A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disea...A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)-II guidelines specify short,intermediate,and long-term treatment goals,documenting specific treatment targets to be achieved at each of these timepoints.Scheduled appraisal of Crohn’s disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified.Consensus treatment targets in Crohn’s disease comprise combination clinical and patient-reported outcome remission,in conjunction with biomarker normalisation and endoscopic healing.Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing,clinicians must consider that this may not always be appropriate,acceptable,or achievable in all patients.This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets.The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques,particularly intestinal ultrasound,holds great promise;as do emerging treatment targets such as transmural healing.Two randomised clinical trials,namely,CALM and STARDUST,have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn’s disease.Findings from these studies reflect that patient subgroups and Crohn’s disease characteristics likely to benefit most from a T2T approach,remain to be clarified.Moreover,outside of clinical trials,data pertaining to the real-world effectiveness of a T2T approach remains scare,highlighting the need for pragmatic real-world studies.Despite the obvious promise of a T2T approach,a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake.This highlights the need to describe strategies,processes,and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice.Hence,this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn’s disease.展开更多
Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biolog...Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.展开更多
BACKGROUND Crohn’s disease(CD)is often misdiagnosed as intestinal tuberculosis(ITB).However,the treatment and prognosis of these two diseases are dramatically different.Therefore,it is important to develop a method t...BACKGROUND Crohn’s disease(CD)is often misdiagnosed as intestinal tuberculosis(ITB).However,the treatment and prognosis of these two diseases are dramatically different.Therefore,it is important to develop a method to identify CD and ITB with high accuracy,specificity,and speed.AIM To develop a method to identify CD and ITB with high accuracy,specificity,and speed.METHODS A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB.Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis.RESULTS The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm^(-1) and 1234 cm^(-1) bands,and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy,specificity,and sensitivity of 91.84%,92.59%,and 90.90%,respectively,for the differential diagnosis of CD and ITB.CONCLUSION Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level,and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.展开更多
BACKGROUND Inflammatory bowel disease,including ulcerative colitis,microscopic colitis,and Crohn’s disease(CD),has a global impact.This review focuses on duodenal CD(DCD),a rare subtype affecting the duodenum.DCD’s ...BACKGROUND Inflammatory bowel disease,including ulcerative colitis,microscopic colitis,and Crohn’s disease(CD),has a global impact.This review focuses on duodenal CD(DCD),a rare subtype affecting the duodenum.DCD’s rarity and asymptomatic nature create diagnostic challenges,impacting prognosis and patient well-being.Delayed diagnosis can worsen DCD outcomes.AIM To report a rare case of DCD and to discuss the diagnostic challenges and its implications on prognosis.METHODS A systematic literature search,following the PRISMA statement,was conducted.Relevant studies were identified and analysed using specific Medical Subject Terms(MeSH)from PubMed/MEDLINE,American Journal of Gastroenterology,and the University of South Wales database.Data collection included information from radiology scans,endoscopy procedures,biopsies,and histopathology results.RESULTS The review considered 8 case reports and 1 observational study,involving 44 participants diagnosed with DCD,some of whom developed complications due to delayed diagnosis.Various diagnostic methods were employed,as there is no gold standard workup for DCD.Radiology scans[magnetic resonance imaging(MRI),computed tomography(CT),and upper gastrointestinal X-ray],endoscopy procedures(colonoscopy and esophagogastroduodenoscopy),biopsies,and clinical suspicions were utilized.CONCLUSION This review discusses DCD diagnosis challenges and the roles of CT,MRI,and fluoroscopy.It notes their limitations and compares findings with endoscopy and histopathology studies.Further research is needed to improve diagnosis,emphasizing scan interpretation,endoscopy procedures,and biopsies,especially in high-risk patients during routine endoscopy.展开更多
Crohn’s disease(CD)is an inflammatory bowel disease characterized by immunemediated flares affecting any region of the intestine alternating with remission periods.In CD,the ileum is frequently affected and about one...Crohn’s disease(CD)is an inflammatory bowel disease characterized by immunemediated flares affecting any region of the intestine alternating with remission periods.In CD,the ileum is frequently affected and about one third of patients presents with a pure ileal type.Moreover,the ileal type of CD presents epidemiological specificities like a younger age at onset and often a strong link with smoking and genetic susceptibility genes.Most of these genes are associated with Paneth cell dysfunction,a cell type found in the intestinal crypts of the ileum.Besides,a Western-type diet is associated in epidemiological studies with CD onset and increasing evidence shows that diet can modulate the composition of bile acids and gut microbiota,which in turn modulates the susceptibility of the ileum to inflammation.Thus,the interplay between environmental factors and the histological and anatomical features of the ileum is thought to explain the specific transcriptome profile observed in CD ileitis.Indeed,both immune response and cellular healing processes harbour differences between ileal and non-ileal CD.Taken together,these findings advocate for a dedicated therapeutic approach to managing ileal CD.Currently,interventional pharmacological studies have failed to clearly demonstrate distinct response profiles according to disease site.However,the high rate of stricturing disease in ileal CD requires the identification of new therapeutic targets to significantly change the natural history of this debilitating disease.展开更多
BACKGROUND Crohn’s disease represents a challenge for patients concerned with the modified diet regimen as well as practitioners who seek the best nutritional therapy.Crohn’s disease can alter the body’s ability to...BACKGROUND Crohn’s disease represents a challenge for patients concerned with the modified diet regimen as well as practitioners who seek the best nutritional therapy.Crohn’s disease can alter the body’s ability to digest food and to absorb nutrients,resulting in severe vitamin deficiencies,malnutrition and sometimes lifethreatening complications.However,a comprehensive bibliometric analysis is lacking to map the current links between nutrition and Crohn’s disease in terms of the number of citations,geographic distribution and growth trends of publications.AIM To introduce the current state of research as well as hotspots in the field of nutrition and Crohn’s disease from a bibliometric standpoint.METHODS We searched the Scopus database and selected the relevant literature on nutrition and Crohn’s disease that met the inclusion criteria.We analyzed the publication trends and research hotspots by using video object segmentation viewer software.RESULTS We included 1237 publications.The number of documents published each year has increased steadily.The United States and the University of Otago,Christchurch,have had the highest productivity,with 208(16.81%)and 29(2.34%)documents,respectively.The“role of exclusive enteral nutrition for complicated Crohn’s disease”and“manipulation of the gut microbiota as a key target for Crohn’s disease”were the major research areas in 2016-2021,and they could be extensively investigated in the future.Meanwhile,research on“malnutrition in patients with Crohn’s disease”appeared to be an area that attracted more research attention before 2016.CONCLUSION This is the first bibliometric analysis to map the knowledge structure and trends regarding nutrition in Crohn’s disease research over the past two decades.The results provide a comprehensive summary and identification of the frontiers of nutrition and Crohn’s disease-related research,which may be used as a resource by researchers in the field.展开更多
