Engeletin attenuates the inflammatory response via inhibiting TLR4-NFκB signaling pathway in Crohn's disease-like colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Smilax glabra rhizome has a long history been used for clinical purposes in traditional Chinese medicinal for treating various inflammatory conditions. Engeletin1 (ENG) is one of the most abundant bioactive compounds found in Smilax glabra rhizome, with anti-inflammatory, antioxidant, and ulcer-preventing activities. AIM OF THE STUDY: The purpose of this study was to investigate the ability of ENG to alleviate inflammatory symptoms and improve epithelial barrier integrity utilize a 2,4,6-trinitrobenzene sulfonic acid2 (TNBS)-induced murine model in Crohn's disease3 (CD)-like colitis, and to characterize the underlying anti-inflammatory mechanisms of action. MATERIALS AND METHODS: A colitis model was established in BALB/c mice and treated with ENG for 7 days. RAW264.7 macrophages were pre-treated with ENG and lipopolysaccharide4 (LPS) stimulation. The mice's weight and colon length were assessed. qPCR and Western blotting were used to analyze gene expression and TLR4-NFκB pathway. Flow cytometry was used to analyze the polarization states of the macrophages. RESULTS: Treatment with ENG was sufficient to significantly alleviate symptoms of inflammation and colonic epithelial barrier integrity in treated mice. Significant inhibition of TNF-α, IL-1ß, and IL-6 expression was observed following ENG treatment in vivo and in vitro. ENG was also determined to be capable of inhibiting the expression of iNOS and CD86, inhibited M1 macrophage polarization in vitro, as well as the TLR4-NFκB signaling pathway. Molecular docking showed a highly stable binding between ENG and TLR4. CONCLUSION: ENG has been proven to alleviate inflammation and ameliorate the damage of epithelial barrier in CD-like colitis. ENG also suppressed the M1 macrophages polarization and the inhibited inflammatory cytokines. TLR4-NFκB signaling pathway, especially TLR4, may be the target of ENG. These data offer a new insight into the therapeutic mechanisms of ENG.

Epidemiological investigation of different types of Crohn's disease patients undergoing first abdominal surgery in the era of biological agents: a population-based cohort study.

BACKGROUND: Before the era of biological agents, most Crohn's disease patients required at least one intestinal resection surgery after diagnosis. However, clinical data regarding the abdominal surgery rates for Crohn's disease patients in the era of biological agents is not yet fully clear and needs to be updated. MATERIALS AND METHODS: We retrospectively collected clinical data from 1115 Crohn's disease patients diagnosed and treated medically at The Second Xiangya Hospital of Central South University from January 2016 to January 2024. Using abdominal intestinal resection surgery as a clinical outcome, propensity score matching was employed to eliminate confounding factors. We explored the timing and proportion of abdominal surgery in patients with different Montreal classifications of Crohn's disease during the natural course of the disease, as well as the impact of the duration of the natural course and the use of biological agents on surgical outcomes. RESULTS: Montreal classification type B had the greatest impact on Crohn's disease surgery, especially with a higher proportion of type B3 patients undergoing surgery. Type A1 Crohn's disease patients underwent surgery earlier than types A2 and A3. The occurrence of behavior changes (B Change) during the natural course of the disease is a poor prognostic signal, indicating a significantly increased likelihood of surgery. The duration of the natural course from the onset of gastrointestinal symptoms to diagnosis and clinical observation outcomes did not directly affect the likelihood of surgery in Crohn's disease patients. Compared with Crohn's disease patients who did not receive biological agents, the surgery rate was significantly lower in patients who used biological agents. Additionally, Crohn's disease patients who received biological agents within 1 month of diagnosis had a significantly lower likelihood of undergoing surgical intervention. Moreover, Crohn's disease patients who received biological agent treatment within 19 months of the onset of gastrointestinal symptoms also had a significantly lower likelihood of undergoing surgery than other Crohn's disease patients. CONCLUSIONS: In the era of biological agents, the risk of surgical intervention varies among Crohn's disease patients with different Montreal classifications, particularly when there is type B3 disease or a B Change. Clinicians should pay closer attention to surgical indications in such cases. For Crohn's disease patients, shortening the natural course before diagnosis and early use of biological agents after diagnosis can significantly reduce the risk of abdominal surgery.

