Chronic Active Disease Research Articles

Mo1906 – Combination Therapy of Vedolizumab and Tofacitinib in IBD Patients with Chronic Active Refractory Disease Course and Spondylarthritis

Mo1906 – Combination Therapy of Vedolizumab and Tofacitinib in IBD Patients with Chronic Active Refractory Disease Course and Spondylarthritis

P147 NOVEL JUNCTIONAL ADHESION MOLECULE-LIKE (JAML) REGULATES NEUTROPHIL TRANSEPITHELIAL MIGRATION DURING INTESTINAL INFLAMMATION

Neutrophil (PMN) migration in the intestine is an essential component of host defense and wound repair. However, dysregulated PMN recruitment is a hallmark of chronic active inflammatory bowel disease (IBD) characterized by persistent inflammation. Disease flares in IBD are associated with marked recruitment of PMN into the intestinal mucosa that results in crypt abscess formation and mucosal ulcerations. Despite the strong association with IBD, the process of PMN transepithelial migration (TEpM) represents a significantly understudied area. PMN migration into the intestinal mucosa requires multiple adhesive interactions between migrating PMN and intestinal epithelial cells (IECs). PMN TEpM is a multi-step process facilitated by complex interactions between PMN and IEC expressed proteins including members of the Juntional Adhesion Molecules (JAMs) family. We have reported that the novel JAM-like protein termed JAML expressed on PMN, associates with the coxsackie and adenovirus receptor (CAR) on epithelial cells. Binding of recombinant JAML ectodomains disrupts JAML-CAR interactions and reduces PMN TEpM. To define the molecular mechanism of JAML regulation of PMN TEpM during intestinal inflammation in-vivo, we generated JAML knockout mice (JAML-/-). PMN TEpM was evaluated using a small intestinal loop model, and PMN migration into the intestinal lumen in response to the chemoattractant LTB4(1nM) for 1h was quantified by flow cytometry. While WT and JAML-/- mice had similar numbers of circulating leukocytes, we observed reduced PMN migration into the intestinal lumen in response to LTB4 in JAML-/- mice compared to WT animals. In addition, there were increased PMN in the epithelial cell fractions derived from intestines of JAML-/- mice suggesting that JAML regulates PMN TEpM in vivo. We also assessed the role of JAML on susceptibility to DSS induced colitis and recovery. Markedly increased disease activity index, inflammation and mucosal ulceration were observed in JAML-/- mice compared to controls. These observations suggest that JAML represents an important adhesion molecule that regulates PMN TEpM. Furthermore, loss of JAML increases susceptibility to colitis. JAML may thus represent a new therapeutic target to dampen excessive PMN migration during intestinal inflammation as seen in IBD.

MicroRNA‑146a inhibits the inflammatory responses induced by interleukin‑17A during the infection of Helicobacter pylori.

Helicobacter pylori (H. pylori) infection is the major cause of chronic active gastritis and peptic ulcer disease. Upregulation of IL‑17A is associated with H. pylori infection in the gastric mucosa; however, the factors involved in the regulation of interleukin (IL)‑17A‑induced inflammatory responses in H. pylori‑associated gastritis remain unknown. MicroRNAs (miRNAs) serve as key post‑transcriptional regulators of gene expression and are associated with the H.pylori infection. The present study aimed to analyze the effects of IL‑17A on the expression of miR‑146a upon infection with H.pylori, as well as to identify the possible impact of miR‑146a dysregulation on the inflammatory response invivo and invitro. Reverse transcription‑quantitative polymerase chain reaction analysis was used to determine the expression levels of miR‑146a in gastric epithelial cells upon IL‑17A stimulation. The effects of miR‑146a mimics on IL‑17A‑induced inflammatory responses in SGC‑7901 cells were evaluated. The effects of miR‑146a mimics on the expression levels of IL‑1 receptor‑associated kinase 1 (IRAK1) and tumor necrosis factor receptor‑associated factor 6 (TRAF6) upon IL‑17A treatment were analyzed, and the IL‑17A‑stimulated inflammation following the silencing of IRAK1 and TRAF6 was observed. In addition, the correlation between miR‑146a and IL‑17A in human gastric mucosa with H. pylori was examined. The results indicated that IL‑17A‑induced miR‑146a may regulate the inflammatory response during the infection of H. pylori in a nuclear factor‑κB‑dependent manner. Furthermore, the expression of miR‑146a and IL‑17A are positively correlated in human gastric mucosa infected with H. pylori. These data suggested that miR‑146a may serve as a biomarker or therapeutic target in gastritis therapy.

