Pediatric stricturing Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disease of the digestive tract. The incidence of pediatric CD is increasing and is currently 2.5-11.4 per 100000 world-wide. Notably, approximately 25% of children with CD develop stricturing CD (SCD) that requires intervention. Symptomatic stricturing diseases refractory to pharmacological management frequently require non-pharmacological interventions. Non-pharmacological therapeutic strategies include endoscopic balloon dilatation, stricturoplasty, and surgical resection of the strictured segment. However, strictures tend to recur postoperatively regardless of treatment modality. The lifetime risk of surgery in patients with childhood SCD remains at 50%-90%. Thus, new and emerging strategies, advanced diagnostic tools, and minimally invasive approaches are under investigation to improve the outcomes and overall quality of life of pediatric patients with SCD.

Is There Evidence of Crohn's Disease Exclusion Diet (CDED) in Remission of Active Disease in Children and Adults? A Systematic Review.

Crohn's disease (CD) is an inflammatory bowel disease. Previous research has explored the impact of diet on CD, as specific dietary components can influence gut microbiota and immune responses, contributing to damage in the gastrointestinal tract. The Crohn's Disease Exclusion Diet (CDED) is based on an exclusion diet; it is a recent dietary approach that is often used alongside partial enteral nutrition (PEN) and aims to induce disease remission by excluding certain dietary components. This study assesses the current evidence for the effectiveness of the CDED + PEN in achieving remission in both children and adults with active CD. Our systematic review followed PRISMA recommendations and was registered in PROSPERO with CRD number 42022335076. The searched databases were PubMed/MEDLINE, Cochrane Library, Scopus, and Web of Science. The included studies were analyzed using Rayyan software, and the risk of bias was assessed with Cochrane RevMan 5.0 software. The primary assessed outcome was clinical remission, evaluated with validated questionnaire scores such as PCDAI, CDAI, or HBI. All analyzed papers yielded promising results. Notably, the CDED + PEN demonstrated better tolerance than exclusive enteral nutrition (EEN), resulting in higher adherence rates. Therefore, the CDED + PEN appears to be a viable alternative for induction remission in active disease for both children and adults with CD.

Pre-Diagnosis Diet Predicts Response to Exclusive Enteral Nutrition and Correlates with Microbiome in Pediatric Crohn Disease.

Exclusive enteral nutrition (EEN) is effective in inducing remission in pediatric Crohn disease (CD). EEN alters the intestinal microbiome, but precise mechanisms are unknown. We hypothesized that pre-diagnosis diet establishes a baseline gut microbiome, which then mediates response to EEN. We analyzed prospectively recorded food frequency questionnaires (FFQs) for pre-diagnosis dietary patterns. Fecal microbiota were sequenced (16SrRNA) at baseline and through an 18-month follow-up period. Dietary patterns, Mediterranean diet adherence, and stool microbiota were associated with EEN treatment outcomes, disease flare, need for anti-tumor necrosis factor (TNF)-α therapy, and long-term clinical outcomes. Ninety-eight patients were included. Baseline disease severity and microbiota were associated with diet. Four dietary patterns were identified by FFQs; a "mature diet" high in fruits, vegetables, and fish was linked to increased baseline microbial diversity, which was associated with fewer disease flares (p < 0.05) and a trend towards a delayed need for anti-TNF therapy (p = 0.086). Baseline stool microbial taxa were increased (Blautia and Faecalibacterium) or decreased (Ruminococcus gnavus group) with the mature diet compared to other diets. Surprisingly, a "pre-packaged" dietary pattern (rich in processed foods) was associated with delayed flares in males (p < 0.05). Long-term pre-diagnosis diet was associated with outcomes of EEN therapy in pediatric CD; diet-microbiota and microbiota-outcome associations may mediate this relationship.

Washed microbiota transplantation for Crohn's disease: A metagenomic, metatranscriptomic, and metabolomic-based study.

BACKGROUND: Fecal microbiota transplantation (FMT) is a promising therapeutic approach for treating Crohn's disease (CD). The new method of FMT, based on the automatic washing process, was named as washed microbiota transplantation (WMT). Most existing studies have focused on observing the clinical phenomena. However, the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome, metatranscriptome, and metabolome-has not yet been reported. AIM: To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT. METHODS: We conducted a prospective, open-label, single-center clinical study. Eleven CD patients underwent WMT. Their clinical responses (defined as a decrease in their CD Activity Index score of > 100 points) and their microbiome (metagenome, metatranscriptome) and metabolome profiles were evaluated three months after the procedure. RESULTS: Seven of the 11 patients (63.6%) showed an optimal clinical response three months post-WMT. Gut microbiome diversity significantly increased after WMT, consistent with improved clinical symptoms. Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains, such as Faecalibacterium prausnitzii, Roseburia intestinalis, and Escherichia coli. In addition, metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors. However, levels of vital amino acids that may be associated with disease progression (e.g., L-glutamic acid, gamma-glutamyl-leucine, and prolyl-glutamine) were reduced after WMT. CONCLUSION: WMT demonstrated therapeutic efficacy in CD treatment, likely due to the effective reconstruction of the patient's microbiome. Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.

