Link between mutations in ACVRL1 and PLA2G4A genes and chronic intestinal ulcers:A case report and review of literature

BACKGROUND Genetic factors of chronic intestinal ulcers are increasingly garnering attention.We present a case of chronic intestinal ulcers and bleeding associated with mu-tations of the activin A receptor type II-like 1(ACVRL1)and phospholipase A2 group IVA(PLA2G4A)genes and review the available relevant literature.CASE SUMMARY A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain,diarrhea,and dark stools.At the onset 6 years ago,the patient had received treatment at a local hospital for abdominal pain persisting for 7 d,under the diagnosis of diffuse peritonitis,acute gangrenous appendicitis with perforation,adhesive intestinal obstruction,and pelvic abscess.The surgical treat-ment included exploratory laparotomy,appendectomy,intestinal adhesiolysis,and pelvic abscess removal.The patient’s condition improved and he was dis-charged.However,the recurrent episodes of abdominal pain and passage of black stools started again one year after discharge.On the basis of these features and results of subsequent colonoscopy,the clinical diagnosis was established as in-flammatory bowel disease(IBD).Accordingly,aminosalicylic acid,immunotherapy,and related symptomatic treatment were administered,but the symptoms of the patient did not improve significantly.Further investigations revealed mutations in the ACVRL1 and PLA2G4A genes.ACVRL1 and PLA2G4A are involved in angiogenesis and coagulation,respectively.This suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A genes.Oral Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical symptoms.CONCLUSION Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in IBD.Orally administered Kangfuxin liquid may have therapeutic potential.

Increased succinate receptor GPR91 involved in the pathogenesis of Mooren's ulcer

AIM： To investigate the expression of succinate receptor GPR91 and its pathogenic roles in Mooren＇s ulcer（MU）.METHODS： Biopsy specimens were obtained from 7 patients with MU and 6 healthy donors. The expression of GPR91 in MU tissues was evaluated using quantitative realtime reverse transcription polymerase chain reaction（qRTPCR） and immunohistochemistry（IHC）. Succinate was used to activate GPR91 signaling, and the effect of GPR91 on the expression of interleukin-1β（IL-1β）, NLRP3, vascular endothelial growth factor（VEGF） and matrix metalloproteinase-13（MMP-13） in human peripheral blood mononuclear cells（PBMCs） was determined. The influence of GPR91 on the nuclear factor-κB（NF-κB） signaling in PBMCs was investigated by detecting the phosphorylation of p65. Moreover, the expression of IL-1β, VEGF, MMP-13 and phosphorylated p65（p-p65） in the tissues of MU was examined by qRT-PCR or IHC.RESULTS： GPR91 mRNA expression showed a higher level in the MU group than in the healthy control group. IHC analysis also revealed that the expression of GPR91 was elevated in patients with MU compared with healthy controls. Moreover, ligation of GPR91 with succinate promoted the lipopolysaccharide-induced production of NLRP3, IL-1β, VEGF and MMP-13 in PBMCs through increased phosphorylation of p65. Pharmacological inhibition of the NF-κB signaling reversed GPR91 induced production of NLRP3, IL-1β, VEGF and MMP-13. These findings, coupled with the elevated amounts of IL-1β, VEGF, MMP-13 and p-p65 observed in the MU biopsies, constituted a rational basis for the involvement of GPR91 in the pathogenesis of MU.CONCLUSION： This study indicates the increased succinate receptor GPR91 in conjunctival or corneal tissues is involved in the pathogenesis of MU through elevated NF-κB activity, which may provide a new therapeutic target for MU.

Increased cGAS/STING signaling components in patients with Mooren's ulcer

AIM:To explore the expression of cGAS/STING signaling components in Mooren’s ulcer(MU).METHODS:Samples were obtained from ten MU patients,and eight residual corneal-scleral rings of healthy donor corneas for controls.Human corneal epithelial cells(HCECs)were used to evaluate the effect of cGAS/STING signaling pathway.Immunohistochemistr y(IHC)and Western blot were used to examine the expression of cGAS,STING,and phosphorylated interferon regulatory factor 3(p-IRF3)in MU tissues.The expression of interferon-β(IFN-β)and interferon-stimulated genes(ISGs)was quantified by real-time polymerase chain reaction(PCR)and enzymelinked immunosorbent assay(ELISA).RESULTS:The protein levels of cGAS and STING in MU samples were significantly elevated when compared with the healthy controls by Western blot and IHC.After stimulation with cGAMP,real-time PCR and ELISA showed a dramatic increase of IFN-βand ISGs(containing CXCL10,IFIT1,and IL-6)in HCECs.Moreover,HCECs treated with cGAMP was characterized by increased phosphorylation and more nuclear translocation of IRF3.Meanwhile,increased p-IRF3 was observed in MU samples via IHC and Western blot.CONCLUSION:The pronounced expression of cGAS/STING signaling components in the patients with MU and probably contribute to the onset and development of MU.

