Colitis in a patient with familial Mediterranean fever: Is it Crohn's disease or ulcerative colitis?

A 24-year-old woman was referred to our hospital with joint pain, fever, abdominal pain, and diarrhea. A colonoscopy revealed longitudinal ulcers with a cobblestone appearance throughout the entire colon, suggestive of Crohn's disease. However, treatment with 5-aminosalicylic acid, azathioprine, and infliximab failed to achieve clinical remission. A colonoscopy 5 months later revealed a diffusely spreading granular mucosa without visible vasculature, compatible with active ulcerative colitis. Based on these serial changes in colonic lesions, we tested the patient for MEFV gene mutations and found variants E148Q and L110P in exon 2. Administration of colchicine resulted in complete clinical remission. Our experience suggests that drastic changes in the features of colonic inflammation may be a clue to the diagnosis of enterocolitis associated with familial Mediterranean fever.

Potential interventions and interactions of bioactive polyphenols and functional polysaccharides to alleviate inflammatory bowel disease - A review.

Inflammatory bowel disease is a multifaceted condition that is influenced by nutritional, microbial, environmental, genetic, psychological, and immunological factors. Polyphenols and polysaccharides have gained recognition for their therapeutic potential. This review emphasizes the biological effects of polyphenols and polysaccharides, and explores their antioxidant, anti-inflammatory, and microbiome-modulating properties in the management of inflammatory bowel disease (IBD). However, polyphenols encounter challenges, such as low stability and low bioavailability in the colon during IBD treatment. Hence, polysaccharide-based encapsulation is a promising solution to achieve targeted delivery, improved bioavailability, reduced toxicity, and enhanced stability. This review also discusses the significance of covalent and non-covalent interactions, and simple and complex encapsulation between polyphenols and polysaccharides. The administration of these compounds in appropriate quantities has proven beneficial in preventing the development of Crohn's disease and ulcerative colitis, ultimately leading to the management of IBD. The use of polyphenols and polysaccharides has been found to reduce histological scores and colon injury associated with IBD, increase the abundance of beneficial microbes, inhibit the development of colitis-associated cancer, promote the production of microbial end-products, such as short-chain fatty acids (SCFAs), and improve anti-inflammatory properties. Despite the combined effects of polyphenols and polysaccharides observed in both in vitro and in vivo studies, further human clinical trials are needed to comprehend their effectiveness on inflammatory bowel disease.

Progression of Crohn's Disease in Newly Diagnosed Patients: Results from an Observational Study Using US Claims Data.

BACKGROUND: Patients with Crohn's disease (CD) experience disease progression over time, including strictures/stenoses, penetrating fistulae, and abscesses. AIMS: This retrospective US population-based study aimed to characterize CD progression in newly diagnosed patients. METHODS: Patient-level data from the Optum® Market Clarity database from January 1, 2016, to June 30, 2020, were used. The study comprised a 12-month baseline period (pre-diagnosis), an index date (diagnosis date), and a follow-up period. The risk of, and time to, CD progression since CD diagnosis, dispensed treatment changes following CD progression, and healthcare resource utilization before and after CD progression were assessed. RESULTS: Overall, 6804 newly diagnosed patients were included. Of these, 1714 (25.2%) experienced CD progression as follows: 19.3% (1183/6117) in the first 6 months, 21.6% (1188/5503) by 1 year, 24.6% (953/3875) by 2 years, and 26.6% (444/1668) by 3 years. Intestinal obstruction/stenosis was more common than fistula or abscess. Among patients with CD progression, the median (interquartile range) estimated time to progression was 2 (0-140) days; the shortest time to progression was seen with a first intestinal obstruction/stenosis (0 [0-137] days). The frequency of several dispensed treatments increased following CD progression. Among patients who experienced progression, CD-related inpatient hospital admissions/visits increased from 436 of 1714 patients (25.4%) in the month before progression to 965 (56.3%) in the month after progression. CONCLUSIONS: Over one quarter of patients with newly diagnosed CD experienced CD progression and complications within 3 years of diagnosis, highlighting the importance of monitoring for progression and early intervention to limit progression.

Identification of novel proteins in inflammatory bowel disease based on the gut-brain axis: a multi-omics integrated analysis.

