In this article,we explored the role of adipose tissue,especially mesenteric adipose tissue and creeping fat,and its association with the gut microbiota in the pathophysiology and progression of Crohn’s disease(CD).C...In this article,we explored the role of adipose tissue,especially mesenteric adipose tissue and creeping fat,and its association with the gut microbiota in the pathophysiology and progression of Crohn’s disease(CD).CD is a form of inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract,influenced by genetic predisposition,gut microbiota dysbiosis,and environmental factors.Gut microbiota plays a crucial role in modulating immune response and intestinal inflammation and is associated with the onset and progression of CD.Further,visceral adipose tissue,particularly creeping fat,a mesenteric adipose tissue characterized by hypertrophy and fibrosis,has been implicated in CD pathogenesis,inflammation,and fibrosis.The bacteria from the gut microbiota may translocate into mesenteric adipose tissue,contributing to the formation of creeping fat and influencing CD progression.Although creeping fat may be a protective barrier against bacterial invasion,its expansion can damage adjacent tissues,leading to complications.Modulating gut microbiota through interventions such as fecal microbiota transplantation,probiotics,and prebiotics has shown potential in managing CD.However,more research is needed to clarify the mechanisms linking gut dysbiosis,creeping fat,and CD progression and develop targeted therapies for microbiota modulation and fat-related complications in patients with CD.展开更多
BACKGROUND Mucosal healing has become an important goal of Crohn’s disease(CD)treat-ments.Modulen,enriched with transforming growth factor-beta 2,and budeso-nide are commonly accepted treatments for mild-moderate CD....BACKGROUND Mucosal healing has become an important goal of Crohn’s disease(CD)treat-ments.Modulen,enriched with transforming growth factor-beta 2,and budeso-nide are commonly accepted treatments for mild-moderate CD.However,their effects on the small bowel(SB)mucosa remain underexplored.AIM To prospectively assess clinical and mucosal responses to Modulen vs budesonide in adults with CD,using SB capsule endoscopy.METHODS Thirty patients were divided into two groups:Modulen+home-based diet(21 patients)and budesonide(9 patients)for an eight-week intervention followed by four weeks of follow-up.Clinical,laboratory,and endoscopic responses were evaluated.The mucosal changes were assessed through SB capsule endoscopy.RESULTS Results indicated significant clinical improvement in the Modulen group with reduced CD activity index(P=0.041)and improved inflammatory bowel disease questionnaire score(P=0.016).Moreover,Modulen was associated with a signifi-cant SB mucosal improvement,evidenced by a decrease in Lewis score(P=0.027).No significant changes were observed in calprotectin or other laboratory parame-ters.Conversely,budesonide exhibited more modest clinical effects,but it improved calprotectin,hemoglobin,and C-reactive protein levels(P=0.051,P=0.014,and P=0.038,respectively).The capsule endoscopy did not reveal a significant mucosal response in the budesonide group.CONCLUSION Both interventions have a role in CD treatment.Yet,their effects differ and may complement each other:Modulen yields clinical and mucosal improvements,while budesonide primarily leads mainly to laboratory improvements.展开更多
BACKGROUND Mucosal healing(MH)is the major therapeutic target for Crohn's disease(CD).As the most commonly involved intestinal segment,small bowel(SB)assessment is crucial for CD patients.Yet,it poses a significan...BACKGROUND Mucosal healing(MH)is the major therapeutic target for Crohn's disease(CD).As the most commonly involved intestinal segment,small bowel(SB)assessment is crucial for CD patients.Yet,it poses a significant challenge due to its limited accessibility through conventional endoscopic methods.AIM To establish a noninvasive radiomic model based on computed tomography enterography(CTE)for MH assessment in SBCD patients.METHODS Seventy-three patients diagnosed with SBCD were included and divided into a training cohort(n=55)and a test cohort(n=18).Radiomic features were obtained from CTE images to establish a radiomic model.Patient demographics were analysed to establish a clinical model.A radiomic-clinical nomogram was constructed by combining significant clinical and radiomic features.The diagnostic efficacy and clinical benefit were evaluated via receiver operating characteristic(ROC)curve analysis and decision curve analysis(DCA),respectively.RESULTS Of the 73 patients enrolled,25 patients achieved MH.The radiomic-clinical nomogram had an area under the ROC curve of 0.961(95%confidence interval:0.886-1.000)in the training cohort and 0.958(0.877-1.000)in the test cohort and provided superior clinical benefit to either the clinical or radiomic models alone,as demonstrated by DCA.CONCLUSION These results indicate that the CTE-based radiomic-clinical nomogram is a promising imaging biomarker for MH and serves as a potential noninvasive alternative to enteroscopy for MH assessment in SBCD patients.展开更多
Extensive research has investigated the etiology of Crohn’s disease(CD),encompassing genetic predisposition,lifestyle factors,and environmental triggers.Recently,the gut microbiome,recognized as the human body’s sec...Extensive research has investigated the etiology of Crohn’s disease(CD),encompassing genetic predisposition,lifestyle factors,and environmental triggers.Recently,the gut microbiome,recognized as the human body’s second-largest gene pool,has garnered significant attention for its crucial role in the patho-genesis of CD.This paper investigates the mechanisms underlying CD,focusing on the role of‘creeping fat’in disease progression and exploring emerging therapeutic strategies,including fecal microbiota transplantation,enteral nutri-tion,and therapeutic diets.Creeping fat has been identified as a unique patho-logical feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome.We characterize this dysbiotic state by identi-fying key microbiome-bacteria,fungi,viruses,and archaea,and their contributions to CD pathogenesis.Additionally,this paper reviews contemporary therapies,empha-sizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions.By elucidating the complex interactions between host-microbiome dynamics and CD pathology,this article aims to advance our under-standing of the disease and guide the development of more effective therapeutic strategies for managing CD.展开更多
Introduction: Crohn’s Disease (CD) is a chronic inflammatory disorder with a heterogeneous presentation. While diarrhea, abdominal pain, and weight loss are hallmarks, atypical manifestations can obscure the diagnosi...Introduction: Crohn’s Disease (CD) is a chronic inflammatory disorder with a heterogeneous presentation. While diarrhea, abdominal pain, and weight loss are hallmarks, atypical manifestations can obscure the diagnosis. This report highlights an unusual presentation of CD to emphasize the need for comprehensive diagnostic strategies. Case Report: A 25-year-old male presented with peripheral edema, anorexia, and abdominal distension but lacked classic gastrointestinal (GI) symptoms. Laboratory findings included microcytic anemia and hypoalbuminemia, while imaging revealed ascites and bowel wall thickening. Elevated fecal calprotectin and positive Anti-Saccharomyces cerevisiae antibodies (ASCA) supported the diagnosis. Endoscopy confirmed ileocolic Crohn’s Disease (L3 + L4). Infliximab therapy resulted in marked clinical improvement. Discussion: This case underscores the complexity of atypical CD presentations. Early use of serological markers, imaging, and endoscopy guided the diagnosis. Recognition of CD’s diverse manifestations is critical for timely intervention. Conclusion: Atypical CD presentations require heightened clinical suspicion and a multidisciplinary approach to reduce diagnostic delays and improve patient outcomes.展开更多