Changes in Local Immune Functions in Mooren's Ulcer

Purpose: To the investigate changes in local immune functions of the cornea and the adjacent conjunctiva, and their roles in the mechanism of the disease. Method: The cornea and adjacent bulbar conjunctiva taken from 14 patients with Mooren’s ulcer were stained immunohistochemically for CD3, CD4, CD8, HLA-DR, GD1 and CD25.Result: An aberrant expression of HLA-DR antigen by a large number of kerato-conjunctival epithelial cells and keratocytes in the corneal stroma was found. The CD4 + /CD8+ ratio is significantly higher than normal control. Conclusion: The aberrant expression of MHC- II antigen in the resident cells at the peripheral cornea and the adjacent conjunctiva, along with a raised local TH/ Ts ratio leading to an excessive autoimmune reactivity is possibly the direct cause of Mooren’s ulcer. Eye Science 1996; 12: 33-35.

Fresh Amniotic Membrane Transplantation Combined Lamellar Keratoplasty for Patients with Recurrent Mooren's Ulcer

Purpose: To investigate the possibility of amniotic membrane as an immunologicalinsulating band to reduce the recurrent frequency of Mooren's ulcer.Methods: Twelve cases(12 eyes)with recurrent Mooren's Ulcer were observed. Amongthem, 4 cases(4 eyes)were male and 8 cases(8 eyes) female, ranging in age between 26and 51 years[mean(41 ± 3)years]. Three eyes recurred once, 5 eyes twice, and 4 eyesthree before. Eleven of 12 cases (11/12 eyes)with frequently recurrent Mooren's ulcerunderwent lamellar keratoplasty combined amniotic membrane transplantation(AMT).One patient who had entire corneal ulceration accepted AMT alone.Results: Follow-up time is 12 to 29 months, [mean (23 ± 6) months]. Before AMT, therecurrent frequency of Mooren's Ulcer of all cases after corneal surgery was 1 ～ 7 months[mean(3 ± 2)months]. Nine of 12 eyes with lamellar keratoplasty combined AMT did notrecur within the observation period; 2 eyes recurred 11 months after the surgery. Threemonths postoperatively, neovascularization was observed, which made it nearly impossibleto decipher between amniotic membrane and its nearby conjunctiva, only at the junctionof the transplant can some trails be observed. One case with entire AMT alone showedgraft resolution and neovascularization in 1 month.Conclusion:AMT combined with lamellar keratoplasty and lesion excision may delayrecurrence of Mooren's Ulcer, reduce its recurrent frequency. Besides the effects ofdecreasing inflammation, it may have immunological insulating function as well. Thisconclusion should be proven by further clinical comparative study of much moresamples.

A Study of Clinical Characteristics and Treatment of Mooren's Ulcer

Objective: To investigate the clinical characteristics and to compare the effects of several therapies of Mooren's corneal ulcer.Methods: 550 consecutive cases of Mooren's corneal ulcer inpatients were analysed, including the age, sex, laterality of the eye, ulcer location , perforative rate, cure rate of surgeries, recurrent rate, and the effects of conjunctiva excision, lamellar keratoplasty (LKP), LKP and plus cyclosporin A eye drop.Results: The average age of onset of the cornea! ulcer was 48.4 years old, the ratio of the male to the female patients was 1:0.74, the bilateral disease was 30% of the total cases, 31.5% of the bilateral disease occurred in the younger group, and 68.5% of the bilateral ulcer occurred in the older group, ulcers located at the limbus of the palpebral fissure were 70% of the total cases, perforative rate was 13.3% , 43.2% of the perforation occurred in the younger group, and 56.8% of the perforation occurred in the older group, recurrent rate of the post-opertion was 25.6%,

MicroRNAs in inflammatory bowel disease:What do we know and what can we expect?

