Computed tomography-based radiomics combined with machine learning allows differentiation between primary intestinal lymphoma and Crohn's disease

BACKGROUND Due to similar clinical manifestations and imaging signs,differential diagnosis of primary intestinal lymphoma(PIL)and Crohn's disease(CD)is a challenge in clinical practice.AIM To investigate the ability of radiomics combined with machine learning methods to differentiate PIL from CD.METHODS We collected contrast-enhanced computed tomography(CECT)and clinical data from 120 patients form center 1.A total of 944 features were extracted singlephase images of CECT scans.Using the last absolute shrinkage and selection operator model,the best predictive radiographic features and clinical indications were screened.Data from 54 patients were collected at center 2 as an external validation set to verify the robustness of the model.The area under the receiver operating characteristic curve,accuracy,sensitivity and specificity were used for evaluation.RESULTS A total of five machine learning models were built to distinguish PIL from CD.Based on the results from the test group,most models performed well with a large area under the curve(AUC)(>0.850)and high accuracy(>0.900).The combined clinical and radiomics model(AUC=1.000,accuracy=1.000)was the best model among all models.CONCLUSION Based on machine learning,a model combining clinical data with radiologic features was constructed that can effectively differentiate PIL from CD.

Contribution of gut microbiota to the development of Crohn's disease:Insights gained from fecal microbiota transplantation studies in mice

We would like to present some new thoughts on the publication in the journalpublished in August 2024 in World Journal of Gastroenterology.We specificallyfocused on the alterations in the intestinal tract,mesenteric adipose tissue(MAT),and systemic inflammatory changes in mice following fecal flora transplantationinto a mouse model of Crohn's disease(CD).Accumulating evidence suggests thatthe occurrence of CD is influenced by environmental factors,host immune status,genetic susceptibility,and flora imbalance.One microbiota-based intervention,fecal microbiota transplantation,has emerged as a potential treatment option forCD.The MAT is considered a"second barrier"around the inflamed intestine.Theinteraction between gut microbes and inflammatory changes in MAT has attractedconsiderable interest.In the study under discussion,the authors transplantedfetal fecal microorganisms from patients with CD and clinically healthy donors,respectively,into 2,4,6-trinitrobenzene sulfonic acid-induced CD mice.Theresearch explored the complex interplay between MAT,creeping fat,inflammation,and intestinal flora in CD by evaluating intestinal and mesenteric lesions,along with the systemic inflammatory state in the mice.This article providesseveral important insights.First,the transplantation of intestinal flora holdssignificant potential as a therapeutic strategy for CD,offering hope for patientswith CD.Second,it presents a novel approach to the diagnosis and treatment ofCD:The inflammatory response in CD could potentially be assessed throughpathological or imaging changes in the MAT,and CD could be treated bytargeting the inflammation of the MAT.

Establishment of a surveillance program for anal cancer in Crohn's disease

This letter discusses the incidence of anal cancer among Crohn's disease(CD)-related malignancies.Patients with CD have been demonstrated to be at a higher risk of developing small bowel and colorectal cancers than healthy individuals.Although CD-associated anal cancer is relatively rare,patients with CD accom-panied by anal or perianal lesions are at increased risk of anal cancer.Addi-tionally,compared to ulcerative colitis,which is also an inflammatory disease,CD-related anal cancer is often detected at an advanced stage owing to the complexity of CD and is associated with a poor prognosis with frequent local recurrences.Therefore,the detection of early-stage cancer is crucial for improving the prognosis.However,the surveillance methods recommended for CD-related malignancies in the United States and Europe are similar to those for ulcerative colitis.They are not appropriate for detecting CD-related malignancies in the recto-anal region.Therefore,there is an urgent need for surveillance programs aimed at the early detection of malignant anorectal lesions in patients with CD.