Gut metabolome and microbiota signatures predict response to treatment with exclusive enteral nutrition in a prospective study in children with active Crohn's disease.

BACKGROUND: Predicting response to exclusive enteral nutrition (EEN) in active Crohn's disease (CD) could lead to therapy personalization and pretreatment optimization. OBJECTIVES: This study aimed to explore the ability of pretreatment parameters to predict fecal calprotectin (FCal) levels at EEN completion in a prospective study in children with CD. METHODS: In children with active CD, clinical parameters, dietary intake, cytokines, inflammation-related blood proteomics, and diet-related metabolites, metabolomics and microbiota in feces, were measured before initiation of 8 wk of EEN. Prediction of FCal levels at EEN completion was performed using machine learning. Data are presented with medians (IQR). RESULTS: Of 37 patients recruited, 15 responded (FCal < 250 µg/g) to EEN (responders) and 22 did not (nonresponders). Clinical and immunological parameters were not associated with response to EEN. Responders had lesser (µmol/g) butyrate [responders: 13.2 (8.63-18.4) compared with nonresponders: 22.3 (12.0-32.0); P = 0.03], acetate [responders: 49.9 (46.4-68.4) compared with nonresponders: 70.4 (57.0-95.5); P = 0.027], phenylacetate [responders: 0.175 (0.013-0.611) compared with nonresponders: 0.943 (0.438-1.35); P = 0.021], and a higher microbiota richness [315 (269-347) compared with nonresponders: 243 (205-297); P = 0.015] in feces than nonresponders. Responders consumed (portions/1000 kcal/d) more confectionery products [responders: 0.55 (0.38-0.72) compared with nonresponders: 0.19 (0.01-0.38); P = 0.045]. A multicomponent model using fecal parameters, dietary data, and clinical and immunological parameters predicted response to EEN with 78% accuracy (sensitivity: 80%; specificity: 77%; positive predictive value: 71%; negative predictive value: 85%). Higher taxon abundance from Ruminococcaceae, Lachnospiraceae, and Bacteroides and phenylacetate, butyrate, and acetate were the most influential variables in predicting lack of response to EEN. CONCLUSIONS: We identify microbial signals and diet-related metabolites in feces, which could comprise targets for pretreatment optimization and personalized nutritional therapy in pediatric CD.

Multicenter registry of pediatric inflammatory bowel disease from a developing country.

BACKGROUND: Despite the rising incidence of pediatric inflammatory bowel disease (PIBD) globally, multicenter collaborative studies of PIBD children among developing countries remain sparse. We therefore aimed to define the initial presentation and short-term outcomes of Thai children with PIBD from a multicenter registry. METHODS: Four teaching hospitals participated in this study. A diagnosis of PIBD requires gastrointestinal endoscopy and histopathology in children aged < 19 years. Besides demographics, we collected clinical information and treatment with the data at 1-year follow up. RESULTS: We included 35 Crohn's disease (CD), one IBD-unclassified, and 36 ulcerative colitis (UC) children (total n = 72 with 60.6% males). The mean age at diagnosis was 7.9 years (SD 4.1) with 38% being very early onset IBD (VEO-IBD). When compared with UC, the CD children were more likely to exhibit fever (42.3 vs. 13.9%), weight loss/failure to thrive (68.6 vs. 33.3%), and hypoalbuminemia (62.9 vs. 36.1%) but less likely to have bloody stools (51.4 vs. 91.7%) (all P < 0.05). No significant differences in demographics, clinical data and medications used with regards to VEO-IBD status. At 1 year after diagnosis (n = 62), 30.7% failed to enter clinical remission and 43.7% remained on systemic corticosteroids. Diarrhea (OR 9.32) and weight issues (OR 4.92) at presentation were independent predictors of failure to enter clinical remission; and females (OR 3.08) and CD (vs. UC) (OR 3.03) were predictors of corticosteroids use at 1-year follow-up. CONCLUSIONS: A high proportion of VEOIBD is noted, and CD was more likely to present with significant inflammatory burden. Diarrhea and weight issues at presentation were independent predictors of failure to enter clinical remission; and females and CD (vs. UC) were predictors of corticosteroids use at 1-year follow-up.