BACKGROUND Discordance between endoscopic and histologic assessments in Crohn’s disease(CD)have been observed,however the prevalence and cause are unclear.AIM To assess if a protocolized approach to biopsy collection...BACKGROUND Discordance between endoscopic and histologic assessments in Crohn’s disease(CD)have been observed,however the prevalence and cause are unclear.AIM To assess if a protocolized approach to biopsy collection facilitates understanding of this discordance in patients with ileal CD.METHODS Patients with known ileal CD underwent colonoscopy with endoscopic disease activity assessment.Three protocolized biopsies were taken respectively from an ulcer edge,7-mm,and 14-mm away from the ulcer edge in patients with discrete ileal ulcer(s).In patients with no ulcers as controls,the same 3-site biopsy protocol was applied in a randomly selected area of endoscopically-unremarkable terminal ileal mucosa.A blinded pathologist assessed mucosal inflammation in each biopsy using 3 validated histologic indices.RESULTS Twenty-four participants had visible ulcer(s)on endoscopy and 12 served as no-ulcer controls.Of biopsies taken from an ulcer edge,only 67%showed histologic evidence of active(neutrophilic)inflammation,and 33%showed histologic features of ulcer or erosion;all were from either large(n=4)or very large(n=4)ulcers.In the no-ulcer controls,no biopsies showed histologic features of ulcer or erosion,but 8%showed active inflammation.CONCLUSION A striking discordance exists between endoscopic and histologic assessments for mucosal inflammation in patients with active ileal CD,even in biopsies targeted at an ulcer edge,while a higher concordance is seen in patients with no endoscopic disease activity.It remains unclear how to incorporate histologic disease activity into the treatment paradigm.Further research is needed to optimize biopsy protocols and histologic assessments for CD.展开更多
Perianal fistulising Crohn’s disease is a challenging complication that can affect up to 20%of patients with Crohn’s disease and is associated with significant morbidity.Despite advances in medical therapies,particu...Perianal fistulising Crohn’s disease is a challenging complication that can affect up to 20%of patients with Crohn’s disease and is associated with significant morbidity.Despite advances in medical therapies,particularly anti-tumor necrosis factor agents,the majority of patients still require surgical intervention.Accurate diagnosis and monitoring are essential to optimise outcomes and guide multidisciplinary management.Although clinical scoring systems such as the perianal disease activity index are widely used,their subjective application limits their reproducibility and reliability,underscoring the need for more objective methods of evaluating perianal fistulising Crohn’s disease activity.Imaging has thus become central to the objective assessment of perianal fistulising Crohn’s disease,with magnetic resonance imaging(MRI)recognised as the gold standard in view of its ability to provide clear,detailed images of the perianal region in a radiation-free manner.Guidelines also endorse the use of imaging modalities such as endoanal ultrasound and transperineal ultrasound as viable alternatives to MRI for the assessment of perianal fistulising Crohn’s disease in centres with appropriate expertise.This article aims to evaluate and compare the diagnostic accuracy and clinical utility of MRI,endoanal ultrasound,and transperineal ultrasound in the assessment of perianal fistulising Crohn’s disease,highlighting their respective strengths,limitations,and roles in clinical practice.展开更多
BACKGROUND At present,there is a lack of non-invasive indicators to evaluate the changes in endoscopic activity between two visits for patients with Crohn's disease(CD).AIM To develop a model for predicting whethe...BACKGROUND At present,there is a lack of non-invasive indicators to evaluate the changes in endoscopic activity between two visits for patients with Crohn's disease(CD).AIM To develop a model for predicting whether endoscopic activity will improve in CD patients.METHODS This is a single-center retrospective study that included patients diagnosed with CD from January 2014 to December 2022.The patients were randomly divided into a modeling group(70%)and an internal validation group(30%),with an external validation group from January 2023 to March 2024.Univariate and binary logistic regression analyses were conducted to identify independent risk factors,which were used to construct a nomogram model.The model's performance was evaluated using receiver operating characteristic curves,calibration curves,and decision curve analysis(DCA).Additionally,further sensitivity analyses were performed.RESULTS One hundred seventy patients were included in the training group,while 64 were included in the external validation group.A binary logistic stepwise regression analysis revealed that the changes in the amplitudes of albumin(ALB)and fibrinogen(FIB)were independent risk factors for endoscopic improvement.A nomogram model was developed based on these risk factors.The area under the curve of the model for the training group,internal validation group,and external validation group were 0.802,0.788,and 0.787,respectively.The average absolute errors of the calibration curves were 0.011,0.016,and 0.018,respectively.DCA indicated that the model performs well in clinical practice.Additionally,sensitivity analysis demonstrated that the model has strong robustness and applicability.CONCLUSION Our study shows that changes in the amplitudes of ALB and FIB are effective predictors of endoscopic improvement in patients with CD during follow-up visits compared to their previous ones.展开更多
This article explores the significant implications of the study by Ovadia et al,which innovatively compares the efficacy of a nutritional intervention(Modulen)to conventional pharmaceutical therapy(budesonide)in promo...This article explores the significant implications of the study by Ovadia et al,which innovatively compares the efficacy of a nutritional intervention(Modulen)to conventional pharmaceutical therapy(budesonide)in promoting mucosal healing in Crohn’s disease.Highlighting the paradox of a well-established yet underutilized nutritional approach,the findings suggest that Modulen may offer comparable therapeutic benefits despite its high withdrawal rate due to adherence challenges.This advancement underscores the evolving paradigm in inflammatory bowel disease treatment,shifting focus toward non-pharmacologic alternatives that target both clinical remission and endoscopic healing.The article advocates for the development of integrative treatment strategies that balance efficacy,patient adherence,and long-term disease management,emphasizing the need for further research to refine and optimize the role of nutritional therapies in clinical practice.展开更多