Advancing perioperative optimization in Crohn's disease surgery with machine learning predictions

This editorial offers commentary on the article which aimed to forecast the likelihood of short-term major postoperative complications(Clavien-Dindo grade≥III),including anastomotic fistula,intra-abdominal sepsis,bleeding,and intestinal obstruction within 30 days,as well as prolonged hospital stays follow-ing ileocecal resection in patients with Crohn’s disease(CD).This prediction re-lied on a machine learning(ML)model trained on a cohort that integrated a no-mogram predictive model derived from logistic regression analysis and a random forest(RF)model.Both the nomogram and RF showed good performance,with the RF model demonstrating superior predictive ability.Key variables identified as potentially critical include a preoperative CD activity index≥220,low preope-rative serum albumin levels,and prolonged operation duration.Applying ML ap-proaches to predict surgical recurrence have the potential to enhance patient risk stratification and facilitate the development of preoperative optimization strate-gies,ultimately aiming to improve post-surgical outcomes.However,there is still room for improvement,particularly by the inclusion of additional relevant clinical parameters,consideration of medical therapies,and potentially integrating mole-cular biomarkers in future research efforts.

Advances in the research of intestinal fungi in Crohn's disease

This article reviews of the original research published by Wu et al in the World Journal of Gastroenterology,delving into the pivotal role of the gut microbiota in the pathogenesis of Crohn's disease(CD).Insights were gained from fecal microbiota transplantation(FMT)in mouse models,revealing the intricate interplay between the gut microbiota,mesenteric adipose tissue(MAT),and creeping fat.The study uncovered the characteristics of inflammation and fibrosis in the MAT and intestinal tissues of patients with CD;moreover,through the FMT mouse model,it observed the impact of samples from healthy patients and those with CD on symptoms.The pathogenesis of CD is complex,and its etiology remains unclear;however,it is widely believed that gut microbiota dysbiosis plays a significant role.Recently,with the development and application of next-generation sequen-cing technology,research on the role of fungi in the pathogenesis and chronicity of CD has deepened.This editorial serves as a supplement to the research by Wu et al who discussed advances related to the study of fungi in CD.

Saccharomyces cerevisiae prevents postoperative recurrence of Crohn's disease modeled by ileocecal resection in HLA-B27 transgenic rats

BACKGROUND Postoperative recurrence(POR)after ileocecal resection(ICR)affects most Crohn's disease patients within 3-5 years after surgery.Adherent-invasive Escherichia coli(AIEC)typified by the LF82 strain are pathobionts that are frequently detected in POR of Crohn's disease and have a potential role in the early stages of the disease pathogenesis.Saccharomyces cerevisiae CNCM I-3856 is a probiotic yeast reported to inhibit AIEC adhesion to intestinal epithelial cells and to favor their elimination from the gut.AIM To evaluate the efficacy of CNCM I-3856 in preventing POR induced by LF82 in an HLA-B27 transgenic(TgB27)rat model.METHODS Sixty-four rats[strain F344,38 TgB27,26 control non-Tg(nTg)]underwent an ICR at the 12th wk(W12)of life and were sacrificed at the 18th wk(W18)of life.TgB27 rats were challenged daily with oral administration of LF82(109 colony forming units(CFUs)/day(d),n=8),PBS(n=5),CNCM I-3856(109 CFUs/d,n=7)or a combination of LF82 and CNCM I-3856(n=18).nTg rats receiving LF82(n=5),PBS(n=5),CNCM I-3856(n=7)or CNCM I-3856 and LF82(n=9)under the same conditions were used as controls.POR was analyzed using macroscopic(from 0 to 4)and histologic(from 0 to 6)scores.Luminal LF82 quantifications were performed weekly for each animal.Adherent LF82 and inflammatory/regulatory cytokines were quantified in biopsies at W12 and W18.Data are expressed as the median with the interquartile range.RESULTS nTg animals did not develop POR.A total of 7/8(87%)of the TgB27 rats receiving LF82 alone had POR(macroscopic score≥2),which was significantly prevented by CNCM I-3856 administration[6/18(33%)TgB27 rats,P=0.01].Macroscopic lesions were located 2 cm above the anastomosis in the TgB27 rats receiving LF82 alone and consisted of ulcerations with a score of 3.5(2-4).Seven out of 18 TgB27 rats(39%)receiving CNCM I-3856 and LF82 had no macroscopic lesions.Compared to untreated TgB27 animals receiving LF82 alone,coadministration of CNCM I-3856 and LF82 significantly reduced the macroscopic[3.5(2-4)vs 1(0-3),P=0.002]and histological lesions by more than 50%[4.5(3.3-5.8)vs 2(1.3-3),P=0.003].The levels of adherent LF82 were correlated with anastomotic macroscopic scores in TgB27 rats(r=0.49,P=0.006),with a higher risk of POR in animals having high levels of luminal LF82(71.4%vs 25%,P=0.02).Administration of CNCM I-3856 significantly reduced the levels of luminal and adherent LF82,increased the production of interleukin(IL)-10 and decreased the production of IL-23 and IL-17 in TgB27 rats.CONCLUSION In a reliable model of POR induced by LF82 in TgB27 rats,CNCM I-3856 prevents macroscopic POR by decreasing LF82 infection and gut inflammation.