BACKGROUND Corticosteroids and anti-tumor necrosis factorαmAbs are widely used to treat Crohn's disease(CD).However,one disadvantage of this treatment is impairment of normal immune function,leading to an increas...BACKGROUND Corticosteroids and anti-tumor necrosis factorαmAbs are widely used to treat Crohn's disease(CD).However,one disadvantage of this treatment is impairment of normal immune function,leading to an increased risk of infection.Cryptococcus infection is an opportunistic infection that occurs mainly in immunocompromised patients and poses a significant diagnostic challenge in patients with CD.CASE SUMMARY Here,we report three cases of pulmonary cryptococcosis in patients with CD after receiving immunomodulatory treatment.The patients presented with no or mild respiratory symptoms.Chest computed tomography scans revealed pulmonary nodules in the unilateral or bilateral lobes.Diagnoses were made using pathological examination and metagenomic sequencing.The patients were treated with fluconazole 400 mg once daily for 1 to 6 mo,and symptoms were resolved.Literature searches were conducted in PubMed,Web of Science,and Embase to retrieve previously reported cases and summarize patient characteristics.CONCLUSION The incidence of cryptococcus infection has increased along with immunomodulator use.Clinical vigilance is required for early identification and standardized treatment.展开更多
BACKGROUND Patients with autoimmune conditions receiving immunosuppressants are at risk of non-Hodgkin lymphomas(NHL).Vedolizumab(anti-α4β7-integrin antibody),a treatment-of-choice for Crohn’s disease(CD),reduces i...BACKGROUND Patients with autoimmune conditions receiving immunosuppressants are at risk of non-Hodgkin lymphomas(NHL).Vedolizumab(anti-α4β7-integrin antibody),a treatment-of-choice for Crohn’s disease(CD),reduces inflammatory lymphocyte trafficking into the intestinal mucosa.This effect is believed to be confined to the colon.CASE SUMMARY We report the case of a CD patient on vedolizumab for five years who developed pediatric-type follicular lymphoma.Work-up prior to therapy revealed a reduction in circulating T-lymphocytes and their suppressed response to mitogens.Rituximab,cyclophosphamide,vincristine,and prednisone chemoimmunotherapy resulted in durable lymphoma remission,and vedolizumab treatment was continued.While the patient’s T-lymphocyte population and immunoglobulin production recovered,the T-lymphocyte mitogen response remained suppressed.CONCLUSION This patient’s NHL may be linked to receiving anti-α4β7 therapy.Further research could be beneficial to determine if proactive surveillance for NHL and other systemic diseases is indicated in patients on vedolizumab.展开更多
The majority of patients affected by Crohn’s disease(CD)develop a chronic condition with persistent inflammation and relapses that may cause progressive and irreversible damage to the bowel,resulting in stricturing o...The majority of patients affected by Crohn’s disease(CD)develop a chronic condition with persistent inflammation and relapses that may cause progressive and irreversible damage to the bowel,resulting in stricturing or penetrating complications in around 50%of patients during the natural history of the disease.Surgery is frequently needed to treat complicated disease when pharmacological therapy failes,with a high risk of repeated operations in time.Intestinal ultrasound(IUS),a non-invasive,cost-effective,radiation free and reproducible method for the diagnosis and follow-up of CD,in expert hands,allow a precise assessment of all the disease manifestations:Bowel characteristics,retrodilation,wrapping fat,fistulas and abscesses.Moreover,IUS is able to assess bowel wall thickness,bowel wall stratification(echo-pattern),vascularization and elasticity,as well as mesenteric hypertrophy,lymph-nodes and mesenteric blood flow.Its role in the disease evaluation and behaviour description is well assessed in literature,but less is known about the potential space of IUS as predictor of prognostic factors suggesting response to a medical treatment or postoperative recurrence.The availability of a low cost exam as IUS,able to recognize which patients are more likely to respond to a specific therapy and which patients are at high risk of surgery or complications,could be a very useful instrument in the hands of IBD physician.The aim of this review is to present current evidence about the prognostic role that IUS can show in predicting response to treatment,disease progression,risk of surgery and risk of post-surgical recurrence in CD.展开更多
BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by th...BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens.Like neutrophils in the context of innate immune responses,immunoglobulin A(IgA)as an acquired immune response partakes in the defense of the intestinal epithelium.Under normal conditions,IgA contributes to the elimination of microbes,but in connection with the loss of tolerance to chitinase 3-like 1(CHI3L1)in IBD,IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms.The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target,the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear.AIM To determine the predictive potential of Ig subtypes of a novel serological marker,anti-CHI3L1 autoantibodies(aCHI3L1)in determining the disease phenotype,therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients.METHODS Sera of 257 Crohn’s disease(CD)and 180 ulcerative colitis(UC)patients from a tertiary IBD referral center of Hungary(Division of Gastroenterology,Department of Internal Medicine,Faculty of Medicine,University of Debrecen)were assayed for IgG,IgA,and secretory IgA(sIgA)type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1,along with 86 healthy controls(HCONT).RESULTS The IgA type was more prevalent in CD than in UC(29.2%vs 11.1%)or HCONT(2.83%;P<0.0001 for both).However,sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT(39.3%and 32.8%vs 4.65%,respectively;P<0.0001).The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement(P<0.0001 and P=0.038,respectively)in patients with CD.Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity(57.1%vs 36.0%,P=0.009).IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group(46.9%vs 25.7%,P=0.005).In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis,positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models.This association disappeared after merging subgroups of different disease locations.CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD.The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.展开更多
Biologic agents with various mechanisms against Crohn’s disease(CD)have been released and are widely used in clinical practice.However,two anti-tumor necrosis factor(TNF)agents,infliximab(IFX)and adalimumab(ADL),are ...Biologic agents with various mechanisms against Crohn’s disease(CD)have been released and are widely used in clinical practice.However,two anti-tumor necrosis factor(TNF)agents,infliximab(IFX)and adalimumab(ADL),are the only biologic agents approved by the Food and Drug Administration for pediatric CD currently.Therefore,in pediatric CD,the choice of biologic agents should be made more carefully to achieve the therapeutic goal.There are currently no headto-head trials of biologic agents in pediatric or adult CD.There is a lack of accumulated data for pediatric CD,which requires the extrapolation of adult data for the positioning of biologics in pediatric CD.From a pharmacokinetic point of view,IFX is more advantageous than ADL when the inflammatory burden is high,and ADL is expected to be advantageous over IFX in sustaining remission in the maintenance phase.Additionally,we reviewed the safety profile,immunogenicity,preference,and compliance between IFX and ADL and provide practical insights into the choice of anti-TNF therapy in pediatric CD.Careful evaluation of clinical indications and disease behavior is essential when prescribing anti-TNF agents.In addition,factors such as the efficacy of induction and maintenance of remission,safety profile,immunogenicity,patient preference,and compliance play an important role in evaluating and selecting treatment options.展开更多