Subcutaneous infliximab in Crohn's disease patients with previous immunogenic failure of intravenous infliximab.

PURPOSE: Immunogenicity is a major reason for secondary loss of response to infliximab (IFX). Recent work suggested potentially lower immunogenicity of subcutaneous (SC) compared to intravenous (IV) IFX. However, it is unknown whether re-exposure to IFX SC after secondary loss of response and immunogenicity to its intravenous formulation is safe and effective. METHODS: In a retrospective cohort study conducted at two medical centers, patients with clinically (Harvey-Bradshaw Index ≥ 5) and/or biochemically (fecal calprotectin > 250 µg/g) active Crohn's disease (CD) and previous immunogenic failure of IFX IV underwent exposure to IFX SC. Harvey-Bradshaw Index, fecal calprotectin, IFX serum concentration, and anti-drug antibodies were assessed until month 12. RESULTS: Twenty CD patients were included. The majority of patients (90%) had previous treatment with three or more biologics. Fifteen (75%) and ten (50%) of 20 patients continued IFX SC treatment until months 6 and 12, respectively. No immediate hypersensitivity reactions were observed. Two patients discontinued IFX SC treatment because of delayed hypersensitivity at week 2 and week 4. IFX serum concentrations increased from baseline to month 12, while anti-drug antibody levels decreased. Combined clinical and biochemical remission at month 12 was observed in seven of 20 patients (35%). CONCLUSION: Subcutaneous infliximab treatment of Crohn's disease patients with previous immunogenic failure of intravenous infliximab was well tolerated and effective in a cohort of patients with refractory Crohn's disease.

Two-sample Mendelian randomization analysis of causal relationship between eczema and autoimmune diseases. / åŒæ ·æœ¬å­Ÿå¾·å°”éšæœºåŒ–åˆ†æžæ¹¿ç–¹ä¸Žè‡ªèº«å ç–«æ€§ç–¾ç— ä¹‹é—´çš„å› æžœå ³ç³»ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: The causal relationship between eczema and autoimmune diseases has not been previously reported. This study aims to evaluate the causal relationship between eczema and autoimmune diseases. METHODS: The two-sample Mendelian randomization (MR) method was used to assess the causal effect of eczema on autoimmune diseases. Summary data from the Genome-Wide Association Study Catalog (GWAS) were obtained from the Integrative Epidemiology Unit (IEU) database. For eczema and autoimmune diseases, genetic instrument variants (GIVs) were identified according to the significant difference (P<5×10-8). Causal effect estimates were generated using the inverse-variance weighted (IVW) method. MR Egger, maximum likelihood, MR-PRESSO, and MR-RAPS methods were used for alternative analyses. Sensitivity tests, including heterogeneity, horizontal pleiotropy, and leave-one-out analyses, were performed. Finally, reverse causality was assessed. RESULTS: Genetic susceptibility to eczema was associated with an increased risk of Crohn's disease (OR=1.444, 95% CI 1.199 to 1.738, P<0.001) and ulcerative colitis (OR=1.002, 95% CI 1.001 to 1.003, P=0.002). However, no causal relationship was found for the other 6 autoimmune diseases, including systemic lupus erythematosus (SLE) (OR=0.932, P=0.401), bullous pemphigoid (BP) (OR=1.191, P=0.642), vitiligo (OR=1.000, P=0.327), multiple sclerosis (MS) (OR=1.000, P=0.965), ankylosing spondylitis (AS) (OR=1.001, P=0.121), rheumatoid arthritis (RA) (OR=1.000, P=0.460). Additionally, no reverse causal relationship was found between autoimmune diseases and eczema. CONCLUSIONS: Eczema is associated with an increased risk of Crohn's disease and ulcerative colitis. No causal relationship is found between eczema and SLE, MS, AS, RA, BP, or vitiligo.