The recent study published by Lee et al examined the discrepancies between endoscopic and histologic evaluations of mucosal inflammation in active ileal Crohn’s disease(CD).While this research contributes to our unde...The recent study published by Lee et al examined the discrepancies between endoscopic and histologic evaluations of mucosal inflammation in active ileal Crohn’s disease(CD).While this research contributes to our understanding of the limitations of current biopsy protocols,it raises several concerns about the generalizability of its findings,sample size,and methodology.One major limitation was the exclusion of patients with ileal strictures,ileostomies,or J-pouches,which reduced the applicability of the results to the wider CD population.Furthermore,the biopsy protocol's focus on single biopsies from specific locations may inadequately capture the patchy inflammation characteristic of CD.The study also uses histologic indices primarily developed for ulcerative colitis,which may not be suitable for assessing CD.It is recommended that multi-center studies be conducted and histologic indices specific to CD be developed to improve the relevance of future research.Additionally,researchers should consider the influence of treatment regimens on the findings.Addressing these limitations would enhance the clinical significance of the study and inform better diagnostic and therapeutic approaches for CD.展开更多
Objectives:A common side effect of inflammatory bowel disease(IBD)is intestinal fibrosis,which frequently leads to intestinal blockage and stricture formation.Although Thalidomide(THD)has shown anti-fibrotic benefits ...Objectives:A common side effect of inflammatory bowel disease(IBD)is intestinal fibrosis,which frequently leads to intestinal blockage and stricture formation.Although Thalidomide(THD)has shown anti-fibrotic benefits in hepatic and renal models,little is known about how it affects intestinal fibrosis and the underlying processes.The present research examines the molecular targets of THD and its potential as a treatment for intestinal fibrosis brought on by colitis.Methods:Clinical samples from Crohn’s disease(CD)patients with intestinal strictures treated with infliximab(IFX)and THD combined with IFX were collected.Dextran sulfate sodium(DSS)was used to develop a mouse model of intestinal fibrosis in C57BL/6 mice.Anti-tumor necrosis factor-alpha(Anti-TNFα),THD,or a combination of the two were administered to the mice.Body weight,colon length,histology,and disease activity index were used to evaluate the disease’s severity.In vitro,THD was tested on colonic fibroblast lines(CCD-18Co and MPF)to assess its effects on cell proliferation,motility,and transdifferentiation.To examine changes in gene expression and signaling pathway modifications,namely in the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)pathway,RNA sequencing,qRT-PCR,and Western blotting were carried out.Results:In DSS-induced colitis,THD therapy lowered fibrosis,as seen by downregulated fibrotic markers(α-smooth muscle actin(α-SMA),collagen I,and collagen III)and decreased collagen deposition.Mechanistically,THD prevented fibroblasts from transdifferentiating and decreased their vitality.Furthermore,THD inhitited the PI3K/AKT/mTOR pathway in vivo and in vitro.Conclusion:THD inhibits the PI3K/AKT/mTOR signaling cascade and suppresses colonic fibroblast transdifferentiation,which protects against DSS-induced colitis-associated fibrosis,especially when combined with anti-TNFαtherapy.展开更多
BACKGROUND Second-line treatment of Crohn’s disease(CD)commonly involves immunosuppressants such as azathioprine,mercaptopurine,or methotrexate(MTX),used either alone or in combination.AIM To investigate the current ...BACKGROUND Second-line treatment of Crohn’s disease(CD)commonly involves immunosuppressants such as azathioprine,mercaptopurine,or methotrexate(MTX),used either alone or in combination.AIM To investigate the current use of MTX among French gastroenterologists.METHODS An online questionnaire was distributed between March and August 2023 to 116 French gastroenterologists managing CD.A total of 87 respondents completed the survey and were included in the analysis.RESULTS Respondents reported a mean annual caseload of 140 CD patients(median:50).Overall,71%prescribed MTX,predominantly in injectable form(92%),either as monotherapy or in combination with biologics or cyclosporin.MTX was prescribed for mild-to-moderate CD by 64%of respondents,and for severe CD by 58%,often in combination with an anti-tumor necrosis factor agent(89%and 94%,respectively).Injectable MTX was favored(84%)in specific clinical scenarios:Patients with articular manifestations(77%),Epstein-Barr virus-negative status(65%),or aged over 65 years(58%).Among the 29%of non-prescribers,the primary reason cited was lack of familiarity with MTX use(60%).Both prescribers and non-prescribers expressed the need for clearer guidelines and real-world data to support MTX use.CONCLUSION Regardless of prescribing habits,most respondents had a favorable opinion of MTX and recognized its good longterm safety profile.French learned societies and medical associations should provide consensus guidelines on MTX use,supported by validated real-world safety and effectiveness data.展开更多
BACKGROUND In the biologic era,postoperative recurrence(POR)of Crohn’s disease(CD)remains a significant concern.The underlying cause of this phenomenon remains unclear at present.AIM To examine whether intestinal fib...BACKGROUND In the biologic era,postoperative recurrence(POR)of Crohn’s disease(CD)remains a significant concern.The underlying cause of this phenomenon remains unclear at present.AIM To examine whether intestinal fibrosis increases the likelihood of POR when antitumor necrosis factor biologics are used following ileocecal resection(ICR).METHODS We performed a single-centre,retrospective cohort study of patients with CD who underwent ICR.Recurrence was defined by endoscopy(Rutgeerts score≥i2),radiography(active inflammation in the neoterminal ileum)or surgery(another resection>3 months post-ICR),and patients were categorised by the presence of intestinal fibrosis on histopathological evaluation.RESULTS Among 102 patients with CD who underwent ICR and received infliximab within 3 months,69(67.6%)had intestinal fibrosis.In addition,60 patients(58.8%)experienced POR in various forms:52.6%,41.2%,and 10.8%had endoscopic,radiographic,and surgical recurrence,respectively.Patients with intestinal fibrosis experienced faster radiographic recurrence(log rank P=0.03).After adjusting for risk factors associated with POR,intestinal fibrosis increased the risk of early radiographic recurrence(adjusted hazard ratio=4;95%confidence interval:1.03-15.56;P=0.045).CONCLUSION Despite the limited sample size,our study revealed a strong correlation between radiographic POR and intestinal fibrosis in patients who received postoperative anti-tumor necrosis factorαprophylaxis.展开更多