MicroRNAs(miRNAs),small non-coding RNAs composed of 18–24 nucleotides,are potent regulators of gene expression,contributing to the regulation of more than 30%of protein-coding genes.Considering that miRNAs are regulators of inflammatory pathways and the differentiation of intestinal epithelial cells,there is an interest in exploring their importance in inflammatory bowel disease(IBD).IBD is a chronic and multifactorial disease of the gastrointestinal tract;the main forms are Crohn's disease and ulcerative colitis.Several studies have investigated the dysregulated expression of miRNAs in IBD,demonstrating their important roles as regulators and potential biomarkers of this disease.This editorial presents what is known and what is expected regarding miRNAs in IBD.Although the important regulatory roles of miRNAs in IBD are clearly established,biomarkers for IBD that can be applied in clinical practice are lacking,emphasizing the importance of further studies.Discoveries regarding the influence of miRNAs on the inflammatory process and the exploration of their role in gene regulation are expected to provide a basis for the use of miRNAs not only as potent biomarkers in IBD but also as therapeutic targets for the control of inflammatory processes in personalized medicine.

Recent trends in the epidemiology and clinical outcomes of inflammatory bowel disease in South Korea,2010-2018

BACKGROUND Inflammatory bowel disease(IBD)was previously regarded as a Western disease;however,its incidence is increasing in the East.The epidemiology of IBD in Asia differs significantly from the patterns in the West.AIM To comprehensively investigate the epidemiology of IBD in South Korea,inclu-ding its incidence,prevalence,medication trends,and outcomes.METHODS We analyzed claims data from the Health Insurance Review and Assessment Service and Rare and Intractable Diseases(RIDs),operated by the National Health Insurance Service of South Korea.Patients with IBD were identified based on the International Classification of Diseases,Tenth Revision,and RID diagnostic codes for Crohn’s disease(CD)and ulcerative colitis(UC)from 2010 to 2018.RESULTS In total,14498 and 31409 patients were newly diagnosed with CD and UC,respectively,between 2010 and 2018.The annual average incidence of CD was 3.11 cases per 105 person-years,and that of UC was 6.74 cases per 10^(5) person-years.Since 2014,the incidence rate of CD has been stable,while that of UC has steadily increased,shifting the peak age group from 50-year-olds in 2010 to 20-year-olds in 2018.The CD and UC prevalence increased consistently over the study period;the use of 5-aminosali-cylates and corticosteroids gradually decreased,while that of immunomodulators and biologics steadily increased in both CD and UC.The clinical outcomes of IBD,such as hospitalization and surgery,decreased during the study period.CONCLUSION The CD incidence has been stable since 2014,but that of UC has increased with a shift to a younger age at peak incidence between 2010 and 2018.IBD clinical outcomes improved over time,with increased use of immunomodu-lators and biologics.

Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease

BACKGROUND Population of patients with inflammatory bowel disease(IBD)is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality.Growth-differentiation factor-15(GDF-15)is often overexpressed under stress conditions,such as inflammation,malignancies,heart failure,myocardial ischemia,and many others.AIM To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases.An additional aim was to determine possible associations between GDF-15 and multiple clinical,anthropometric and laboratory parameters in patients with IBD.METHODS This cross-sectional study included 90 adult patients diagnosed with IBD,encompassing both Crohn’s disease(CD)and ulcerative colitis(UC),and 67 healthy age-and sex-matched controls.All patients underwent an extensive workup,including colonoscopy with subsequent histopathological analysis.Disease activity was assessed by two independent gastroenterology consultants specialized in IBD,employing well-established clinical and endoscopic scoring systems.GDF-15 serum concentrations were determined following an overnight fasting,using electrochemiluminescence immunoassay.RESULTS In patients with IBD,serum GDF-15 concentrations were significantly higher in comparison to the healthy controls[800(512-1154)pg/mL vs 412(407-424)pg/mL,P<0.001],whereas no difference in GDF-15 was found between patients with CD and UC[807(554-1451)pg/mL vs 790(509-956)pg/mL,P=0.324].Moreover,multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age,sex,and C-reactive protein levels(P=0.016 and P=0.049,respectively).Finally,an association between GDF-15 and indices of anemia was established.Specifically,negative correlations were found between GDF-15 and serum iron levels(r=-0.248,P=0.021),as well as GDF-15 and hemoglobin(r=-0.351,P=0.021).Accordingly,in comparison to IBD patients with normal hemoglobin levels,GDF-15 serum levels were higher in patients with anemia(1256(502-2100)pg/mL vs 444(412-795)pg/mL,P<0.001).CONCLUSION For the first time,we demonstrated that serum concentrations of GDF-15 are elevated in patients with IBD in comparison to healthy controls,and the results imply that GDF-15 might be involved in IBD pathophysiology.Yet,it remains elusive whether GDF-15 could serve as a prognostic indicator in these patients.

