Need for infliximab dose intensification in Crohn's disease and ulcerative colitis

AIM: To compare the need for infliximab dose intensification in two cohorts of patients with Crohn's disease(CD) or ulcerative colitis(UC).METHODS: Single centre, uncontrolled, observational study. Consecutive patients with CD and UC who responded to infliximab induction doses were included. Data collected in a prospectively maintained database were retrospectively analysed. Differences in the rates of dose intensification per patient-month and the intensification-free survival time were compared. We also evaluated the interval between the first infliximab induction dose and the first infliximab escalated dose. The weight-adjusted infliximab administration costs were also calculated.RESULTS: Fifty nine patients with CD and 38 patients with UC were enrolled. The rate of intensification per patient-month was 3.9% for UC and 1.4% for CD(P = 0.005). The median time from baseline to intensification was significantly shorter in UC compared to CD [6.6 mo(IQR: 4.2-9.5 mo) vs 10.7 mo(IQR: 8.9-11.7 mo), P = 0.005]. In the survival analysis, the cumulative probability of avoiding infliximab dose intensification was significantly higher in CD(P = 0.002). In the multivariate analysis, disease(UC vs CD) was the only factor significantly associated with dose intensification. The infiximab administration costs during the first year were significantly higher for UC compared to CD(mean ± SD 234.9 ± 53.3 Euros/kg vs 212.3 ± 15.1 Euros/kg, P = 0.03).CONCLUSION: The rate of infliximab dose intensification per patient-month is significantly higher in UC patients. The infliximab administration costs are also significantly higher in patients with UC.

MicroRNAs expression influence in ulcerative colitis and Crohn's disease:A pilot study for the identification of diagnostic biomarkers

BACKGROUND Inflammatory bowel disease(IBD)comprises two distinct diseases,Crohn’s disease(CD)and ulcerative colitis(UC),both of which are chronic,relapsing inflammatory disorders of the gastrointestinal tract with a mostly unknown etiology.The incidence and prevalence of IBD are continually increasing,indicating the need for further studies to investigate the genetic determinants of these diseases.Since microRNAs(miRNAs)regulate protein translation via complementary binding to mRNA,discovering differentially expressed miRNAs(DE)in UC or CD patients could be important for diagnostic biomarker identification,assisting in the appropriate disease differentiation progressing the understanding of IBD pathogenesis.AIM To determine the miRNA expression profile in UC and CD patients and the potential pathophysiological contributions of differentially expressed miRNA.METHODS A total of 20 formalin-fixed paraffin-embedded colonic samples were collected from the Pathology Department of Botucatu Medical School at São Paulo State University(Unesp).The diagnosis of UC or CD was based on clinical,endoscopic,radiologic,and histological criteria and confirmed by histopathological analysis at the time of selection.The TaqMan™Array Human MicroRNA A+B Cards Set v3.0(Applied Biosystems™)platform was used to analyze 754 miRNAs.Targets of DE-miRNAs were predicted using miRNA Data Integration Portal(mirDIP)and the miRNA Target Interaction database(MiRTarBase).All statistical analyses were conducted using GraphPad Prism software.Parametric and nonparametric data were analyzed using t-tests and Mann-Whitney U tests,respectively.RESULTS The results showed that of the 754 miRNAs that were initially evaluated,643 miRNAs were found to be expressed in at least five of the patients who were diagnosed with either CD or UC;the remaining 111 miRNAs were not considered to be expressed in these patients.The expression levels of 28 miRNAs were significantly different between the CD and UC patients(P≤0.05);13 miRNAs demonstrated a fold-change in expression level greater than 1.Five miRNAs with a downregulated expression were selected for enrichment analysis.The miRNAs whose expression levels were significantly lower in UC patients than in CD patients were enriched in certain signaling pathways that were mostly correlated with cancer-related processes and respective biomarkers.CONCLUSION MiRNAs could be used to differentiate UC from CD,and differently expressed miRNAs could help explain the distinct pathophysiology of each disease.

Frequency and prognostic role of mucosal healing in patients with Crohn's disease and ulcerative colitis after one-year of biological therapy

AIM:To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn’s disease(CD)and ulcerative colitis(UC).METHODS:The data from 41 patients with CD and 22 patients with UC were assessed.Twenty-four CD patients received infliximab,and 17 received adalimumab.The endoscopic severity of CD was quantified with the simplified endoscopic activity score for Crohn’s disease in CD and with the Mayo endoscopic subscore in UC.RESULTS:Mucosal healing was achieved in 23 CD and7 UC patients.Biological therapy had to be restarted in78%of patients achieving complete mucosal healing with CD and in 100%of patients with UC.Neither clinical remission nor mucosal healing was associated with the time to restarting the biological therapy in either CD or UC.CONCLUSION:Mucosal healing did not predict sustained clinical remission in patients in whom the biological therapies had been stopped.

