, 1.24-1.41) increased risk of UC, with risk increasing with worsening AD.

In this cohort study, children and adults with AD had an increased risk of IBD, with risk varying by age, AD severity, and IBD subtype. These findings provide new insights into the association between AD and IBD. Clinicians should be aware of these risks, particularly when selecting systemic treatments for AD in patients who may have coincident gastrointestinal symptoms.

Background: Reconstruction techniques after subtotal colectomy (STC) and end ileostomy for ulcerative colitis (UC), include ileal pouch-anal anastomosis (IPAA), ileorectal anastomosis (IRA) and continent ileostomy. Aim: To assess surgical strategies and outcomes after subtotal colectomy for UC by calculating the proportions of patients who had further surgery 10 years post-STC and those who did not undergo surgery but who were under surveillance, and histological analysis of pathology specimens from STC and proctectomy. Methods: Patients who had STC for UC from 2002 to 2018 were identified. Variables of interest were extracted from electronic records. Survival analysis on reconstruction surgery was performed using Kaplan-Meier curves. Curves were censored for loss from follow-up and death. Subtotal colectomy and proctectomy specimens were assessed by a pathologist for acute inflammation at the distal resection margin and within the resected bowel, and for dysplasia or cancer. Results: One hundred and ninety-two patients were included. Eighty-nine (46.3%) underwent proctectomy: eight had panproctocolectomy; thirty had completion proctectomy and the remaining fifty-one of the eighty-nine patients (27%) had IPAA. One patient who did not undergo a proctectomy had an ileorectal anastomosis. Sixty-one (69%) proctectomy specimens had active inflammation, with 29 (48%) including the resection margins. Of the 103 patients who did not have completion surgery, 72 (69%) were under surveillance as of August 2021. No patients in this non-operative group had developed cancer of the residual rectum at follow up. Conclusions: At 10 years after STC for UC, eighty-nine (46.4%) patients had proctectomy, of which fifty-two had IPAA (27%). However, no inflammation was found in the proctectomy specimen in one third of these patients. Therefore, it is possible that IRA may still have a role in the occasional patient with UC.

An emerging but less explored shared pathophysiology across microbiota-gut-brain axis disorders is aberrant miRNA expression, which may represent novel therapeutic targets. miRNAs are small, endogenous non-coding RNAs that are important transcriptional repressors of gene expression. Most importantly, they regulate the integrity of the intestinal epithelial and blood-brain barriers and serve as an important communication channel between the gut microbiome and the host. A well-defined understanding of the mode of action, therapeutic strategies and delivery mechanisms of miRNAs is pivotal in translating the clinical applications of miRNA-based therapeutics. Accumulating evidence links disorders of the microbiota-gut-brain axis with a compromised gut-blood-brain-barrier, causing gut contents such as immune cells and microbiota to enter the bloodstream leading to low-grade systemic inflammation. This has the potential to affect all organs, including the brain, causing central inflammation and the development of neurodegenerative and neuropsychiatric diseases. In this review, we have examined in detail miRNA biogenesis, strategies for therapeutic application, delivery mechanisms, as well as their pathophysiology and clinical applications in inflammatory gut-brain disorders. The research data in this review was drawn from the following databases: PubMed, Google Scholar, and Clinicaltrials.gov. With increasing evidence of the pathophysiological importance for miRNAs in microbiota-gut-brain axis disorders, therapeutic targeting of cross-regulated miRNAs in these disorders displays potentially transformative and translational potential. Further preclinical research and human clinical trials are required to further advance this area of research.

Data on the optimum positioning of biologics in the treatment of inflammatory bowel disease (IBD) are limited.

This was a longitudinal retrospective study of linked health-care data from northwest London, UK, for adults who started ustekinumab for IBD from 1 April 20161 April 2016 to 1 April 20211 April 2021. We compared outcomes by line of therapy (1 vs. 2 or 3+) and age group (18‒59 years or ≥ 60 years). In an analysis of CD patients, we calculated risks of IBD-related hospitalization, IBD-related abdominal surgery, ustekinumab persistence, and switching by line of therapy.