Ossicular Involvement and Types of Pathology in Chronic Otitis Media Squamous Active Disease

Background: Chronic otitis media (COM) squamous type is commonly as­sociated with cholesteatoma. In COM squamous type with active disease, there is retraction of pars flaccida or pars tensa with retention of squamous epithelial debris and is associated with inflammation and production of pus. It is potentially dangerous because it can cause resorption of bone, leading to ossicular erosion and destruction of bony plates of middle ear. The objective of this study is to determine the effect of chronic otitis media squamous type on the ossicular chain as well as to observe the types of pathology in this disease.
 Methods and materials: Fifty cases of chronic otitis media squa­mous type who underwent surgical management were included. The status of ossicular chain was evaluated intraoperatively. The type of pathology in­volving middle ear was also studied. Cases admitted for revision surgery were excluded from the study.
 Results: Of the total fifty cases, ossicular changes were observed in forty eight cases and in two cases all ossicles were intact. Long process of incus is the most frequently involved ossicle. The most common pathology was found to be mixed type (52%).
 Conclusion: The conclusion of this study is that ossicular chain is commonly involved in chronic otitis media squamous type and mixed pathology consisting of cholesteatoma and granulation tissue is the most frequent pathology.

Interferon alpha as antiviral therapy in chronic active Epstein-Barr virus disease with interstitial pneumonia - case report

BackgroundChronic active Epstein-Barr virus (EBV) disease (CAEBV) is defined as a severe, progressive lymphoproliferative disorder associated with active EBV infection persisting longer than 6 months and developing in patients without recognised immunodeficiency. Rarely, interstitial pneumonitis (IP) occurs as a serious complication in CAEBV patients. The standard therapeutic regimen for IP in CAEBV has not yet been defined. Although interferon alpha (IFN-alpha) is known to suppress viral DNA replication by affecting its basal promoter activation process, it is rarely used in CAEBV patients.Case presentationA 22-year-old Caucasian woman, diagnosed with CAEBV 1.5 years earlier, was admitted to the Immunology Clinic due to a 4-week history of productive cough, fever and general weakness. Cultures of blood, urine and sputum were negative, but EBV DNA copies were found in the sputum, whole blood, isolated peripheral blood lymphocytes as well as in the blood plasma. Cytokine assessment in peripheral blood revealed the lack of IFN-alpha synthesis. Disseminated maculate infiltrative areas in both lungs were observed on a computed tomography (CT) chest scan. The patient was not qualified for the allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to the risk of immunosuppression-related complications of infectious IP. Inhaled (1.5 million units 3 times a day) and subcutaneous (6 million units 3 times a week) IFN-alpha was implemented. To the best of our knowledge, this was the first documented use of inhaled IFN-alpha in a patient with CAEBV and concomitant IP. Patient’s status has improved, and she was eventually qualified to allo-HSCT with reduced conditioning. Currently, the patient feels well, no EBV was detected and further regression of pulmonary changes was documented.ConclusionsCAEBV should be considered in patients who present with interstitial lung infiltration and involvement of other organs. Although more promising results have been obtained with allo-HSCT, inhaled IFN-alpha may also be a therapeutic option in patients with CAEBV and a concomitant IP.

The clinical characteristics and the features of immunophenotype of peripheral lymphocytes of adult onset chronic active Epstein-Barr virus disease at a Tertiary Care Hospital in Beijing.