Why is damage limited to the mucosa in ulcerative colitis but transmural in Crohn's disease?

It has been a big puzzle as why the inflammation of ulcerative colitis (UC) is limited to the mucosa, while in Crohn's disease (CD) the inflammation is transmural and can be seen in all layers of the gut. Here, I give a tentative explanation extended from the unified hypothesis I proposed on the etiology of inflammatory bowel disease. This hypothesis suggested that both UC and CD are caused by weakening of the gut barrier due to damage of the protective mucus layer and the underlying tissue by the poorly inactivated digestive proteases resulting from a reduction of gut bacteria by dietary chemicals like saccharin and sucralose. However, the large amounts of bacteria in the colon make the recruitment of neutrophils and formation of crypt abscess the main manifestation of UC, while the infiltration of antigens and dietary particles in the small and large intestine mainly cause the recruitment of macrophages and formation of granulomas as the main manifestations in CD. The fast reacting and short life span of neutrophils make the fight and damage limited to the surface of the mucosa. In contrast, the long life span and constant movement of macrophages may bring the harmful agents deep into the tissue. Therefore, the pathogenesis of UC may be more like bacterial pneumonia, while CD may be more like pneumoconiosis or tuberculosis of the lung.

Evaluation of inflammatory activity in Crohn's disease and ulcerative colitis

Crohn's disease and ulcerative colitis evolve with a relapsing and remitting course.Determination of inflammatory state is crucial for the assessment of disease activity and for tailoring therapy.However,no simple diagnostic test for monitoring intestinal inflammation is available.Noninvasive markers give only indirect assessments of disease activity.Histopathological or endoscopical examinations accurately assess inflammatory activity,but they are invasive,time consuming and expensive and therefore are unsuitable for routine use.Imaging procedures are not applicable for ulcerative colitis.The usefulness of ultrasound and Doppler imag-ing in assessing disease activity is still a matter of discussion for Crohn's disease,and an increased interest in computed tomography enterograph (CTE) has been seen,mainly because it can delineate the extent and severity of bowel wall inflammation,besides detecting extraluminal findings.Until now,the available data concerning the accuracy of magnetic resonance enterography in detecting disease activity is less than CTE.Due to this,clinical activity indices are still commonly used for both diseases.

Use of blood based biomarkers in the evaluation of Crohn's disease and ulcerative colitis

Despite significant improvements in our understanding of Crohn's disease(CD) and ulcerative colitis(UC) in recent years, questions remain regarding the best approaches to assessment and management of these chronic diseases during periods of both relapse and remission. Various serologic biomarkers have been used in the evaluation of patients with both suspected and documented inflammatory bowel disease(IBD), and while each has potential utility in the assessment of patients with IBD, potential limitation remain with each method of assessment. Given these potential shortcomings, there has been increased interest in other means of evaluation of patients with IBD, including an expanding interest in the role of gene expression profiling. Among patients with IBD, gene expression profiles obtained from whole blood have been used to differentiate active from inactive CD, as well as to differentiate between CD, UC, and non-inflammatory diarrheal conditions. There are many opportunities for a non-invasive, blood based test to aid in the assessment of patients with IBD, particularly when considering more invasive means of evaluation including endoscopy with biopsy. Furthermore, as the emphasis on personalized medicine continues to increase, the potential ability of gene expression analysis to predict patient response to individual therapies offers great promise. While whole blood gene expression analysis may not completely replace more traditional means of evaluating patients with suspected or known IBD, it does offer significant potential to expand our knowledge of the underlying genes involved in the development of these diseases.