Of 163 patients screened, 149 were eligible. Age had no effect on outcomes. Elective all-cause hospital admissions were significantly higher when ustekinumab was used as second-line or third-line therapy compared with first-line treatment (p = 0.0048 and p = 0.001, respectively). In CD patients the numbers of hospital admissions were also higher with second-line or third-line therapy (p = 0.040 and p = 0.018, respectively). Use of ustekinumab as third-line therapy significantly increased the risk of IBD-related hospitalization (hazard ratio 2.5, 95% CI 1.1‒5.6, p = 0.029), IBD-related abdominal surgery (9.45, 1.2‒75.7, p = 0.03), and switching (14.6, 1.6‒131.0, p = 0.02). Drug persistence risks did not differ.

These findings support the use of ustekinumab as first-line therapy.

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by mucosal inflammation. Endocan, a proteoglycan secreted by endothelial cells in response to inflammatory cytokines, has been reported to be overexpressed in inflammatory conditions. In this study, we aimed to evaluate the utility of endocan level in determining the extent and severity of disease in patients with ulcerative colitis and to determine whether it can be a candidate marker for noninvasive evaluation and monitoring since there is not enough data in the literature.

Sixty-five people were included in the study, including thirty-five with ulcerative colitis and thirty in the control group. Patients with first diagnosed ulcerative colitis clinically, endoscopically, and histopathologically, without any treatment, and with normal liver and kidney tests were included in the study. Endoscopic scoring of all patients was performed according to the Mayo endoscopic scoring (MES) system. Blood samples for CRP (C-reactive protein) and endocan were taken from the patients simultaneously.

There was a significant statistical difference between all patients with ulcerative colitis and the control group in both endocan level and CRP level (p < 0.001). There was a statistically significant difference between endocan levels and CRP levels between the left-distal group and pancolitis (diffuse colitis) patients, but there was no statistical difference between age and MES.

Serum endocan level can be useful in determining the extent of ulcerative colitis and planning treatment.

While the incidence of inflammatory bowel disease (IBD) is rising globally, it has been suggested to stabilize in westernized countries, but this has not yet been shown in exhaustive and large cohorts. We generated an IBD cohort in North Denmark (NorDIBD) of 6,158 patients with IBD diagnosed from 1978 to 2020, based on all recorded and verified IBD diagnoses in the region. While describing the establishment of this cohort, we aimed to present the accurate incidence and prevalence of IBD over 4 decades.

The NorDIBD cohort covered all pediatric and adult patients with an IBD diagnosis dated between January 1, 1978, and December 31, 2020, and living in North Denmark, hence forming an unselected population-based patient cohort. IBD incidence rates between 1978 and 2020 and IBD point prevalences between 2003 and 2020 were calculated.

We observed a 4-fold increase in the incidence of IBD from 11.5 per 100,000 persons (95% confidence interval [CI] 8.4-14.6) in the year 1978 to 51.3/100,000 (95% CI 45.5-57.1) in the year 2014, whereas in 2020, this rate stabilized. The overall prevalence of IBD more than doubled from 2003 to 2020, from 424 (95% CI 407-443) in 2003 to 872 (95% CI 849-896) IBD cases per 100,000 persons in 2020.

Our population-based NorDIBD cohort suggests stabilizing of the incidence of IBD in Denmark, whereas the prevalence continues to rise. Because the data represent a 10% sample of the entire Danish IBD population, we believe that data can be extrapolated to the IBD population in general and used for healthcare planning.

Grifola frondosa is an edible medicinal mushroom that has been proven to have a variety of health benefits. The main active ingredients of this mushroom are polysaccharides. In this study, ultrasonic-assisted extraction was used to obtain crude Grifola frondosa polysaccharides (GFPs). Then, purified GFP was obtained after purification. The optimum extraction conditions were an extraction time of 71 min, an extraction temperature of 90°C in a solid-to-liquid ratio of 1:37 g/mL, and an ultrasonic power of 500 W. GFP was purified using DEAE-52 and Sephadex G-100. The structural characterization of GFP was performed using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), ion chromatography (IC), and ultraviolet (UV) visible photometry. The morphology of GFP was analyzed by scanning electron microscopy (SEM), thermogravimetric differential scanning calorimetry (TG-DSC), and Congo red testing. In addition, the administration of GFP in oxazolone (OXZ)-induced ulcerative colitis (UC) in mice was found to prevent weight loss. Different doses of GFP (80, 160, and 320 mg/kg body weight) were used, and sulfapyridine (SASP) was used as a positive control (370 mg/kg body weight) for the treatment of OXZ-induced UC. After treatment, the mice were killed, and blood and colon tissue samples were collected. GFP was found to prevent decreases in colon length and the levels of leukocytes, platelets, and neutrophils in UC mice. Moreover, GFP also decreased the expression of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1 β], increased IL-10, and reduced colon injury in UC mice. The results showed that Under these conditions, the predicted polysaccharide yield was 21.72%, and the actual extraction rate was 21.13%. The polysaccharide composition (molar ratio) was composed of fucose (0.025), glucosamine hydrochloride (0.004), galactose (0.063), glucose (0.869), and mannose (0.038). GFP was also found to have a typical absorption peak, and the GFP extracted using the ultrasound-assisted extraction protocol was mainly β-glucan. These results indicate that ultrasound-assisted extraction of GFP could reduce OXZ-induced intestinal inflammation as a promising candidate for the treatment of UC, with the potential for development as a food supplement to improve intestinal diseases.