BACKGROUND Thalidomide is an effective treatment for refractory Crohn’s disease(CD).However,thalidomide-induced peripheral neuropathy(TiPN),which has a large individual variation,is a major cause of treatment failure...BACKGROUND Thalidomide is an effective treatment for refractory Crohn’s disease(CD).However,thalidomide-induced peripheral neuropathy(TiPN),which has a large individual variation,is a major cause of treatment failure.TiPN is rarely predictable and recognized,especially in CD.It is necessary to develop a risk model to predict TiPN occurrence.AIM To develop and compare a predictive model of TiPN using machine learning based on comprehensive clinical and genetic variables.METHODS A retrospective cohort of 164 CD patients from January 2016 to June 2022 was used to establish the model.The National Cancer Institute Common Toxicity Criteria Sensory Scale(version 4.0)was used to assess TiPN.With 18 clinical features and 150 genetic variables,five predictive models were established and evaluated by the confusion matrix receiver operating characteristic curve(AUROC),area under the precision-recall curve(AUPRC),specificity,sensitivity(recall rate),precision,accuracy,and F1 score.RESULTS The top-ranking five risk variables associated with TiPN were interleukin-12 rs1353248[P=0.0004,odds ratio(OR):8.983,95%confidence interval(CI):2.497-30.90],dose(mg/d,P=0.002),brainderived neurotrophic factor(BDNF)rs2030324(P=0.001,OR:3.164,95%CI:1.561-6.434),BDNF rs6265(P=0.001,OR:3.150,95%CI:1.546-6.073)and BDNF rs11030104(P=0.001,OR:3.091,95%CI:1.525-5.960).In the training set,gradient boosting decision tree(GBDT),extremely random trees(ET),random forest,logistic regression and extreme gradient boosting(XGBoost)obtained AUROC values>0.90 and AUPRC>0.87.Among these models,XGBoost and GBDT obtained the first two highest AUROC(0.90 and 1),AUPRC(0.98 and 1),accuracy(0.96 and 0.98),precision(0.90 and 0.95),F1 score(0.95 and 0.98),specificity(0.94 and 0.97),and sensitivity(1).In the validation set,XGBoost algorithm exhibited the best predictive performance with the highest specificity(0.857),accuracy(0.818),AUPRC(0.86)and AUROC(0.89).ET and GBDT obtained the highest sensitivity(1)and F1 score(0.8).Overall,compared with other state-of-the-art classifiers such as ET,GBDT and RF,XGBoost algorithm not only showed a more stable performance,but also yielded higher ROC-AUC and PRC-AUC scores,demonstrating its high accuracy in prediction of TiPN occurrence.CONCLUSION The powerful XGBoost algorithm accurately predicts TiPN using 18 clinical features and 14 genetic variables.With the ability to identify high-risk patients using single nucleotide polymorphisms,it offers a feasible option for improving thalidomide efficacy in CD patients.展开更多
Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumo...Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumor necrosis factor alpha(TNF-α)in the diagnosis of Crohn’s disease.Methods CD patients(n=76)and healthy subjects(n=76)were enrolled between May 2019 and December 2020.The serum 25-hydroxyvitamin D[25(OH)D]levels,BMI,and TNF-αlevels,together with other biochemical parameters,were assessed before treatment.The diagnostic efficacy of the single and joint detection of serum 25(OH)D,BMI,and TNF-αwas determined using receiver operating characteristic(ROC)curves.Results The levels of 25(OH)D,BMI,and nutritional indicators,including hemoglobin,total protein,albumin,and high-density lipoprotein cholesterol,were much lower,and the TNF-αlevels were much higher in the CD patients than in the healthy subjects(P<0.05 for all).The areas under the ROC curve for the single detection of 25(OH)D,BMI,and TNF-αwere 0.887,0.896,and 0.838,respectively,with the optimal cutoff values being 20.64 ng/mL,19.77 kg/m^(2),and 6.85 fmol/mL,respectively.The diagnostic efficacy of the joint detection of 25(OH)D,BMI,and TNF-αwas the highest,with an area under the ROC curve of 0.988(95%CI:0.968–1.000).Conclusion The joint detection of 25(OH)D,TNF-α,and BMI showed high sensitivity,specificity,and accuracy in CD diagnosis;thus,it would be effective for the diagnosis of CD in clinical practice.展开更多
BACKGROUND Although the gastrointestinal tract is the most affected by Crohn’s disease(CD),the condition triggers other consequent manifestations,and iron deficiency anemia(IDA)is one of the most common.Intravenous(I...BACKGROUND Although the gastrointestinal tract is the most affected by Crohn’s disease(CD),the condition triggers other consequent manifestations,and iron deficiency anemia(IDA)is one of the most common.Intravenous(IV)iron replacement is currently available through several drugs,such as ferric hydroxide sucrose and ferric carboxymaltose(FCM).However,the clinical management of these conditions can be challenging.AIM To elucidate the drug’s effectiveness,the present study analyzed,through medical records,the clinical and epidemiological data of a cohort of patients with active CD who received IV FCM for the IDA treatment.METHODS This retrospective observational study included 25 patients with active CD,severe anemia,and refractory to previous conventional treatments.Patients were evaluated two times:During the last treatment with ferric hydroxide sucrose and treatment with FCM.RESULTS After treatment with FCM,parameters of IDA assessment significantly improved,serum hemoglobin(Hb)levels increased in 93%of patients(P<0.0001),and in 44%,there was an increase of≥2 g/dL in a single application.In addition,86%of the patients showed an increase in serum iron(P<0.0001)and ferritin(P=0.0008)and 50%in transferrin saturation(P=0.01).The serum iron levels at baseline showed a negative association with the ileal and colonic CD and use of biologics and a positive association with patients who developed CD later in life after the age of 40(A3)and with a stenosing(B2)and fistulizing(B3)phenotype.The values of Hb and hematocrit after ferric hydroxide sucrose treatment remained similar to those found before treatment.CONCLUSION This study demonstrated that FCM is an important therapeutic strategy for treating IDA in CD patients,achieving satisfactory results in refractory cases.展开更多
BACKGROUND Small bowel adenocarcinomas(SBA) are rare malignancies with exceedingly low survival rates, with different presentation in Crohn’s disease(CD). CD-induced SBA poses diagnostic challenges given overlapping ...BACKGROUND Small bowel adenocarcinomas(SBA) are rare malignancies with exceedingly low survival rates, with different presentation in Crohn’s disease(CD). CD-induced SBA poses diagnostic challenges given overlapping presentation with stricturing CD and lack of diagnostics for early detection. Moreover, guidance is lacking on the impact of recently approved therapeutics in CD on SBA management. Here, we aim to highlight the future of CD-induced SBA management and discuss the potential merit of balloon enteroscopy and genetic testing for earlier detection.CASE SUMMARY We report the case of a 60-year-old female with longstanding Crohn’s ileitis, presenting with acute obstructive symptoms attributed to stricturing phenotype. Her obstructive symptoms were refractory to intravenous(Ⅳ) steroids, with further investigation via computed tomography enterography not providing additional diagnostic yield. Ultimately, surgical resection revealed SBA in the neoterminal ileum, with oncologic therapy plan created. However, this therapy plan could not be initiated due to continued obstructive symptoms attributed to active CD. Ultimately, infused biologic therapy was initiated, but her obstructive symptoms continued to remain dependent on Ⅳ corticosteroids. Review of diagnostics by a multidisciplinary care team suggested metastatic disease in the peritoneum, lending to a shift in the goals of care to comfort.CONCLUSION With the diagnostic and therapeutic challenges of concurrent SBA and CD, multidisciplinary care and algorithmic management can optimize outcomes.展开更多
BACKGROUND Inflammatory bowel disease(IBD)is an autoimmune condition treated with immunosuppressive drugs.However,the need for immune system suppression becomes questionable when infection with the human immunodeficie...BACKGROUND Inflammatory bowel disease(IBD)is an autoimmune condition treated with immunosuppressive drugs.However,the need for immune system suppression becomes questionable when infection with the human immunodeficiency virus(HIV)occurs simultaneously and impacts the course of IBD.Our reported case represents the clinical course,prescribed treatment and its effect,as well as clinical challenges faced by physicians in a combination of such diseases.We also present a comprehensive literature review of similar cases.CASE SUMMARY A 49-year-old woman suffering from a newly diagnosed Crohn’s disease was hospitalized due to exacerbated symptoms(abdominal pain,fever,and weight loss).During her hospital stay,she tested positive for HIV.With conservative treatment,the patient improved and was discharged.In the outpatient clinic,her HIV infection was confirmed as stage C3,and antiretroviral treatment was initiated immediately.That notwithstanding,soon the patient was rehospitalized with pulmonary embolism and developed a series of complications because of the subsequent coexistence of IBD and HIV.After intensive and meticulous treatment,the patient’s condition has improved and she remains in remission.CONCLUSION The paucity of studies and data on the coexistence of HIV and IBD leaves clinicians doubting the optimal treatment options.展开更多
