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.

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.

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.

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.

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。

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.

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.

Progress of ulcerative colitis patients during the COVID-19 pandemic

BACKGROUND We have previously demonstrated that the first wave of the coronavirus disease 2019(COVID-19)pandemic caused exacerbations in ulcerative colitis(UC)patients,probably through psychological and physical stress.However,successive waves of the COVID-19 pandemic continuously followed the first.The effects of this chronic stress on the disease condition in UC patients are of interest.AIM To clarify the effect of chronic stress from COVID-19 on disease condition in patients aggravated after the first wave.METHODS Our previous study investigated 289 consecutive UC outpatients treated in one center during March and April 2020,the period of the first wave of the COVID-19 pandemic.In this study,an identical group of 289 UC patients was evaluated using UC-disease activity index(UC-DAI),endoscopic mucosal appearance score,and Matts pathological grade scoring.RESULTS Of the 289 UC patients included in the study in 2020,10 patients dropped out as of 2021 and another 11 patients dropped out as of 2022,making three groups for 2020,2021 and 2022.No significant differences in characteristics were found among the three groups.UC-DAI scores had aggravated during the period of the first wave of the COVID-19 pandemic,but significantly recovered in 2021 and remained stable in 2022.Matts grade scores significantly recovered in 2021 from those in 2020 and remained stable in 2022.CONCLUSION Disease activity of UC patients recovered in 2021 and remained stable in 2022,aggravated by the stress of the first wave of COVID-19 in 2020 despite persistence of the pandemic.

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.

Predictors of disease severity in ulcerative colitis patients from Southwestern Ontario

AIM:To understand the demographic characteristics of patients in Southwestern Ontario,Canada with ulcerative colitis(UC)in order to predict disease severity. METHODS:Records from 1996 to 2001 were exam- ined to create a database of UC patients seen in the London Health Sciences Centre South Street Hospital Inflammatory Bowel Disease Clinic.To be included, patients'charts were required to have information of their disease presentation and a minimum of 5 years of follow-up.Charts were reviewed using standardized data collection forms.Disease severity was generated during the chart review process,and non-endoscopic Mayo Score criteria were collected into a composite. RESULTS:One hundred and two consecutive patients'data were entered into the database.Demographic analyses revealed that 51%of the patients were male, the mean age at diagnosis was 39 years,13.7%had a first degree relative with inflammatory bowel disease (IBD),61.8%were nonsmokers and 24.5%were ex-smokers.In 22.5%of patients the disease was limited to the rectum,in 21.6%disease was limited to the sigmoid colon,in 22.5%disease was limited to the left colon,and 32.4%of patients had pancolitis. Standard multiple regression analysis which regressed a composite of physician global assessment of disease severity,average number of bowel movements,and average amount of blood in bowel movements on year of diagnosis and age at time of diagnosis was significant,R 2=0.306,F(7,74)=4.66,P<0.01. Delay from symptoms to diagnosis of UC,gender, family history of IBD,smoking status and disease severity at the time of diagnosis didnot significantly predict the composite measure. CONCLUSION:UC severity is associated with younger age at diagnosis and year of diagnosis in a longitudinal cohort of UC patients,and may identify prognostic UC indicators.

Natural polysaccharides for ulcerative colitis: A general overview

Ulcerative colitis is a colonic disease characterized by the disruption of the mucosal epithelial layer and inflammation. For the treatment of this disease, various chemotherapeutic agents are available.However, the toxicities associated with chemotherapeutics greatly hamper treatment. Polysaccharide from natural resources is emerging as a potentially therapeutic substance with comparative minimum adverse effects. In this article, we are discussing polysaccharide from diverse sources(plants, edible mushrooms,and algae) which are being used in the treatment of ulcerative colitis. These polysaccharides exert their therapeutic action on ulcerative colitis through several mechanisms, including suppression of inflammatory cascades NF-κB, MAPK, IL-6/JAK2/STAT3,preventing the release of certain inflammatory mediators, modulating the intestinal microbiome, maintaining the integrity of intestinal barriers, and regulating the certain inflammatory markers. The present review compiles the role of different polysaccharides being used successfully in the management/treatment of ulcerative colitis.Special emphasis was given to explaining the biomolecular pathway.