BACKGROUND Data regarding complex Crohn’s perianal fistulas(CPF)epidemiology are limited,and optimal treatment strategies are elusive.An improved understanding of how CPF treatment options are used in the real-world ...BACKGROUND Data regarding complex Crohn’s perianal fistulas(CPF)epidemiology are limited,and optimal treatment strategies are elusive.An improved understanding of how CPF treatment options are used in the real-world setting and factors associated with CPF development,treatment failure,and reasons for undergoing multiple surgeries may help to inform optimal patient management strategies,reduce treatment burden,and improve outcomes in patients with CPF.AIM To describe the epidemiology,treatments,outcomes,and associated risk/protective factors for complex CPF.METHODS Electronic databases(MEDLINE,EMBASE,EBM Reviews,EconLit)were searched.Two reviewers independently used populations,interventions,comparators,outcomes,study designs,and time criteria to identify relevant studies.Observational studies published in English from January 1,2015 to February 17,2022 with>50 patients were included,even if complex CPF was not defined.Items of interest included complex CPF definitions,epidemiology,treatment patterns,morbidity,mortality,and risk factors associated with complex CPF development,treatment failure,and undergoing multiple surgeries.Data were reported using descriptive statistics.RESULTS Overall,140 studies were included.Complex CPF definitions were heterogeneous and rarely reported(24 studies).Hence,data mostly related to CPF in general.CPF prevalence was variable(range:1.5%-81.0%).Incidence was wide-ranging and mostly reported cumulatively at 1-year post-Crohn’s disease diagnosis(range:3.5%-50.1%).Overall healing and failure rates after treatment were in the range of 10.5%-80.2%and 3.6%-83.0%,respectively.Abscesses were the most frequently reported morbidity(n=18).No CPF-related deaths were reported.No consistent risk or protective factors were identified.CONCLUSION Epidemiology,treatment patterns,and risk factors for CPF vary,likely due to inconsistent CPF and clinical outcome definitions.Standardization would facilitate comparability,which may inform optimal complex CPF treatment strategies.展开更多
Studies have indicated that approximately half of individuals with Crohn’s disease(CD)may undergo surgery at some point during their lifetime.Ileocolic resection(ICR)is the most frequently performed procedure for tre...Studies have indicated that approximately half of individuals with Crohn’s disease(CD)may undergo surgery at some point during their lifetime.Ileocolic resection(ICR)is the most frequently performed procedure for treating CD.Addressing anastomotic leak(AL)remains a critical focus in the perioperative and postoperative care of CD patients.A research study published in the World Journal of Gastrointestinal Surgery by Cwaliński et al included 77 individuals who had open ICR and primary stapled anastomosis to assess the risk factors linked to anastomotic insufficiency.At present,research on anastomotic insufficiency has focused on AL.Therefore,this editorial mainly analyzes the current risk factors linked to AL after ICR and discusses potential prevention strategies.We comprehensively consider risk factors such as body weight,medication use,surgical history,smoking,penetrating behaviour,and albumin levels to stratify patient risk.Based on recent research insights,we propose that individualized surgical timing,approaches,and techniques should be selected according to the patient's risk level.展开更多
This article discusses Yang and Zhang’s review on Crohn’s disease and ulcerative colitis pathogenesis,emphasizing immune dysregulation,genetics,microbiota,and environmental factors.It highlights the need for persona...This article discusses Yang and Zhang’s review on Crohn’s disease and ulcerative colitis pathogenesis,emphasizing immune dysregulation,genetics,microbiota,and environmental factors.It highlights the need for personalized approaches,longitudinal studies,and better diagnostic tools to improve treatment strategies and patient outcomes in inflammatory bowel disease.展开更多
BACKGROUND Submucosal tumors arise from the subepithelial layer anywhere along the gastr-ointestinal tract,most commonly in the stomach.A wide range of lesions,from benign to malignant,may present as gastric submucosa...BACKGROUND Submucosal tumors arise from the subepithelial layer anywhere along the gastr-ointestinal tract,most commonly in the stomach.A wide range of lesions,from benign to malignant,may present as gastric submucosal tumors.However,the gastric involvement of Crohn’s disease(CD)is generally not considered in the differential diagnosis of such lesions.CASE SUMMARY A 23-year-old male patient presented with a gastric subepithelial tumor.The medical history included CD.Diagnostic workup revealed a 3-cm mucosal lesion with a central ulceration on the posterior wall of the distal antrum.The patient underwent laparoscopic wedge resection of stomach,and the postoperative course was uneventful.Histopathological analysis confirmed a diagnosis of gastric CD presenting as a subepithelial tumor.CONCLUSION Despite its rarity,upper gastrointestinal CD can present as a gastric subepithelial tumor,warranting consideration in young patients with CD.展开更多
In this manuscript,we comment on the article by Hasnaoui et al.Specifically,we delve into the characteristic manifestation of Crohn’s disease(CD)known as creeping fat(CF).Our primary focus is to investigate the poten...In this manuscript,we comment on the article by Hasnaoui et al.Specifically,we delve into the characteristic manifestation of Crohn’s disease(CD)known as creeping fat(CF).Our primary focus is to investigate the potential of imaging features of CF in predicting the response of small bowel CD to biologic therapies and fecal microbiota transplantation.We believe that further research should be dedicated to developing methods for quantifying CF in order to provide more accurate predictive tools for the treatment of small bowel CD.展开更多
This editorial discusses Pellegrino and Gravina's essay.Crohn’s disease(CD)is a complex and multifactorial disease that is influenced by a combination of genetic and environmental factors.While genetic factors pl...This editorial discusses Pellegrino and Gravina's essay.Crohn’s disease(CD)is a complex and multifactorial disease that is influenced by a combination of genetic and environmental factors.While genetic factors play a key role in the deve-lopment of the disease,environmental factors also play a significant role in influencing the risk of developing CD.By looking at present understanding of CD pathogenesis,we emphasize the important factors involved in the development of this illness,such as nucleotide-binding oligomerization domain-2,smoking,and vitamin D.Understanding the interplay between genetic and environmental factors is crucial for developing effective strategies for preventing and treating this chronic inflammatory bowel disease.展开更多
Inflammatory bowel disease(IBD)is an incurable disease of the digestive system;however,the therapeutic methods for IBD remain limited.The pathogenesis of IBD was systematically discussed and compared in this paper,pri...Inflammatory bowel disease(IBD)is an incurable disease of the digestive system;however,the therapeutic methods for IBD remain limited.The pathogenesis of IBD was systematically discussed and compared in this paper,primarily comprising Crohn’s disease and ulcerative colitis.This paper focused on six common aspects:(1)Dysregulated immune responses;(2)Gene function changes;(3)Intestinal microbes disorder and imbalance;(4)Microbial infections;(5)Associations between IBD and other inflammatory diseases;and(6)Other factors.In addition,the pathogenesis differences between these two forms of IBD were unraveled and clearly distinguished.These unique aspects of pathogenesis provide crucial insights for the precise treatment of both Crohn’s disease and ulcerative colitis.This paper illustrates the root causes and beneficial factors of resistance to IBD,which provides novel insights on early prevention,development of new therapeutic agents,and treatment options of this disease.展开更多
基金Supported by the Postdoctoral Scholarship Grant,No.5552/2024 PROPG/PROPE N°06/2024.
