More on the interplay between gut microbiota, autophagy, and inflammatory bowel disease is needed.

The concept of inflammatory bowel disease (IBD), which encompasses Crohn's disease and ulcerative colitis, represents a complex and growing global health concern resulting from a multifactorial etiology. Both dysfunctional autophagy and dysbiosis contribute to IBD, with their combined effects exacerbating the related inflammatory condition. As a result, the existing interconnection between gut microbiota, autophagy, and the host's immune system is a decisive factor in the occurrence of IBD. The factors that influence the gut microbiota and their impact are another important point in this regard. Based on this initial perspective, this manuscript briefly highlighted the intricate interplay between the gut microbiota, autophagy, and IBD pathogenesis. In addition, it also addressed the potential targeting of the microbiota and modulating autophagic pathways for IBD therapy and proposed suggestions for future research within a more specific and expanded context. Further studies are warranted to explore restoring microbial balance and regulating autophagy mechanisms, which may offer new therapeutic avenues for IBD management and to delve into personalized treatment to alleviate the related burden.

Management of Complications in Crohn's Disease.

Complications of Crohn's disease reach far beyond postsurgical leak, infection, and enterocutaneous fistula. Malnutrition, intestinal failure, and recurrent disease all will require ongoing attentions. The management of these patients may further be complicated by the need for chronic immunosuppression. The underlying principles continue to include optimization of nutritional status, and preservation of bowel length when possible. However, there have been several recent advances in both the medical and surgical management of the disease. Understanding the contribution of the mesentery to inflammation, new surgical techniques such as the Kono-S anastomosis and extended mesenteric resection is decreasing the need for repeated resections.

Upper Gastrointestinal Involvement in Crohn's Disease as an Independent Predictor of New-Onset Strictures: Insights from an Extensive Retrospective Cohort Analysis.

BACKGROUND/AIMS: Crohn's Disease (CD) can affect the entire gastrointestinal tract, including the upper sections (UGI), which is often overlooked, especially in Asian populations. There's a notable gap in research regarding the impact of UGI involvement on the intricate landscape of ensuing complications. This study aims to address this gap. METHODS: Conducting a retrospective study at Chang Gung Memorial Hospital from January 2001 to September 2023, we compared CD patients with UGI (Montreal L4) involvement against non-L4 counterparts, focusing on baseline characteristics, post-diagnosis complications, and overall outcomes. Routine UGI endoscopy was performed around the time of diagnosis in all patients followed in our inflammatory bowel disease (IBD) center, and all CD patients with adequate follow-up were included in this study. RESULTS: The study included 212 CD patients, 111 in the L4 group and 101 in the non-L4 group, with an average follow-up of 40.8 ± 15.1 months. At baseline, individuals in the L4 category demonstrated elevated smoking rates, increased Crohn's Disease Activity Index scores, a higher prevalence of strictures, and a more prevalent usage of biologics and proton pump inhibitors. Moreover, this group was characterized by reduced albumin levels. Upon concluding the follow-up, those with L4 involvement continued to show escalated CDAI scores and hospitalization frequencies, alongside heightened C-reactive protein levels and diminished albumin concentrations. Additionally, the occurrence of UGI involvement, stricturing disease at the time of diagnosis, and a younger age at the onset of CD were pinpointed as independent predictors for the development of new-onset strictures. CONCLUSIONS: CD patients with UGI involvement exhibit elevated disease activity and serve as independent predictors for the development of intestinal strictures. Thorough UGI evaluations at the time of diagnosis, coupled with assertive treatment strategies, are essential for managing these patients effectively.

The etiological profile of chronic organic non-bloody diarrhea in India: Emergence of inflammatory bowel disease as a dominant cause.