[Role of diet in the prevention and development of Crohn's Disease]. / Papel de la dieta en la prevención y el desarrollo de la enfermedad de Crohn.

Introduction: Crohn's disease (CD) is a chronic recurrent inflammatory bowel disease (IBD) with frequent ileocolic location, although it can affect the entire gastrointestinal tract. It is characterized by the development of skipped lesions and transmural inflammation and its incidence is increasing. The etiology and pathogenesis are related to genetic susceptibility, intestinal microbiota, dysbiosis, immunological abnormalities and environmental factors (tobacco use, NSAIDs, oral contraceptives and diet). Diet may play a key role in the development and prevention of CD. Dietary patterns with high inflammatory potential (high intake of saturated fat, sugars, proteins, salt, as well as low consumption of fruits and vegetables) are associated with a higher risk of CD, while the consumption of a healthy diet, together with the practice of Exercise is a protective factor against relapses in IBD and reduces the risk of CD. Regarding dietary components, the consumption of fiber, as well as dietary polyphenols, has been related to the maintenance of the intestinal barrier by preventing erosion of the mucosal layer. ω-3 fatty acids, in addition to their anti-inflammatory activity, promote the balance of the intestinal microbiota and their supplementation reduces postoperative complications and accelerates recovery in patients with CD. Vitamin D also plays an important role in the integrity of the intestinal barrier by reducing permeability, in addition to having an immunomodulatory and anti-inflammatory effect, being a useful tool in the improvement of patients with CD. Prebiotics and probiotics may be useful in the treatment of IBD patients by stimulating mucus production, reducing inflammation and dysbiosis, and maintaining the integrity of the intestinal barrier.

Introducción: La enfermedad de Crohn (EC) es una enfermedad inflamatoria intestinal (EII) crónica recurrente con localización frecuente ileocólica, aunque puede afectar a todo el tracto gastrointestinal. Se caracteriza por el desarrollo de lesiones salteadas e inflamación transmural y su incidencia es cada vez mayor. La etiología y la patogénesis está relacionada con la susceptibilidad genética, la microbiota intestinal, la disbiosis, anomalías inmunológicas y factores ambientales (consumo de tabaco, AINE, anticonceptivos orales y la dieta). La dieta puede tener un papel clave en el desarrollo y en la prevención de la EC. Los patrones dietéticos con alto potencial inflamatorio (elevada ingesta de grasa saturada, azúcares, proteínas y sal, así como bajo consumo de frutas y verduras) se asocian con mayor riesgo de EC, mientras que el consumo de una dieta saludable, unida a la práctica de ejercicio, es un factor protector frente a recaídas en EII y disminuye el riesgo de EC. Respecto a los componentes alimentarios, el consumo de fibra, así como de polifenoles dietéticos, se ha relacionado con el mantenimiento de la barrera intestinal al prevenir la erosión de la capa mucosa. Los ácidos grasos ω-3, además de su actividad antiinflamatoria, favorecen el equilibrio de la microbiota intestinal y su suplementación disminuye las complicaciones posoperatorias y acelera la recuperación en pacientes con EC. También la vitamina D desempeña un papel importante en la integridad de la barrera intestinal al disminuir la permeabilidad, además de presentar un efecto inmunomodulador y antiinflamatorio. Es una herramienta útil en la mejora del paciente con EC. Los prebióticos y los probióticos pueden ser útiles en el tratamiento de pacientes con EII al estimular la producción de moco, reducir la inflamación y disbiosis y mantener la integridad de la barrera intestinal.

Management of complications in patients with an ileostomy: an umbrella review of systematic reviews for the EndOTrial Consortium.