Crohn’s disease (CD) is a chronic inflammatory disease whose pathogenesis involves disturbances of the gastrointestinal microbiota. As the prevalence of CD increases, the need for a more effective and safe treatment ...Crohn’s disease (CD) is a chronic inflammatory disease whose pathogenesis involves disturbances of the gastrointestinal microbiota. As the prevalence of CD increases, the need for a more effective and safe treatment is integral. Probiotics have been reported to be beneficial for numerous gastrointestinal diseases, providing health benefits and considering the microbial characteristics of CD’s pathogenesis. However, our knowledge of the efficacy of probiotic therapy in preventing relapse in CD is limited. How gastroenterologists have incorporated probiotics into their practice or probiotics observed implications for patients with CD has not been assessed. A quantitative survey was distributed to determine how gastroenterologists perceive and use probiotic-based therapies in CD practice. The second objective was to conduct a meta-analysis of the efficacy of probiotics for maintaining remission and preventing clinical and endoscopic relapse in CD. Performing a meta-analysis and survey will examine the role of probiotics in CD treatment. Surveyed gastroenterologists cited that probiotics have an adjunctive role and have been observed to alleviate common CD symptoms. Probiotics seem effective in reducing the relapse rate, specifically those of the multi-strain variety are more likely to be effective in maintaining CD remission. Further research with larger trials is required to replicate and solidify this efficacy. The meta-analysis only assessed the efficacy of probiotics as a maintenance treatment as measured by the risk of relapse;thus, no evidence supports probiotics’ ability to induce remission. The results of the meta-analysis and survey indicate that probiotics cannot treat CD without accompanying conventional drug therapies;nevertheless, independent of treatment capacities, probiotics still yield health benefits for CD patients.展开更多
BACKGROUND Perianal fistulising Crohn's disease(PFCD)and glandular anal fistula have many similarities on conventional magnetic resonance imaging.However,many patients with PFCD show concomitant active proctitis,b...BACKGROUND Perianal fistulising Crohn's disease(PFCD)and glandular anal fistula have many similarities on conventional magnetic resonance imaging.However,many patients with PFCD show concomitant active proctitis,but only few patients with glandular anal fistula have active proctitis.AIM To explore the value of differential diagnosis of PFCD and glandular anal fistula by comparing the textural feature parameters of the rectum and anal canal in fat suppression T2-weighted imaging(FS-T2WI).METHODS Patients with rectal water sac implantation were screened from the first part of this study(48 patients with PFCD and 22 patients with glandular anal fistula).Open-source software ITK-SNAP(Version 3.6.0,http://www.itksnap.org/)was used to delineate the region of interest(ROI)of the entire rectum and anal canal wall on every axial section,and then the ROIs were input in the Analysis Kit software(version V3.0.0.R,GE Healthcare)to calculate the textural feature parameters.Textural feature parameter differences of the rectum and anal canal wall between the PFCD group vs the glandular anal fistula group were analyzed using Mann-Whitney U test.The redundant textural parameters were screened by bivariate Spearman correlation analysis,and binary logistic regression analysis was used to establish the model of textural feature parameters.Finally,diagnostic accuracy was assessed by receiver operating characteristic-area under the curve(AUC)analysis.RESULTS In all,385 textural parameters were obtained,including 37 parameters with statistically significant differences between the PFCD and glandular anal fistula groups.Then,16 texture feature parameters remained after bivariate Spearman correlation analysis,including one histogram parameter(Histogram energy);four grey level co-occurrence matrix(GLCM)parameters(GLCM energy_all direction_offset1_SD,GLCM entropy_all direction_offset4_SD,GLCM entropy_all direction_offset7_SD,and Haralick correlation_all direction_offset7_SD);four texture parameters(Correlation_all direction_offset1_SD,cluster prominence_angle 90_offset4,Inertia_all direction_offset7_SD,and cluster shade_angle 45_offset7);five grey level run-length matrix parameters(grey level nonuniformity_angle 90_offset1,grey level nonuniformity_all direction_offset4_SD,long run high grey level emphasis_all direction_offset1_SD,long run emphasis_all direction_offset4_SD,and long run high grey level emphasis_all direction_offset4_SD);and two form factor parameters(surface area and maximum 3D diameter).The AUC,sensitivity,and specificity of the model of textural feature parameters were 0.917,85.42%,and 86.36%,respectively.CONCLUSION The model of textural feature parameters showed good diagnostic performance for PFCD.The texture feature parameters of the rectum and anal canal in FS-T2WI are helpful to distinguish PFCD from glandular anal fistula.展开更多
Crohn’s disease might result from a complex interplay between genetic susceptibility, environmental factors, and altered gut microbiota, leading to dysregulated innate and adaptive immune responses. The reported case...Crohn’s disease might result from a complex interplay between genetic susceptibility, environmental factors, and altered gut microbiota, leading to dysregulated innate and adaptive immune responses. The reported case presents a patient with intestinal subocclusion associated with a pharmacobezoar who had a good evolution with clinical treatment. This case report aims to demonstrate the complexity of diagnostic search, even with the classic version of the disease. And it also comes to show the need for a thorough medical history and differential diagnosis investigation.展开更多
BACKGROUND The pediatric Crohn’s disease activity index(PCDAI)is used as a standard tool to assess disease activity in clinical trials for pediatric Crohn’s disease.AIM To examine which items on the PCDAI drive asse...BACKGROUND The pediatric Crohn’s disease activity index(PCDAI)is used as a standard tool to assess disease activity in clinical trials for pediatric Crohn’s disease.AIM To examine which items on the PCDAI drive assessment of disease activity,and how subgroups of subjective and objective items reflect change in disease state over time.METHODS Selective raw data from three prospectively collected datasets were combined,including 703 children with full PCDAI data at baseline,at 3-mo(Q1,n=670),and 1-year(Q4,n=474).Change in individual PCDAI scores from baseline to Q1 and to Q4 were examined using the non-weighted PCDAI.RESULTS Abdominal pain,well-being,weight,and stooling had the highest change scores over time.Objective indicators including albumin,abdominal exam,and height velocity followed.Change scores for well-being and abdominal exam did not explain significant variance at Q1 but were significant predictors at Q4(P<0.001 and P<0.05).Subjective and objective subgroups of items predicted less variance(18%and 22%)on total PCDAI scores at Q1 and Q4 compared to the full PCDAI,or a composite scale(both 32%)containing significant predictors.CONCLUSION Although subjective items on the PCDAI change the most over time,the full PCDAI or a smaller composite of items including a combination of subjective and objective components classifies disease activity better than a subgroup of either subjective or objective items alone.Reliance on subjective or objective items as stand-alone proxies for disease activity measurement could result in misclassification of disease state.展开更多
文摘A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)-II guidelines specify short,intermediate,and long-term treatment goals,documenting specific treatment targets to be achieved at each of these timepoints.Scheduled appraisal of Crohn’s disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified.Consensus treatment targets in Crohn’s disease comprise combination clinical and patient-reported outcome remission,in conjunction with biomarker normalisation and endoscopic healing.Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing,clinicians must consider that this may not always be appropriate,acceptable,or achievable in all patients.This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets.The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques,particularly intestinal ultrasound,holds great promise;as do emerging treatment targets such as transmural healing.Two randomised clinical trials,namely,CALM and STARDUST,have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn’s disease.Findings from these studies reflect that patient subgroups and Crohn’s disease characteristics likely to benefit most from a T2T approach,remain to be clarified.Moreover,outside of clinical trials,data pertaining to the real-world effectiveness of a T2T approach remains scare,highlighting the need for pragmatic real-world studies.Despite the obvious promise of a T2T approach,a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake.This highlights the need to describe strategies,processes,and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice.Hence,this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn’s disease.