BACKGROUND: Chronic non-bloody diarrhea may be attributed either to functional or organic diseases. The latter category may present with malabsorption syndrome if there is extensive involvement of the small bowel, whereas diseases of the large bowel may only present with diarrhea sans malabsorption. Indian data has predominantly focussed on the etiological spectrum of malabsorption syndrome in adults. The primary aim of the current study was to evaluate etiological spectrum of chronic organic non-bloody diarrhea in India. METHODS: This prospective observational study was done at a tertiary care hospital in North India. Patients ≥ 18 years presenting with chronic non-bloody diarrhea of > 4 weeks duration were enrolled in the study after exclusion of patients with IBS and anal incontinence. RESULTS: During the study period of 12 months, 100 patients with chronic organic non-bloody diarrhea were evaluated. A definite etiological diagnosis was made in 97 patients (97%). The mean age of the patients was 48 ± 16.7 years (58% males). The median duration of diarrhea was 5.5 months (interquartile range [IQR] 3.5, 11). Inflammatory bowel disease (IBD) accounted for 45% of the cases making it the predominant cause for organic diarrhea. GI infections and adult-onset celiac disease accounted for 18% and 9% of the cases, respectively. Pancreatic disease, benign or neoplastic, accounted for 6% of the total cases. Notably, gastrointestinal (GI) malignancies manifesting as chronic non-bloody diarrhea were diagnosed in 5% of the patients. CONCLUSION: Our data suggests a paradigm shift in the etiological spectrum of chronic organic non-bloody diarrhea in India with the emergence of IBD as the predominant cause displacing GI infections.

Capsule endoscopy for small bowel bleed: Current update.

Small intestine, hitherto an obscure area for endoscopists before 2000, is now easily evaluated non-invasively using capsule endoscopy and invasively by device-assisted enteroscopies. Major advances in understanding the causes and management of small bowel diseases have been in obscure gastrointestinal (GI) bleed, currently re-named as small bowel bleed, after the discovery of capsule endoscopy. The current article is a narrative review of the technology of capsule endoscopy, its advantages and limitations, future perspective and Indian studies on its utility in patients with small bowel bleed. Till date, eight large series reporting 2319 patients with obscure GI bleed (1554 overt and 765 occult) undergoing capsule endoscopy have been reported from India. Overall yield of capsule endoscopy to detect lesions in these studies varied from 43.5% to 90%. The major causes detected in various studies for small bowel bleed include vascular malformation, portal hypertensive enteropathy, ulcer, stricture, tumor, polyps, etc. Hookworm can cause both occult as well as overt small bowel bleed as shown mainly from India. Capsule endoscopy has also been quite safe in patients with small bowel bleed as despite 0.6% to 15% retention of imaging capsule in Indian studies, development of clinically evident small bowel obstruction has rarely been reported. The major limitations of capsule endoscopy include lack of maneuvrability and therapeutic capability. Research is in progress to overcome some of the limitations of the current capsule endoscopy system. It is concluded that discovery of capsule endoscopy has brought a new paradigm in GI endoscopy and explored a hitherto unexplored area of GI tract, i.e. small bowel that continued to be a black box for the endoscopists.

Perianal disease in inflammatory bowel disease: Broadening treatment and surveillance strategies for anal cancer.

The perianal disease affects up to one-third of individuals with Crohn's disease (CD), causing disabling symptoms and significant impairment in quality of life, particularly for those with perianal fistulising CD (PFCD). The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing. Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents, endoscopic procedures and surgical techniques that show promising results. Among these, mesenchymal stem cells injection is a particularly hopeful therapy. In addition to the burden of fistulas, individuals with perianal CD may face an increased risk of developing anal cancer. This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes. Currently, there is no established formal anal screening programme. In this review, we provide an overview of the current state of the art in managing PFCD, including novel medical, endoscopic and surgical approaches. The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD, intending to propose a risk-based surveillance algorithm. The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.

Mirikizumab Sustained Impact on Fatigue in Patients with Moderately to Severely Active Crohn's Disease in the Phase 2 AMAG Study.