Perceptions, behaviours and barriers towards exercise practices in inflammatory bowel disease.

Inflammatory bowel disease (IBD), a chronic disease affecting the digestive tract, has a significant impact on health-related quality of life. Pharmaceutical treatment is typically adopted, yet exercise is increasingly becoming recognized as an adjunct therapy. This study aimed to explore the perspectives, behaviours, and barriers of IBD patients in terms of their exercise habits. A 16-item closed-ended questionnaire was completed by 463 adult IBD patients (Ulcerative colitis = 57.02%, Crohn's dis-ease = 40.60% and Other = 2.38%) (Female = 76.67%, Male = 22.46 and Non-binary = 0.86%). The questionnaire was divided into three sections: baseline/demographic characteristics, disease characteristics, and exercise perceptions, beliefs, and behaviours. Significantly (P<0.001) more participants (63.07%) reported that they engage regularly with exercise compared to those who do not; however, engagement was significantly lower in female patients (59.72%) compared to males (74.04%). Respondents also rated significantly (P<0.001) that a combination of factors prevents engagement in exercise (74.30%). Moderate intensity exercise was the predominant (P<0.001) aerobic modality (39.04%), the majority (P<0.001) response was that patients undertake no resistance training (27.74%), and significantly more (P<0.001) patients indicated that they don't know whether resistance training can influence IBD either positively (57.53%) or negatively (62.33%). Whilst it is encouraging that IBD patients are engaging regularly with exercise, the reduced levels of engagement in females and lack of knowledge/ engagement with resistance training, indicate that future implementation and educational developments are necessary to enhance exercise in females and resistance training engagement in all IBD patients.

Prognosis of Patients with Crohn's Disease and Ulcerative Colitis Following Percutaneous Coronary Intervention Procedures.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk after percutaneous coronary intervention (PCI). OBJECTIVES: To compare the clinical outcomes within 30 days, one year, and five years of undergoing PCI. METHODS: We conducted a retrospective cohort study of adult patients with IBD who underwent PCI in a tertiary care center from January 2009 to December 2019. RESULTS: We included 44 patients, 26 with Crohn's disease (CD) and 18 with ulcerative colitis (UC), who underwent PCI. Patients with CD underwent PCI at a younger age compared to UC (57.8 vs. 68.9 years, P < 0.001) and were more likely to be male (88.46% of CD vs. 61.1% of UC, P < 0.03). CD patients had a higher rate of non-steroidal treatment compared to UC patients (50% vs. 5.56%, P < 0.001). Acute coronary syndromes (ACS) and/or the need for revascularization (e.g., PCI) were the most common clinical events to occur following PCI, in both groups. Of patients who experienced ACS and/or unplanned revascularization within 5 years, 25% of UC vs. 40% of CD had target lesion failure (TLF) due to in-stent restenosis and 10% of CD had TLF due to stent thrombosis. CONCLUSIONS: We observed higher rates of TLF in IBD patients compared to the general population as well as differences in clinical outcomes between UC and CD patients. A better understanding of the prognostic factors and pathophysiology of these differences may have clinical importance in tailoring the appropriate treatment or type of revascularization for this high-risk group.

Efficacy of exclusive enteral nutrition on the mucosal healing of different gastrointestinal segments in children with Crohn's disease.

OBJECTIVE: To investigate the association between disease location and segmental mucosal healing (SMH) following exclusive enteral nutrition (EEN) in children with Crohn's disease (CD). METHODS: Treatment-naive pediatric patients with endoscopically active CD treated with EEN alone as induction therapy were retrospectively enrolled from January 1, 2017 to June 30, 2022. The simple endoscopic score for CD (SES-CD) was employed to score disease activity in the upper gastrointestinal (GI) tract (esophagus, stomach, duodenum), rectum, left colon, transverse colon, right colon, and terminal ileum. While the Lewis score assessed that of the small bowel from the jejunum to the proximal ileum (except the terminal ileum). The variation in the total scores for each segment and SES-CD subscores for each ileocolonic segment from baseline to 1 year after EEN therapy and the segmental endoscopic outcomes and potential predictors associated with SMH for the segments scored by SES-CD were evaluated. RESULTS: Overall, 82 children with CD were enrolled. Except for the upper GI segment, scores in other segments declined significantly from baseline to EEN completion (all P < 0.001). We analyzed 486 segments (79, 80, 81, 82, 82 and 82 from upper GI tract, terminal ileum, right colon, transverse colon, left colon, and rectum) and found that the segmental SES-CD at baseline (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.55-0.70, P < 0.001) and upper GI location (OR 0.25, 95% CI 0.11-0.55, P = 0.001) were associated with SMH at EEN completion. CONCLUSION: Disease location of the upper GI segment in pediatric CD was associated with SMH following EEN therapy.