文摘Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.
基金the National Natural Science Foundation of China,No.61975069 and No.62005056Natural Science Foundation of Guangxi Province,No.2021JJB110003+2 种基金Natural Science Foundation of Guangdong Province,No.2018A0303131000Academician Workstation of Guangdong Province,No.2014B090905001Key Project of Scientific and Technological Projects of Guangzhou,No.201604040007 and No.201604020168.
文摘BACKGROUND Crohn’s disease(CD)is often misdiagnosed as intestinal tuberculosis(ITB).However,the treatment and prognosis of these two diseases are dramatically different.Therefore,it is important to develop a method to identify CD and ITB with high accuracy,specificity,and speed.AIM To develop a method to identify CD and ITB with high accuracy,specificity,and speed.METHODS A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB.Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis.RESULTS The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm^(-1) and 1234 cm^(-1) bands,and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy,specificity,and sensitivity of 91.84%,92.59%,and 90.90%,respectively,for the differential diagnosis of CD and ITB.CONCLUSION Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level,and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.
文摘BACKGROUND Inflammatory bowel disease,including ulcerative colitis,microscopic colitis,and Crohn’s disease(CD),has a global impact.This review focuses on duodenal CD(DCD),a rare subtype affecting the duodenum.DCD’s rarity and asymptomatic nature create diagnostic challenges,impacting prognosis and patient well-being.Delayed diagnosis can worsen DCD outcomes.AIM To report a rare case of DCD and to discuss the diagnostic challenges and its implications on prognosis.METHODS A systematic literature search,following the PRISMA statement,was conducted.Relevant studies were identified and analysed using specific Medical Subject Terms(MeSH)from PubMed/MEDLINE,American Journal of Gastroenterology,and the University of South Wales database.Data collection included information from radiology scans,endoscopy procedures,biopsies,and histopathology results.RESULTS The review considered 8 case reports and 1 observational study,involving 44 participants diagnosed with DCD,some of whom developed complications due to delayed diagnosis.Various diagnostic methods were employed,as there is no gold standard workup for DCD.Radiology scans[magnetic resonance imaging(MRI),computed tomography(CT),and upper gastrointestinal X-ray],endoscopy procedures(colonoscopy and esophagogastroduodenoscopy),biopsies,and clinical suspicions were utilized.CONCLUSION This review discusses DCD diagnosis challenges and the roles of CT,MRI,and fluoroscopy.It notes their limitations and compares findings with endoscopy and histopathology studies.Further research is needed to improve diagnosis,emphasizing scan interpretation,endoscopy procedures,and biopsies,especially in high-risk patients during routine endoscopy.
文摘Crohn’s disease(CD)is an inflammatory bowel disease characterized by immunemediated flares affecting any region of the intestine alternating with remission periods.In CD,the ileum is frequently affected and about one third of patients presents with a pure ileal type.Moreover,the ileal type of CD presents epidemiological specificities like a younger age at onset and often a strong link with smoking and genetic susceptibility genes.Most of these genes are associated with Paneth cell dysfunction,a cell type found in the intestinal crypts of the ileum.Besides,a Western-type diet is associated in epidemiological studies with CD onset and increasing evidence shows that diet can modulate the composition of bile acids and gut microbiota,which in turn modulates the susceptibility of the ileum to inflammation.Thus,the interplay between environmental factors and the histological and anatomical features of the ileum is thought to explain the specific transcriptome profile observed in CD ileitis.Indeed,both immune response and cellular healing processes harbour differences between ileal and non-ileal CD.Taken together,these findings advocate for a dedicated therapeutic approach to managing ileal CD.Currently,interventional pharmacological studies have failed to clearly demonstrate distinct response profiles according to disease site.However,the high rate of stricturing disease in ileal CD requires the identification of new therapeutic targets to significantly change the natural history of this debilitating disease.
文摘BACKGROUND Crohn’s disease represents a challenge for patients concerned with the modified diet regimen as well as practitioners who seek the best nutritional therapy.Crohn’s disease can alter the body’s ability to digest food and to absorb nutrients,resulting in severe vitamin deficiencies,malnutrition and sometimes lifethreatening complications.However,a comprehensive bibliometric analysis is lacking to map the current links between nutrition and Crohn’s disease in terms of the number of citations,geographic distribution and growth trends of publications.AIM To introduce the current state of research as well as hotspots in the field of nutrition and Crohn’s disease from a bibliometric standpoint.METHODS We searched the Scopus database and selected the relevant literature on nutrition and Crohn’s disease that met the inclusion criteria.We analyzed the publication trends and research hotspots by using video object segmentation viewer software.RESULTS We included 1237 publications.The number of documents published each year has increased steadily.The United States and the University of Otago,Christchurch,have had the highest productivity,with 208(16.81%)and 29(2.34%)documents,respectively.The“role of exclusive enteral nutrition for complicated Crohn’s disease”and“manipulation of the gut microbiota as a key target for Crohn’s disease”were the major research areas in 2016-2021,and they could be extensively investigated in the future.Meanwhile,research on“malnutrition in patients with Crohn’s disease”appeared to be an area that attracted more research attention before 2016.CONCLUSION This is the first bibliometric analysis to map the knowledge structure and trends regarding nutrition in Crohn’s disease research over the past two decades.The results provide a comprehensive summary and identification of the frontiers of nutrition and Crohn’s disease-related research,which may be used as a resource by researchers in the field.