BACKGROUND: Fatigue is a burdensome, under-recognized, multidimensional symptom experienced by patients with Crohn's disease (CD). We evaluated the impact of mirikizumab on fatigue and the association between changes in select patient-reported outcomes and clinical measures with changes in fatigue from baseline to week 104 (W104). METHODS: Patients (N = 191) were randomized (2:1:1:2) to receive placebo (PBO), 200 mg, 600 mg, or 1000 mg of mirikizumab, administered intravenously (IV) every 4 weeks at W0, W4, and W8. Patients who achieved ≥1 point improvement in Simple Endoscopic Score for Crohn's Disease (SES-CD) and received mirikizumab at W12 (rerandomized maintenance cohort) were rerandomized to continue induction IV treatment assignment (IV-C) or received 300 mg of mirikizumab subcutaneously (SC) until W52. Nonrandomized maintenance cohort had endoscopic nonimprovers (1000 mg) and PBO patients (PBO/1000 mg) who received 1000 mg of mirikizumab until W52. Subjects from the maintenance period with clinical benefit received 300 mg SC Q4W from W52 to W104. The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire was used to assess fatigue, and the FACIT-F associations were assessed using Pearson correlation coefficient. RESULTS: At W12, mirikizumab groups reported improved FACIT-F scores compared with PBO, and improvement was maintained through W52 and W104. Changes in FACIT-F at W52 and W104 had strong correlations with changes at the same time point in quality of life (QoL) scores but lacked correlations with changes in inflammatory biomarkers. CONCLUSIONS: Mirikizumab treatment significantly improved fatigue in patients with moderately to severely active CD, which was sustained to W104. The improvement in fatigue was correlated with improvement in clinical measures and was strongly correlated with improvement in QoL.

Fatigue is a common symptom of Crohn's disease that negatively impacts quality of life. Mirikizumab treatment improved FACIT-Fatigue scores compared with placebo up to week 104. Improvement in fatigue was also associated with improved emotional, social, and physical concepts.

Mucocutaneous manifestations of inflammatory bowel disease.

Mucocutaneous manifestations can be indicative of a variety of gastrointestinal diseases, and the dermatologist needs to know how to recognize them to refer the right patients to the gastroenterologist. Conversely, the gastroenterologist is often confronted with mucocutaneous lesions that raise the question of a possible association with a known digestive disease. Among the extra-intestinal manifestations of inflammatory bowel disease (IBD), mucocutaneous manifestations are the most common. This review will provide a breakdown by classifying them into 4 groups: 1) reactive manifestations, which include neutrophilic dermatoses, aphthous stomatitis, erythema nodosum, and vasculitis; 2) Crohn's disease-specific granulomatous skin lesions, which are histologically characterized by tuberculoid granulomas similar to those found in the gastrointestinal tract; 3) nutritional deficiency manifestations secondary to anorexia, malabsorption, loss, and drug interactions; and 3) a variety of autonomous autoimmune or inflammatory skin diseases. Dermatologists may also be involved in the management of the adverse effects of IBD treatments, especially the so-called "paradoxical" psoriatic eruptions.

Small molecules for inflammatory bowel disease and the risk of infection and malignancy: A systematic review and meta-Analysis.

OBJECTIVES: This meta-analysis aimed to ascertain whether small molecule drugs increase the risk of infection or malignancy in adult IBD patients. METHODS: A comprehensive search of eight databases was conducted from their inception to November 2023. The risk of infections or malignancies in adult IBD patients treated with JAK inhibitors and S1P receptor modulators was compared. Fixed-effects or random-effects models were performed, and relative risk (RR) and 95 % confidence interval (CI) were calculated. RESULTS: 27 RCTs from 14 studies were included (n = 10,623). The evidence indicates that small molecule drugs increase the risk of any infections (RR: 1.23, 95 %CI: 1.05-1.44) and herpes zoster (RR: 2.23, 95 %CI: 1.39-3.57). Specifically, UC patients on Filgotinib and Tofacitinib, and CD patients on Upadacitinib, showed elevated risks of any infections (RR: 1.27, 95 % CI: 1.04-1.56; RR: 1.42, 95 % CI: 1.16-1.75; RR: 1.57, 95 % CI: 1.11-2.22). CD patients on Upadacitinib also had a significantly higher risk of herpes zoster (RR: 2.64, 95 %CI: 1.16-5.99). No infections were associated with S1P receptor modulators, and similarly, no malignancies were linked to small molecule drugs. CONCLUSIONS: JAK inhibitors increase the risk of any infections and herpes zoster Over a one-year follow-up period in IBD patients. Continuous monitoring of their long-term safety is necessary.

Predictors of improvement in disease activity in childhood and adolescent Crohn's disease: an analysis of age, localization, initial severity and drug therapy - data from the Saxon Registry for Inflammatory Bowel Disease in Children in Germany (2000-2014).