STRUCTURAL EVALUATION OF INFLAMMATORY BOWEL DISEASE COMPREHENSIVE CARE UNITS IN BRAZIL.

BACKGROUND: The most efficient way to prevent complications from inflammatory bowel disease (IBD) is to provide patients with optimized care. Nonetheless, in Brazil, there is no validated methodology for evaluating health services recognized as comprehensive care units (CCU), making it difficult to assess the quality of care provided. OBJECTIVE: To understand the current scenario, map the distribution of centers and identify strengths and weaknesses, considering local and regional characteristics. METHODS: The study was carried out in three phases. Initially, the Brazilian Organization for Crohn's disease and colitis (GEDIIB) developed 22 questions to characterize CCU in Brazil. In the second phase, all GEDIIB members were invited to respond to the survey with the 11 questions considered most relevant. In the last phase, an interim analysis of the results was performed, using the IBM SPSS Statistics v 29.0.1.0 software. Descriptive statistics were used to characterize the center's profile. The chi-square test was used to compare categorical variables. RESULTS: There were 53 responses from public centers (11 excluded). Most centers were concentrated in the Southeastern (n=22/52.4%) and only 1 (2.4%) in the Northern region of Brazil. Thirty-nine centers (92.9%) perform endoscopic procedures, but only 9 (21.4%) have access to enteroscopy and/or small bowel capsule endoscopy. Thirty-three centers (78.6%) offer infusion therapy locally, 26 (61.9%) maintain IBD patient records, 13 (31.0%) reported having an IBD nurse, 34 (81.0%) have specific evidence-based protocols and only 7 (16.7%) have a patient satisfaction methodology. In the private scenario there were 56 responses (10 excluded). There is also a concentration in the Southeastern and Southern regions. Thirty-nine centers (84.8%) have access to endoscopic procedures and 19 perform enteroscopy and/or small bowel capsule endoscopy, more than what is observed in the public environment. Infusion therapy is available in 24 centers (52.2%). Thirty-nine centers (84.8%) maintain a specific IBD patient database, 17 (37%) have an IBD nurse, 36 (78.3%) have specific evidence-based protocols, and 22 (47. 8%) apply a patient satisfaction methodology. CONCLUSION: IBD CCU in Brazil were mainly located in the Southeastern and Southern regions of the country. Most centers have dedicated multidisciplinary teams and IBD specialists. There is still a current need to improve the proportion of IBD nurses in IBD care in Brazil. BACKGROUND: •In Brazil, there is no validated methodology for evaluating health services recognized as comprehensive care units (CCU), making it difficult to assess the quality of care provided. BACKGROUND: •Most CCU were concentrated in the Southeast region and only one (2.4%) in the Northeast region of Brazil. This pattern follows the epidemiological trends of IBD in the country. BACKGROUND: •There is still difficulty in accessing enteroscopy and/or small bowel capsule endoscopy in the public health system. BACKGROUND: •Most centers have dedicated multidisciplinary teams and IBD specialist doctors. BACKGROUND: •There is still a current need to improve the proportion of nurses treating IBD in Brazil.

Crohn's disease.

Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract that might lead to progressive bowel damage and disability. The exact cause of Crohn's disease is unknown, but evidence points towards multifactorial events causing dysregulation of the innate immune system in genetically susceptible people. Commonly affecting the terminal ileum and proximal colon, Crohn's disease inflammation is often discontinuous and patchy, segmental, and transmural. Identification of characteristic findings on ileocolonoscopy and histology remains the diagnostic gold standard, but complete assessment involves laboratory abnormalities, including micronutrient deficiencies, cross-sectional imaging to identify transmural disease extent, severity and complications, and a psychosocial assessment. Treatment strategies for patients with Crohn's disease now go beyond achieving clinical remission to include deeper targets of endoscopic healing and consideration of adjunctive histological and transmural targets to alter disease progression potentially further. The use of early effective advanced therapies and development of therapies targeting alternative novel pathways with improved safety profiles have resulted in a new era of healing in Crohn's disease management. Future combination of advanced therapies with diet or other biological drugs and small molecules, together with improvements in tight control monitoring tools and predictive biomarkers might continue to improve outcomes for patients with Crohn's disease.

Understanding the role of the primary care physician in the management of patients with Crohn's perianal fistulas.

