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.

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.

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%,

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。

Epidemiology and gene markers of ulcerative colitis in the Chinese

Inflammatory bowel disease （IBD） includes two similar yet distinct conditions called ulcerative colitis （UC） and Crohn＇s disease （CD）. These diseases affect the digestive system and cause the inflammation of intestinal tissue, form sores and bleed easily. Most children with IBD are diagnosed in late childhood and adolescence. However, both UC and CD have been reported as early as in infancy. Most information pertaining to the epidemiology of IBD is based upon adult studies. Symptoms include abdominal pain, cramping, fatigue and diarrhea. Genetic factors play a significant role in determining IBD susceptibility. Epidemiological data support a genetic contribution to the pathogenesis of IBD. Recently, numerous new genes have been identified as being involved in the genetic susceptibility to IBD： TNF- 308A, CARD15 （NOD2）, MIF-173, N-acetyltransferase 2 （NAT2）, NKG2D （natural killer cell 2D）, STAT6 （signal transducer and activator of transcription 6）, CTLA-4 （cytotoxic T lymphocyte antigen-4）, MICA-MICB （major histocompatibility complex A and B）, HLA-DRB1, HLA class-Ⅱ, IL-18, IL-4, MICA-A5, CD14, TI R4, Fas-670, p53 and NF-kB. The characterization of these novel genes has the potential to identify therapeutic agents and aid clinical assessment of phenotype and prognosis in patients with IBD （UC and 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.

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.

Intestinal Behcet's disease with esophageal ulcers and colonic longitudinal ulcers

Intestinal Behcet＇s disease in a 38-year-old woman was diagnosed because of the history of recurrent oral aphthous ulcers, erythema nodosum-like eruptions, genital ulcer, and endoscopic findings of esophageal and Ueocolonic punched-out ulcers with colonic longitudinal ulcers. Esophageal lesions and colonic longitudinal ulcers are rarely seen in intestinal Behcet＇s disease. The ulcers of esophagus and ileocolon healed with 3 wk of treatment with prednisolone and mesalazine without any adverse effect. Mesalazine may decrease the total dose of prednisolone required to treat the disease.

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).

Systemic interleukin-9 in inflammatory bowel disease: Association with mucosal healing in ulcerative colitis

To evaluate circulating IL9 in inflammatory bowel disease and disease-associated anemia/cachexia and assess its potential as a mucosal healing marker.METHODSSerum IL9 as well as other cytokines (IL1β, IL6, IL13, IFNγ, TNFα, and VEGF-A) were determined in 293 individuals: 97 patients with Crohn’s disease (CD) and 74 with ulcerative colitis (UC) and in 122 apparently healthy controls. The clinical activity of CD and UC was expressed in terms of the Crohn’s Disease Activity Index (CDAI) and the Mayo Scoring System (MDAI), respectively, and the severity of bowel inflammation in UC patients was assessed using Mayo endoscopic score. Cytokine concentrations were measured by a flow cytometry-based method using Luminex xMAP® technology. High-sensitive C-reactive protein concentrations (hsCRP) were determined in CD and UC patients using the enhanced immunoturbidimetric method.RESULTSSystemic IL9 was significantly lower in healthy individuals [9 pg/mL (95%CI: 8.2-10)] than in patients with inflammatory bowel disease (IBD): both inactive [14.3 pg/mL (11.9-19.9)] and active [27.6 pg/mL (24.5-32), P < 0.0001]. Cytokine concentrations were significantly higher in active CD [27.4 pg/mL (23.4-32.2)] and in active UC [32.7 pg/mL (27-38.9)] compared to inactive diseases [15.9 pg/mL (10.8-23.4) in CD and 19.4 pg/mL (13.9-27.1) in UC, P = 0.001]. IL9 correlated weakly with CDAI (ρ = 0.32, P = 0.003) and MDAI (ρ = 0.35, P = 0.002) and strongly with endoscopic inflammation in UC (ρ = 0.74, P < 0.0001). As a negative marker of mucosal healing (MH), IL9 had an accuracy superior to hsCRP and IL6 [97% (P < 0.0001), 67% (P = 0.071), and 55% (P = 0.525), respectively]. IL9 was significantly higher in cachectic IBD patients [30.25 pg/mL (24.4-37.5) vs 21.88 pg/mL (18-26.5), P = 0.026] and negatively correlated with hemoglobin concentrations (ρ = -0.27, P < 0.001). Multiple regression showed IL1β and IL13 to be the independent predictors of circulating IL9 in healthy individuals, IFNγ or IL6 in active and inactive UC, respectively, and IL13 and VEGF-A in both active and inactive CD.CONCLUSIONThe systemic IL9 level is higher in IBD and corresponds with endoscopic inflammation, suggesting its possible application as a negative marker of mucosal healing in UC.