Population-based studies of inflammatory bowel disease (IBD) in Cardiff have recorded data back to 1930 for Crohn's disease (CD) and 1968 for ulcerative colitis (UC). This study compares incidence and phenotype for 2005-2016 with past data.

All new IBD cases resident in the Cardiff at diagnosis were collected retrospectively for the 12-year period 2005-2016, and compared with previous Cardiff data for trends in incidence and phenotype. Overall incidence was age/sex corrected to the UK population.

There were 991 new patients: 34% had CD, 5.4% IBD unclassified (IBD-U) and 60.5% had UC. The corrected incidence of CD was 7.7 per 100,000 person years [95% CI 6.9-8.6]. CD incidence is significantly higher than previous Cardiff studies, but the annual percentage change (APC) for 1980-2016 of 0.06; [95%CI -0.02 to 0.14] is not significant, with a previous higher APC for 1953-1980 of 0.18, [95%CI 0.13 to 0.23]. Uncorrected IBD-U incidence was 1.3 per 100,000 person years [95% CI 1.0-1.7]. UC corrected incidence was 14.4 per 100,000 person years [95% CI 13.3-15.6]. Incidence of UC is greater than in previous studies but did not increase during the current 12-year period. CD distribution at diagnosis continues to change as in previous Cardiff studies, with further increase in colonic disease and ileocolonic, (42% L2, 28% L3) and reduction in isolated terminal ileal disease (29% L1).

Incidence of both CD and UC are no longer rising significantly, but the location of CD at diagnosis continues to change with an increase in colonic location.Key messagesWhat is already known? It is unclear whether the incidence of IBD has now plateaued in urbanised nations. Changes in Crohn's disease location are often not reported in incidence studies and terminal ileal disease has usually been reported as the commonest site of diseaseWhat is new here? The incidence of UC and Crohn's is no longer rising in Cardiff UK, but the phenotype has changed progressively over time with a continuing increase in colonic disease location and decrease in isolated terminal ileal diseaseHow can this study help patient care? Understanding that Crohn's colitis is the predominant location has implications for diagnostic tests and implications for treatment optionsIMPACT STATEMENTThis work shows that although IBD incidence is no longer rising, the pattern of Crohn's disease is changing with more colonic disease and less isolated terminal ileal disease.PRACTITIONER RELEVANCE STATEMENTThe changing pattern of Crohn's disease location has implications for diagnostic assessment and treatment of this disease.

Healthcare systems face rising demand and unsustainable cost pressures. In response, health policymakers are adopting Value-Based Health Care (VBHC), targeting available resources to achieve the best possible patient outcomes at the lowest possible cost and actively disinvesting in care of low-value. This requires the evaluation of longitudinal clinical and patient reported outcome measures (PROMs) at an individual-level and population-scale, which can create significant data challenges. Achieving this through routinely collected electronic health record (EHR) data-linkage could facilitate the implementation of VBHC without an unacceptable data burden on patients or health systems and release time for higher-value activities.

Our study tested the ability to report an international, patient-centred outcome dataset (ICHOM-IBD) using only anonymised individual-level population-scale linked electronic health record (EHR) data sources, including clinical and patient-reported outcomes, in a cohort of patients with moderate-to-severe ulcerative colitis (UC), receiving biopharmaceutical therapies ("biologics") in a single, publicly funded, healthcare system.

We identified a cohort of 17,632 patients with UC in Wales and a cohort from two Health Boards of 447 patients with UC receiving biologics. 112 of these patients had completed 866 condition-specific PROMs during their biologics treatment. 44 out of 59 (74.6%) items in the ICHOM-IBD could be derived from routinely collected data of which a primary care source was essential for eight items and desirable for 21.