BACKGROUND: The gut-brain axis has garnered increasing attention, with observational studies suggesting its involvement in the disease activity and progression of inflammatory bowel disease (IBD), but the precise mechanisms remain unclear. MATERIALS AND METHODS: In this study, we aimed to investigate "novel proteins" underlying IBD in the brain using a comprehensive multi-omics analysis approach. We performed integrated analyses of proteomics and transcriptomics in the human prefrontal cortex (PFC) tissue, coupled with genome-wide association studies (GWAS) of IBD, crohn's disease (CD), and ulcerative colitis (UC). This included performing protein-wide association studies (PWAS), transcriptome-wide association studies (TWAS), Mendelian randomization (MR), and colocalization analysis to identify brain proteins associated with IBD and its subtypes. RESULTS: PWAS analyses identified and confirmation 9, 9, and 6 brain proteins strongly associated with IBD, CD, and UC, respectively. Subsequent MR analyses revealed that increased abundance of GPSM1, AUH, TYK2, SULT1A1, and FDPS, along with corresponding gene expression, led to decreased risk of IBD. For CD, increased abundance of FDPS, SULT1A1, and PDLIM4, along with corresponding gene expression, also decreased CD risk. Regarding UC, only increased abundance of AUH, along with corresponding gene expression, was significantly associated with decreased UC risk. Further TWAS and colocalization analyses at the transcriptome level supported strong associations of SULT1A1 and FDPS proteins with reduced risk of IBD and CD. CONCLUSION: The two "novel proteins," SULT1A1 and FDPS, are strongly associated with IBD and CD, elucidating their causal relationship in reducing the risk of IBD and CD. This provides new clues for identifying the pathogenesis and potential therapeutic targets for IBD and CD.

Primary Sclerosing Cholangitis and Crohn's Disease: A Rare Association.

Inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) are closely associated disease entities that, when present in combination, create a phenotypically different summative disease referred to as PSC-IBD. The hallmark of Crohn's disease is persistent inflammation that can affect any part of the gastrointestinal system, from the mouth to the anus, although the terminal ileum and proximal colon are most frequently affected. Crohn's disease can sporadically impact the duodenum and stomach. Here, we present the case of a 12-year-old child who presented with per rectal bleed, hematemesis, and persistent elevated transaminasemia. A biopsy revealed micro-granulomas from the stomach's antrum and colonic mucosa, as well as focally exacerbated colitis. For a prolonged increased cholestatic pattern of liver enzymes, we performed an autoimmune panel and magnetic retrograde cholangiopancreatography, which revealed PSC. The patient was started on steroids and immunosuppressants.

TOpClass Class 4 Perineal Crohn's Disease: A Systematic Review and Meta-analysis of Perineal Wound Complication After Proctectomy in Crohn's Patients.

BACKGROUND: Nonhealing perineal wounds have been reported to be common after proctectomy for Crohn's disease (CD). We performed a systematic review and meta-analysis of perineal wound healing after proctectomy for CD and assessed the risk factors for nonhealing. METHODS: A comprehensive literature search was conducted in PubMed, Embase, and Scopus databases from 2010 to 2023, and articles reporting perineal wound healing rates after proctectomy for CD were included. Data on study characteristics and proportion of healed wounds, and risk factors, were extracted. Random-effects meta-analysis was performed to estimate the pooled proportion and 95% CIs using the "meta" package in R. Heterogeneity was assessed using the I2 statistic. RESULTS: We identified 501 articles, of which 252 remained after de-duplication. After screening, 4 retrospective cohort studies involving 333 patients were included. Across the 4 studies, the pooled proportion of completely healed perineal wounds at 6 months was 65% (95% CI 52%-80%), and 70% (95% CI 60%-83%) at 12 months. Significant heterogeneity was found between studies (I2 = 86% at 6 months). Three studies examined risk factors for impaired healing after proctectomy. One study identified preoperative perineal sepsis as the only independent factor associated with impaired healing (P = .001) on multivariable analysis. In 1 study, male sex, shorter time from diversion to proctectomy, and higher preoperative C-reactive protein levels were all associated with delayed healing in univariate analysis. Another study found that close rectal dissection was associated with significantly lower healing rates than total mesorectal excision (P = .01). Prior use of tumor necrosis factor inhibitors was not associated with wound healing outcomes. CONCLUSIONS: This meta-analysis revealed complete perineal healing in only 70% of patients 12 months after proctectomy for CD. This highlights knowledge gaps, including the identification of modifiable risk factors and methods for preventing or as rescue therapy, such as vacuum-assisted closure and flap reconstruction, for nonhealing perineal wounds after proctectomy for CD. Poor perineal wound healing outcomes are likely related to imperfectly understood underlying inflammatory dysregulation and systemically impaired wound healing in patients with CD.