Effects of proton pump inhibitors on inflammatory bowel disease:An updated review

Inflammatory bowel disease(IBD)is believed to be caused by various factors,including abnormalities in disease susceptibility genes,environmental factors,immune factors,and intestinal bacteria.Proton pump inhibitors(PPIs)are the primary drugs used to treat acid-related diseases.They are also commonly prescribed to patients with IBD.Recent studies have suggested a potential association between the use of certain medications,such as PPIs,and the occurrence and progression of IBD.In this review,we summarize the potential impact of PPIs on IBD and analyze the underlying mechanisms.Our findings may provide insights for conducting further investigations into the effects of PPIs on IBD and serve as an important reminder for physicians to exercise caution when prescribing PPIs to patients with IBD.

Excess non-COVID-19-related mortality among inflammatory bowel disease decedents during the COVID-19 pandemic

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic disrupted healthcare in the United States.AIM To investigate COVID-19-related and non-COVID-19-related death and characteristics associated with excess death among inflammatory bowel disease(IBD)decedents.METHODS We performed a register-based study using data from the National Vital Statistics System,which reports death data from over 99%of the United States population,from January 1,2006 through December 31,2021.IBD-related deaths among adults 25 years and older were stratified by age,sex,race/ethnicity,place of death,and primary cause of death.Predicted and actual age-standardized mortality rates(ASMRs)per 100000 persons were compared.RESULTS 49782 IBD-related deaths occurred during the study period.Non-COVID-19-related deaths increased by 13.14%in 2020 and 18.12%in 2021[2020 ASMR:1.55 actual vs 1.37 predicted,95%confidence interval(CI):1.26-1.49;2021 ASMR:1.63 actual vs 1.38 predicted,95%CI:1.26-1.49].In 2020,non-COVID-19-related mortality increased by 17.65%in ulcerative colitis(UC)patients between the ages of 25 and 65 and 36.36%in non-Hispanic black(NHB)Crohn’s disease(CD)patients.During the pandemic,deaths at home or on arrival and at medical facilities as well as deaths due to neoplasms also increased.CONCLUSION IBD patients suffered excess non-COVID-19-related death during the pandemic.Excess death was associated with younger age among UC patients,and with NHB race among CD patients.Increased death at home or on arrival and due to neoplasms suggests that delayed presentation and difficulty accessing healthcare may have led to increased IBD mortality.

Discontinuation of therapy in inflammatory bowel disease: Current views

The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease(IBD).The therapeutic approach is still evolving in terms of the mechanism of action but also in terms of the possibility of maintaining remission.In patients with achieved long-term remission,the question of de-escalation or discontinuation of therapy arises,considering the possible side effects and economic burden of long-term therapy.For each of the drugs used in IBD(5-aminosalycaltes,immunomodulators,biological drugs,small molecules)there is a risk of relapse.Furthermore,studies show that more than 50%of patients who discontinue therapy will relapse.Based on the findings of large studies and meta-analysis,relapse of disease can be expected in about half of the patients after therapy withdrawal,in case of monotherapy with aminosalicylates,immunomodulators or biological therapy.However,longer relapse-free periods are recorded with withdrawal of medication in patients who had previously been on combination therapies immunomodulators and anti-tumor necrosis factor.It needs to be stressed that randomised clinical trials regarding withdrawal from medications are still lacking.Before making a decision on discontinuation of therapy,it is important to distinguish potential candidates and predictive factors for the possibility of disease relapse.Fecal calprotectin level has currently been identified as the strongest predictive factor for relapse.Several other predictive factors have also been identified,such as:High Crohn's disease activity index or Harvey Bradshaw index,younger age(<40 years),longer disease duration(>40 years),smoking,young age of disease onset,steroid use 6-12 months before cessation.An important factor in the decision to withdraw medication is the success of re-treatment with the same or other drugs.The decision to discontinue therapy must be based on individual approach,taking into account the severity,extension,and duration of the disease,the possibility of side adverse effects,the risk of relapse,and patient’s preferences.