BACKGROUND: Standardized clinical care processes for patients with Crohn's disease (CD) and a permanent ileostomy (PI) are lacking. The EndOTrial consortium aims to address this gap by developing pathways for care. METHODS: In this umbrella review, we searched major databases for relevant systematic reviews (SRs) or scoping reviews (ScR) published until January 5, 2024. Screening, data extraction, and quality appraisal (AMSTAR 2) were performed by two independent reviewers. RESULTS: Of 1349 screened papers, 22 reviews met our inclusion criteria, including 20 SRs (eight with meta-analysis) and 2 ScRs. None exclusively focused on PI. Furthermore, nine reviews did not mention patients with inflammatory bowel disease (IBD), and only two reviews included patients with high-output ileostomy, highlighting a large evidence gap. The identified reviews covered six categories with nine types of interventions, including ostomy care pathways, peristomal skin care, patient education, clinical management of high-output stoma, management and prevention of postoperative ileus, dietary and nutritional support, nursing and supporting care, telemedicine, and self-management interventions. Most SRs including nursing interventions for stoma care highlighted nurses' role in a variety of standard and specialized treatments. Notably, none of the reviews exclusively examined disease recurrence, stoma pouching systems or adhesives, behavioral interventions, or mental health in patients living with ileostomy. CONCLUSIONS: Evidence for best practice interventions to treat complications and improve quality of life in patients living with an ileostomy for CD is limited and heterogeneous. These results outline the need for standardized clinical care processes and pathways tailored to the unique needs of this patient population.

Serum amyloid A for predicting prognosis in patients with newly diagnosed Crohn's disease.

OBJECTIVE: Serum amyloid A (SAA) was found to be positively correlated with the activity of Crohn's disease (CD); however, its prognostic value remains uncertain. Here, we examined its predictive ability in newly diagnosed CD and explored genetic association. METHODS: This retrospective cohort study included patients newly diagnosed as CD at the First Affiliated Hospital of Sun Yat-sen University between June 2010 and March 2022. We employed receiver operating characteristic curve, Cox proportional hazard regression models and restricted cubic splines to investigate the prognostic performance of SAA for surgery and disease progression. To assess possible causality, a two-sample Mendelian randomisation (MR) of published genome-wide association study data was conducted. RESULTS: During 2187.6 person-years (median age, 28 years, 72.4% male), 87 surgery and 153 disease progression events were documented. A 100-unit increment in SAA level generated 14% higher risk for surgery (adjusted HR (95% CI): 1.14 (1.05-1.23), p=0.001) and 12% for disease progression (1.12 (1.05-1.19), p<0.001). Baseline SAA level ≥89.2 mg/L led to significantly elevated risks for surgery (2.08 (1.31-3.28), p=0.002) and disease progression (1.72 (1.22-2.41), p=0.002). Such associations were assessed as linear. Adding SAA into a scheduled model significantly improved its predictive performances for surgery and disease progression (p for net reclassification indexes and integrated discrimination indexes <0.001). Unfortunately, no genetic causality between SAA and CD was observed in MR analysis. Sensitivity analyses showed robust results. CONCLUSION: Although causality was not found, baseline SAA level was an independent predictor of surgery and disease progression in newly diagnosed CD, and had additive benefit to existing prediction models.

UnTWISTing intestinal fibrosis: single-cell transcriptomics deciphers fibroblast heterogeneity, uncovers molecular pathways, and identifies therapeutic targets.

Intestinal fibrosis is a severe complication of Crohn's disease, often requiring surgical intervention. Despite extensive research efforts, an effective treatment to prevent or reverse intestinal fibrosis remains elusive. In this issue of the JCI, Zhang, Wang, and colleagues employed single-cell RNA sequencing to uncover mechanisms of the fibrotic process. They identified a key fibroblast subset of TWIST1+FAP+ cells that interacts with CXCL9+ macrophages. TWIST1 emerged as a central regulator of the fibrotic microenvironment, representing a promising therapeutic target for effectively treating intestinal fibrosis.