Identification of pathologic features associated with “ulcerative colitis-like” Crohn's disease

AIM: To identify pathologic features associated with this "ulcerative colitis(UC)-like" subgroup of Crohn's disease(CD).METHODS: Seventeen subjects diagnosed as having UC who underwent proctocolectomy(RPC) from 2003-2007 and subsequently developed CD of the ileal pouch were identified. UC was diagnosed based on preoperative clinical, endoscopic, and pathologic studies. Eighteen patients who underwent RPC for UC within the same time period without subsequently developing CD were randomly selected and used as controls. Pathology reports and histological slides were reviewed for a wide range of gross and microscopic pathological features, as well as extent of disease. The demographics, gross description and histopathology of the resection specimens were reviewed and compared between the two groups. RESULTS: Patients with "UC-like" CD were on average 13 years younger than those with "true" UC(P < 0.01). More severe disease in the proximal involved region and active ileitis with/without architectural distortion were observed in 6 of 17(35%) and 7 of 17(41%) "UC-like" CD cases, respectively, but in none of the "true" UC cases(P < 0.05). Active appendicitis occurred in 8 of 16(50%) "UC-like" CD cases but in only two(11%) "true" UC cases(P < 0.05). Conspicuous lamina propria neutrophils were more specific for "UClike" CD(76% vs 22%, P < 0.05). In addition, prominent lymphoid aggregates tended to be more common in "UC-like" CD(P = 0.07). The "true" UC group contained a greater number of cases with severe activity(78% vs 47%). Therefore, the features more commonly seen in "UC-like" CD were not due to a more severe disease process. Crohn's granulomas and transmural inflammation in non-ulcerated areas were absent in both groups.CONCLUSION: More severe disease in the proximal involved region, terminal ileum involvement, active appendicitis, and prominent lamina propria neutrophils may be morphological factors associated with "UC-like" CD.

No association of the cytotoxic T-lymphocyte associated gene CTLA4 +49A/G polymorphisms with Crohn's disease and ulcerative colitis in Hungarian population samples

瞄准：当前的工作的目标细胞毒素的 T 淋巴细胞抗原是分析 +49A/G 的流行变体的在有 Crohn 的匈牙利病人的 4 基因(CTLA4 )?&#713;s 疾病(CD ) 和 ulcerative (UC ) 。方法：有 CD 的 130 个无关的题目的一个总数并且 150 与 UC，和 170 匹配的控制是为单个核苷酸多型性(SNP ) 的 genotyped。遗传型被使用 PCR/RFLP 测试决定。结果：G 等位基因频率和 GG 遗传型的流行在 CD 组，是 38.1% 和 12.3%40.6% 和 18.6% 在 UC 病人，并且 37.4% 和 15.9% 在控制组分别地。结论：当前的学习的结果显示出 +49G SNP 的那辆马车在异质接合或不在匈牙利人口为 CD 或为 UC 在同型结合的形式授与风险任何一个。

Disease clearance in ulcerative colitis:A new therapeutic target for the future

Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression.This has fueled the identification of molecular targets,resulting in a rapidly expanding therapeutic armamentarium.Subsequently,management strategies have evolved from symptomatic resolution to well-defined objective endpoints,including clinical remission,endoscopic remission and mucosal healing.While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications,studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures.Current recommendations lack consideration of histological healing.The simultaneous achievement of clinical,endoscopic,and histologic remission has not been fully investigated.This has laid the groundwork for a novel therapeutic outcome termed disease clearance(DC).This article summarizes the concept of DC and its current evidence.

High prevalence of viable Mycobacterium avium subspecies paratuberculosis in Crohn's disease

AIM:To examine the detection rate of viable Mycobacterium avium subspecies paratuberculosis(MAP) in patients with inflammatory bowel disease [Crohn's disease(CD) and ulcerative colitis(UC)].METHODS:Thirty patients with CD(15 with at least one NOD2/CARD15 mutation),29 with UC,and 10 with no inflammatory bowel disease(IBD).were tested for MAP by polymerase chain reaction(specific IS900 fragment) and blood culture.RESULTS:MAP DNA was detected in all original blood samples and 8-wk blood cultures(CD,UC and non-IBD).Positive MAP DNA status was confirmed by dot blot assays.All 69 cultures were negative by acid-fast Ziehl-Neelsen staining.Viable MAP,in spheroplast form,was isolated from the 18-mo blood cultures of all 30 CD patients,one UC patient,and none of the non-IBD controls.No association was found between positive MAP cultures and use of immunosuppressive drugs or CDassociated single nucleotide polymorphisms.CONCLUSION:MAP is widely present in our area and MAP DNA can be recovered from the blood of CD,UC and non-IBD patients.However,MAP spheroplasts were only found in CD patients.

Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn's disease

AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) patients.METHODS: About 458 consecutive patients [Crohn's disease(CD): 271 and ulcerative colitis(UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course(development f complicated disease phenotype and need for surgery),occurrence of thrombotic events, actual state of diseaseactivity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up,(median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls(HC) were tested on individual anti-β2-Glycoprotein-I(anti-β2-GPI IgA/M/G), anti-cardiolipin(ACA IgA/M/G)and anti-phosphatidylserine/prothrombin(anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies(ASCA IgA/G) by enzyme-linked immunosorbent assay(ELISA). In a subgroup of CD(n = 198) and UC patients(n = 103), obtaining consecutive samples over various arbitrary timepoints during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally,we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed.RESULTS: Patients with CD had significantly higher prevalence of both ACA(23.4%) and anti-PS/PT(20.4%) antibodies than UC(4.8%, p < 0.0001 and10.2%, p = 0.004) and HC(2.9%, p < 0.0001 and15.5%, p = NS). No difference was found for the prevalence of anti-β2-GPI between different groups(7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients.Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes.Changes in antibody status were more remarkable in CD than UC(ACA IgA: 49.9% vs 23.3% and ACA IgG:21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis.CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However,presence of different APLAs were not associated with the clinical phenotype or disease course.

Pathogenesis of Crohn's disease: Bug or no bug

The possibility of an infectious origin in inflammatory bowel disease(IBD)has been postulated since the first description of Crohn’s disease(CD).Many observations implicate bacteria as a trigger for the development of CD:lesions occur in regions with higher bacterial concentrations;aphthous ulcers occur in Peyer’s patches;inflammation resolves when the fecal stream is diverted and is reactivated following reinfusion ofbowel contents;severity of the disease is correlated with bacterial density in the mucosa;granulomas can contain bacteria;and susceptible mice raised in germfree conditions develop inflammation when bacteria are introduced in the 1990’s,several studies sought to establish a relationship with viral infections and the onset of IBD,finally concluding that no direct link had been demonstrated.In the past fifteen years,evidence relating IBD pathogenesis to Mycobacterium avium paratuberculosis,salmonella,campylobacter,etc.,has been found.The tendency now under discussion to regard microbiota as the primary catalyst has led to the latest studies on microbiota as pathogens,focusing on Escherichia coli,mainly in ileal CD.The present review discusses the literature available on these"bugs".

Smoking increases the risk of extraintestinal manifestations in Crohn's disease

AIM:To demonstrate a high prevalence of extraintestinal manifestations(EIMs)in a prospective populationbased cohort of inflammatory bowel disease(IBD)patients at first diagnosis as well as during the early course of the disease.METHODS:EIMs are common in patients with IBD.Data on the frequency of EIMs have mostly been assessed in patients from tertiary centers;however,data about the prevalence of EIMs at first diagnosis as well as factors influencing their incidence during the early course of disease from prospective population-based cohorts are scarce.We present data of patients of our population-based"Oberpfalz cohort"(Bavaria,Germany)from first diagnosis(up to 3 mo after first diagnosis)as well as during the early course of the disease.Possible risk factors were assessed by calculating the relative risk(RR)as well as using logistic regression analysis.RESULTS:In total,data of 257 newly diagnosed patients with IBD were evaluated[161 Crohn’s disease(CD),96 ulcerative colitis(UC)].Median duration of follow-up was 50 mo after first diagnosis.In 63.4%of all patients(n=163),an EIM was diagnosed at any point during the observation period.At first diagnosis,patients with CD had a significantly increased risk of an EIM[n=69(42.9%)]compared with UC patients[n=21(21.9%);P<0.001;RR=1.96;95%CI:1.30-2.98].Active smoking increased the risk of CD patients developing an EIM during the early course of the disease,but notably not of UC patients(P=0.046;RR=1.96;95%CI:1.01-3.79).In addition,using logistic regression analysis,the need for IBD-related surgery and a young age at first diagnosis were identified as risk factors for the development of an EIM in CD patients.No association with EIMs was found for the factors sex,localization of the disease and positive family history of IBD.In contrast,no key factors which increased the risk of development of an EIM could be identified in UC patients.CONCLUSION:We found a high prevalence of EIM in this cohort at first diagnosis and during the early course of the disease.In patients with CD,smoking,need for surgery and younger age at first diagnosis were risk factors for the development of an EIM.