The escalating worldwide prevalence of Crohn's disease (CD) among children and adolescents, coupled with a trend toward earlier onset, presents significant challenges for healthcare systems. Moreover, the chronicity of this condition imposes substantial individual burdens. Consequently, the principal objective of CD treatment revolves around rapid inducing remission. This study scrutinizes the impact of age, gender, initial disease localization, and therapy on the duration to achieve disease activity amelioration. Data from the Saxon Pediatric IBD Registry in Germany were analyzed over a period of 15 years. In addition to descriptive methods, logistic and linear regression analyses were conducted to identify correlations. Furthermore, survival analyses and Cox regressions were utilized to identify factors influencing the time to improvement in disease activity. These effects were expressed as Hazard Ratios (HR) with 95% confidence intervals. Data on the clinical course of 338 children and adolescents with CD were available in the registry. The analyses showed a significant correlation between a young age of onset and the severity of disease activity. It was evident that treatment with anti-TNF (Infliximab) was associated with a more favorable prognosis in terms of the time required for improvement in disease activity. Similarly, favorable outcomes were observed with the combination therapies of infliximab with enteral nutrition therapy and Infliximab with immunosuppressants.Conclusion: Our analysis of data from the Saxon Pediatric IBD Registry revealed that the timeframe for improvement of disease activity in pediatric Crohn's disease is influenced by several factors. Specifically, patient age, treatment modality, and initial site of inflammation were found to be significant factors. The study provides important findings that underline the need for individualized treatment.

Altered Function and Structure of the Cerebellum Associated with Gut-Brain Regulation in Crohn's Disease: a Structural and Functional MRI Study.

This study employed structural and functional magnetic resonance imaging (MRI) to investigate changes in the function and structure of the cerebellum associated with gut-brain axis (GBA) regulation in patients diagnosed with Crohn's disease (CD). The study comprised 20 CD patients, including 12 with active disease (CD-A) and 8 in remission (CD-R), as well as 21 healthy controls. Voxel-based morphometry (VBM) was utilized for structural analysis of cerebellar gray matter volume, while independent component analysis (ICA) was applied for functional analysis of cerebellar functional connectivity (FC). The results showed significant GMV reduction in the left posterior cerebellar lobe across all CD patients compared to HCs, with more pronounced differences in the CD-A subgroup. Additionally, an increase in mean FC of the cerebellar network was observed in all CD patients, particularly in the CD-A subgroup, which demonstrated elevated FC in the vermis and bilateral posterior cerebellum. Correlation analysis revealed a positive relationship between cerebellar FC and the Crohn's Disease Activity Index (CDAI) and a trend toward a negative association with the reciprocal of the Self-rating Depression Scale (SDS) score in CD patients. The study's findings suggest that the cerebellum may play a role in the abnormal regulation of the GBA in CD patients, contributing to a better understanding of the neural mechanisms underlying CD and highlighting the cerebellum's potential role in modulating gut-brain interactions.

MYO5B and the Polygenic Landscape of Very Early-Onset Inflammatory Bowel Disease in an Ethnically Diverse Population.

BACKGROUND: Genetic discovery in very early-onset inflammatory bowel disease (VEO-IBD) can elucidate not only the origins of VEO-IBD, but also later-onset inflammatory bowel disease. We aimed to investigate the polygenic origins of VEO-IBD in a cohort with a high proportion of Hispanic patients. METHODS: Patients with VEO-IBD who underwent whole exome sequencing at our center were included. Genes were categorized as genes of interest (GOIs) (129 genes previously described to be associated with VEO-IBD) or non-GOIs. VEO-IBD "susceptibility" single nucleotide variants (SNVs) were identified through enrichment compared with gnomAD (Genome Aggregation Database) and ALFA (Allele Frequency Aggregator) and were scored by Combined Annotation Dependent Depletion for deleteriousness. Gene networks carrying susceptibility SNVs were created. Myosin 5b immunofluorescence was also studied. RESULTS: Fifty-six patients met inclusion criteria, and 32.1% identified as Hispanic. Monogenic disease was infrequent (8.9%). Significant enrichment of GOI susceptibility SNVs was observed, notably in MYO5B, especially in Hispanics. MEFV, TNFAIP3, SH3TC2, and NCF2 were also central participants in the GOI networks. Myosin 5b immunofluorescence in colonic mucosa was significantly reduced in those with MYO5B susceptibility SNVs compared with control subjects. Seven genes (ESRRA, HLA-DQ1, RETSAT, PABPC1, PARP4, CCDC102A, and SUSD2) were central participants in the non-GOI networks. CONCLUSIONS: Our results support the polygenic nature of VEO-IBD, in which key participants, like MYO5B, were identified through network analytics. Rare variant load within susceptibility genes may be relevant not only for the genetic origins of inflammatory bowel disease, but also for the age of disease onset. Our findings could guide future work in precision medicine.