Evaluation of adverse clinical outcomes in patients with inflammatory bowel disease receiving different sequences of first- and second-line biologic treatments: findings from ROTARY.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at risk of developing dysplasia and, subsequently, colorectal cancer (CRC) owing to chronic inflammation. Patients may also experience other severe disease complications, such as hospitalization and surgery. Several biologics are available for the treatment of patients with IBD and some patients require multiple lines of treatment owing to loss of response or tolerability to their prescribed biologic. Previous studies suggest that the choice of initial biologic treatment may impact the outcomes of later treatment lines. In this study, we assessed adverse clinical outcomes in patients with Crohn's disease (CD) or ulcerative colitis (UC) who received different biologic treatment sequences. METHODS: ROTARY part B was a retrospective cohort study using the Optum® Clinical Database that evaluated the incidences of IBD-related hospitalization, IBD-related surgery, dysplasia, CRC, and infections in patients with CD or UC who received two biologics successively. First-line biologics included adalimumab, infliximab, ustekinumab (CD only), and vedolizumab; second-line biologics included infliximab and adalimumab. RESULTS: In patients with CD, the treatment sequence of ustekinumab to infliximab was associated with the highest overall incidences of hospitalization (51.9%), surgery (40.7%), CRC (3.7%), and infection (37.0%). Vedolizumab followed by an anti-tumor necrosis factor alpha (anti-TNFα) treatment was associated with a significantly lower risk of experiencing an adverse medical event (hospitalization, surgery, or infection) than two successive anti-TNFα treatments (odds ratio, 1.526; 95% confidence interval, 1.004-2.320; P < 0.05). In patients with UC, the treatment sequence of vedolizumab to adalimumab resulted in the lowest overall incidence of adverse outcomes (20.3%, 6.3%, 0.0%, 6.3%, and 4.7% for hospitalization, surgery, CRC, dysplasia, and infection, respectively). CONCLUSIONS: We describe differences in adverse clinical outcomes associated with sequencing of biologics in patients with CD or UC and demonstrate favorable results in patients who received vedolizumab as a first-line biologic. These results provide potential guidance to clinicians choosing sequences of biologic treatments in patients with IBD.

A disturbed metabolite-GPCR axis is associated with microbial dysbiosis in IBD patients: Potential role of GPR109A in macrophages.

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by disrupted immune function. Indeed, gut microbiota dysbiosis and metabolomic profile alterations, are hallmarks of IBD. In this scenario, metabolite-sensing G-protein coupled receptors (GPCRs), involved in several biological processes, have emerged as pivotal players in the pathophysiology of IBD. The aim of this study was to characterize the axis microbiota-metabolite-GPCR in intestinal surgical resections from IBD patients. Results showed that UC patients had a lower microbiota richness and bacterial load, with a higher proportion of the genus Cellulosimicrobium and a reduced proportion of Escherichia, whereas CD patients showed a decreased abundance of Enterococcus. Furthermore, metabolomic analysis revealed alterations in carboxylic acids, fatty acids, and amino acids in UC and CD samples. These patients also exhibited upregulated expression of most metabolite-sensing GPCRs analysed, which positively correlated with pro-inflammatory and pro-fibrotic markers. The role of GPR109A was studied in depth and increased expression of this receptor was detected in epithelial cells and cells from lamina propria, including CD68+ macrophages, in IBD patients. The treatment with ß-hydroxybutyrate increased gene expression of GPR109A, CD86, IL1B and NOS2 in U937-derived macrophages. Besides, when GPR109A was transiently silenced, the mRNA expression and secretion of IL-1ß, IL-6 and TNF-α were impaired in M1 macrophages. Finally, the secretome from siGPR109A M1 macrophages reduced the gene and protein expression of COL1A1 and COL3A1 in intestinal fibroblasts. A better understanding of metabolite-sensing GPCRs, such as GPR109A, could establish their potential as therapeutic targets for managing IBD.