文摘In this article,we explored the role of adipose tissue,especially mesenteric adipose tissue and creeping fat,and its association with the gut microbiota in the pathophysiology and progression of Crohn’s disease(CD).CD is a form of inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract,influenced by genetic predisposition,gut microbiota dysbiosis,and environmental factors.Gut microbiota plays a crucial role in modulating immune response and intestinal inflammation and is associated with the onset and progression of CD.Further,visceral adipose tissue,particularly creeping fat,a mesenteric adipose tissue characterized by hypertrophy and fibrosis,has been implicated in CD pathogenesis,inflammation,and fibrosis.The bacteria from the gut microbiota may translocate into mesenteric adipose tissue,contributing to the formation of creeping fat and influencing CD progression.Although creeping fat may be a protective barrier against bacterial invasion,its expansion can damage adjacent tissues,leading to complications.Modulating gut microbiota through interventions such as fecal microbiota transplantation,probiotics,and prebiotics has shown potential in managing CD.However,more research is needed to clarify the mechanisms linking gut dysbiosis,creeping fat,and CD progression and develop targeted therapies for microbiota modulation and fat-related complications in patients with CD.
文摘BACKGROUND Mucosal healing has become an important goal of Crohn’s disease(CD)treat-ments.Modulen,enriched with transforming growth factor-beta 2,and budeso-nide are commonly accepted treatments for mild-moderate CD.However,their effects on the small bowel(SB)mucosa remain underexplored.AIM To prospectively assess clinical and mucosal responses to Modulen vs budesonide in adults with CD,using SB capsule endoscopy.METHODS Thirty patients were divided into two groups:Modulen+home-based diet(21 patients)and budesonide(9 patients)for an eight-week intervention followed by four weeks of follow-up.Clinical,laboratory,and endoscopic responses were evaluated.The mucosal changes were assessed through SB capsule endoscopy.RESULTS Results indicated significant clinical improvement in the Modulen group with reduced CD activity index(P=0.041)and improved inflammatory bowel disease questionnaire score(P=0.016).Moreover,Modulen was associated with a signifi-cant SB mucosal improvement,evidenced by a decrease in Lewis score(P=0.027).No significant changes were observed in calprotectin or other laboratory parame-ters.Conversely,budesonide exhibited more modest clinical effects,but it improved calprotectin,hemoglobin,and C-reactive protein levels(P=0.051,P=0.014,and P=0.038,respectively).The capsule endoscopy did not reveal a significant mucosal response in the budesonide group.CONCLUSION Both interventions have a role in CD treatment.Yet,their effects differ and may complement each other:Modulen yields clinical and mucosal improvements,while budesonide primarily leads mainly to laboratory improvements.
基金Supported by Natural Science Foundation of Anhui Medical University,No.2023xkj130.
文摘BACKGROUND Mucosal healing(MH)is the major therapeutic target for Crohn's disease(CD).As the most commonly involved intestinal segment,small bowel(SB)assessment is crucial for CD patients.Yet,it poses a significant challenge due to its limited accessibility through conventional endoscopic methods.AIM To establish a noninvasive radiomic model based on computed tomography enterography(CTE)for MH assessment in SBCD patients.METHODS Seventy-three patients diagnosed with SBCD were included and divided into a training cohort(n=55)and a test cohort(n=18).Radiomic features were obtained from CTE images to establish a radiomic model.Patient demographics were analysed to establish a clinical model.A radiomic-clinical nomogram was constructed by combining significant clinical and radiomic features.The diagnostic efficacy and clinical benefit were evaluated via receiver operating characteristic(ROC)curve analysis and decision curve analysis(DCA),respectively.RESULTS Of the 73 patients enrolled,25 patients achieved MH.The radiomic-clinical nomogram had an area under the ROC curve of 0.961(95%confidence interval:0.886-1.000)in the training cohort and 0.958(0.877-1.000)in the test cohort and provided superior clinical benefit to either the clinical or radiomic models alone,as demonstrated by DCA.CONCLUSION These results indicate that the CTE-based radiomic-clinical nomogram is a promising imaging biomarker for MH and serves as a potential noninvasive alternative to enteroscopy for MH assessment in SBCD patients.
文摘Extensive research has investigated the etiology of Crohn’s disease(CD),encompassing genetic predisposition,lifestyle factors,and environmental triggers.Recently,the gut microbiome,recognized as the human body’s second-largest gene pool,has garnered significant attention for its crucial role in the patho-genesis of CD.This paper investigates the mechanisms underlying CD,focusing on the role of‘creeping fat’in disease progression and exploring emerging therapeutic strategies,including fecal microbiota transplantation,enteral nutri-tion,and therapeutic diets.Creeping fat has been identified as a unique patho-logical feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome.We characterize this dysbiotic state by identi-fying key microbiome-bacteria,fungi,viruses,and archaea,and their contributions to CD pathogenesis.Additionally,this paper reviews contemporary therapies,empha-sizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions.By elucidating the complex interactions between host-microbiome dynamics and CD pathology,this article aims to advance our under-standing of the disease and guide the development of more effective therapeutic strategies for managing CD.