Crohn's disease and clinical management today:How it does?

Crohn’s Disease(CD)is an Inflammatory Bowel Disease and is characterized by an immune-mediated nature.Its etiology results from the interaction between genetic,enviromental and microbial factors.Regarding pathophysiology,it involves high levels of interleukin(IL)-12,IL-17,and Th1 profile,along with loss of tolerance mechanisms,an increase in pro-inflammatory interleukins,beyond the possibility to affect any part of the gastrointestinal tract.Its symptoms include abdominal pain,chronic diarrhea,weight loss,anorexia,and fatigue,as well as blood in the stool or rectum.Additionally,conditions comprising musculoskeletal,cutaneous,ocular,hepatic,and hematological alterations may be associated with this scenario and extra-intestinal presentation,such as erythema nodosum,anterior uveitis,osteoporosis,and arthritis can also occur.Today,clinical history,exams as fecal calprotectin,ileocolonocopy,and capsule endoscopy can be performed in the diagnosis investigation,along with treatments to induce and maintain remission.In this sense,anti-inflammatory drugs,such as corticosteroids,immunomodulators,and biological agents,as well as surgery and non-pharmacological interventions plays a role in its therapy.The aim of this review is to bring more current evidence to clinical management of CD,as well as to briefly discuss aspects of its pathophysiology,surveillance,and associated disorders.

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

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

Melanocortin 3,5 receptors immunohistochemical expression in colonic mucosa of inflammatory bowel disease patients:A matter of disease activity?

BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin family.However,data regarding their role in inflammatory bowel diseases(IBD)are currently unavailable.AIM This study aims to ascertain their expression profiles in the colonic mucosa of Crohn’s disease(CD)and ulcerative colitis(UC),aligning them with IBD disease endoscopic and histologic activity.METHODS Colonic mucosal biopsies from CD/UC patients were sampled,and immunohisto-chemical analyses were conducted to evaluate the expression of MC3R and MC5R.Colonic sampling was performed on both traits with endoscopic scores(Mayo endoscopic score and CD endoscopic index of severity)consistent with inflamed mucosa and not consistent with disease activity(i.e.,normal appearing mucosa).RESULTS In both CD and UC inflamed mucosa,MC3R(CD:+7.7 fold vs normal mucosa,P<0.01;UC:+12 fold vs normal mucosa,P<0.01)and MC5R(CD:+5.5 fold vs normal mucosa,P<0.01;UC:+8.1 fold vs normal mucosa,P<0.01)were significantly more expressed compared to normal mucosa.CONCLUSION MC3R and MC5R are expressed in the colon of IBD patients.Furthermore,expression may differ according to disease endoscopic activity,with a higher degree of expression in the traits affected by disease activity in both CD and UC,suggesting a potential use of these receptors in IBD pharmacology.