Meta-analysis of perineal healing after proctectomy for Crohn's revealed only 70% of patients at 12 months; the only independent risk factor was preoperative perineal sepsis; biologics did not affect healing. This highlights knowledge gaps, including best practices for prevention and treatment.

The Pouch Corner: Perianal Fistulas and Ileal Pouches: Examining Fistulas Before and After Pouch Creation.

Patients with ulcerative colitis (UC) and Crohn's disease (CD) proctocolitis are candidates for an ileal pouch-anal anastomosis (IPAA), provided they do not suffer from complex perianal fistulas or small bowel inflammation. UC patients who develop a simple perianal fistula may still be candidates for an IPAA; however, patients with complex perianal fistulas are precluded from having an ileal pouch. After an IPAA, patients may develop perianal fistulas that arise acutely from a technical complication or an anastomotic leak, or as late-onset fistulas as a result of CD-like inflammation of the pouch.

Placebo rates in Crohn's disease randomized clinical trials: An individual patient data meta-analysis.

BACKGROUND & AIMS: Understanding placebo rates is critical for efficient clinical trial design. We assessed placebo rates and associated factors using individual patient data (IPD) from Crohn's disease (CD) trials. METHODS: We conducted a meta-analysis of phase 2/3 placebo-controlled trials evaluating advanced therapies in moderate-to-severe CD (2010-2021). Deidentified IPD were obtained through Vivli Inc. and Yale University Open Data Access Project. Primary outcomes were clinical response and remission. Pooled placebo rates and 95% confidence intervals (CIs) were estimated using one- and two-stage meta-analytical approaches. Regression analyses identified patient-level factors associated with placebo rates. RESULTS: Using IPD from eight induction (n=1147) and four maintenance (n=524) trials, overall placebo clinical response and remission rates for induction were 27% (95%CI=23-32%) and 10% (95%CI=8-14%) respectively, and 32% (95%CI=23-42%) and 22% (95%CI=14-33%) for maintenance, respectively. Among bio-naïve patients, placebo response and remission rates during induction were 29% (95%CI=24-35%) and 11% (95%CI=8-15%) respectively, and 26% (95% CI=20-33%) and 10% (95% CI=8-14%) for bio-exposed, respectively. During maintenance, bio-naïve response and remission rates were 41% (95%CI=34-48%) and 32% (95%CI=24-40%), respectively, and 29% (95%CI=24-34%) and 16% (95%CI=13-21%) for bio-exposed, respectively. Higher baseline C-reactive protein concentration predicted lower placebo rates, while higher baseline albumin levels and body mass index increased the odds of placebo outcomes. Increased baseline Crohn's Disease Activity Index and 2-item patient-reported outcome scores predicted higher response rates in induction, lower response rates in maintenance, and lower remission rates in induction and maintenance. CONCLUSION: Patient- and trial-level characteristics influence placebo rates in CD trials. Careful implementation of eligibility criteria, outcome definitions, and patient stratification may reduce placebo rates.

The role of antibiotic exposure as risk factor for IBD epidemic: an updated meta-analysis.

BACKGROUND AND AIM: The rising prevalence of IBD globally has raised concerns about antibiotic exposure. This study's meta-analysis examines antibiotic exposure, frequency, year before diagnosis, regional differences, and IBD incidence. METHODS: The literature review used PubMed, Web of Science, Elsevier, ScienceDirect, and Cochrane CENTRAL databases up to June 2024 to explore the link between antibiotic exposure and IBD risk. Stratified analysis was conducted by years of antibiotic exposure before IBD diagnosis, frequency, and region. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were combined using a random effects model. RESULTS: Eighteen case-control studies and five cohort studies were included (n = 99, 104 IBD patients and n = 2 273 336 controls). The findings indicate that antibiotic exposure significantly has a positive association with the risk of developing IBD (OR, 1.66; 95% CI, 1.28-2.16). Antibiotic exposure of ≥3 years (OR, 1.49; 95% CI, 1.12-1.98), 2 years (OR, 1.46; 95% CI, 1.37-1.55), and ≤1 year (OR, 1.55; 95% CI, 1.17-2.04) prior to the diagnosis of IBD is associated with a higher risk of developing IBD. Cumulative exposure of ≥3 dispensations (OR, 2.02; 95% CI, 1.49-2.74) and two dispensations (OR, 1.36; 95% CI, 1.03-1.78) also had a positive association with IBD risk, while one dispensation did not (OR, 0.96; 95% CI, 0.72-1.26). No significant association was found in developing countries (OR, 1.92; 95% CI, 0.71-5.19), but developed countries showed a significant positive association with the risk (OR, 1.58; 95% CI, 1.27-1.96). CONCLUSION: The meta-analysis suggests that antibiotic use has a positive association with the risk of IBD, and limiting unnecessary antibiotic use may be one way to reduce the risk of developing IBD.