文摘Introduction: Crohn’s Disease (CD) is a chronic inflammatory disorder with a heterogeneous presentation. While diarrhea, abdominal pain, and weight loss are hallmarks, atypical manifestations can obscure the diagnosis. This report highlights an unusual presentation of CD to emphasize the need for comprehensive diagnostic strategies. Case Report: A 25-year-old male presented with peripheral edema, anorexia, and abdominal distension but lacked classic gastrointestinal (GI) symptoms. Laboratory findings included microcytic anemia and hypoalbuminemia, while imaging revealed ascites and bowel wall thickening. Elevated fecal calprotectin and positive Anti-Saccharomyces cerevisiae antibodies (ASCA) supported the diagnosis. Endoscopy confirmed ileocolic Crohn’s Disease (L3 + L4). Infliximab therapy resulted in marked clinical improvement. Discussion: This case underscores the complexity of atypical CD presentations. Early use of serological markers, imaging, and endoscopy guided the diagnosis. Recognition of CD’s diverse manifestations is critical for timely intervention. Conclusion: Atypical CD presentations require heightened clinical suspicion and a multidisciplinary approach to reduce diagnostic delays and improve patient outcomes.
文摘BACKGROUND Discordance between endoscopic and histologic assessments in Crohn’s disease(CD)have been observed,however the prevalence and cause are unclear.AIM To assess if a protocolized approach to biopsy collection facilitates understanding of this discordance in patients with ileal CD.METHODS Patients with known ileal CD underwent colonoscopy with endoscopic disease activity assessment.Three protocolized biopsies were taken respectively from an ulcer edge,7-mm,and 14-mm away from the ulcer edge in patients with discrete ileal ulcer(s).In patients with no ulcers as controls,the same 3-site biopsy protocol was applied in a randomly selected area of endoscopically-unremarkable terminal ileal mucosa.A blinded pathologist assessed mucosal inflammation in each biopsy using 3 validated histologic indices.RESULTS Twenty-four participants had visible ulcer(s)on endoscopy and 12 served as no-ulcer controls.Of biopsies taken from an ulcer edge,only 67%showed histologic evidence of active(neutrophilic)inflammation,and 33%showed histologic features of ulcer or erosion;all were from either large(n=4)or very large(n=4)ulcers.In the no-ulcer controls,no biopsies showed histologic features of ulcer or erosion,but 8%showed active inflammation.CONCLUSION A striking discordance exists between endoscopic and histologic assessments for mucosal inflammation in patients with active ileal CD,even in biopsies targeted at an ulcer edge,while a higher concordance is seen in patients with no endoscopic disease activity.It remains unclear how to incorporate histologic disease activity into the treatment paradigm.Further research is needed to optimize biopsy protocols and histologic assessments for CD.
文摘Perianal fistulising Crohn’s disease is a challenging complication that can affect up to 20%of patients with Crohn’s disease and is associated with significant morbidity.Despite advances in medical therapies,particularly anti-tumor necrosis factor agents,the majority of patients still require surgical intervention.Accurate diagnosis and monitoring are essential to optimise outcomes and guide multidisciplinary management.Although clinical scoring systems such as the perianal disease activity index are widely used,their subjective application limits their reproducibility and reliability,underscoring the need for more objective methods of evaluating perianal fistulising Crohn’s disease activity.Imaging has thus become central to the objective assessment of perianal fistulising Crohn’s disease,with magnetic resonance imaging(MRI)recognised as the gold standard in view of its ability to provide clear,detailed images of the perianal region in a radiation-free manner.Guidelines also endorse the use of imaging modalities such as endoanal ultrasound and transperineal ultrasound as viable alternatives to MRI for the assessment of perianal fistulising Crohn’s disease in centres with appropriate expertise.This article aims to evaluate and compare the diagnostic accuracy and clinical utility of MRI,endoanal ultrasound,and transperineal ultrasound in the assessment of perianal fistulising Crohn’s disease,highlighting their respective strengths,limitations,and roles in clinical practice.
文摘BACKGROUND At present,there is a lack of non-invasive indicators to evaluate the changes in endoscopic activity between two visits for patients with Crohn's disease(CD).AIM To develop a model for predicting whether endoscopic activity will improve in CD patients.METHODS This is a single-center retrospective study that included patients diagnosed with CD from January 2014 to December 2022.The patients were randomly divided into a modeling group(70%)and an internal validation group(30%),with an external validation group from January 2023 to March 2024.Univariate and binary logistic regression analyses were conducted to identify independent risk factors,which were used to construct a nomogram model.The model's performance was evaluated using receiver operating characteristic curves,calibration curves,and decision curve analysis(DCA).Additionally,further sensitivity analyses were performed.RESULTS One hundred seventy patients were included in the training group,while 64 were included in the external validation group.A binary logistic stepwise regression analysis revealed that the changes in the amplitudes of albumin(ALB)and fibrinogen(FIB)were independent risk factors for endoscopic improvement.A nomogram model was developed based on these risk factors.The area under the curve of the model for the training group,internal validation group,and external validation group were 0.802,0.788,and 0.787,respectively.The average absolute errors of the calibration curves were 0.011,0.016,and 0.018,respectively.DCA indicated that the model performs well in clinical practice.Additionally,sensitivity analysis demonstrated that the model has strong robustness and applicability.CONCLUSION Our study shows that changes in the amplitudes of ALB and FIB are effective predictors of endoscopic improvement in patients with CD during follow-up visits compared to their previous ones.
文摘This article explores the significant implications of the study by Ovadia et al,which innovatively compares the efficacy of a nutritional intervention(Modulen)to conventional pharmaceutical therapy(budesonide)in promoting mucosal healing in Crohn’s disease.Highlighting the paradox of a well-established yet underutilized nutritional approach,the findings suggest that Modulen may offer comparable therapeutic benefits despite its high withdrawal rate due to adherence challenges.This advancement underscores the evolving paradigm in inflammatory bowel disease treatment,shifting focus toward non-pharmacologic alternatives that target both clinical remission and endoscopic healing.The article advocates for the development of integrative treatment strategies that balance efficacy,patient adherence,and long-term disease management,emphasizing the need for further research to refine and optimize the role of nutritional therapies in clinical practice.