Chronic active Epstein-Barr virus (CAEBV) infection is a rare disease with high mortality. Most of CAEBV patients have been reported from Japan and are pediatric cases.The goal was to describe the clinical characteristics and the immunophenotypic features of peripheral lymphocytes in adult onset CAEBV patients.We retrospectively reviewed and analyzed all adult onset CAEBV cases admitted to Peking Union Medical College Hospital (PUMCH) between 2012 and 2016. Demographic, clinical, laboratory data, and the immunophentyping data of peripheral lymphocytes were collected.There were 28 adult onset CAEBV patients. The median age was 45 (range, 20–81). Most of the patients presented with fever; splenomegaly; lymphadenopathy and hepatitis. Unlike pediatric cases reported, the manifestations of cardiovascular diseases in our patients were pulmonary arterial hypertension, decreased cardiac function and aorta vasculitis. Prevalence of interstitial pneumonitis in our patients were comparatively higher and prevalence of hypersensitivity to mosquito bites were comparatively lower than that reported by Japan. In this study, CAEBV patients had decreased B cell, NK cell, CD4 cell and CD8 cell counts. The prevalence of low level of B cells, NK cells, CD4 cells was relatively higher than reported ever.Chinese adult onset CAEBV patients have different clinical characteristics and are featured by an immunosuppression status as demonstrated by decreased B cell, NK cell, CD4 cell and CD8 cell.

GATA2 Deficiency and Epstein-Barr Virus Disease.

GATA2 is a transcription factor that binds to the promoter of hematopoietic genes. Mutations in one copy of the gene are associated with haploinsufficiency and reduced levels of protein. This results in reduced numbers of several cell types important for immune surveillance including dendritic cells, monocytes, CD4, and NK cells, as well as impaired NK cell function. Recently, GATA2 has been associated with several different presentations of severe Epstein–Barr virus (EBV) disease including primary infection requiring repeated hospitalizations, chronic active EBV disease, EBV-associated hydroa vacciniforme with hemophagocytosis, and EBV-positive smooth muscle tumors. EBV was found predominantly in B cells in each of the cases in which it was studied, unlike most cases of chronic active EBV disease in which the virus is usually present in T or NK cells. The variety of EBV-associated diseases seen in patients with GATA2 deficiency suggest that additional forms of severe EBV disease may be found in patients with GATA2 deficiency in the future.

Persistent hematuria in patients with antineutrophil cytoplasmic antibody-associated vasculitis during clinical remission: chronic glomerular lesion or low-grade active renal vasculitis?

BackgroundWhether persistent hematuria in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) during clinical remission reflects active disease or chronic glomerular injury is uncertain. This study aimed to investigate the significance of persistent hematuria during clinical remission in a large cohort of AAV patients.MethodsA cohort of 219 AAV patients in complete clinical remission after induction therapy at our center was retrospectively studied, and their clinical and laboratory data as well as long-term outcomes were analyzed.ResultsA total of 80 out of 219 patients had persistent hematuria during clinical remission of AAV. Compared with patients without hematuria during remission, the slope of eGFR decline in patients with persistent hematuria was significantly higher during the long-term follow-up [3.6 (IQR 1.2, 7.2) vs. 1.5 (IQR 0.2, 4.0) mL/min/1.73 m2/year, P < 0.001]. Among the 80 patients with persistent hematuria during remission, there was little difference between those with fast and slow decline of eGFR, as divided by either median or interquartile range of the slope of eGFR decline. We also compared patients without hematuria who had a slope of eGFR decline that was lower than the median level of the slope of eGFR decline with those with persistent hematuria, and found that patients with hematuria had significantly lower levels of CRP and ESR at baseline and higher levels of ANCA at remission.ConclusionsAmong the AAV patients who achieved clinical remission after immunosuppressive therapy, those with persistent hematuria are not rare and may reflect either chronic renal damage or low-grade active renal disease.

Comparative Study of Outcome of Type I Tympanoplasty in Chronic Otitis Media Active Mucosal Disease (Wet Ear) Versus Chronic Otitis Media Inactive Mucosal Disease (Dry Ear).

To compare the outcome of type I tympanoplasty with cortical mastoidectomy in chronic otitis media active mucosal disease (wet ear) versus chronic otitis media inactive mucosal disease (dry ear). An observational analytic study was conducted and data collection was done from August 2014 to August 2016. All patients of chronic otitis media with mucosal disease were divided into two groups, one with active disease (group A) and another with inactive disease (group B). The outcome was studied in the form of graft take up rate. Total 103 patients were studied, group A (wet ear) had 67 and group B (dry ear) had 36 patients. Graft take up rate was 94% in wet ear and 100% in dry ear and p value was 0.2. There was no statistically significant difference found between the two groups.