OBJECTIVES: To understand the role of primary care physicians (PCPs) in the recognition, diagnosis, and management of Crohn's perianal fistulas (CPF) and their referral patterns and treatment expectations. METHODS: This survey-based study was conducted between September 2020 and October 2020. US-based PCPs managing at least one patient with Crohn's disease per week were included. Participants were presented with two case vignettes relevant to primary care practice; Case Vignette 1 comprised three parts and focused on initial CPF presentation and progression to partial response; Case Vignette 2 focused on recurrent CPF. Survey questions elicited the physician's clinical approach to each case. Data were presented as descriptive statistics. RESULTS: Overall, 151 PCPs (median 23 years in practice) who saw about three patients per month with new/existing CPF responded. For Case Vignette 1, upon identification of a fistulous tract, 89% of respondents would refer the patient, mostly to a colorectal surgeon or gastroenterologist. Most PCPs (69%) would begin the patient on medication; 46% would conduct a diagnostic/imaging study. Treatment expectations after referral varied: 55% of respondents believed surgeons would place a seton or use one prior to surgery; 23% expected medical management only; 23% were unsure. Case Vignette 2 revealed that 98% of PCPs preferred to be involved in patient care after referral; however, only 49% were. Of these, 76% considered reinforcing patient treatment adherence as their primary role. While 80% of PCPs were at least moderately satisfied with communication and care coordination with multidisciplinary teams, 52% considered lack of access to specialists as at least a moderate barrier to multidisciplinary team management. CONCLUSION: PCPs want more involvement in multidisciplinary management of patients with CPF. Continuing education providing PCPs with up-to-date information on diagnostic modalities, treatment options, early diagnosis, the role of PCPs within a multidisciplinary team, and effective initial CPF care is required.

What were the study's aims?To understand how primary care physicians recognize, treat, and monitor patients with Crohn's disease-related perianal fistulas (small tunnels between the bowel and skin near the anus).How was the study done?US-based primary care physicians, including internists, were included if they had experience in treating patients with Crohn's disease. Descriptions of the history and symptoms of two hypothetical patients were provided: one patient who may have Crohn's perianal fistulas and another patient whose Crohn's perianal fistulas had returned after being treated. After reading these descriptions, the physicians completed a questionnaire designed to show how they would help each patient.What did the study find out?Not all physicians treat patients with Crohn's perianal fistulas in the same way in terms of diagnostic tests and medical treatments, although most said they would refer them to a specialist if a fistula was identified. Many wanted to be involved in patient care after referral to a specialist but only half were. Of those, most thought their main role was to ensure patients followed the treatments given by specialists. More than half of primary care physicians thought a lack of access to specialists could be a barrier to care.How does this impact care?The physicians surveyed want more involvement in multidisciplinary teams who look after patients with Crohn's perianal fistulas. To do this, they need more education about the diagnosis and treatment of Crohn's perianal fistulas, and clarity around their role within multidisciplinary teams who manage these patients.

An update on dietary therapies in paediatric Crohn's disease.

PURPOSE OF REVIEW: This article provides a literature update on original articles published in the past 18 months (May 2022-November 2023) in the dietary management of paediatric Crohn's disease. RECENT FINDINGS: There is more data to support the use of exclusive enteral nutrition in the management of active Crohn's disease in children. Several food-based dietary therapies have been proposed for the management of Crohn's disease. There is an interest in precision nutritional therapy in Crohn's disease, but current data are scarce. SUMMARY: Exclusive enteral nutrition is an effective treatment for paediatric Crohn's disease. Predictors of response to exclusive enteral nutrition include mild disease phenotype and ileal disease involvement, although data remain inconclusive. Adherence to exclusive enteral nutrition is cornerstone to its efficacy. Treatment with exclusive enteral nutrition modifies the gut microbiome, modulates bile acid metabolism and has significant effects on host immune responses. More studies are expected in which drugs need to be combined with dietary therapies and microbial therapeutics. The efficacy of Crohn's disease exclusion diet coupled with partial enteral nutrition is supported by independent studies, but tolerance remains an issue, particularly for long-term disease management. More research is anticipated in precision nutritional therapy in paediatric Crohn's disease, but currently no recommendations can be made.

Precision nutrition in pediatric IBD: A position paper from the ESPGHAN special interest group for basic science and translational research, the IBD Porto group, and allied health professionals.