Addressing diagnostic delays in inflammatory bowel diseases in Germany

Inflammatory bowel diseases(IBDs),including Crohn's disease(CD)and ulcerative colitis,are chronic inflammatory conditions of the gastrointestinal tract that necessitate timely diagnosis to prevent complications and improve patient outcomes.Despite advancements in medical knowledge and diagnostic techniques,significant diagnostic delays persist,particularly in CD.The study by Blüthner et al,published in the World Journal of Gastroenterology,elucidates the diagnostic delays experienced by German patients with IBD and identifies key risk factors contributing to these delays.

Clinical characteristics and north-south differences of inflammatory bowel disease in China: A cross-sectional study and meta-analysis

Objective:This study aimed to estimate the incidence rate and clinical characteristics of inflammatory bowel disease(IBD)in the Chinese population,specially comparing the North and South regions.Methods:We designed a questionnaire survey for patients diagnosed with IBD and conducted a systematic literature search in PubMed,China National Knowledge Internet,and Wanfang digital database,covering studies published between 2012 and 2022.Meta-analysis was performed to determine the overall incidence rate and prevalence of clinical manifestations of Crohn's disease(CD)and ulcerative colitis(UC)in China's Mainland.Clinical phenotypes and demographic characteristics were calculated with 95%confidence intervals(CI).A comparison between the northern and southern regions was also conducted.Results:The questionnaire survey included 440 patients,and 64 publications were included for Meta-analysis.The overall incidence rates of IBD,CD,and UC were 1.36(95%CI:0.79-2.33)per 100,000 person-years,0.23(95%CI:0.09-0.58)per 100,000 person-years,and 1.12(95%CI:0.69-1.80)per 100,000 person-years,respectively.The incidence rates of IBD,CD,and UC were all higher in southern China compared to the North.Clinical characteristics of 440 IBD patients from the questionnaire and 2,821 CD patients and 12,809 UC patients from the literature were analyzed.There were more male patients compared to female patients.CD cases in the North exhibited earlier disease diagnosis(P<0.01),more upper gastrointestinal lesions(P<0.01),and higher hospitalizations rates(P<0.01)compared to the South.UC cases in the North had higher severity(P<0.01),anemia rates(P<0.01),and weight loss(P<0.01)compared to the South.Conclusions:The incidence rates of IBD,CD,and UC were higher in southern China than in the North.Northern patients exhibited more severe symptoms compared to their southern counterparts.

Moxibustion combined with acupuncture increases tight junction protein expression in Crohn's disease patients

AIM:To investigate the effect of herb-partitioned moxibustion combined with acupuncture on the expression of intestinal epithelial tight junction(TJ) proteins.METHODS:Sixty patients diagnosed with mild to moderate Crohn’s disease(CD)were allocated into the herb-partitioned moxibustion combined with acupuncture(HMA)group(n=30)or the mesalazine(MESA)group(n=30)using a parallel control method.There were 2 sets of acupoints used alternately for HMA treatment.The following points were included in Set A:ST25(Tianshu),RN6(Qihai),and RN9(Shuifen)for herb-partitioned moxibustion and ST36(Zusanli),ST37(Shangjuxu),LI11(Quchi),and LI4(Hegu)for acupuncture.The points for Set B included BL23(Shenshu)and BL25(Dachangshu)for herb-partitioned moxibustion and EX-B2 of T6-T1(Jiajixue)fo r acupuncture.The patients received the same treatment6 times a week for 12 consecutive weeks.The MESA group received 1 g of mesalazine enteric coated tablets4 times daily for 12 consecutive weeks.Intestinaltissues were stained and examined to compare the morphological and ultrastructural changes before and after the treatment session.Immunohistochemistry and in situ hybridization assays were used to detect the expression of intestinal epithelial TJ proteins zonula occludens-1(ZO-1),occludin,and claudin-1.The m RNA levels were also evaluated.RESULTS:After the treatment,both herb-partitioned moxibustion combined with acupuncture and mesalazine improved intestinal morphology and ultrastructure of CD patients;the patients treated with HMA showed better improvement.HMA significantly increased the expression of ZO-1(P=0.000),occludin(P=0.021),and claudin-1(P=0.016).MESA significantly increased the expression of ZO-1(P=0.016)and occludin(P=0.026).However,there was no significant increase in the expression of claudin-1(P=0.935).There was no statistically significant difference between the two groups for the expression of occludin and claudin-1(P>0.05).The HMA group showed a significant improvement in ZO-1 expression compared to the MESA group(2333.34±352.51 vs 2160.38±307.08,P=0.047).HMA significantly increased the expression of ZO-1 m RNA(P=0.000),occludin m RNA(P=0.017),and claudin-1 m RNA(P=0.017).MESA significantly increased the expression of ZO-1 m RNA(P=0.000),occludin m RNA(P=0.042),and claudin-1 m RNA(P=0.041).There was no statistically significant difference between the two groups in the expression of occludin and claudin-1 m RNA(P>0.05).However,the HMA group showed a significant improvement in ZO-1 m RNA expression compared with the MESA group(2378.17±308.77 vs 2200.56±281.88,P=0.023).CONCLUSION:HMA can repair intestinal epithelial barrier lesions and relieve inflammation by upregulating the expression of TJ proteins and their m RNAs.