文摘BACKGROUND Corticosteroids and anti-tumor necrosis factorαmAbs are widely used to treat Crohn's disease(CD).However,one disadvantage of this treatment is impairment of normal immune function,leading to an increased risk of infection.Cryptococcus infection is an opportunistic infection that occurs mainly in immunocompromised patients and poses a significant diagnostic challenge in patients with CD.CASE SUMMARY Here,we report three cases of pulmonary cryptococcosis in patients with CD after receiving immunomodulatory treatment.The patients presented with no or mild respiratory symptoms.Chest computed tomography scans revealed pulmonary nodules in the unilateral or bilateral lobes.Diagnoses were made using pathological examination and metagenomic sequencing.The patients were treated with fluconazole 400 mg once daily for 1 to 6 mo,and symptoms were resolved.Literature searches were conducted in PubMed,Web of Science,and Embase to retrieve previously reported cases and summarize patient characteristics.CONCLUSION The incidence of cryptococcus infection has increased along with immunomodulator use.Clinical vigilance is required for early identification and standardized treatment.
文摘BACKGROUND Patients with autoimmune conditions receiving immunosuppressants are at risk of non-Hodgkin lymphomas(NHL).Vedolizumab(anti-α4β7-integrin antibody),a treatment-of-choice for Crohn’s disease(CD),reduces inflammatory lymphocyte trafficking into the intestinal mucosa.This effect is believed to be confined to the colon.CASE SUMMARY We report the case of a CD patient on vedolizumab for five years who developed pediatric-type follicular lymphoma.Work-up prior to therapy revealed a reduction in circulating T-lymphocytes and their suppressed response to mitogens.Rituximab,cyclophosphamide,vincristine,and prednisone chemoimmunotherapy resulted in durable lymphoma remission,and vedolizumab treatment was continued.While the patient’s T-lymphocyte population and immunoglobulin production recovered,the T-lymphocyte mitogen response remained suppressed.CONCLUSION This patient’s NHL may be linked to receiving anti-α4β7 therapy.Further research could be beneficial to determine if proactive surveillance for NHL and other systemic diseases is indicated in patients on vedolizumab.
文摘The majority of patients affected by Crohn’s disease(CD)develop a chronic condition with persistent inflammation and relapses that may cause progressive and irreversible damage to the bowel,resulting in stricturing or penetrating complications in around 50%of patients during the natural history of the disease.Surgery is frequently needed to treat complicated disease when pharmacological therapy failes,with a high risk of repeated operations in time.Intestinal ultrasound(IUS),a non-invasive,cost-effective,radiation free and reproducible method for the diagnosis and follow-up of CD,in expert hands,allow a precise assessment of all the disease manifestations:Bowel characteristics,retrodilation,wrapping fat,fistulas and abscesses.Moreover,IUS is able to assess bowel wall thickness,bowel wall stratification(echo-pattern),vascularization and elasticity,as well as mesenteric hypertrophy,lymph-nodes and mesenteric blood flow.Its role in the disease evaluation and behaviour description is well assessed in literature,but less is known about the potential space of IUS as predictor of prognostic factors suggesting response to a medical treatment or postoperative recurrence.The availability of a low cost exam as IUS,able to recognize which patients are more likely to respond to a specific therapy and which patients are at high risk of surgery or complications,could be a very useful instrument in the hands of IBD physician.The aim of this review is to present current evidence about the prognostic role that IUS can show in predicting response to treatment,disease progression,risk of surgery and risk of post-surgical recurrence in CD.
基金Supported by the German Federal Ministry of Education and Research(BMBF-Wachstumskern-PRAEMED.BIO),03WKDB2Csupported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences,BO/00232/17/5+1 种基金Research Grants of National Research Development and Innovation Office,K115818/2015/1New National Excellence Program of the Ministry of Human Capacities,ÚNKP-18-4 Bolyai Plus.
文摘BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens.Like neutrophils in the context of innate immune responses,immunoglobulin A(IgA)as an acquired immune response partakes in the defense of the intestinal epithelium.Under normal conditions,IgA contributes to the elimination of microbes,but in connection with the loss of tolerance to chitinase 3-like 1(CHI3L1)in IBD,IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms.The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target,the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear.AIM To determine the predictive potential of Ig subtypes of a novel serological marker,anti-CHI3L1 autoantibodies(aCHI3L1)in determining the disease phenotype,therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients.METHODS Sera of 257 Crohn’s disease(CD)and 180 ulcerative colitis(UC)patients from a tertiary IBD referral center of Hungary(Division of Gastroenterology,Department of Internal Medicine,Faculty of Medicine,University of Debrecen)were assayed for IgG,IgA,and secretory IgA(sIgA)type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1,along with 86 healthy controls(HCONT).RESULTS The IgA type was more prevalent in CD than in UC(29.2%vs 11.1%)or HCONT(2.83%;P<0.0001 for both).However,sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT(39.3%and 32.8%vs 4.65%,respectively;P<0.0001).The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement(P<0.0001 and P=0.038,respectively)in patients with CD.Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity(57.1%vs 36.0%,P=0.009).IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group(46.9%vs 25.7%,P=0.005).In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis,positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models.This association disappeared after merging subgroups of different disease locations.CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD.The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.
文摘Biologic agents with various mechanisms against Crohn’s disease(CD)have been released and are widely used in clinical practice.However,two anti-tumor necrosis factor(TNF)agents,infliximab(IFX)and adalimumab(ADL),are the only biologic agents approved by the Food and Drug Administration for pediatric CD currently.Therefore,in pediatric CD,the choice of biologic agents should be made more carefully to achieve the therapeutic goal.There are currently no headto-head trials of biologic agents in pediatric or adult CD.There is a lack of accumulated data for pediatric CD,which requires the extrapolation of adult data for the positioning of biologics in pediatric CD.From a pharmacokinetic point of view,IFX is more advantageous than ADL when the inflammatory burden is high,and ADL is expected to be advantageous over IFX in sustaining remission in the maintenance phase.Additionally,we reviewed the safety profile,immunogenicity,preference,and compliance between IFX and ADL and provide practical insights into the choice of anti-TNF therapy in pediatric CD.Careful evaluation of clinical indications and disease behavior is essential when prescribing anti-TNF agents.In addition,factors such as the efficacy of induction and maintenance of remission,safety profile,immunogenicity,patient preference,and compliance play an important role in evaluating and selecting treatment options.
基金National Natural Science Foundation of China,No.81973398,No.81730103,No.81573507 and No.82020108031The National Key Research and Development Program,No.2017YFC0909300 and No.2016YFC0905001+5 种基金Guangdong Provincial Key Laboratory of Construction Foundation,No.2017B030314030 and No.2020B1212060034Science and Technology Program of Guangzhou,No.201607020031National Engineering and Technology Research Center for New Drug Druggability Evaluation(Seed Program of Guangdong Province),No.2017B090903004The 111 Project,No.B16047China Postdoctoral Science Foundation,No.2019M66324,No.2020M683140 and No.2020M683139Natural Science Foundation of Guangdong Province,No.2022A1515012549 and No.2023A1515012667.