文摘The recent study published by Lee et al examined the discrepancies between endoscopic and histologic evaluations of mucosal inflammation in active ileal Crohn’s disease(CD).While this research contributes to our understanding of the limitations of current biopsy protocols,it raises several concerns about the generalizability of its findings,sample size,and methodology.One major limitation was the exclusion of patients with ileal strictures,ileostomies,or J-pouches,which reduced the applicability of the results to the wider CD population.Furthermore,the biopsy protocol's focus on single biopsies from specific locations may inadequately capture the patchy inflammation characteristic of CD.The study also uses histologic indices primarily developed for ulcerative colitis,which may not be suitable for assessing CD.It is recommended that multi-center studies be conducted and histologic indices specific to CD be developed to improve the relevance of future research.Additionally,researchers should consider the influence of treatment regimens on the findings.Addressing these limitations would enhance the clinical significance of the study and inform better diagnostic and therapeutic approaches for CD.
文摘Objectives:A common side effect of inflammatory bowel disease(IBD)is intestinal fibrosis,which frequently leads to intestinal blockage and stricture formation.Although Thalidomide(THD)has shown anti-fibrotic benefits in hepatic and renal models,little is known about how it affects intestinal fibrosis and the underlying processes.The present research examines the molecular targets of THD and its potential as a treatment for intestinal fibrosis brought on by colitis.Methods:Clinical samples from Crohn’s disease(CD)patients with intestinal strictures treated with infliximab(IFX)and THD combined with IFX were collected.Dextran sulfate sodium(DSS)was used to develop a mouse model of intestinal fibrosis in C57BL/6 mice.Anti-tumor necrosis factor-alpha(Anti-TNFα),THD,or a combination of the two were administered to the mice.Body weight,colon length,histology,and disease activity index were used to evaluate the disease’s severity.In vitro,THD was tested on colonic fibroblast lines(CCD-18Co and MPF)to assess its effects on cell proliferation,motility,and transdifferentiation.To examine changes in gene expression and signaling pathway modifications,namely in the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)pathway,RNA sequencing,qRT-PCR,and Western blotting were carried out.Results:In DSS-induced colitis,THD therapy lowered fibrosis,as seen by downregulated fibrotic markers(α-smooth muscle actin(α-SMA),collagen I,and collagen III)and decreased collagen deposition.Mechanistically,THD prevented fibroblasts from transdifferentiating and decreased their vitality.Furthermore,THD inhitited the PI3K/AKT/mTOR pathway in vivo and in vitro.Conclusion:THD inhibits the PI3K/AKT/mTOR signaling cascade and suppresses colonic fibroblast transdifferentiation,which protects against DSS-induced colitis-associated fibrosis,especially when combined with anti-TNFαtherapy.
文摘BACKGROUND Second-line treatment of Crohn’s disease(CD)commonly involves immunosuppressants such as azathioprine,mercaptopurine,or methotrexate(MTX),used either alone or in combination.AIM To investigate the current use of MTX among French gastroenterologists.METHODS An online questionnaire was distributed between March and August 2023 to 116 French gastroenterologists managing CD.A total of 87 respondents completed the survey and were included in the analysis.RESULTS Respondents reported a mean annual caseload of 140 CD patients(median:50).Overall,71%prescribed MTX,predominantly in injectable form(92%),either as monotherapy or in combination with biologics or cyclosporin.MTX was prescribed for mild-to-moderate CD by 64%of respondents,and for severe CD by 58%,often in combination with an anti-tumor necrosis factor agent(89%and 94%,respectively).Injectable MTX was favored(84%)in specific clinical scenarios:Patients with articular manifestations(77%),Epstein-Barr virus-negative status(65%),or aged over 65 years(58%).Among the 29%of non-prescribers,the primary reason cited was lack of familiarity with MTX use(60%).Both prescribers and non-prescribers expressed the need for clearer guidelines and real-world data to support MTX use.CONCLUSION Regardless of prescribing habits,most respondents had a favorable opinion of MTX and recognized its good longterm safety profile.French learned societies and medical associations should provide consensus guidelines on MTX use,supported by validated real-world safety and effectiveness data.
基金Supported by the National Natural Science Foundation of China,No.82200621the Original Research Projects,Shanghai Ninth People’s Hospital,No.2022LHA08 and No.YBKB202220.
文摘BACKGROUND In the biologic era,postoperative recurrence(POR)of Crohn’s disease(CD)remains a significant concern.The underlying cause of this phenomenon remains unclear at present.AIM To examine whether intestinal fibrosis increases the likelihood of POR when antitumor necrosis factor biologics are used following ileocecal resection(ICR).METHODS We performed a single-centre,retrospective cohort study of patients with CD who underwent ICR.Recurrence was defined by endoscopy(Rutgeerts score≥i2),radiography(active inflammation in the neoterminal ileum)or surgery(another resection>3 months post-ICR),and patients were categorised by the presence of intestinal fibrosis on histopathological evaluation.RESULTS Among 102 patients with CD who underwent ICR and received infliximab within 3 months,69(67.6%)had intestinal fibrosis.In addition,60 patients(58.8%)experienced POR in various forms:52.6%,41.2%,and 10.8%had endoscopic,radiographic,and surgical recurrence,respectively.Patients with intestinal fibrosis experienced faster radiographic recurrence(log rank P=0.03).After adjusting for risk factors associated with POR,intestinal fibrosis increased the risk of early radiographic recurrence(adjusted hazard ratio=4;95%confidence interval:1.03-15.56;P=0.045).CONCLUSION Despite the limited sample size,our study revealed a strong correlation between radiographic POR and intestinal fibrosis in patients who received postoperative anti-tumor necrosis factorαprophylaxis.
基金Supported by Takeda Pharmaceuticals USA,Inc.Medical writing support was provided by Luke Humphreys,PhD,of Oxford PharmaGenesis,Oxford,UK and was funded by Takeda Development Center Americas,Inc.