Stratified and precision nutrition refers to disease management or prevention of disease onset, based on dietary interventions tailored to a person's characteristics, biology, gut microbiome, and environmental exposures. Such treatment models may lead to more effective management of inflammatory bowel disease (IBD) and reduce risk of disease development. This societal position paper aimed to report advances made in stratified and precision nutritional therapy in IBD. Following a structured literature search, limited to human studies, we identified four relevant themes: (a) nutritional epidemiology for risk prediction of IBD development, (b) food-based dietary interventions in IBD, (c) exclusive enteral nutrition (EEN) for Crohn's disease (CD) management, and (d) pre- and probiotics for IBD management. There is scarce literature upon which we can make recommendations for precision or stratified dietary therapy for IBD, both for risk of disease development and disease management. Certain single-nucleotide polymorphisms related to polyunsaturated fatty acid (PUFA) metabolism may modify the effect dietary PUFA have in increasing the risk of IBD development. Non-colonic CD, mild-to-moderate CD, and high microbiota richness may predict success of EEN and may be used both for prediction of treatment continuation, but also for early cessation in nonresponders. There is currently insufficient evidence to make recommendations for precision or stratified dietary therapy for patients with established IBD. Despite the great interest in stratified and precision nutrition, we currently lack data to support conclusive recommendations. Replication of early findings by independent research groups and within structured clinical interventions is required.

Efficacy and safety of stem cell therapy for Crohn's disease: a meta-analysis of randomized controlled trials.

PURPOSE: Small-scale clinical trials have provided evidence suggesting the effectiveness of stem-cell therapy (SCT) for patients diagnosed with Crohn's disease (CD). The objective of the research was to systematically assess the effectiveness and safety of SCT for individuals diagnosed with CD through a comprehensive review and meta-analysis. METHODS: A search was conducted in Medline (PubMed), CENTER (Cochrane Library), and Embase (Ovid) to find randomized controlled trials (RCTs) that assessed the impact of SCT on the occurrence of clinical remission (CR) and severe adverse events (SAE) among patients diagnosed with CD. The Cochrane Q test and estimation of I2 were used to assess heterogeneity among studies. After incorporating heterogeneity, a random-effects model was employed for data pooling. RESULTS: Overall, 12 RCTs involving 632 adult patients with medically refractory CD or CD-related fistula were included. In comparison with placebo or no treatment, SCT showed a greater likelihood of CR (odds ratio [OR] 2.08, 95% CI 1.39-3.12, p < 0.001) without any notable heterogeneity (I2 = 0%). Consistent results were observed in subgroup analyses based on study design, patient diagnosis, source and type of stem cells, and follow-up durations, with all p-values for subgroup analyses being greater than 0.05. The occurrence of SAE was similar among patients assigned to SCT and the placebo/no treatment cohorts (OR 0.70, 95% CI 0.37-1.33, p = 0.28; I2 = 0%). CONCLUSIONS: For patients with medically refractory CD or CD-related fistula, SCT may be an alternatively effective and safe treatment.

Perianal fistulizing Crohn's disease: Current perspectives on diagnosis, monitoring and management with a focus on emerging therapies.

Crohn's disease (CD), a chronic inflammatory bowel disorder, manifests in various phenotypes, with fistulizing perianal CD (CD-PAF) being one of its most severe phenotypes. Characterized by fistula formation and abscesses, CD-PAF impacts 17% to 34% of all CD cases and with a significantly deleterious impact on patient's quality of life, while increasing the risk for anorectal cancers. The pathogenesis involves a complex interplay of genetic, immunological and environmental factors, with cytokines such as tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-ß) playing pivotal roles. Diagnostic protocols require a multi-disciplinary approach including colonoscopy, examination under anesthesia and magnetic resonance imaging. In terms of treatment, biologics alone often prove inadequate, making surgical interventions such as setons and fistula surgeries essential. Emerging therapies such as mesenchymal stem cells are under study. The South Asian context adds layers of complexity, including diagnostic ambiguities related to high tuberculosis prevalence, healthcare access limitations and cultural stigma toward perianal Crohn's disease and ostomy surgery. Effective management necessitates an integrated, multi-disciplinary approach, especially in resource-constrained settings. Despite advances, there remain significant gaps in understanding the disease's pathophysiology and a dearth of standardized outcome measures, underscoring the urgent need for comprehensive research.

Challenges in the diagnosis and treatment of inflammatory bowel disease in Latin America.

The incidence and prevalence of inflammatory bowel disease (IBD), namely Crohn's disease and ulcerative colitis, have increased in Latin America over the past few decades. Although incidence is accelerating in some countries in the region, other areas in Latin America are already transitioning into the next epidemiological stage-ie, compounding prevalence-with a similar epidemiological profile to the western world. Consequently, more attention must be given to the diagnosis and management of IBD in Latin America. In this Review, we provide an overview of epidemiology, potential local environmental risk factors, challenges in the management of IBD, and limitations due to the heterogenity of health-care systems, both public and private, in Latin America. Unresolved issues in the region include inadequate access to diagnostic resources, biological therapies, tight disease monitoring (including treat to target therapy, surveillance and prevention of complications, drug monitoring), and specialised IBD surgery. Local guidelines are an important effort to overcome barriers in IBD management. Advancements in long-term health-care policies will be important to promote early diagnosis, access to new treatments, and improvements in research in Latin America. These improvements will not only affect overall health care but will also lead to optimal prioritisation of IBD-related costs and resources and enhance the quality of life of people with IBD in Latin America.