文摘BACKGROUND Thalidomide is an effective treatment for refractory Crohn’s disease(CD).However,thalidomide-induced peripheral neuropathy(TiPN),which has a large individual variation,is a major cause of treatment failure.TiPN is rarely predictable and recognized,especially in CD.It is necessary to develop a risk model to predict TiPN occurrence.AIM To develop and compare a predictive model of TiPN using machine learning based on comprehensive clinical and genetic variables.METHODS A retrospective cohort of 164 CD patients from January 2016 to June 2022 was used to establish the model.The National Cancer Institute Common Toxicity Criteria Sensory Scale(version 4.0)was used to assess TiPN.With 18 clinical features and 150 genetic variables,five predictive models were established and evaluated by the confusion matrix receiver operating characteristic curve(AUROC),area under the precision-recall curve(AUPRC),specificity,sensitivity(recall rate),precision,accuracy,and F1 score.RESULTS The top-ranking five risk variables associated with TiPN were interleukin-12 rs1353248[P=0.0004,odds ratio(OR):8.983,95%confidence interval(CI):2.497-30.90],dose(mg/d,P=0.002),brainderived neurotrophic factor(BDNF)rs2030324(P=0.001,OR:3.164,95%CI:1.561-6.434),BDNF rs6265(P=0.001,OR:3.150,95%CI:1.546-6.073)and BDNF rs11030104(P=0.001,OR:3.091,95%CI:1.525-5.960).In the training set,gradient boosting decision tree(GBDT),extremely random trees(ET),random forest,logistic regression and extreme gradient boosting(XGBoost)obtained AUROC values>0.90 and AUPRC>0.87.Among these models,XGBoost and GBDT obtained the first two highest AUROC(0.90 and 1),AUPRC(0.98 and 1),accuracy(0.96 and 0.98),precision(0.90 and 0.95),F1 score(0.95 and 0.98),specificity(0.94 and 0.97),and sensitivity(1).In the validation set,XGBoost algorithm exhibited the best predictive performance with the highest specificity(0.857),accuracy(0.818),AUPRC(0.86)and AUROC(0.89).ET and GBDT obtained the highest sensitivity(1)and F1 score(0.8).Overall,compared with other state-of-the-art classifiers such as ET,GBDT and RF,XGBoost algorithm not only showed a more stable performance,but also yielded higher ROC-AUC and PRC-AUC scores,demonstrating its high accuracy in prediction of TiPN occurrence.CONCLUSION The powerful XGBoost algorithm accurately predicts TiPN using 18 clinical features and 14 genetic variables.With the ability to identify high-risk patients using single nucleotide polymorphisms,it offers a feasible option for improving thalidomide efficacy in CD patients.
基金This research was funded by Guangzhou Science and Technology Plan Projects(No.202002020066)the Young Scientists to the NSFC Application of Guangdong Provincial People’s Hospital(No.8210120306)the Open Foundation of the State Key Laboratory of Bioactive Seaweed Substance(No.SKL-BMSG2022-03)。
文摘Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumor necrosis factor alpha(TNF-α)in the diagnosis of Crohn’s disease.Methods CD patients(n=76)and healthy subjects(n=76)were enrolled between May 2019 and December 2020.The serum 25-hydroxyvitamin D[25(OH)D]levels,BMI,and TNF-αlevels,together with other biochemical parameters,were assessed before treatment.The diagnostic efficacy of the single and joint detection of serum 25(OH)D,BMI,and TNF-αwas determined using receiver operating characteristic(ROC)curves.Results The levels of 25(OH)D,BMI,and nutritional indicators,including hemoglobin,total protein,albumin,and high-density lipoprotein cholesterol,were much lower,and the TNF-αlevels were much higher in the CD patients than in the healthy subjects(P<0.05 for all).The areas under the ROC curve for the single detection of 25(OH)D,BMI,and TNF-αwere 0.887,0.896,and 0.838,respectively,with the optimal cutoff values being 20.64 ng/mL,19.77 kg/m^(2),and 6.85 fmol/mL,respectively.The diagnostic efficacy of the joint detection of 25(OH)D,BMI,and TNF-αwas the highest,with an area under the ROC curve of 0.988(95%CI:0.968–1.000).Conclusion The joint detection of 25(OH)D,TNF-α,and BMI showed high sensitivity,specificity,and accuracy in CD diagnosis;thus,it would be effective for the diagnosis of CD in clinical practice.
基金Supported by the National Council for Scientific and Technological Development(CNPq),No.302557/2021-0(to Leal RF)the Brazilian Coordination for the Improvement of Higher Education Personnel[CAPES(Coordenação de Aperfeiçoamento de Pessoal de Nível Superior),Brazil],No.001(to Siqueira NSN),the São Paulo Research Foundation(FAPESP),No.2021/02997-9(to D.O.S.A.).
文摘BACKGROUND Although the gastrointestinal tract is the most affected by Crohn’s disease(CD),the condition triggers other consequent manifestations,and iron deficiency anemia(IDA)is one of the most common.Intravenous(IV)iron replacement is currently available through several drugs,such as ferric hydroxide sucrose and ferric carboxymaltose(FCM).However,the clinical management of these conditions can be challenging.AIM To elucidate the drug’s effectiveness,the present study analyzed,through medical records,the clinical and epidemiological data of a cohort of patients with active CD who received IV FCM for the IDA treatment.METHODS This retrospective observational study included 25 patients with active CD,severe anemia,and refractory to previous conventional treatments.Patients were evaluated two times:During the last treatment with ferric hydroxide sucrose and treatment with FCM.RESULTS After treatment with FCM,parameters of IDA assessment significantly improved,serum hemoglobin(Hb)levels increased in 93%of patients(P<0.0001),and in 44%,there was an increase of≥2 g/dL in a single application.In addition,86%of the patients showed an increase in serum iron(P<0.0001)and ferritin(P=0.0008)and 50%in transferrin saturation(P=0.01).The serum iron levels at baseline showed a negative association with the ileal and colonic CD and use of biologics and a positive association with patients who developed CD later in life after the age of 40(A3)and with a stenosing(B2)and fistulizing(B3)phenotype.The values of Hb and hematocrit after ferric hydroxide sucrose treatment remained similar to those found before treatment.CONCLUSION This study demonstrated that FCM is an important therapeutic strategy for treating IDA in CD patients,achieving satisfactory results in refractory cases.
文摘BACKGROUND Small bowel adenocarcinomas(SBA) are rare malignancies with exceedingly low survival rates, with different presentation in Crohn’s disease(CD). CD-induced SBA poses diagnostic challenges given overlapping presentation with stricturing CD and lack of diagnostics for early detection. Moreover, guidance is lacking on the impact of recently approved therapeutics in CD on SBA management. Here, we aim to highlight the future of CD-induced SBA management and discuss the potential merit of balloon enteroscopy and genetic testing for earlier detection.CASE SUMMARY We report the case of a 60-year-old female with longstanding Crohn’s ileitis, presenting with acute obstructive symptoms attributed to stricturing phenotype. Her obstructive symptoms were refractory to intravenous(Ⅳ) steroids, with further investigation via computed tomography enterography not providing additional diagnostic yield. Ultimately, surgical resection revealed SBA in the neoterminal ileum, with oncologic therapy plan created. However, this therapy plan could not be initiated due to continued obstructive symptoms attributed to active CD. Ultimately, infused biologic therapy was initiated, but her obstructive symptoms continued to remain dependent on Ⅳ corticosteroids. Review of diagnostics by a multidisciplinary care team suggested metastatic disease in the peritoneum, lending to a shift in the goals of care to comfort.CONCLUSION With the diagnostic and therapeutic challenges of concurrent SBA and CD, multidisciplinary care and algorithmic management can optimize outcomes.