We demonstrated that it is possible to report most but not all the ICHOM-IBD outcomes using routinely collected data from multiple sources without additional system burden, potentially supporting Value-Based Health Care implementation with population data science. As digital collection of PROMs and use of condition-specific registries grow, greater utility of this approach can be anticipated. We have identified that the availability of longitudinal primary and secondary care data linked with PROMs is essential for this to be possible.

Hemophagocytic lymphohistiocytosis (HLH) is rare, results in high mortality, and is increasingly being diagnosed. We aimed to quantify the incidence of diagnosed HLH and examine temporal trends in relation to age and associated diseases. Using national linked electronic health data from hospital admissions and death certification cases of HLH that were diagnosed in England between January 1, 2003, and December 31, 2018. We calculated incidence rates of diagnosed HLH per million population by calendar year, age group, sex, and associated comorbidity (hematological malignancy, inflammatory rheumatological or bowel diseases [IBD]). We modeled trends in incidence and the interactions between calendar year, age, and associated comorbidity using Poisson regression. There were 1674 people with HLH diagnosed in England between 2003 and 2018. The incidence rate quadrupled (incidence rate ratio [IRR] 2018 compared to 2003: 3.88, 95% confidence interval [CI] 2.91 to 5.28), increasing 11% annually (adjusted IRR 1.11, 95% CI 1.09 to 1.12). There was a transition across age groups with greater increases in those aged 5-14 years of HLH associated with rheumatological disease/IBD compared with hematological malignancy, with similar increases in HLH associated with both comorbidities for those 15-54, and greater increases in HLH associated with hematological malignancies for those 55 years and older. The incidence of HLH in England has quadrupled between 2003 and 2018. Substantial variation in the incidence occurred with inflammatory rheumatological diseases/IBD-associated HLH increasing more among the younger age groups, whereas in older age groups, the largest increase was seen with hematological malignancy-associated HLH.

Background: The cardioprotective diet was reported to be associated with several chronic cardiometabolic diseases through an anti-inflammation effect. However, the association between the cardioprotective diet and the risk of inflammatory bowel disease (IBD) was unclear and deserved to be further explored. Methods: We calculated the cardioprotective diet score based on the consumptions of seven common food groups using the validated food frequency questionnaire data in the UK Biobank. Incident IBD was ascertained from primary care data, inpatient data, and the death registry. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between the cardioprotective diet score and the risk of IBD. Results: During a mean follow-up of 12.1 years, we documented 2717 incident IBD cases, including 851 cases of Crohn’s disease and 1866 cases of ulcerative colitis. Compared to participants with a cardioprotective diet score of 0−1, we observed a decreased risk of IBD among participants with cardioprotective diet scores of 3 (HR 0.85, 95% CI 0.73−0.99), 4 (HR 0.84, 95% CI 0.72−0.98), and 5−7 (HR 0.77, 95% CI 0.66−0.89) (p-trend < 0.001). Conclusions: A greater adherence to the cardioprotective diet was associated with a lower risk of IBD. Our finding highlighted the importance of focusing on the cardioprotective diet to prevent IBD.

Although essential tremor (ET) is considered a common adult movement disorder, evidence on its incidence is still scant. This study aims at estimating ET incidence in two European countries, namely, the UK and France.

Incident cases of ET were identified within the Health Improvement Network (THIN®) database between 1st January 2014 and 31 December 2019. Yearly crude and standardized incidence rates (IR) were estimated across the study period for both countries. Poisson regression models were built to assess temporal trends in IRs and differences between sexes and age classes.

In total, 4,970 and 4,905 incident cases of ET were identified in the UK and France, respectively. The yearly average crude IR (per 100,000 person-years) was 18.20 (95%CI: 15.09-21.32) in UK and 21.42 (17.83-25.00) in France, whereas standardized ones were 19.51 (18.97-20.01) and 19.50 (18.97-20.05). Regression analyses showed slightly increasing trends in both countries, higher incidence among males, and a significant increase with age. Yearly average IR increased from 3.96 (0.95-6.97) and 5.28 (1.12-9.44) in subjects aged <20 years to 49.27 (26.29-72.24) and 51.52 (30.19-72.86) in those aged >80 year in UK and France.

Standardized ET incidence was comparable in the UK and France, showing a slight increase in both countries, reporting a higher value among people aged 60 years and older. This study outlines the need to conduct future studies to estimate the burden of ET in terms of disease control and healthcare resource utilization.

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.