May ChatGPT be a tool producing medical information for common inflammatory bowel disease patients’questions?An evidencecontrolled analysis

Artificial intelligence is increasingly entering everyday healthcare.Large language model(LLM)systems such as Chat Generative Pre-trained Transformer(ChatGPT)have become potentially accessible to everyone,including patients with inflammatory bowel diseases(IBD).However,significant ethical issues and pitfalls exist in innovative LLM tools.The hype generated by such systems may lead to unweighted patient trust in these systems.Therefore,it is necessary to understand whether LLMs(trendy ones,such as ChatGPT)can produce plausible medical information(MI)for patients.This review examined ChatGPT’s potential to provide MI regarding questions commonly addressed by patients with IBD to their gastroenterologists.From the review of the outputs provided by ChatGPT,this tool showed some attractive potential while having significant limitations in updating and detailing information and providing inaccurate information in some cases.Further studies and refinement of the ChatGPT,possibly aligning the outputs with the leading medical evidence provided by reliable databases,are needed.

Role of Oncostatin M in the prognosis of inflammatory bowel disease: A meta-analysis

BACKGROUND Oncostatin M(OSM)is a pleiotropic cytokine which is implicated in the path-ogenesis of inflammatory bowel disease(IBD).AIM To evaluate the prognostic role of OSM in IBD patients.METHODS Literature search was conducted in electronic databases(Google Scholar,Embase,PubMed,Science Direct,Springer,and Wiley).Studies were selected if they reported prognostic information about OSM in IBD patients.Outcome data were synthesized,and meta-analyses were performed to estimate standardized mean differences(SMDs)in OSM levels between treatment responders and non-res-ponders and to seek overall correlations of OSM with other inflammatory bio-markers.RESULTS Sixteen studies(818 Crohn’s disease and 686 ulcerative colitis patients treated with anti-tumor necrosis factor-based therapies)were included.OSM levels were associated with IBD severity.A meta-analysis found significantly higher OSM levels in non-responders than in responders to therapy[SMD 0.80(0.33,1.27);P=0.001],in non-remitters than in remitters[SMD 0.75(95%CI:0.35 to 1.16);P<0.0001]and in patients with no mucosal healing than in those with mucosal heal-ing[SMD 0.63(0.30,0.95);P<0.0001].Area under receiver operator curve values showed considerable variability between studies but in general higher OSM levels were associated with poor prognosis.OSM had significant correlations with Simple Endoscopic Score of Crohn’s disease[r=0.47(95%CI:0.25 to 0.64);P<0.0001],Mayo Endoscopic Score[r=0.35(95%CI:0.28 to 0.41);P<0.0001],fecal calprotectin[r=0.19(95%CI:0.08 to 0.3);P=0.001],C-reactive protein[r=0.25(95%CI:0.11 to 0.39);P<0.0001],and platelet count[r=0.28(95%CI:0.17 to 0.39);P<0.0001].CONCLUSION OSM is a potential candidate for determining the severity of disease and predicting the outcomes of anti-tumor necrosis factor-based therapies in IBD patients.

Surgical treatment of inflammatory bowel disease:From the gastroenterologist’s stand-point

Treatment of ulcerative colitis(UC)and Crohn’s disease(CD)represents,in the majority of cases,a real challenge to the gastroenterologist’s abilities and skills as well as a clinical test concerning his/her levels of medical knowledge and experience.During the last two decades,our pharmaceutical arsenal was significantly strengthened,especially after the introduction of the so-called biological agents,drugs which to a large extent not only improved the results of conservative treatment but also changed the natural history of the disease.However,colectomy is still necessary for some patients with severe UC although smaller compared to the past,precisely because of the improvements achieved in the available conservative treatment.Nevertheless,surgeries to treat colon dysplasia and cancer are increasing to some extent.At the same time,satisfactory improvements in surgical techniques,the pre-and post-operative care of patients,as well as the selection of the appropriate time for performing the surgery have been noticed.Regarding patients with CD,the improvement of conservative treatment did not significantly change the need for surgical treatment since two-thirds of patients need to undergo surgery at some point in the course of their disease.On the other hand,the outcome of the operation has improved through good preoperative care as well as the wide application of more conservative surgical techniques aimed at keeping as much of the bowel in situ as possible.This article discusses the indications for surgical management of UC patients from the gastroenterologist’s point of view,the results of the emerging new techniques such as transanal surgery and robotics,as well as alternative operations to the classic ileo-anal-pouch anastomosis.The author also discusses the basic principles of surgical management of patients with CD based on the results of the relevant literature.The self-evident is emphasized,that is,to achieve an excellent therapeutic result in patients with severe inflammatory bowel disease in today’s era;the close cooperation of gastroenterologists with surgeons,pathologists,imaging,and nutritionists is of paramount importance.