文摘BACKGROUND Inflammatory bowel disease(IBD)is an autoimmune condition treated with immunosuppressive drugs.However,the need for immune system suppression becomes questionable when infection with the human immunodeficiency virus(HIV)occurs simultaneously and impacts the course of IBD.Our reported case represents the clinical course,prescribed treatment and its effect,as well as clinical challenges faced by physicians in a combination of such diseases.We also present a comprehensive literature review of similar cases.CASE SUMMARY A 49-year-old woman suffering from a newly diagnosed Crohn’s disease was hospitalized due to exacerbated symptoms(abdominal pain,fever,and weight loss).During her hospital stay,she tested positive for HIV.With conservative treatment,the patient improved and was discharged.In the outpatient clinic,her HIV infection was confirmed as stage C3,and antiretroviral treatment was initiated immediately.That notwithstanding,soon the patient was rehospitalized with pulmonary embolism and developed a series of complications because of the subsequent coexistence of IBD and HIV.After intensive and meticulous treatment,the patient’s condition has improved and she remains in remission.CONCLUSION The paucity of studies and data on the coexistence of HIV and IBD leaves clinicians doubting the optimal treatment options.
文摘Crohn’s disease (CD) is a chronic inflammatory disease whose pathogenesis involves disturbances of the gastrointestinal microbiota. As the prevalence of CD increases, the need for a more effective and safe treatment is integral. Probiotics have been reported to be beneficial for numerous gastrointestinal diseases, providing health benefits and considering the microbial characteristics of CD’s pathogenesis. However, our knowledge of the efficacy of probiotic therapy in preventing relapse in CD is limited. How gastroenterologists have incorporated probiotics into their practice or probiotics observed implications for patients with CD has not been assessed. A quantitative survey was distributed to determine how gastroenterologists perceive and use probiotic-based therapies in CD practice. The second objective was to conduct a meta-analysis of the efficacy of probiotics for maintaining remission and preventing clinical and endoscopic relapse in CD. Performing a meta-analysis and survey will examine the role of probiotics in CD treatment. Surveyed gastroenterologists cited that probiotics have an adjunctive role and have been observed to alleviate common CD symptoms. Probiotics seem effective in reducing the relapse rate, specifically those of the multi-strain variety are more likely to be effective in maintaining CD remission. Further research with larger trials is required to replicate and solidify this efficacy. The meta-analysis only assessed the efficacy of probiotics as a maintenance treatment as measured by the risk of relapse;thus, no evidence supports probiotics’ ability to induce remission. The results of the meta-analysis and survey indicate that probiotics cannot treat CD without accompanying conventional drug therapies;nevertheless, independent of treatment capacities, probiotics still yield health benefits for CD patients.
文摘BACKGROUND Perianal fistulising Crohn's disease(PFCD)and glandular anal fistula have many similarities on conventional magnetic resonance imaging.However,many patients with PFCD show concomitant active proctitis,but only few patients with glandular anal fistula have active proctitis.AIM To explore the value of differential diagnosis of PFCD and glandular anal fistula by comparing the textural feature parameters of the rectum and anal canal in fat suppression T2-weighted imaging(FS-T2WI).METHODS Patients with rectal water sac implantation were screened from the first part of this study(48 patients with PFCD and 22 patients with glandular anal fistula).Open-source software ITK-SNAP(Version 3.6.0,http://www.itksnap.org/)was used to delineate the region of interest(ROI)of the entire rectum and anal canal wall on every axial section,and then the ROIs were input in the Analysis Kit software(version V3.0.0.R,GE Healthcare)to calculate the textural feature parameters.Textural feature parameter differences of the rectum and anal canal wall between the PFCD group vs the glandular anal fistula group were analyzed using Mann-Whitney U test.The redundant textural parameters were screened by bivariate Spearman correlation analysis,and binary logistic regression analysis was used to establish the model of textural feature parameters.Finally,diagnostic accuracy was assessed by receiver operating characteristic-area under the curve(AUC)analysis.RESULTS In all,385 textural parameters were obtained,including 37 parameters with statistically significant differences between the PFCD and glandular anal fistula groups.Then,16 texture feature parameters remained after bivariate Spearman correlation analysis,including one histogram parameter(Histogram energy);four grey level co-occurrence matrix(GLCM)parameters(GLCM energy_all direction_offset1_SD,GLCM entropy_all direction_offset4_SD,GLCM entropy_all direction_offset7_SD,and Haralick correlation_all direction_offset7_SD);four texture parameters(Correlation_all direction_offset1_SD,cluster prominence_angle 90_offset4,Inertia_all direction_offset7_SD,and cluster shade_angle 45_offset7);five grey level run-length matrix parameters(grey level nonuniformity_angle 90_offset1,grey level nonuniformity_all direction_offset4_SD,long run high grey level emphasis_all direction_offset1_SD,long run emphasis_all direction_offset4_SD,and long run high grey level emphasis_all direction_offset4_SD);and two form factor parameters(surface area and maximum 3D diameter).The AUC,sensitivity,and specificity of the model of textural feature parameters were 0.917,85.42%,and 86.36%,respectively.CONCLUSION The model of textural feature parameters showed good diagnostic performance for PFCD.The texture feature parameters of the rectum and anal canal in FS-T2WI are helpful to distinguish PFCD from glandular anal fistula.
文摘Crohn’s disease might result from a complex interplay between genetic susceptibility, environmental factors, and altered gut microbiota, leading to dysregulated innate and adaptive immune responses. The reported case presents a patient with intestinal subocclusion associated with a pharmacobezoar who had a good evolution with clinical treatment. This case report aims to demonstrate the complexity of diagnostic search, even with the classic version of the disease. And it also comes to show the need for a thorough medical history and differential diagnosis investigation.
文摘BACKGROUND The pediatric Crohn’s disease activity index(PCDAI)is used as a standard tool to assess disease activity in clinical trials for pediatric Crohn’s disease.AIM To examine which items on the PCDAI drive assessment of disease activity,and how subgroups of subjective and objective items reflect change in disease state over time.METHODS Selective raw data from three prospectively collected datasets were combined,including 703 children with full PCDAI data at baseline,at 3-mo(Q1,n=670),and 1-year(Q4,n=474).Change in individual PCDAI scores from baseline to Q1 and to Q4 were examined using the non-weighted PCDAI.RESULTS Abdominal pain,well-being,weight,and stooling had the highest change scores over time.Objective indicators including albumin,abdominal exam,and height velocity followed.Change scores for well-being and abdominal exam did not explain significant variance at Q1 but were significant predictors at Q4(P<0.001 and P<0.05).Subjective and objective subgroups of items predicted less variance(18%and 22%)on total PCDAI scores at Q1 and Q4 compared to the full PCDAI,or a composite scale(both 32%)containing significant predictors.CONCLUSION Although subjective items on the PCDAI change the most over time,the full PCDAI or a smaller composite of items including a combination of subjective and objective components classifies disease activity better than a subgroup of either subjective or objective items alone.Reliance on subjective or objective items as stand-alone proxies for disease activity measurement could result in misclassification of disease state.