We used a network tool to determine how multiple genes might play a combined role in the development of inflammatory bowel disease and identified key participants in this network, such as MYO5B.

Comparative Safety and Effectiveness of Ustekinumab and Anti-TNF in Elderly Crohn's Disease Patients.

BACKGROUND: Biologic therapies are associated with increased infection risk among elderly patients with inflammatory bowel disease (IBD). However, there are few data on the safety and effectiveness of ustekinumab compared with anti-tumor necrosis factor (anti-TNF) agents in the elderly. METHODS: The study sought to compare the safety and effectiveness of ustekinumab and anti-TNF agents in elderly Crohn's disease (CD) patients. Patients ≥60 years of age who commenced ustekinumab or an anti-TNF agent for CD were included in this retrospective multicenter cohort. The primary outcome was incidence of serious infections requiring hospitalization. Effectiveness was assessed by clinical remission, clinical response, and treatment persistence rates at 6 months. We adjusted for confounders using inverse probability of treatment weighting (IPTW) and performed a logistic regression analysis to assess factors associated with serious infections, clinical remission, and treatment persistence. RESULTS: Eighty-three patients commencing ustekinumab and 124 commencing anti-TNF therapy were included. There was no difference in serious infection rates between anti-TNF agents (2.8%) and ustekinumab (3.1%) (P = .924) after propensity adjustment. Clinical remission rates were comparable at 6 months for ustekinumab (55.9%) and anti-TNF agents (52.4%) (P = .762). There was a significant reduction in HBI at 6 months in both groups. Treatment persistence was comparable between ustekinumab (90.6%) and anti-TNF agents (90.0%) at 6 months. Cox regression analysis did not show differences in treatment persistence (hazard ratio, 1.23; 95% confidence interval, 0.57-2.61; P = .594) and serious infection incidence (hazard ratio, 1.38; 95% confidence interval, 0.25-7.57; P = .709) by 6 months. CONCLUSIONS: We observed comparable safety and effectiveness for ustekinumab and anti-TNF agents in treating elderly CD patients.

In this retrospective multicenter cohort study, we report equal safety and effectiveness for ustekinumab and anti-tumor necrosis factor agents in treating older adults with Crohn's disease over a 6-month period.

Unraveling Twisted Pouch Syndrome: A Narrative Review of Classification, Diagnosis, Treatment, and Prevention.

BACKGROUND: We recently described a cluster of symptoms known as twisted pouch syndrome that rarely affects patients with ileoanal pouches. Herein, we present a narrative review in which we describe the diagnosis, treatment, and prevention of twisted pouch syndrome, with a focus on a simple classification schema. METHODS: Diagnostic signs from endoscopic and radiological examinations, treatment, and prevention strategies are presented. RESULTS: Patients with twisted pouch syndrome suffer from a triad of obstructive symptoms, erratic bowel habits, and pain which may be severe, debilitating visceral pain, all in the setting of a mechanical pouch abnormality. Diagnostic modalities include imaging, careful pouchoscopy, functional testing, diagnostic laparoscopy or laparotomy, and recently 3-dimensional pouchography. Classification of twisted pouch syndrome is based on the location and degree of rotation of the pouch and its mesentery. Outlet twists may result when the distal pouch rotates >90° to 360° clockwise inadvertently during anastomosis; when only the distal most pouch is twisted, it results in an iris-like deformity of the pouch outlet, or when the distal half of the pouch is twisted, a mid-pouch stenosis and an hourglass-shaped pouch may result. Inlet twists are either a full 360° (mesentery posterior), unintentional 180° (mesentery anterior), or 90° counterclockwise twists. Both inlet and outlet twists are fixed deformities and may only be reduced by disconnecting the entire pouch from the anus. If they result in twisted pouch syndrome, a redo pouch procedure or pouch excision is required to reduce the twist; 90° counterclockwise twists may undergo pouch inlet transposition. Adhesive twists result when the pouch becomes fixed in the pelvis in an abnormal configuration, such as when the efferent limb becomes twisted underneath the afferent limb secondary to an occult tip of the J leak, and may be reduced by pelvic adhesiolysis with or without pouch revision. CONCLUSIONS: Pouches may rarely be inadvertently twisted during construction or twisted owing to adhesive disease or leaks. A high index of suspicion is needed to establish the diagnosis. We present a simple classification of twisted pouch syndrome that may aid in the prevention and recognition of these often difficult to diagnose postoperative complications.