Laboratory markers in ulcerative colitis: Current insights and future advances

Ulcerative colitis(UC)and Crohn’s disease(CD)are the major forms of inflammatory bowel diseases(IBD)in man.Despite some common features,these forms can be distinguished by different genetic predisposition,risk factors and clinical,endoscopic and histological characteristics.The aetiology of both CD and UC remains unknown,but several evidences suggest that CD and perhaps UC are due to an excessive immuneresponse directed against normal constituents of the intestinal bacterial flora.Tests sometimes invasive are routine for the diagnosis and care of patients with IBD.Diagnosis of UC is based on clinical symptoms combined with radiological and endoscopic investigations.The employment of non-invasive biomarkers is needed.These biomarkers have the potential to avoid invasive diagnostic tests that may result in discomfort and potential complications.The ability to determine the type,severity,prognosis and response to therapy of UC,using biomarkers has long been a goal of clinical researchers.We describe the biomarkers assessed in UC,with special reference to acute-phase proteins and serologic markers and thereafter,we describe the new biological markers and the biological markers could be developed in the future:(1)serum markers of acute phase response:The laboratory tests most used to measure the acute-phase proteins in clinical practice are the serum concentration of C-reactive protein and the erythrocyte sedimentation rate.Other biomarkers of inflammation in UC include platelet count,leukocyte count,and serum albumin and serum orosomucoid concentrations;(2)serologic markers/antibodies:In the last decades serological and immunologic biomarkers have been studied extensively in immunology and have been used in clinical practice to detect specific pathologies.In UC,the presence of these antibodies can aid as surrogate markers for the aberrant host immune response;and(3)future biomarkers:The development of biomarkers in UC will be very important in the future.The progress of molecular biology tools(microarrays,proteomics and nanotechnology)have revolutionised the field of the biomarker discovery.The advances in bioinformatics coupled with cross-disciplinary collaborations have greatly enhanced our ability to retrieve,characterize and analyse large amounts of data generated by the technological advances.The techniques available for biomarkers development are genomics(single nucleotide polymorphism genotyping,pharmacogenetics and gene expression analyses)and proteomics.In the future,the additionof new serological markers will add significant benefit.Correlating serologic markers with genotypes and clinical phenotypes should enhance our understanding of pathophysiology of UC.

Multifocal stenosing ulceration of the small intestine

Several reports have described an apparently uncommon clinicopathological disorder that is characterized by multifocal stenosing small-intestinal ulceration.Compared to Crohn's disease,the ulcers are not transmural and typically remain shallow,and involve only the mucosa and submucosa.The disorder seems to be localized in the jejunum and proximal ileum only,and not the distal ileum or colon.Only nonspecif ic inflammatory changes are present without giant cells or other typical features of granulomatous inflammation.Most patients present clinically with recurrent obstructive events that usually respond to steroids,surgical resection,or both.With the development of newer imaging modalities to visualize the small-intestinal mucosa,such as double-balloon enteroscopy,improved understanding of the long-term natural history of this apparently distinctive disorder should emerge.