Use of the tumor necrosis factor-blockers for Crohn's disease

The use of anti-tumor necrosis factor-therapy for inflammatory bowel disease represents the most important advance in the care of these patients since the publication of the National Co-operative Crohn's disease study thirty years ago.The recommendations of numerous consensus groups worldwide are now supported by a wealth of clinical trials and several meta-analyses.In general,it is suggested that tumor necrosis factor-blockers(TNFBs) are indicated(1) for persons with moderately-severe Crohn's disease or ulcerative colitis(UC) who have failed two or more causes of glucocorticosteroids and an acceptably long cause(8 wk to 12 wk) of an immune modulator such as azathioprine or methotrexate;(2) non-responsive perianal disease;and(3) severe UC not responding to a 3-d to 5-d course of steroids.Once TNFBs have been introduced and the patient is responsive,therapy given by the IV and SC rate must be continued.It remains open to definitive evidence if concomitant immune modulators are required with TNFB maintenance therapy,and when or if TNFB may be weaned and discontinued.The supportive evidence from a single study on the role of early versus later introduction of TNFB in the course of a patient's illness needs to be confirmed.The risk/benefit profile of TNFB appears to be acceptable as long as the patient is immunized and tested for tuberculosis and viral hepatitis before the initiation of TNFB,and as long as the long-term adverse effects on the development of lymphoma and other tumors do not prone to be problematic.Because the rates of benefits to TNFB are modest from a population perspective and the cost of therapy is very high,the ultimate application of use of TNFBs will likely be established by cost/benefit studies.

Altered pattern of tumor necrosis factor-alpha production in peripheral blood monocytes from Crohn's disease

AIM To evaluate the inflammatory state in Crohn's disease(CD) patients and correlate it with genetic background and microbial spreading.METHODS By means of flow cytometry, production of tumor necrosis factor-alpha(TNF-α) was measured in peripheral blood monocytes from patients suffering from CD, ulcerative colitis(UC) and in healthy subjects after stimulation of the NOD2 and TLR pathways. CD patients were genotyped for the three most common NOD2 variants(R702W, G908 R and L1007Pfs*2) and basal production of TNF-α was correlated to NOD2 genotype. Also, production of TNF-α was correlated to plasmatic levels of LPS Binding Protein(LBP), soluble(s) CD14 and to the activity state of the disease.RESULTS The patients with CD were characterized by a significantly higher monocyte basal expression of TNF-αcompared with healthy subjects and UC patients, and after stimulation with Pam3CSK4(ligand of TLR2/1) and MDP-L18(ligand of NOD2) this difference was maintained, while other microbial stimuli(LPS, ligand of TLR4 and Poly I:C, ligand of TLR3) induced massive activation in CD monocytes as well as in UC and in healthy control cells. There was no significant difference in the production of TNF- α between patients who carried CD-associated heterozygous or homozygous variants in NOD2 and patients with wild type NOD2 genotype. Although serum LBP levels have been shown to correlate positively with the state of activity of the disease, TNF-α production did not show a clear correlation with either LBP or s CD14 levels in plasma. Moreover, no clear correlation was seen between TNF-α production and activity indices in either CD or UC.CONCLUSION Peripheral monocytes from CD express higher basal and stimulated TNF-α than controls, regardless of NOD2 genotype and without a clear correlation with disease activity.

Patients'perspectives on smoking and inflammatory bowel disease:An online survey in collaboration with European Federation of Crohn's and Ulcerative Colitis Associations

BACKGROUNDSmoking has detrimental effects on Crohn’s disease (CD) activity while data onulcerative colitis (UC) are conflicting. Little is known about the use and impact ofalternative smoking products in inflammatory bowel diseases (IBD).AIMTo understand the patients’ perceptions of the impact of smoking on their IBDand to assess differences between CD and UC patients.METHODSThe questionnaire was developed by Philip Morris Products SA in cooperationwith European Federation of Crohn's and Ulcerative Colitis Associations. Thefinal survey questionnaire consisted of 41 questions divided in 8 categories: (1)Subject screener;(2) Smoking history;(3) Background information;(4) IBD diseasebackground;(5) Current disease status;(6) Current therapeutics and medications;and (7) Current nicotine/cigarettes use and awareness of the impacts of smokingon IBD. The questionnaire was submitted online from 4th November 2019 to 11th March 2020 through the European Federation of Crohn's and Ulcerative ColitisAssociations website to IBD patients who were current smokers or had a historyof smoking.RESULTSIn total 1050 IBD patients speaking nine languages participated to the survey.Among them, 807 (76.9%) patients declared to have ever smoked or consumed analternative smoking product, with a higher proportion of current cigarettesmokers among CD patients (CD: 63.1% vs UC: 54.1%, P = 0.012). About twothirdsof the participants declared to have ever stopped cigarette smoking andrestarted (67.0%), with a significantly higher proportion among UC patientscompared to CD patients (73.1% vs 62.0%, P = 0.001). We also found significantdifferences between CD and UC patients in the awareness of the healthconsequences of smoking in their disease and in the perceived impact of smokingon disease activity, for both cigarettes and alternative smoking products.CONCLUSIONThis survey found significant differences between CD and UC patients in bothawareness and perception of the impact of smoking on their disease. Furtherefforts should be done to encourage smoking cessation for all IBD patients,including UC patients.