Fecal microbiota transplantation cured epilepsy in a case with Crohn's disease: The first report

Fecal microbiota transplantation(FMT)is a promising strategy that involves reconstruction of gut microbiota.Recently,it has been considered as a treatment of Crohn’s disease(CD)and certain neurological diseases.Here,to the best of our knowledge,we report the first case that used FMT to achieve remission of intestinal and neurological symptoms in a girl with CD and a 17-year history of epilepsy.During the 20 mo of follow-up,FMT has proved its efficacy in preventing relapse of seizures after withdrawing the antiepileptic drugs.Furthermore,this finding highlights the role of microbiota-gut-brain axis and inspires a novel treatment for epilepsy through remodeling gut microbiota.

Differentiating Crohn's disease from intestinal tuberculosis

Differentiating Crohn's disease(CD) and intestinal tuberculosis(ITB) has remained a dilemma for most of the clinicians in the developing world, which are endemic for ITB, and where the disease burden of inflammatory bowel disease is on the rise. Although, there are certain clinical(diarrhea/hematochezia/perianal disease common in CD; fever/night sweats common in ITB), endoscopic(longitudinal/aphthous ulcers common in CD; transverse ulcers/patulous ileocaecal valve common in ITB), histologic(caseating/confluent/large granuloma common in ITB; microgranuloma common in CD), microbiologic(positive stain/culture for acid fast-bacillus in ITB), radiologic(long segment involvement/comb sign/skip lesions common in CD; necrotic lymph node/contiguous ileocaecal involvement common in ITB), and serologic differences between CD and ITB, the only exclusive features are caseation necrosis on biopsy, positive smear for acid-fast bacillus(AFB) and/or AFB culture, and necrotic lymph node on cross-sectional imaging in ITB. However,these exclusive features are limited by poor sensitivity, and this has led to the development of multiple multi-parametric predictive models. These models are also limited by complex formulae, small sample size and lack of validation across other populations. Several new parameters have come up including the latest Bayesian meta-analysis, enumeration of peripheral blood T-regulatory cells, and updated computed tomography based predictive score. However, therapeutic anti-tubercular therapy(ATT) trial, and subsequent clinical and endoscopic response to ATT is still required in a significant proportion of patients to establish the diagnosis. Therapeutic ATT trial is associated with a delay in the diagnosis of CD, and there is a need for better modalities for improved differentiation and reduction in the need for ATT trial.