Fecal microbiota transplantation for the maintenance of remission in patients with ulcerative colitis:A randomized controlled trial

BACKGROUND Fecal microbial transplantation(FMT)is a promising new method for treating active ulcerative colitis(UC),but knowledge regarding FMT for quiescent UC is scarce.AIM To investigate FMT for the maintenance of remission in UC patients.METHODS Forty-eight UC patients were randomized to receive a single-dose FMT or autologous transplant via colonoscopy.The primary endpoint was set to the maintenance of remission,a fecal calprotectin level below 200μg/g,and a clinical Mayo score below three throughout the 12-mo follow-up.As secondary endpoints,we recorded the patient’s quality of life,fecal calprotectin,blood chemistry,and endoscopic findings at 12 mo.RESULTS The main endpoint was achieved by 13 out of 24(54%)patients in the FMT group and by 10 out of 24(41%)patients in the placebo group(log-rank test,P=0.660).Four months after FMT,the quality-of-life scores decreased in the FMT group compared to the placebo group(P=0.017).In addition,the disease-specific quality of life measure was higher in the placebo group than in the FMT group at the same time point(P=0.003).There were no differences in blood chemistry,fecal calprotectin,or endoscopic findings among the study groups at 12 mo.The adverse events were infrequent,mild,and distributed equally between the groups.CONCLUSION There were no differences in the number of relapses between the study groups at the 12-mo follow-up.Thus,our results do not support the use of a single-dose FMT for the maintenance of remission in UC.

Intrahepatic cholangiocarcinoma in patients with primary sclerosing cholangitis and ulcerative colitis: Two case reports

BACKGROUND Primary sclerosing cholangitis(PSC)is an extraintestinal manifestation of ulcerative colitis(UC).PSC is a well-known risk factor for intrahepatic cholangiocarcinoma(ICC),and ICC is known to have a poor prognosis.CASE SUMMARY We present two cases of ICC in patients with PSC associated with UC.In the first case,a tumor was found by magnetic resonance imaging(MRI)in the liver of a patient with PSC and UC who presented to our hospital with right-sided rib pain.The second patient was asymptomatic,but we unexpectedly detected two liver tumors in an MRI performed to evaluate bile duct stenosis associated with PSC.ICC was strongly suspected by computed tomography and MRI in both cases,and surgery was performed,but unfortunately,the first patient died of ICC recurrence 16 mo postoperatively,and the second patient died of liver failure 14 mo postoperatively.CONCLUSION Careful follow-up of patients with UC and PSC with imaging and blood tests is necessary for early detection of ICC.

Serological profiling of Crohn’s disease and ulcerative colitis patients reveals anti-microbial antibody signatures

BACKGROUND The healthcare burden of inflammatory bowel disease(IBD)is rising globally and there are limited non-invasive biomarkers for accurate and early diagnosis.AIM To understand the important role that intestinal microbiota play in IBD pathogenesis and identify anti-microbial antibody signatures that benefit clinical management of IBD patients.METHODS We performed serological profiling of 100 Crohn’s disease(CD)patients,100 ulcerative colitis(UC)patients and 100 healthy controls against 1173 bacterial and 397 viral proteins from 50 bacteria and 33 viruses on protein microarrays.The study subjects were randomly divided into discovery(n=150)and validation(n=150)sets.Statistical analysis was performed using R packages.RESULTS Anti-bacterial antibody responses showed greater differential prevalence among the three subject groups than anti-viral antibody responses.We identified novel antibodies against the antigens of Bacteroidetes vulgatus(BVU_0562)and Streptococcus pneumoniae(SP_1992)showing higher prevalence in CD patients relative to healthy controls.We also identified antibodies against the antigen of Streptococcus pyogenes(SPy_2009)showing higher prevalence in healthy controls relative to UC patients.Using these novel antibodies,we built biomarker panels with area under the curve(AUC)of 0.81,0.87,and 0.82 distinguishing CD vs control,UC vs control,and CD vs UC,respectively.Subgroup analysis revealed that penetrating CD behavior,colonic CD location,CD patients with a history of surgery,and extensive UC exhibited highest antibody prevalence among all patients.We demonstrated that autoantibodies and anti-microbial antibodies in CD patients had minimal correlation.CONCLUSION We have identified antibody signatures for CD and UC using a comprehensive analysis of antimicrobial antibody response in IBD.These antibodies and the source microorganisms of their target antigens improve our understanding of the role of specific microorganisms in IBD pathogenesis and,after future validation,should aid early and accurate diagnosis of IBD.