Clinical value of the Toronto inflammatory bowel disease global endoscopic reporting score in ulcerative colitis

BACKGROUND Endoscopic evaluation in diagnosing and managing ulcerative colitis(UC)is becoming increasingly important.Several endoscopic scoring systems have been established,including the Ulcerative Colitis Endoscopic Index of Severity(UCEIS)score and Mayo Endoscopic Subscore(MES).Furthermore,the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting(TIGER)score for UC has recently been proposed;however,its clinical value remains unclear.AIM To investigate the clinical value of the TIGER score in UC by comparing it with the UCEIS score and MES.METHODS This retrospective study included 166 patients with UC who underwent total colonoscopy between January 2017 and March 2023 at the Affiliated Hospital of Qingdao University(Qingdao,China).We retrospectively analysed endoscopic scores,laboratory and clinical data,treatment,and readmissions within 1 year.Spearman’s rank correlation coefficient,receiver operating characteristic curve,and univariate and multivariable logistic regression analyses were performed using IBM SPSS Statistics for Windows,version 26.0(IBM Corp.,Armonk,NY,United States)and GraphPad Prism version 9.0.0 for Windows(GraphPad Software,Boston,Massachusetts,United States).RESULTS The TIGER score significantly correlated with the UCEIS score and MES(r=0.721,0.626,both P<0.001),showed good differentiating values for clinical severity among mild,moderate,and severe UC[8(4-112.75)vs 210(109–219)vs 328(219–426),all P<0.001],and exhibited predictive value in diagnosing patients with severe UC[area under the curve(AUC)=0.897,P<0.001].Additionally,the TIGER(r=0.639,0,551,0.488,0.376,all P<0.001)and UCEIS scores(r=0.622,0,540,0.494,and 0.375,all P<0.001)showed stronger correlations with laboratory and clinical parameters,including C-reactive protein,erythrocyte sedimentation rate,length of hospitalisation,and hospitalisation costs,than MES(r=0.509,0,351,0.339,and 0.270,all P<0.001).The TIGER score showed the best predictability for patients'recent advanced treatment,including systemic corticosteroids,biologics,or immunomodulators(AUC=0.848,P<0.001)and 1-year readmission(AUC=0.700,P<0.001)compared with the UCEIS score(AUC=0.762,P<0.001;0.627,P<0.05)and MES(AUC=0.684,P<0.001;0.578,P=0.132).Furthermore,a TIGER score of≥317 was identified as an independent risk factor for advanced UC treatment(P=0.011).CONCLUSION The TIGER score may be superior to the UCIES score and MES in improving the accuracy of clinical disease severity assessment,guiding therapeutic decision-making,and predicting short-term prognosis.

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.

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.

Differential regulation of JAK/STAT-signaling in patients with ulcerative colitis and Crohn’s disease

In 2018,the pan-Janus kinase(JAK)inhibitor tofacitinib was launched for the treatment of ulcerative colitis(UC).Although tofacitinib has proven efficacious in patients with active UC,it failed in patients with Crohn’s disease(CD).This finding strongly hints at a different contribution of JAK signaling in both entities.Here,we review the current knowledge on the interplay between the JAK/signal transducer and activator of transcription(STAT)pathway and inflammatory bowel diseases(IBD).In particular,we provide a detailed overview of the differences and similarities of JAK/STAT-signaling in UC and CD,highlight the impact of the JAK/STAT pathway in experimental colitis models and summarize the published evidence on JAK/STAT-signaling in immune cells of IBD as well as the genetic association between the JAK/STAT pathway and IBD.Finally,we describe novel treatment strategies targeting JAK/STAT inhibition in UC and CD and comment on the limitations and challenges of the new drug class.