Diagnostic classification of endosonography for differentiating colorectal ulcerative diseases: A new statistical method

AIM To establish a classification method for differential diagnosis of colorectal ulcerative diseases, especially Crohn's disease(CD), primary intestinal lymphoma(PIL) and intestinal tuberculosis(ITB).METHODS We searched the in-patient medical record database for confirmed cases of CD, PIL and ITB from 2008 to 2015 at our center, collected data on endoscopic ultrasound(EUS) from randomly-chosen patients who formed the training set, conducted univariate logistic regression analysis to summarize EUS features of CD, PIL and ITB, and created a diagnostic classification method. All cases found to have colorectal ulcers using EUS were obtained from the endoscopy database and formed the test set. We then removed the cases which were easily diagnosed, and the remaining cases formed the perplexing test set. We re-diagnosed the cases in the three sets using the classification method, determined EUS diagnostic accuracies, and adjusted the classification accordingly. Finally, the re-diagnosing and accuracy-calculating steps were repeated.RESULTS In total, 272 CD, 60 PIL and 39 ITB cases were diagnosed from 2008 to 2015 based on the in-patient database, and 200 CD, 30 PIL and 20 ITB cases were randomly chosen to form the training set. The EUS features were summarized as follows: CD: Thickened submucosa with a slightly high echo level and visible layer; PIL: Absent layer and diffuse hypoechoic mass; and ITB: Thickened mucosa with a high or slightly high echo level and visible layer. The test set consisted of 77 CD, 30 PIL, 23 ITB and 140 cases of other diseases obtained from the endoscopy database. Seventy-four cases were excluded to form the perplexing test set. After adjustment of the classification, EUS diagnostic accuracies for CD, PIL and ITB were 83.6%(209/250), 97.2%(243/250) and 85.6%(214/250) in the training set, were 89.3%(241/270), 97.8%(264/270) and 84.1%(227/270) in the test set, and were 86.7%(170/196), 98.0%(192/196) and 85.2%(167/196) in the perplexing set, respectively.CONCLUSION The EUS features of CD, PIL and ITB are different. The diagnostic classification method is reliable in the differential diagnosis of colorectal ulcerative diseases.

Gastrointestinal endoscopy biopsy derived proteomic patterns predict indeterminate colitis into ulcerative colitis and Crohn's colitis

Patients with indeterminate colitis(IC) are significantly younger at diagnosis with onset of symptoms before the age of 18 years with significant morbidity in the interim. The successful care of IC is based on microscopic visual predict precision of eventual ulcerative colitis(UC) or Crohn's colitis(CC) which is not offered in 15%-30% of inflammatory bowel disease(IBD) patients even after a combined state-of-the-art classification system of clinical, visual endoscopic, radiologic and histologic examination. These figures have not changed over the past 3 decades despite the introduction of newer diagnostic modalities. The patient outcomes after restorative proctocolectomy and ileal pouch-anal anastomosis may be painstaking if IC turns into CC. Our approach is aiming at developing a single sensitive and absolute accurate diagnostic test tool during the first clinic visit through endoscopic biopsy derived proteomic patterns. Matrix-assisted-laser desorption/ionization mass spectrometry(MS) and/or imaging MS technologies permit a histology-directed cellular test of endoscopy biopsy which identifies phenotype specific proteins, as biomarker that would assist clinicians more accurately delineate IC as beingeither a UC or CC or a non-IBD condition. These novel studies are underway on larger cohorts and are highly innovative with significances in differentiating a UC from CC in patients with IC and could lend mechanistic insights into IBD pathogenesis.

Adherence to surveillance guidelines for dysplasia and colorectal carcinoma in ulcerative and Crohn's colitis patients in the Netherlands

AIM: To study adherence to the widely accepted surveillance guidelines for patients with long-standing colitis in the Netherlands. METHODS: A questionnaire was sent to all 244 gastroenterologists in the Netherlands. RESULTS: The response rate was 63%. Of all gastroenterologists, 95% performed endoscopic surveillance in ulcerative colitis (UC) patients and 65% in patients with Crohn's colitis. The American Gastroenterological Association (AGA) guidelines were followed by 27%, while 27% and 46% followed their local hospital protocol or no specific protocol, respectively. The surveillance was correctly initiated in cases of pancolitis by 53%, and in cases of left-sided colitis by 44% of the gastroenterologists. Although guidelines recommend 4 biopsies every 10 cm, less than 30 biopsies per colonoscopy were taken by 73% of the responders. Only 31%, 68% and 58% of the gastroenterologists referred patients for colectomy when low-grade dysplasia, high-grade dysplasia (HGD) or Dysplasia Associated Lesion or Mass (DALM) was present, respectively. CONCLUSION: Most Dutch gastroenterologists performendoscopic surveillance without following international recommended guidelines. This practice potentially leads to a decreased sensitivity for dysplasia, rendering screening for colorectal cancer in this population highly ineffective.