Factors affecting recurrence after surgery for Crohn's disease

Although in Crohn's disease post-operative recurrence is common, the determinants of disease recurrence remain speculative. The aim of this study was to examine factors affecting post-operative recurrence of Crohn's disease. A Medline-based literature review was carried out. The following factors were investigated: age at onset of disease, sex, family history of Crohn's disease,smoking, duration of Crohn's disease before surgery,prophylactic medical treatment (corticosteroids, 5-amino salicylic acid [5-ASA] and immunosuppressants),anatomical site of involvement, indication for surgery (perforating or non-perforating disease), length of resected bowel, anast-omotic technique, presence of granuloma in the specimen, involvement of disease at the resection margin, blood transfusions and postoperative complications. Smoking significantly increases the risk of recurrence (risk is approximately twice as high), especially in women and heavy smokers. Quitting smoking reduces the post-operative recurrence rate. A number of studies have shown a higher risk when the duration of the disease before surgery was short. There were, however, different definitions of 'short' among the studies. Prophylactic cortic-osteroids therapy is not effective in reducing the post-operative recurrence. A number of randomized controlled trials offered evidence of the efficacy of 5-ASA (mesalazine) in reducing post-operative recurrence. Recently, the thera-peutic efficacy of immunosuppressive drugs (azathioprine and 6-mercaptopurine) in the prevention of post-operative recurrence has been investigated and several studies have reported that these drugs might help prevent the recurrence. Further clinical trials would be necessary to evaluate the prophylactic efficacy of immunosuppressants.Several studies showed a higher recurrence rate in patients with perforating disease than in those with non-perforating disease. However, evidence for differing recurrence rates in perforating and non-perforating diseases is inconclusive.A number of retrospective studies reported that a stapled functional end-to-end anastomosis was associated with a lower recurrence rate compared with other types of anastomosis. However, prospective randomized studies would be necessary to draw a definite conclusion. Many studies found no difference in the recurrence rates between patients with radical resection and non-radical resection. Therefore, minimal surgery including strictureplasty has been justified in the management of Crohn's disease. In this review, the following factors do not seem to be predictive of post-operative recurrence:age at onset of disease, sex, family history of Crohn's disease, anatomical site of disease, length of resected bowel, presence of granuloma in the specimen, blood transfusions and post-operative complications. The most significant factor affecting post-operative recurrence of Crohn's disease is smoking. Smoking significantly increases the risk of recurrence. A short disease duration before surgery seems, albeit to a very minor degree, to be associated with a higher recurrence rate. 5-ASA has been shown with some degree of confidence to lead to a lower recurrence rate. The prophylactic efficacy of immunosuppressive drugs should be assessed in future.A wider anastomotic technique after resection may reduce the post-operative recurrence rate, though this should be investigated with prospective randomized controlled trials.

Response to strict and liberalized specific carbohydrate dietin pediatric Crohn's disease

AIM: To investigate the specific carbohydrate diet(SCD) as nutritional therapy for maintenance of remission in pediatric Crohn's disease(CD). METHODS: Retrospective chart review was conducted in 11 pediatric patients with CD who initiated the SCD as therapy at time of diagnosis or flare. Two groups defined as SCD simple(diet alone, antibiotics or 5-ASA) or SCD with immunomodulators(corticosteroids and/or stable thiopurine dosing) were followed for one year and compared on disease characteristics, laboratory values and anthropometrics.RESULTS: The mean age at start of the SCD was 11.8 ± 3.0 years(range 6.6-17.6 years) with five patients starting the SCD within 5 wk of diagnosis. Three patients maintained a strict SCD diet for the study period and the mean time for liberalization was 7.7 ± 4.0 mo(range 1-12) for the remaining patients. In both groups, hematocrit, albumin and ESR values improved while on strict SCD and appeared stable after liberalization(P-value 0.006, 0.002, 0.002 respectively). The majority of children gained in weight and height percentile while on strict SCD, with small loss in weight percentile documented with liberalization. CONCLUSION: Disease control may be attainable with the SCD in pediatric CD. Further studies are needed to assess adherence, impact on mucosal healing and growth.

Randomized controlled trial: Moxibustion and acupuncture for the treatment of Crohn's disease

AIM: To evaluate the clinical efficacy and safety of acupuncture and moxibustion for the treatment of active Crohn&#x02019;s disease (CD).

Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: Phenotype-genotype correlations

AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. RESULTS: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%,P<0.0001). SNP8/R702W (10.8% vs 6%, P= 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P= 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (ORhet=1.71, 95%CI=1.12-2.6, P= 0.0001, ORtwo-risk alleles = 25.2, 95%CI =4.37- ,P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P=0.0006), ileal disease (81.9% (?) 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P= 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69,95%CI = 1.13-2.55, P= 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P= 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. CONCLUSION: These results confirm that variant NOD2/ CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.

Circulating miR-125a but not miR-125b is decreased in active disease status and negatively correlates with disease severity as well as inflammatory cytokines in patients with Crohn's disease

AIM To determine the association of circulating mi R-125 a/b expression with the risk and disease severity of Crohn's disease(CD), and with inflammatory cytokines.METHODS Plasma samples were collected from patients with active CD(A-CD), or CD in remission(R-CD) and from healthy controls(HCs). The levels of the inflammatory cytokines interleukin-17(IL-17), tumour necrosis factor-α(TNF-α), and interferon-γ(IFN-γ) were measured by enzyme-linked immunosorbent assay. The expression of mi R-125 a/b was assessed by quantitative polymerase chain reaction(q PCR).RESULTS Twenty-nine A-CD patients, 37 R-CD patients, and 37 HCs were included in the study. Plasma mi R-125 a expression was decreased in A-CD patients comparedwith that in R-CD patients(P < 0.001) and HCs(P < 0.001). mi R-125 a expression levels enabled the differentiation of A-CD from R-CD patients [area under curve(AUC) = 0.854] and from HCs(AUC = 0.780), whereas mi R-125 b expression did not. mi R-125 a was negatively correlated with C-reaction protein(CRP)(P = 0.017), erythrocyte sedimentation rate(ESR)(P = 0.026), Crohn's disease activity index(CDAI)(P = 0.003), IL-17(P = 0.015), and TNF-α(P = 0.004) in A-CD patients. Furthermore, mi R-125 a was negatively associated with CRP(P = 0.038) and CDAI(P = 0.021) in R-CD patients. Regarding mi R-125 b, no association with CRP, CDAI, IL-17, TNF-α, or IFN-γ was found in A-CD or in R-CD patients. mi R-125 a levels gradually increased in A-CD patients who achieved clinical remission(P = 0.009) after 3-mo treatment, whereas they remained unchanged among patients who failed to achieve remission. No changes in mi R-125 b expression were detected in remission or non-remission patients after treatment. CONCLUSION Circulating mi R-125 a but not mi R-125 b is decreased in patients with active disease status and negatively correlates with disease severity and inflammatory cytokines in patients with CD.

Clinical significance of granuloma in Crohn's disease

AIM: Granuloma is considered the hallmark of microscopic diagnosis in Crohn's disease (CD), but granulomas can be detected in only 21-60% of CD patients. The aim of this study was to evaluate the frequency of granulomas by multiple endoscopic biopsies in patients with CD and to examine whether group of patients with or without granuloma exhibit a different clinical course. METHODS: Fifty-six patients with newly diagnosed CD were included in the study. Jejunoscopy, enteroclysis and ileo-colonoscopy were performed in all patients. At least two biopsy specimens from each examined gastrointestinal segment were examined microscopically searching granuloma. The clinical course was followed in all patients, and extraintestinal manifestations as well as details of any immunosuppressive therapy and surgical intervention were noted. RESULTS: Granuloma was found in 44.6% of the cases (25 patients). Patients with granuloma had higher activity parameters at the time of the biopsies. Extraintestinal manifestations were observed and surgical interventions were performed more often in the granuloma group. The need of immunosuppressive therapy was significantly more frequent in the patients with granuloma. Granuloma formation is mote often seen in younger patients, and mainly in the severe, active penetrating disease. CONCLUSION: The significantly higher frequency of surgical interventions and immunosuppressive therapy suggests that granuloma formation is associated with a more severe disease course during the first years of CD.