[A PhD completed. Oral manifestations in inflammatory bowel diseases]. / Serie: Hora est. Orale manifestaties van inflammatoire darmziekten.

Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the gastrointestinal tract. In addition to bowel symptoms, patients may also have oral manifestations. This thesis investigated potential associations between disease activity in the gut, oral health, salivary gland function, and saliva composition. Patients with Crohn's disease had a significantly higher DMFT index, but showed no difference in periodontal diseases compared to a healthy control group. The saliva composition in patients with active bowel disease differed from that in patients with inactive bowel disease, suggesting that saliva analysis could potentially be used in the future to determine the degree and severity of bowel disease. The knowledge of gastroenterologists and dentists regarding oral manifestations of bowel diseases was found to be limited. Gastroenterologists and dentists valued interdisciplinary patient consultation as very useful, but the frequency of consultation was considered insufficient.

ANS-SCMC: A matrix completion method based on adaptive neighbourhood similarity and sparse constraints for predicting microbe-disease associations.

The use of matrix completion methods to predict the association between microbes and diseases can effectively improve treatment efficiency. However, the similarity measures used in the existing methods are often influenced by various factors such as neighbourhood size, choice of similarity metric, or multiple parameters for similarity fusion, making it challenging. Additionally, matrix completion is currently limited by the sparsity of the initial association matrix, which restricts its predictive performance. To address these problems, we propose a matrix completion method based on adaptive neighbourhood similarity and sparse constraints (ANS-SCMC) for predict microbe-disease potential associations. Adaptive neighbourhood similarity learning dynamically uses the decomposition results as effective information for the next learning iteration by simultaneously performing local manifold structure learning and decomposition. This approach effectively preserves fine local structure information and avoids the influence of weight parameters directly involved in similarity measurement. Additionally, the sparse constraint-based matrix completion approach can better handle the sparsity challenge in the association matrix. Finally, the algorithm we proposed has achieved significantly higher predictive performance in the validation compared to several commonly used prediction methods proposed to date. Furthermore, in the case study, the prediction algorithm achieved an accuracy of up to 80% for the top 10 microbes associated with type 1 diabetes and 100% for Crohn's disease respectively.

Chylothorax in a Young Woman With Crohn Disease.

Chylothorax, which accounts for 1% to 3% of pleural effusions, typically results from either surgery (traumatic) or underlying malignancy (nontraumatic). Less common causes of nontraumatic chylothorax are numerous and include congenital lymphatic abnormalities, connective tissue diseases, cirrhosis, and infection, among others.1 We describe what appears to be the first reported case of chylothorax caused by chylous ascites in Crohn disease. This case highlights the importance of using diagnostic evidence to link new symptoms to preexisting diseases whenever possible, as well as the systemic nature of Crohn disease.

Deubiquitinase USP14 is upregulated in Crohn's disease and inhibits the NOD2 pathway mediated inflammatory response in vitro.

The nucleotide binding oligomerization domain containing 2 (NOD2) protein and its ligand N-acetyl muramyl dipeptide (MDP) are crucially involved in Crohn's disease (CD). However, the mechanism by which NOD2 signaling is regulated in CD patients remains unclear. Ubiquitin specific protease (USP14) is a deubiquitylase that plays an important role in immunity. This study aimed to investigate the mechanism by which UPS14 regulates NOD2 induced inflammatory response in CD and inflammatory bowel diseases (IBD). Our results showed that USP14 protein and mRNA levels in intestinal tissues of CD patients were significantly higher than those in healthy controls. In addition, USP14 was upregulated in IBD mouse model. While treatment with MDP, TNF-α or the Toll-like receptor 1/2 agonist Pam3CSK4 all led to significantly higher mRNA levels of TNF-α, IL-8 and IL-1ß in THP-1 cells, pretreatment with USP14 inhibitor IU1 could stimulate further upregulation of TNF-α, IL-8 and IL-1ß. In particular, MDP promoted the activation of JNK, ERK1/2 and p38 as well as NF-kB in THP-1 cells, and IU1 significantly enhanced the MDP-induced activation of these proteins without effects on USP14 protein level. Furthermore, the JNK inhibitor sp600125, ERK1/2 inhibitor U0126 or P38 MAPK inhibitor PD169316 significantly decreased the mRNA levels of TNF-α, IL-8 and IL-1ß in THP-1 cells stimulated by both IU1 and MDP. In conclusion, our findings suggest that USP14 could inhibit MDP-induced activation of MAPK signaling and the inflammation response involved in IBD, and that USP14 is a potential therapeutic target for IBD.