Positions of selective leukocytapheresis in the medical therapy of ulcerative colitis

Ulcerative colitis （UC） and Crohn＇s disease （CD） are the major forms of idiopathic inflammatory bowel disease （IBD）. Both UC and CD are debilitating chronic disorders that afflict millions of individuals throughout the world with symptoms which impair function and quality of life. The etiology of IBD is inadequately understood and therefore, drug therapy has been empirical instead of being based on sound understanding of IBD pathogenesis. This is a major factor for poor drug efficacy and drug related side effects that often add to the disease complexity. The development of biologicals notably infliximab to intercept tumor necrosis factor （TNF）-α reflects some progress, albeit major concern about their side effects and lack of long-term safety and efficacy profiles. However, IBD seems to be perpetuated by inflammatory cytokines like TNF-α, interleukin （IL）-Iβ, IL-6 and IL-8 for which activated peripheral granulocytes and monocytes/macrophages （GH） are major sources. Further, in IBD, peripheral GHs are elevated with activation behavior, increased survival time and are found in vast numbers within the inflamed intestinal mucosa; they are suspected to be major factors in the immunopathogenesis of IBD. Hence, peripheral blood GMs should be appropriate targets of therapy. The Adacolumn is a medical device developed for selective depletion of GH by receptor-mediated adsorption （GHA）. Clinical data show GMA, in patients with steroid dependent or steroid refractory UC, is associated with up to 85% efficacy and tapering or discontinuation of steroids, while in steroid nai＇ve patients （the best responders）, GHA spares patients from exposure to steroids. Likewise, GMA at appropriate intervals in patients at a high risk of clinical relapse suppresses relapse thus sparing the patients from the morbidity associated with IBD relapse. Further, GHA appears to reduce the number of patients being submitted to colectomy or exposure to unsafe immunosupressants. First UC episode, steroid naivety and short disease duration appear good predictors of response to GMA and based on the available data, GMA seems to have an excellent safety profile.

Periodontitis combined with smoking increases risk of the ulcerative colitis: A national cohort study

BACKGROUND Periodontitis is a chronic inflammation of periodontal tissues.The effect of periodontitis on the development of inflammatory bowel disease(IBD)remains unclear.AIM To assessed the risk of IBD among patients with periodontitis,and the risk factors for IBD related to periodontitis.METHODS A nationwide population-based cohort study was performed using claims data from the Korean National Healthcare Insurance Service.In total,9950548 individuals aged≥20 years who underwent national health screening in 2009 were included.Newly diagnosed IBD[Crohn’s disease(CD),ulcerative colitis(UC)]using the International Classification of Disease 10th revision and rare intractable disease codes,was compared between the periodontitis and nonperiodontitis groups until 2017.RESULTS A total of 1092825 individuals(11.0%)had periodontitis.Periodontitis was significantly associated with older age,male gender,higher body mass index,quitting smoking,not drinking alcohol,and regular exercise.The mean age was 51.4±12.9 years in the periodontitis group and 46.6±14.2 years in the nonperiodontitis group(P<0.01),respectively.The mean body mass index was 23.9±3.1 and 23.7±3.2 in the periodontitis and non-periodontitis groups,respectively(P<0.01).Men were 604307(55.3%)and 4844383(54.7%)in the periodontitis and non-periodontitis groups,respectively.The mean follow-up duration was 7.26 years.Individuals with periodontitis had a significantly higher risk of UC than those without periodontitis[adjusted hazard ratio:1.091;95%confidence interval(CI):1.008-1.182],but not CD(adjusted hazard ratio:0.879;95%confidence interval:0.731-1.057).The risks for UC were significant in the subgroups of age≥65 years,male gender,alcohol drinker,current smoker,and reduced physical activity.Current smokers aged≥65 years with periodontitis were at a 1.9-fold increased risk of UC than non-smokers aged≥65 years without periodontitis.CONCLUSION Periodontitis was significantly associated with the risk of developing UC,but not CD,particularly in current smokers aged≥65 years.