Imaging in Inflammatory Bowel Disease.

The incidence of inflammatory bowel disease (IBD) is rising globally. We need more tools and techniques in our armamentarium for early diagnosis, tight monitoring, and to assess disease complications of IBD. This article reviews the role of cross-sectional imaging, mainly computed tomography, MRI, and intestinal ultrasound (IUS) in IBD and its advantages, disadvantages, and limitations. While popular in other parts of the world, IUS is underutilized in the United States. It is safe, accurate, can be repeated multiple times and provides quick and actionable results in IBD care without the risk of radiation and contrast.

Efficacy of vedolizumab and ustekinumab in pediatric-onset inflammatory bowel disease: A real-world multicenter study.

OBJECTIVES: Vedolizumab and ustekinumab are effective in inducing and maintaining corticosteroid-free clinical remission (CFR) in adult patients with inflammatory bowel disease (IBD). This study describes the efficacy and safety of vedolizumab and ustekinumab in pediatric IBD. METHODS: All patients ≤18 years of age with Crohn's disease (CD) or ulcerative colitis (UC) treated with vedolizumab or ustekinumab in three centers in Northern France were followed retrospectively. The primary outcome was CFR at Week 14 (W14). RESULTS: Twenty-five patients (9 CD, 16 UC) and 33 patients (28 CD, 5 UC) were started on vedolizumab and ustekinumab respectively between 2016 and 2021. All were previously treated with antitumor necrosis factor (TNF). The median time from diagnosis to treatment initiation was 21.0 (12.0-44.0) and 42.0 (22.0-73.5) months for vedolizumab and ustekinumab respectively. Among vedolizumab-treated patients, 36% were in CFR at W14, including 22% in CD and 44% in UC. At W52, 56% were in CFR, including 33% in CD and 69% in UC. Among ustekinumab-treated patients, 49% were in CFR at W14, including 54% in CD and 20% in UC. At W52, 55% were in CFR, including 57% in CD and 40% in UC. There was a significant increase in median growth velocity between W0 and W52 of +2 SD in vedolizumab-treated patients (p = 0.0002). Four adverse events were reported during vedolizumab treatment, none for ustekinumab-treated patients. CONCLUSIONS: Vedolizumab and ustekinumab appear to be effective in inducing and maintaining CFR in pediatric-onset IBD. Randomized controlled trials are needed to confirm these results.

New onset inflammatory bowel disease after initiation of anti-IL-17a treatment: a case series.

Immune mediated inflammatory diseases (IMIDs) are a heterogenous group of inflammatory disorders of joint, skin, and gut characterized by both shared and distinct pathological pathways. This complexity has therapeutic implications, as not all IMIDs exhibit responsiveness to available biologicals. Moreover, cases have been documented where patients undergoing biologic therapy experience paradoxical occurrences of either a new IMID or a flare-up of a previously asymptomatic one. Treatment with anti- IL-17a has been approved for ankylosing spondylitis, psoriasis, and psoriatic arthritis, but was not found effective for the treatment of inflammatory bowel disease (IBD). This case series describes four patients with new onset IBD under treatment with an IL-17a inhibitor for a rheumatological or dermatological indication.

Durable Immune Response and Long-term Efficacy of COVID-19 Vaccination in Children With Inflammatory Bowel Disease.