[Impact of short-peptide exclusive enteral nutrition therapy on physical growth and nutritional status in children with Crohn's disease]. / çŸ­è‚½åž‹å ¨è‚ å† è¥å »ç–—æ³•å¯¹å ‹ç½—æ©ç— æ‚£å„¿ä½“æ ¼ç”Ÿé•¿åŠè¥å »çŠ¶æ€çš„å½±å“.

OBJECTIVES: To evaluate the clinical efficacy of short-peptide exclusive enteral nutrition (EEN) therapy in inducing remission during active Crohn's disease (CD) in children, as well as changes in physical growth and nutritional indicators before and after treatment. METHODS: A prospective study included 43 children with active CD who were admitted to the Department of Gastroenterology, Children's Hospital of Nanjing Medical University from January 2017 to January 2024. The participants were randomly divided into a medication treatment group (13 children) and a short-peptide + medication treatment group (30 children). The changes in the Pediatric Crohn's Disease Activity Index (PCDAI) scores, physical growth, and nutritional indicators before and after treatment were analyzed in both groups. RESULTS: The PCDAI scores in the short-peptide + medication treatment group were lower than those in the medication treatment group after treatment (P<0.05). The Z-scores for weight-for-age, body mass index, and albumin levels were higher in the short-peptide + medication treatment group compared to the medication treatment group (P<0.05). In the patients with moderate to severe CD, total protein levels in the short-peptide + medication treatment group were significantly higher than those in the medication treatment group (P<0.05). CONCLUSIONS: Short-peptide EEN therapy can induce clinical remission in children with active CD and promote their physical growth while improving their nutritional status.

[A case report of Crohn's disease in a child with trisomy 8]. / ä¼´8å·æŸ“è‰²ä½“ä¸‰ä½“çš„å„¿ç«¥å ‹ç½—æ©ç— 1例报告.

The patient is a 12-year-old male who has experienced recurrent perianal abscesses for over 10 years, along with recurrent oral ulcers and deformities in the joints of hands and feet. Gastrointestinal endoscopy and capsule endoscopy revealed multiple ulcers in the digestive tract. Combined with his histopathological examinations, the patient was diagnosed with Crohn's disease. Whole exome sequencing and peripheral blood karyotype analysis indicated a karyotype of 47,XY,+8. The patient was treated with a "step-up" strategy. His clinical symptoms were under control, with significant improvement observed during endoscopic examination. This case suggests that early-onset inflammatory bowel disease may have genetic susceptibility, and when accompanied by other multi-system involvement, the possibility of chromosomal abnormalities, such as trisomy 8, should be considered and given due attention.

Causal association of inflammatory bowel disease with sarcoidosis and the mediating role of primary biliary cholangitis.