Impact of adalimumab on disease burden in moderate-to-severe ulcerative colitis patients: The one-year, real-world UCanADA study

BACKGROUND A gap remains in documenting the impact of anti-tumor necrosis factor therapy on disease burden in ulcerative colitis(UC)patients treated in a real-world setting.The use of patient-reported outcomes(PROs)has been discussed as a primary endpoint in the context of the FDA PRO Guidance,for labelling purposes.Specifically,the efficacy and safety of adalimumab have been demonstrated in pivotal trials;however,data are needed to understand how clinical results translate into improvements in key aspects of the daily lives of UC patients,such as symptoms,health-related quality of life(HRQoL),and disability.AIM To assess real-world effectiveness of adalimumab on PRO measures in patients with moderate-to-severe UC.METHODS UCanADA was a single arm,prospective,1-year multicenter Canadian post-marketing observational study in which multiple PRO questionnaires were completed—with psychologic distress/depression symptoms as the primary endpoint—by patients with moderate-to-severe UC.Assessments were performed during patients’routine care visit schedule,which was at the initiation of adalimumab(baseline),after induction(approximately 8 wk),and 52 wk after baseline.Additional optional assessments between weeks 8 and 52 were collected at least once but no more than two times during this period.Serious safety events and per-protocol adverse events were collected.RESULTS From 23 Canadian centres,100 patients were enrolled and 48 completed the study.Measured with the Patient Health Questionnaire–9 items at week 52,61.5%(40/65)[95%confidence interval(CI):49.7%-73.4%]of the patients improved in psychologic distress/depression symptoms,which was slightly higher in completers[65.9%(29/44);95%CI:51.9%-79.9%].At week 52,clinical response and clinical remission were achieved respectively by 65.7%(44/73)and 47.8%(32/73)of the patients.The odds of improving depressive symptoms for those achieving a clinical remission at week 52 was 7.94 higher compared with those not achieving a clinical remission(CI:1.42,44.41;P=0.018).Significant changes from baseline to weeks 8 and 52 were observed in disability,HRQoL,and fatigue.Meaningful improvement was reported in work impairment.CONCLUSION At week 52,over 60%of the UCanADA patients had depressive symptoms significantly reduced,as well as HRQoL,fatigue symptoms,and work impairment improved.No new safety signals were detected.

Vedolizumab-associated diffuse interstitial lung disease in patients with ulcerative colitis:A case report

BACKGROUND Vedolizumab,a newer class of integrin antagonist biological agents,has been applied to treat patients with moderate-to-severe Crohn’s disease(CD)and ulcerative colitis(UC),especially for patients who are refractory to traditional therapies and tumor necrosis factor antagonists.However,some rare but lifethreatening adverse effects warrant pharmacovigilance.We describe the first fatal case of vedolizumab-associated severe diffuse interstitial lung disease in China.CASE SUMMARY We present a case of new-onset diffuse parenchymal lung disease developing under treatment with vedolizumab in a patient with UC.After two doses of vedolizumab,he developed persistent fever and progressively worsening dyspnea.Extensive workups,including bronchoalveolar lavage,transbronchial lung biopsy and metagenomic next-generation sequencing,identified no infectious causes,and other potential causes(such as tumors and cardiogenic pulmonary edema)were also excluded.As a result,a diagnosis of vedolizumabrelated interstitial lung disease was established.Unfortunately,although corticosteroids and empiric antibiotics were administered,the patient eventually died of respiratory failure.CONCLUSION Vedolizumab-related interstitial lung disease in patients with UC is rare but potentially lethal.Gastroenterologists and pulmonologists should be aware of vedolizumab-related adverse drug reactions.