BACKGROUND: Children with inflammatory bowel disease (IBD) may have diminished serologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and increased risk for subsequent severe coronavirus disease 2019 (COVID-19) infection. We sought to describe outcomes among those who developed SARS-CoV-2 infection following vaccination, characterize SARS-CoV-2 antibodies 1 year post-vaccination, and identify factors associated with durable serologic response. METHODS: We recruited children with IBD who received ≥2 doses of SARS-CoV-2 vaccine and prospectively collected data on (1) demographics, IBD characteristics, and therapy and (2) SARS-CoV-2 vaccination, testing, and infection symptoms. Serum was obtained for measurement of anti-receptor-binding domain IgG antibodies following a 2-part immunization at 12 and 52 weeks. RESULTS: We enrolled 298 participants (mean age 11.9 ±â€…3.82, 50% female, 67% Crohn's disease). Symptomatic COVID-19 infection after vaccination occurred in half of the participants, although only 2 (1%) required hospitalization. Anti-tumor necrosis factor alpha (TNF-α) was associated with higher likelihood of symptomatic COVID-19 infection, with an adjusted hazard ratio of 2.7 (95% CI, 1.5-5.0; P = .001). Nearly all participants (99%) had detectable antibody at Week 52. Children aged 1-5 years had lower 52-week antibody level compared to older children (P = .04), as did those on anti-TNF-α therapy (P = .007) and those who received only 2 vaccine doses prior to Week 52 (P < .001). CONCLUSIONS: SARS-CoV-2 vaccination provides lasting serologic response and protection against severe COVID-19 for most children with IBD, despite the use of lower vaccine doses in younger children and wide-ranging classes of immunosuppressive therapies.

We demonstrate high rates of durable antibody response and low rates of coronavirus disease 2019-related hospitalization 1 year following severe acute respiratory syndrome coronavirus 2 vaccination in children with inflammatory bowel disease. Anti-tumor necrosis factor alpha therapy, young age, and fewer vaccine doses were associated with lower 52-week antibody level.

Controversies in Venous Thromboembolism Risk Assessment in Inflammatory Bowel Disease: A Narrative Review.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract with increasing rates of incidence and prevalence across the world. Complex inflammatory and prothrombotic pathophysiology in IBD makes venous thromboembolism (VTE) a common complication with significant morbidity and mortality. This risk is increased in pregnancy. As we continue to understand the pathogenesis of IBD, this article highlights the continued risk of VTE following discharge, for which there is currently no clear guidance, yet the risk of VTE remains high. Furthermore, we discuss this increased VTE risk in the context of pregnant IBD patients and the relevant current guidelines. Alongside this, medications that are used to manage IBD carry their own thrombotic risk, which clinicians should be aware of. Assessing VTE risks in IBD populations using newer medications should be a focus of future research.

PTGER4 signaling regulates class IIa HDAC function and SPINK4 mRNA levels in rectal epithelial cells.

BACKGROUND: The prostaglandin receptor PTGER4 facilitates homeostasis in the gut. Previous reports indicate that goblet cells, marked by SPINK4 expression, might be affected by PTGER4 activity. Current evidence suggests that prostaglandin E2 (PGE2) produced by mesenchymal stromal cells (MSC) stimulates PTGER4 in epithelial cells during inflammatory conditions. Here, we investigate the subcellular mechanisms and mRNA levels downstream of PTGER4 activity in epithelial cells. METHODS: Mucosal cells, organoids, and MSC were obtained from patient biopsies harvested by endoscopy. Using independent and co-cultures, we manipulated the activity of PTGER4, the downstream enzymes, and mRNA levels, by using PGE2, in combination with chemical inhibitors, L-161982, H89, LB100, DAPT, LMK-235, or with butyrate. Immunofluorescence, single cell sequencing, RNAscope, ELISA, real time PCR, and Western blotting were used to examine these samples. RESULTS: SPINK4 mRNA levels were increased in organoids by co-culture with MSC or exogenous stimulation with PGE2 that could be blocked by L-161982 or LMK-235, PTGER4 or HDAC4 inhibitors, respectively. Expression of PTGER4 was co-localized with JAM-A in the basolateral surfaces in rectal epithelial cells grown as organoids. PGE2 treatment of rectal organoids decreased HDAC4, 5, and 7 phosphorylation levels that could be blocked by L-161982 treatment. Butyrate treatment, or addition of L-161982, increased the phosphorylated levels of HDAC4, 5, and 7. CONCLUSIONS: These findings suggest a mechanism during mucosal injury whereby MSC production of PGE2 increases HDAC4, 5, and 7 activities in epithelial cells by upregulating PTGER4 signaling, ultimately increasing SPINK4 mRNA levels and extracellular release of SPINK4.