Objectives: Previous observational epidemiological studies have identified a potential association between inflammatory bowel disease (IBD) and sarcoidosis. Nonetheless, the precise biological mechanisms underlying this association remain unclear. Therefore, we adopted a Mendelian randomization (MR) approach to investigate the causal relationship between IBD with genetic susceptibility to sarcoidosis, as well as to explore the potential mediating role. Methods: The genetic associations were obtained from publicly available genome-wide association studies (GWASs) of European ancestry. The IBD dataset has 31,665 cases and 33,977 controls, consisting of 13,768 individuals with ulcerative colitis (UC) and 17,897 individuals with Crohn's disease (CD). The genetic associations of sarcoidosis with 4,854 cases and 446,523 controls. A bidirectional causality between IBD and sarcoidosis was implemented to be determined by a two-sample MR approach. The inverse variance weighted (IVW) method was utilized as the main statistical method, and a series of sensitivity analyses were performed to detect heterogeneity and horizontal pleiotropy. A two-step MR approach was used to investigate whether the mediating pathway from IBD to sarcoidosis was mediated by PBC. Results: The forward MR analysis indicated that genetic predisposition to IBD was significantly linked to an increased risk of sarcoidosis (OR = 1.088, 95% CI: 1.023-1.158, pIBD-sar = 7.498e-03). Similar causal associations were observed in CD (OR = 1.082, 95% CI: 1.028-1.138, pCD-sar = 2.397e-03) and UC (OR = 1.079, 95% CI: 1.006-1.158, pUC-sar = 0.034). Reverse MR analysis revealed that genetic susceptibility to sarcoidosis was correlated with an augmented risk of CD (OR = 1.306, 95% CI: 1.110-1.537, psar-CD = 1.290e-03) but not IBD or UC. The mediation analysis via two-step MR showed that the causal influence of IBD and CD on sarcoidosis effects was partly mediated by PBC, and the mediating effect was 0.018 (95% CI: 0.005-0.031, p = 7.596e-03) with a mediated proportion of 21.397% in IBD, and 0.014 (95% CI: 0.004-0.024, p = 7.800e-03) with a mediated proportion of 17.737% in CD. Conclusions: The MR analysis provided evidence substantiating the causal effect of IBD (CD and UC) on an increased risk of sarcoidosis, with PBC playing a mediating role in IBD and CD. However, sarcoidosis only enhances the risk of developing CD, but not IBD or UC. These findings illuminate the etiology of sarcoidosis and contribute to the management of IBD patients.

Effect of Kono-S anastomosis on reducing postoperative recurrence rates in Crohn's disease: a systematic review and meta-analysis.

BACKGROUND: Kono-S anastomosis has gained increasing interest although evaluation of its impact on reducing Crohn's recurrence shows conflicting results. This study aimed to evaluate the short- and long-term outcomes for patients with Crohn's disease requiring surgery with Kono-S compared to conventional anastomosis. METHODS: A systematic review and meta-analysis included patients with Crohn's disease treated with bowel resection and Kono-S anastomosis reconstruction versus a comparator arm of conventional anastomosis technique. Recurrence outcomes examined were endoscopic recurrence rates, mean postoperative Rutgeerts score, surgical recurrence, clinical recurrence, and postoperative biologics use. Short-term postoperative outcomes include anastomotic leaks, surgical site infection, postoperative ileus, and mean operative time. RESULTS: A total of 873 studies were identified with 15 remaining after abstract review encompassing 1501 patients, 765 with Kono-S and 736 with conventional anastomosis. Recurrence was significantly lower in the Kono-S arm, with endoscopic recurrence rates of 41% vs 48% (RR 0.86, 95% CI 0.73-1.00, p = 0.05) and surgical recurrence rates of 2.7% vs 21.0% (RR 0.13, 95% CI 0.06-0.30, p < 0.001). There was a significantly lower anastomotic leak rate in the Kono-S arm when compared to conventional anastomosis, 1.7% vs 4.9% (RR 0.37, 95% CI 0.19-0.74, p = 0.005). Mean operative time was similar between both groups. CONCLUSIONS: Kono-S is a safe and feasible anastomotic technique with lower rates of endoscopic and surgical postoperative recurrence. While we await further trials to substantiate this benefit, Kono-S anastomosis should be considered as an important tool in the armamentarium of a surgeon in anastomotic construction to reduce recurrence.