Infliximab for maintenance of medically-induced remission in Crohn's disease.

BACKGROUND: Infliximab is a monoclonal antibody that binds and neutralises tumour necrosis factor-alpha (TNF-α) which is present in high levels in the blood serum, mucosa and stool of patients with Crohn's disease. OBJECTIVES: To determine the efficacy and safety of infliximab for maintaining remission in patients with Crohn's disease. SEARCH METHODS: On 31 August, 2021 and 23 June, 2023, we searched CENTRAL, Embase, MEDLINE, ClinicalTrials.gov, and WHO ICTRP. SELECTION CRITERIA: Randomised controlled trials (RCTs) in which infliximab was compared to placebo or another active comparator for maintenance, remission, or response in patients with Crohn's disease. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently selected studies and conducted data extraction and risk of bias assessment. We expressed outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using GRADE. Our primary outcome was clinical relapse. Secondary outcomes were loss of clinical response, endoscopic relapse, and withdrawal due to serious and adverse events. MAIN RESULTS: Nine RCTs with 1257 participants were included. They were conducted between 1999 and 2022; seven RCTs included biologically-naive patients, and the remaining two included a mix of naive/not naive patients. Three studies included patients in clinical remission, five included patients with a mix of activity scores, and one study included biologic responders with active disease at baseline. All studies allowed some form of concomitant medication during their duration. One study exclusively included patients with fistulating disease. The age of the participants ranged from 18 to 69 years old. All but one single-centre RCT were multicentre RCTs. Four studies were funded by pharmaceutical companies, two had a mix of commercial and public funding, and two had public funding. Infliximab is probably superior to placebo in preventing clinical relapse in patients who have mixed levels of clinical disease activity at baseline, and are not naive to biologics (56% vs 75%, RR 0.73, 95% CI 0.63 to 0.84, NNTB = 5, moderate-certainty evidence). We cannot draw any conclusions on loss of clinical response (RR 0.59, 95% CI 0.37 to 0.96), withdrawals due to adverse events (RR 0.66, 95% CI 0.37 to 1.19), or serious adverse events (RR 0.60, 95% CI 0.36 to 1.00) because the evidence is very low certainty. Infliximab combined with purine analogues is probably superior to purine analogues for clinical relapse (12% vs 59%, RR 0.20, 95% CI 0.10 to 0.42, NNTB = 2, moderate-certainty evidence), for patients in remission, and who are not naive to biologics. We cannot draw any conclusions on withdrawals due to adverse events (RR 0.47, 95% CI 0.15 to 1.49), and serious adverse events (RR 1.19, 95% CI 0.54 to 2.64) because the evidence is very low certainty. We cannot draw any conclusions about the effects of infliximab on serious adverse events compared to purine analogues (RR 0.79, 95% CI 0.37 to 1.68) for a population in remission at baseline because the evidence is very low certainty. There was no evidence available for the outcomes of clinical relapse, loss of clinical response, and withdrawal due to adverse events. Infliximab may be equivalent to biosimilar for clinical relapse (47% vs 40% RR 1.18, 95% CI 0.82 to 1.69), and it may be slightly less effective in averting loss of clinical response (49% vs 32%, RR 1.50, 95% CI 1.01 to 2.23, low-certainty evidence), for a population with mixed/low disease activity at baseline. Infliximab may be less effective than biosimilar in averting withdrawals due to adverse events (27% vs 0%, RR 20.73, 95% CI 2.86 to 150.33, low-certainty evidence). Infliximab may be equivalent to biosimilar for serious adverse events (10% vs 10%, RR 0.99, 95% CI 0.39 to 2.50, low-certainty evidence). We cannot draw any conclusions on the effects of subcutaneous biosimilar compared with intravenous biosimilar on clinical relapse (RR 1.01, 95% CI 0.65 to 1.57), loss of clinical response (RR 0.94, 95% CI 0.70 to 1.25), and withdrawals due to adverse events (RR 0.77, 95% CI 0.30 to 1.97) for an active disease population with clinical response at baseline because the evidence is of very low certainty. We cannot draw any conclusions on the effects of infliximab compared to adalimumab on loss of clinical response (RR 0.68, 95% CI 0.29 to 1.59), withdrawals due to adverse events (RR 0.10, 95% CI 0.01 to 0.72), serious adverse events (RR 0.09, 95% CI 0.01 to 1.54) for an active disease population with clinical response at baseline because the evidence is of very low certainty. There was no evidence available for the outcome of clinical relapse. AUTHORS' CONCLUSIONS: Infliximab is probably more effective in preventing clinical relapse than placebo (moderate-certainty evidence). Infliximab in combination with purine analogues is probably more effective in preventing clinical and endoscopic relapse than purine analogues alone (moderate-certainty evidence). No conclusions can be drawn regarding prevention of loss of clinical response, occurrence of withdrawals due to adverse events, or total adverse events due to very low-certainty evidence for both of these comparisons. There may be little or no difference in prevention of clinical relapse, withdrawal due to adverse events or total adverse events between infliximab and a biosimilar (low-certainty evidence). Infliximab may lead to more loss of clinical response than a biosimilar (low-certainty evidence). We were unable to draw meaningful conclusions about other comparisons and outcomes related to missing data or very low-certainty evidence due to serious concerns about imprecision and risk of bias. Further research should focus on comparisons with other active therapies for maintaining remission, as well as ensuring adequate power calculations and reporting of methods.