Ten-year outcomes of a prospective population-based incidence cohort of inflammatory bowel disease patients from Canterbury, New Zealand.

Background and Aim: Inflammatory bowel disease (IBD) is a progressive condition where ongoing inflammation in the gastrointestinal tract can lead to complications such as strictures, and fistulae. The long-term outcomes of newly diagnosed patients under current medical therapy can be used to plan health service provision and guide patients. Methods: Prospective population-based data on all incident patients diagnosed with IBD in Canterbury was gathered in 2014 (n = 205). The medical records of these patients were followed for medication use, disease progression, hospitalization, surgery and mortality, in the 10 years since their diagnosis. Survival analysis and cox regression determined characteristics associated with earlier time to these outcomes. Results: Medical records of 184 IBD patients were able to be retrieved. Immunomodulators were used by 62% and biologics by 35%; hospitalization occurred for 42% and surgery for 15%. Montreal phenotype progression occurred for 21 and 7% of the cohort died. Younger age at diagnosis hazard ratio (HR) 2.1 (95% confidence interval [CI] 1.1-4.0) and Crohn's disease HR 1.7 (95% CI 1.1-2.6) was associated with immunomodulator use. Younger age was also associated with biologic use HR 2.9 (95% CI 1.2-6.9). Male gender was associated with surgery HR 2.8 (95% CI 1.2-6.4). Perianal disease at diagnosis (14.7%) was associated with immunomodulator use HR 2.58 (95% CI 1.44-4.59) and Montreal phenotype progression HR 2.93 (95% CI 1.10-7.77). Conclusion: In the 10 years since diagnosis disease progression and treatment escalation occurred for most of this population-based cohort. Earlier intervention for patients with higher-risk characteristics may improve long-term outcomes reducing the burden on health systems.

Prescribed cumulative dosage of corticosteroids to patients with inflammatory bowel disease diagnosed between 2006 and 2020: a retrospective observational study.

Background: Treatments and strategies for inflammatory bowel disease (IBD) have gradually evolved in the 2000s. Objectives: We investigated whether the prescription of corticosteroids (prednisolone and budesonide) in patients with IBD in the first 5 years after diagnosis changed in patients diagnosed between 2006 and 2018. Design: Retrospective observational study. Methods: The cumulative prescribed dosage of corticosteroids for the first 5 years after diagnosis was registered in all patients with IBD (n = 386) at our clinic for those diagnosed between 2006 and 2018. Results: The proportion of patients with IBD who were prescribed at least one prescription of corticosteroids in year 1-5 after diagnosis was 55.3%, 27.9%, 22.7%, 14.1%, and 14.6%, respectively. The proportion of patients who had a cumulative dose of prednisolone >1 g in the first 5 years after diagnosis was 40.1% for ulcerative colitis and 34.9% for Crohn's disease (CD). The cumulative prescribed dosage (within 3 years after diagnosis) of prednisolone had declined (rs = -0.164, p = 001), but had increased for budesonide (rs = 0.202, p < 0.001) between 2006 and 2020. The prescription of any immunomodulator for IBD in the first 5 years from diagnosis was stable between 2006 and 2018 (rs = 0.056, p = 0.257), but there was a minor increase in the prescription of Tumor Necrosis Factor (TNF)-inhibitors (rs = 0.119, p = 0.020). The use of five-acetyl salicylic acid (5-ASA) decreased in patients with CD (rs = -201, p = 0.012). Conclusion: There was a decrease in the prescription of prednisolone and an increase in the prescription of budesonide treatment from 2006 to 2023; however, the cumulative exposure to corticosteroids in patients with IBD remains at a relatively high level.