A Comprehensive Analysis of Efficacy and Safety of Probiotics in Inflammatory Bowel Disease

Introduction: Inflammatory bowel disease (IBD) affects approximately 7 million people worldwide. In the U.S. alone, per the CDC, 1.3% of adults, which is approximately 3,000,000 people, are diagnosed with inflammatory bowel disease-either, Crohn’s disease, or ulcerative colitis. The estimated cost of treatment can be close to $23,000 annually, with treatment regimens comprising biologic agents and anti-inflammatory therapies. Probiotics have recently gathered interest as a low-cost additional therapy option that, in addition to the current regimen of IBD management, allows for reductions in rates of IBD flare-ups by significantly reducing the number of emergency room visits and avoiding the need to constantly escalate treatment by addition of biologic agents in achieving remission. The Analysis Goal: Our research project aimed to see if there was a significant difference in the addition of probiotics to standard therapy in inflammatory bowel disease by comparing existing research studies and trials. We analyzed RCTs published in PubMed to assess the efficacy and safety of probiotics in patients with IBD in preventing frequent disease flare-ups and reducing the cost of care. Research Methods: We did a comparative analysis of available RCTs using a PubMed search and included studies that researched the addition of probiotic strains in patients with IBD (ulcerative colitis and Crohn’s disease). After reviewing the inclusion and exclusion criteria, the trials selected for analysis were reviewed by two independent reviewers. Results: We analyzed 21 RCTs, and 16 RCTs (76.2%) showed that probiotics are an effective therapy for IBD, inducing remission and reducing flare-up rates in patients on a standard treatment regimen. Conclusion: Probiotics given in combination with standard therapy in IBD are effective in decreasing disease activity rates and reducing remission rates. No significant adverse reactions to probiotics were noticed.

1例板层角膜联合羊膜移植治疗Mooren’s病并角膜穿孔的护理

对采用新鲜全板层角膜联合单膜移植治疗的1例蚕食性角膜溃疡病人.进行手术前后的精心护理。结果追 踪随访10个月,病人均未发生免疫排斥现象等并发症。

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.

miR-20b, miR-98, miR-125b-1*, and let-7e* as new potential diagnostic biomarkers in ulcerative colitis

AIM:To use microarray-based miRNA profiling of colonic mucosal biopsies from patients with ulcerative colitis (UC), Crohn's disease (CD), and controls in order to identify new potential miRNA biomarkers in inflammatory bowel disease. METHODS:Colonic mucosal pinch biopsies from the descending part were obtained endoscopically from patients with active UC or CD, quiescent UC or CD, as well as healthy controls. Total RNA was isolated and miRNA expression assessed using the miRNA microarray Geniom Biochip miRNA Homo sapiens (Febit GmbH, Heidelberg, Germany). Data analysis was carried out by principal component analysis and projection to latent structure-discriminant analysis using the SIMCA-P+12 software package (Umetrics, Umea, Sweden). The microarray data were subsequently validated by quantitative real-time polymerase chain reaction (qPCR) performed on colonic tissue samples from active UC patients (n = 20), patients with quiescent UC (n = 19), and healthy controls (n = 20). The qPCR results were analyzed with Mann-WhitneyU test.In silico prediction analysis were performed to identify potential miRNA target genes and the predicted miRNA targets were then compared with all UC associated susceptibility genes reported in the literature. RESULTS:The colonic mucosal miRNA transcriptome differs significantly between UC and controls, UC and CD, as well as between UC patients with mucosal inflammation and those without. However, no clear differences in the transcriptome of patients with CD and controls were found. The miRNAs with the strongest differential power were identified (miR-20b, miR-99a, miR-203, miR-26b, and miR-98) and found to be upregulated more than a 10-fold in active UC as compared to quiescent UC, CD, and controls. Two miRNAs, miR-125b-1* and let-7e*, were up-regulated more than 5-fold in quiescent UC compared to active UC, CD, and controls. Four of the seven miRNAs (miR-20b, miR-98, miR-125b-1*, and let-7e*) were validated by qPCR and found to be specifically upregulated in patients with UC. Usingin silico analysis we found several predicted pro-inflammatory target genes involved in various pathways, such as mitogen-activated protein kinase and cytokine signaling, which are both key signaling pathways in UC.CONCLUSION:The present study provides the first evidence that miR-20b, miR-98, miR-125b-1*, and let7e* are deregulated in patients with UC. The level of these miRNAs may serve as new potential biomarkers for this chronic 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.