Prospective study of an adalimumab combined with partial enteral nutrition in the induction period of Crohn's disease.

BACKGROUND: Adalimumab monotherapy can suppress gut inflammation and induce remission in active Crohn's disease but has some limitations. Exclusive enteral nutrition (EEN) is recommended for patients with mild to moderate Crohn's disease (CD), but implementation is challenging. AIM: To evaluate the effectiveness of adalimumab combined with partial enteral nutrition (PEN) in the induction therapy for Crohn's disease. METHODS: A prospective cohort study was designed and a total of 56 patients with active CD who met the criteria for enteral nutrition (EN) treatment in our hospital were selected. The baseline data of all patients were collected including age, sex and other general information. The changes in fecal calprotectin, C-reactive protein (CRP), albumin(Alb), hemoglobin (Hb), platelets (Plt), erythrocyte sedimentation rate (ESR), Crohn's disease activity index score (CDAI), simple endoscopic score (SES-CD) and body mass index (BMI) were compared between the adalimumab combined with enteral nutrition (ADA+EN) group (N = 37) the adalimumab group (ADA) (N = 19) at week 0 (W0) and treatment outcomes at week 12(W12). Additionally, the differences between the two groups before and after treatment were evaluated. Then the ADA+EN group was divided into an adalimumab combined with exclusive enteral nutrition subgroup (ADA+EEN) and an adalimumab combined with partial nutrition subgroup (ADA+PEN) according to enteral nutrition intake. The changes in fecal calprotectin, CRP, Alb, Hb, Plt, ESR and CDAI, SES-CD and BMI were compared between the  ADA+EEN group and the ADA+PEN group at week 0 (W0) and treatment outcomes at week 12(W12). The differences between the two groups before and after treatment were evaluated. To evaluate the effectiveness of the two treatments on patients' quality of life, nutritional recovery and body composition, patients in the ADA+EN group were needed to complete the Inflammatory Bowel Disease Questionnaire (IBDQ), EQ-5D-5L, the EuroQol visual analogue scale (EQ-VAS) and body composition analysis.A total of 28 patients completed all questionnaires and body composition analyses at week 0 and week 12, including 10 patients in the ADA+EEN group and 18 patients in the ADA+PEN group, respectively. The differences of in IBDQ, EQ-5D-5L and body composition analysis were compared between the two groups at week 0 (W0) and treatment outcomes at week 12(W12). Additionally, the differences between the two groups before and after treatment were evaluated. RESULTS: These investigated indexes such as calprotectin, Hb, Plt, ESR, Alb, BMI, CRP, CDAI and SES-CD scores were significantly different before and after treatment  in the ADA+EN group (p < 0.01). However, fecal calprotectin, Hb, SES-CD scores and Alb in the ADA group were not statistically significantly different from W0 to W12 (p > 0.05). The fecal calprotectin and CDAI scores in the ADA+EN group were significantly lower than those in the ADA group after treatment. The differences in all factors before and after treatment between the ADA+PEN group and the ADA+EEN group were statistically significant (p < 0.05). However, there was no significant difference between the two groups at week 12 (p > 0.05). CONCLUSION: Adalimumab combined with EN are more effective than ADA monotherapy in terms of endoscopy and clinical remission. By comparing the investigated indicators such as calprotectin, Hb, Plt, ESR ,CRP and SES-CD scores, it was proven that adalimumab combined with partial enteral nutrition or exclusive enteral nutrition has the same remission effect in induced Crohn's disease. The combination of biological agents and partial nutrition can improve medical order compliance, psychological burden and quality of life. Therefore, adalimumab combined with partial nutrition can be used as the first-line treatment for CD induced remission.