The use of steroids in patients with inflammatory bowel disease diagnosed between 2006 and 2020 In the 1950s, corticosteroids and immunomodulators were introduced, and in combination with improved surgery, the mortality rates dramatically decreased in patients with inflammatory bowel disease (IBD) Although corticosteroids are effective in the short term they have no proven efficacy in long-term therapy for IBD, and owing to the risk of side effects, their long-term use should be restricted. Based on the evolution of treatments and treatment strategies for IBD in the 2000s, we aimed to study to the extent to which corticosteroids have been used in the first five years after diagnosis for patients with IBD diagnosed at our clinic between 2006 and 2020. To what extent is prednisolone prescribed in the first five years after diagnosis? Has the pattern of corticosteroid prescription changed after the introduction of advanced therapy and biosimilars to TNF inhibitors? We found that the proportion of patients with IBD who were prescribed at least one prescription of corticosteroids in year one to five after diagnosis was 55.3%, 27.9%, 22.7%, 14.1%, and 14.6%, respectively. The proportion of patients who had a cumulative dose of prednisolone >1g in the first five years after diagnosis was 40.1% for ulcerative colitis (UC) and 34.9% for Crohns disease (CD). The cumulative prescribed dosage (within 3 years after diagnosis) of prednisolone had declined but increased for budesonide between 2006-2020. The prescription of any immunomodulator for IBD in the first five years from diagnosis was stable between the years 2006-2018, but there was a minor increase in the prescription of TNF-inhibitors. The use of 5-ASA decreased in patients with CD. We conclude that there was a decrease in the prescription of prednisolone and an increase in the prescription of budesonide treatment from 2006 to 2023; however, the cumulative exposure to corticosteroids in patients with IBD remains on relatively high level.

Refractory Crohn's Disease: Perspectives, Unmet Needs and Innovations.

Crohn's disease (CD) is a complex, chronic inflammatory bowel disease characterized by unpredictable flare-ups and periods of remission. Despite advances in treatment, CD remains a significant health burden, leading to substantial direct healthcare costs and out-of-pocket expenses for patients, especially in the first-year post-diagnosis. The impact of CD on patients' quality of life is profound, with significant reductions in physical, emotional, and social well-being. Despite advancements in therapeutic options, including biologics, immunomodulators, and small molecules, many patients struggle to achieve or maintain remission, leading to a considerable therapeutic ceiling. This has led to an increased focus on novel and emerging treatments. This context underscores the importance of exploring advanced and innovative treatment options for managing refractory CD. By examining the latest approaches, including immunomodulators, combination therapies, stem cell therapies, and emerging treatments like fecal microbiota transplantation and dietary interventions, there is an opportunity to gain a comprehensive understanding of how best to address and manage refractory cases of CD.

Interrupting inflammatory bowel disease therapy: why, who, when and how to consider medication holidays.

INTRODUCTION: Medication holidays in inflammatory bowel disease (IBD) offer a potential means to balance disease management, costs, and quality of life. This concept is increasingly relevant in light of the chronic nature of IBD, the cumulative side effects associated with long-term pharmacotherapy, and the evolving treatment landscape that now includes a large armamentarium of effective induction, maintenance, and rescue therapies paired with disease monitoring tools that enable early intervention. AREAS COVERED: This review critically examines the rationale, implementation, and risks of medication holidays in IBD. Recent evidence is reviewed to help guide the risks of relapse involved with cessation of therapy. The selection criteria for patients, the necessary monitoring protocols, and strategies for managing potential relapses are outlined. EXPERT OPINION: Despite the potential benefits, medication holidays in IBD involve significant risks and require careful patient selection and active management. Current research highlights a need for improved predictive models and a deeper understanding of patient-specific outcomes and consequences. The future of medication holidays will depend heavily on advancements in noninvasive monitoring technologies and more personalized approaches to therapy. Ultimately, establishing clearer guidelines for safely conducting medication holidays will be crucial in integrating this strategy into routine clinical practice.

The co-expression of Crohn's disease and colon cancer network was analyzed by bioinformatics-CXCL1 tumour microenvironment and prognosis-related gene CXCL1.

PURPOSE: This study aimed to investigate the molecular links and mechanisms between Crohn's disease (CD) and colorectal cancer (CRC). METHODS: This study used the Gene Expression Omnibus (GEO) database to identify Differentially expressed genes (DEGs) in CD (GSE112366) and CRC (GSE110224), analyzed by 'edgeR' and 'limma'. The Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes explored DEG functions, and the Search Tool for the Retrieval of Interacting Genes (STRING) informed the protein-protein interaction network construction visualized in Cytoscape (version 3.7.2). Cyto-Hubba identified key genes, whose biomarker potential for CD and CRC was evaluated. RESULTS: The study discovered 61 DEGs, with 44 up- and 17 down-regulated, linked to immune responses and signaling pathways. CXCL1, highly expressed in colon cancer, correlated with better prognosis and lower staging. It also showed associations with immune infiltration and checkpoint molecules, suggesting a role in cancer progression and retreat. CONCLUSION: CXCL1 may play a role in the development of colorectal cancer from inflammatory bowel disease.