In this article, we report a simple classification system for the mechanical pouch complication known as twisted pouch syndrome, including diagnostic signs from endoscopic and radiological examinations, treatment, and prevention strategies.

One-year Safety and Effectiveness of Ustekinumab in Patients With Crohn's Disease: The K-STAR Study.

BACKGROUND: This study investigated the safety and effectiveness of ustekinumab (UST) in Korean patients with Crohn's disease (CD). METHODS: Adult patients with CD treated with UST were prospectively enrolled in the K-STAR (Post-MarKeting Surveillance for Crohn's Disease patients treated with STelARa) study between April 2018 and April 2022. Both the clinical effectiveness and adverse effects of UST therapy were analyzed. Missing data were handled using nonresponder imputation (ClinicalTrials.gov Identifier: NCT03942120). RESULTS: Of the 464 patients enrolled from 44 hospitals across Korea, 457 and 428 patients (Crohn's disease activity index ≥150) were included in the safety analysis and effectiveness analysis sets, respectively. At weeks 16 to 20 after initiating UST, clinical response, clinical remission, and corticosteroid-free remission rates were 75.0% (321 of 428), 64.0% (274 of 428), and 61.9% (265 of 428), respectively. At week 52 to 66, clinical response, clinical remission, and corticosteroid-free remission rates were 62.4% (267 of 428), 52.6% (225 of 428), and 50.0% (214 of 428), respectively. Combined effectiveness (clinical response + biochemical response) was achieved in 40.0% (171 of 428) and 41.6% (178 of 428) at week 16 to 20 and week 52 to 66, respectively. Biologic-naïve patients exhibited significantly higher rates of combined effectiveness than biologic-experienced patients (50.3% vs 30.7% at week 16-20, P < .001; 47.7% vs 36.0% at week 52-66, P = .014). No additional benefits were observed with the concomitant use of immunomodulators. Ileal location was independently associated with a higher probability of clinical remission compared with colonic or ileocolonic location at week 52 to 66. Adverse and serious adverse events were observed in 28.2% (129 of 457) and 12.7% (58 of 457), respectively, with no new safety signal associated with UST treatment. CONCLUSIONS: Ustekinumab was well-tolerated, effective, and safe as induction and maintenance therapy for CD in Korea.

Ustekinumab was well-tolerated and safe for Koran patients with Crohn's disease with no new safety signal as induction and maintenance therapy. Biologic-naïve patients exhibited better effectiveness outcomes, whereas combination therapy with immunomodulators was not superior to ustekinumab monotherapy.

Evaluating the role of large language models in inflammatory bowel disease patient information.

This letter evaluates the article by Gravina et al on ChatGPT's potential in providing medical information for inflammatory bowel disease patients. While promising, it highlights the need for advanced techniques like reasoning + action and retrieval-augmented generation to improve accuracy and reliability. Emphasizing that simple question and answer testing is insufficient, it calls for more nuanced evaluation methods to truly gauge large language models' capabilities in clinical applications.

Diagnostic delay in inflammatory bowel diseases in a German population.

BACKGROUND: Early diagnosis is key to prevent bowel damage in inflammatory bowel disease (IBD). Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients exists. AIM: To identify risk factors leading to prolonged diagnostic time in a German IBD cohort. METHODS: Between 2012 and 2022, 430 IBD patients from four Berlin hospitals were enrolled in a prospective study and asked to complete a 16-item questionnaire to determine features of the path leading to IBD diagnosis. Total diagnostic time was defined as the time from symptom onset to consulting a physician (patient waiting time) and from first consultation to IBD diagnosis (physician diagnostic time). Univariate and multivariate analyses were performed to identify risk factors for each time period. RESULTS: The total diagnostic time was significantly longer in Crohn's disease (CD) compared to ulcerative colitis (UC) patients (12.0 vs 4.0 mo; P < 0.001), mainly due to increased physician diagnostic time (5.5 vs 1.0 mo; P < 0.001). In a multivariate analysis, the predominant symptoms diarrhea (P = 0.012) and skin lesions (P = 0.028) as well as performed gastroscopy (P = 0.042) were associated with longer physician diagnostic time in CD patients. In UC, fever was correlated (P = 0.020) with shorter physician diagnostic time, while fatigue (P = 0.011) and positive family history (P = 0.046) were correlated with longer physician diagnostic time. CONCLUSION: We demonstrated that CD patients compared to UC are at risk of long diagnostic delay. Future efforts should focus on shortening the diagnostic delay for a better outcome in these patients.