文摘BACKGROUND Data regarding complex Crohn’s perianal fistulas(CPF)epidemiology are limited,and optimal treatment strategies are elusive.An improved understanding of how CPF treatment options are used in the real-world setting and factors associated with CPF development,treatment failure,and reasons for undergoing multiple surgeries may help to inform optimal patient management strategies,reduce treatment burden,and improve outcomes in patients with CPF.AIM To describe the epidemiology,treatments,outcomes,and associated risk/protective factors for complex CPF.METHODS Electronic databases(MEDLINE,EMBASE,EBM Reviews,EconLit)were searched.Two reviewers independently used populations,interventions,comparators,outcomes,study designs,and time criteria to identify relevant studies.Observational studies published in English from January 1,2015 to February 17,2022 with>50 patients were included,even if complex CPF was not defined.Items of interest included complex CPF definitions,epidemiology,treatment patterns,morbidity,mortality,and risk factors associated with complex CPF development,treatment failure,and undergoing multiple surgeries.Data were reported using descriptive statistics.RESULTS Overall,140 studies were included.Complex CPF definitions were heterogeneous and rarely reported(24 studies).Hence,data mostly related to CPF in general.CPF prevalence was variable(range:1.5%-81.0%).Incidence was wide-ranging and mostly reported cumulatively at 1-year post-Crohn’s disease diagnosis(range:3.5%-50.1%).Overall healing and failure rates after treatment were in the range of 10.5%-80.2%and 3.6%-83.0%,respectively.Abscesses were the most frequently reported morbidity(n=18).No CPF-related deaths were reported.No consistent risk or protective factors were identified.CONCLUSION Epidemiology,treatment patterns,and risk factors for CPF vary,likely due to inconsistent CPF and clinical outcome definitions.Standardization would facilitate comparability,which may inform optimal complex CPF treatment strategies.
基金Supported by National Natural Science Foundation of China,No.NSFC 82070540the Taishan Scholars Program of Shandong Province,No.tsqn202211309ECCM Program of Clinical Research Center of Shandong University,No.2021SDUCRCB003.
文摘Studies have indicated that approximately half of individuals with Crohn’s disease(CD)may undergo surgery at some point during their lifetime.Ileocolic resection(ICR)is the most frequently performed procedure for treating CD.Addressing anastomotic leak(AL)remains a critical focus in the perioperative and postoperative care of CD patients.A research study published in the World Journal of Gastrointestinal Surgery by Cwaliński et al included 77 individuals who had open ICR and primary stapled anastomosis to assess the risk factors linked to anastomotic insufficiency.At present,research on anastomotic insufficiency has focused on AL.Therefore,this editorial mainly analyzes the current risk factors linked to AL after ICR and discusses potential prevention strategies.We comprehensively consider risk factors such as body weight,medication use,surgical history,smoking,penetrating behaviour,and albumin levels to stratify patient risk.Based on recent research insights,we propose that individualized surgical timing,approaches,and techniques should be selected according to the patient's risk level.
文摘This article discusses Yang and Zhang’s review on Crohn’s disease and ulcerative colitis pathogenesis,emphasizing immune dysregulation,genetics,microbiota,and environmental factors.It highlights the need for personalized approaches,longitudinal studies,and better diagnostic tools to improve treatment strategies and patient outcomes in inflammatory bowel disease.
文摘BACKGROUND Submucosal tumors arise from the subepithelial layer anywhere along the gastr-ointestinal tract,most commonly in the stomach.A wide range of lesions,from benign to malignant,may present as gastric submucosal tumors.However,the gastric involvement of Crohn’s disease(CD)is generally not considered in the differential diagnosis of such lesions.CASE SUMMARY A 23-year-old male patient presented with a gastric subepithelial tumor.The medical history included CD.Diagnostic workup revealed a 3-cm mucosal lesion with a central ulceration on the posterior wall of the distal antrum.The patient underwent laparoscopic wedge resection of stomach,and the postoperative course was uneventful.Histopathological analysis confirmed a diagnosis of gastric CD presenting as a subepithelial tumor.CONCLUSION Despite its rarity,upper gastrointestinal CD can present as a gastric subepithelial tumor,warranting consideration in young patients with CD.
文摘In this manuscript,we comment on the article by Hasnaoui et al.Specifically,we delve into the characteristic manifestation of Crohn’s disease(CD)known as creeping fat(CF).Our primary focus is to investigate the potential of imaging features of CF in predicting the response of small bowel CD to biologic therapies and fecal microbiota transplantation.We believe that further research should be dedicated to developing methods for quantifying CF in order to provide more accurate predictive tools for the treatment of small bowel CD.
文摘This editorial discusses Pellegrino and Gravina's essay.Crohn’s disease(CD)is a complex and multifactorial disease that is influenced by a combination of genetic and environmental factors.While genetic factors play a key role in the deve-lopment of the disease,environmental factors also play a significant role in influencing the risk of developing CD.By looking at present understanding of CD pathogenesis,we emphasize the important factors involved in the development of this illness,such as nucleotide-binding oligomerization domain-2,smoking,and vitamin D.Understanding the interplay between genetic and environmental factors is crucial for developing effective strategies for preventing and treating this chronic inflammatory bowel disease.
基金Supported by Tianjin Municipal Science and Technology Commission Grant,No.24ZXRKSY00010Program for Innovative Research Team in Peking Union Medical College,CAMS Initiative for Innovative Medicine,No.2023-I2M-2-008.
文摘Inflammatory bowel disease(IBD)is an incurable disease of the digestive system;however,the therapeutic methods for IBD remain limited.The pathogenesis of IBD was systematically discussed and compared in this paper,primarily comprising Crohn’s disease and ulcerative colitis.This paper focused on six common aspects:(1)Dysregulated immune responses;(2)Gene function changes;(3)Intestinal microbes disorder and imbalance;(4)Microbial infections;(5)Associations between IBD and other inflammatory diseases;and(6)Other factors.In addition,the pathogenesis differences between these two forms of IBD were unraveled and clearly distinguished.These unique aspects of pathogenesis provide crucial insights for the precise treatment of both Crohn’s disease and ulcerative colitis.This paper illustrates the root causes and beneficial factors of resistance to IBD,which provides novel insights on early prevention,development of new therapeutic agents,and treatment options of this disease.