Epidemiology of pediatric inflammatory bowel disease categorized by age subgroups in Korea.

BACKGROUND: Pediatric inflammatory bowel disease (PIBD) affects different age groups and its incidence is increasing worldwide. However, there is a lack of research focusing on age subgroups in Asian countries. In this nationwide population-based study, we investigated the epidemiology of PIBD among different age subgroups in Korea. METHODS: We analyzed Korean health administration data from 2005 to 2016. Data were divided by age at diagnosis as follows: group 1, 0-1 years; group 2, 2-5 years; group 3, 6-9 years; group 4, 10-16 years. We analyzed the overall incidence, temporal changes, and regional differences by age subgroups, using Poisson regression analysis. RESULTS: From 2005 to 2016, 2734 inflammatory bowel disease (IBD) cases were diagnosed among patients under 17 years of age. In the overall population, the incidence rate of PIBD over the entire study period was 2.248/105 person-years (PY), significantly increasing from 1.173/105 PY in 2005-2007 to 3.267/105 PY in 2014-2016. The incidence rates in groups 1 and 2 remained unchanged, whereas those of groups 3 and 4 increased significantly. The same trend was observed when analyzed separately for Crohn's disease (CD) and ulcerative colitis (UC). The incidence rates of CD in groups 3 and 4 showed differences between metropolitan and non-metropolitan areas, whereas those in groups 1 and 2, and UC of all age subgroups showed no difference. CONCLUSIONS: The temporal trend and regional differences of PIBD differed among age subgroups, suggesting that genetic and environmental factors have varying impacts on IBD development across different subgroups.

Real-World Long-Term Persistence and Surgical Procedure-Free Period Among Bio-naïve Patients with Crohn's Disease and Fistula Initiated on Ustekinumab.

INTRODUCTION: Fistula is a common complication of Crohn's disease (CD). Treatment with biologics has been associated with fistula healing. Long-term persistence is an important factor for a chronic inflammatory process such as fistula. This study described 24-month persistence and time-to-surgery endpoints among bio-naïve patients with CD and intestinal fistula who were initiated on ustekinumab. METHODS: Adults with CD and any enteric or perianal fistula initiated on ustekinumab (index date) between September 23, 2016, and March 2, 2022, were selected from the IQVIA PharMetrics® Plus database and followed up to 24 months. Persistence on ustekinumab (no gaps in days of supply of > 120 days) and composite endpoints of being persistent while on monotherapy and persistent while corticosteroid free were also assessed. The date of surgery was defined as the date of first claim for any CD-related surgeries. Persistence and time-to-surgery endpoints were assessed from the index date until the earliest of discontinuation (event), immunomodulator or other biologic use (event), corticosteroid use (event), date of surgery (event), 24-month follow-up or data end (censoring) using Kaplan-Meier analyses. RESULTS: The sample included 445 patients (mean age: 42.8 years; 56.6% female). The most common type of fistula was anal fistula (36.0%). At 24 months after ustekinumab initiation, 64.2% of patients remained persistent (95% confidence interval [CI] 55.8-71.4). Furthermore, 53.3% of patients were persistent while on monotherapy (95% CI 45.1-60.7), and 45.6% of patients were persistent while being corticosteroid free (95% CI 36.9-53.8). At 24 months, 22.8% (95% CI 17.0-30.3) of patients underwent any CD-related surgery. CONCLUSION: This study quantified long-term persistence on ustekinumab among bio-naïve patients with CD and fistula. Over half of patients initiated on ustekinumab were persistent and persistent while on monotherapy 24 months after initiation. Time-to-surgery estimate was comparable to existing evidence. These findings support ustekinumab as a treatment option for long-term management of CD with fistula.