Ankylosing Spondylitis and Axial Spondyloarthritis in Patients With Long-term Inflammatory Bowel Disease: Results From 20 Years of Follow-up in the IBSEN Study.

Patients with inflammatory bowel disease [IBD] often suffer from rheumatic manifestations, including inflammatory back disorders. The prevalence of these disorders late in the course of IBD is poorly investigated. The aim of this study was to estimate the prevalence of inflammatory back disorders in patients with IBD 20 years after diagnosis, and to investigate possible associations with IBD severity, HLA-B27, and the NOD2 genotype. A population-based cohort [the IBSEN study] was followed prospectively for 20 years. Information covering IBD activity and rheumatic diseases was collected at the regular follow-ups. HLA-B27 and NOD2 were analysed as present or absent. At 20 years, 599 members of the original cohort were alive, of whom 470 [78.5%] were investigated [314 ulcerative colitis and 156 Crohn's disease patients]. Ankylosing spondylitis was diagnosed in 21 patients [4.5%], axial spondyloarthritis was diagnosed in 36 patients [7.7%], and inflammatory back pain was diagnosed in 54 patients [11.5%]. Chronic back pain [back pain > 3 months] was present in 220 patients [46.8%]. HLA-B27 was associated with ankylosing spondylitis, axial spondyloarthritis, and inflammatory back pain, whereas no significant association was found for NOD2. A more chronic IBD course was associated with axial spondyloarthritis. Our data revealed a high prevalence of ankylosing spondylitis, axial spondyloarthritis, and inflammatory back pain 20 years after the IBD diagnosis. HLA-B27 but not NOD-2 was a predisposing factor for the inflammatory back disorders in IBD patients. Axial spondyloarthritis was associated with a more chronic active IBD disease course.

Low Discontinuation Rate of Infliximab Treatment in Steroid-Dependent/Refractory Crohn’s Disease Patients

Background: Many patients with moderate to severe Crohn’s disease (CD) are treated with infliximab (IFX). As most of these patients experience a long-lasting therapy, the outcome and withdrawal of IFX treatment are important clinical questions. Methods: In this retrospective study, we analyzed the treatment outcome in moderate to severe CD patients with a steroid-dependent/refractory disease course started on IFX. Withdrawal of IFX was evaluated in patients with deep remission defined as clinical (Harvey-Bradshaw Index ≤4), biochemical (fecal calprotectin [FC] ≤150 μg/g stool) over a period of 2 years, and endoscopic and histological remission before discontinuation of IFX. Results: After induction with IFX, clinical remission was observed in 45/109 patients (41.3%) and clinical response in 61/109 patients (56.0%). Only 8/109 patients (7.3%) achieved deep remission and therefore could be discontinued from IFX therapy. In 4 of these patients (50%), relapse was observed after discontinuation of IFX treatment. FC decreased in these 8 patients in deep remission from 652 ± 168 μg/g stool (mean ± SE) at baseline to 24.9 ± 8.1 μg/g stool at 14 weeks. When compared to patients in deep remission, FC had decreased significantly less at 14 weeks in patients in clinical remission after induction with IFX (n = 31; 154 ± 55 μg/g stool; p = 0.01), in patients with clinical response after induction achieving clinical remission during the maintenance phase (n = 11; 352 ± 67 μg/g stool; p = 0.004), or in patients with chronic active disease course on maintenance therapy (n = 50; 645 ± 93 μg/g stool; p < 0.001). Conclusion: A low discontinuation rate was observed for steroid-dependent/refractory moderate to severe CD patients with IFX treatment. As FC showed a more or less pronounced decrease depending on the response to the IFX treatment, monitoring of FC may become a noninvasive tool for tailoring biological therapy in CD patients.

Simultaneous determination of drugs used for chronic active gastritis disease by chemometric methods

Simultaneous determination of drugs used for chronic active gastritis disease by chemometric methods

Clinical and financial burden of active lupus in Greece: a nationwide study.

Analyses of the medical and economic burden of chronic disorders such as systemic lupus erythematosus (SLE) are valuable for clinical and health policy decisions. We performed a chart-based review of 215 adult SLE patients with active autoantibody-positive disease at the predefined ratio of 30% severe (involvement of major organs requiring treatment) and 70% non-severe, followed at seven hospital centres in Greece. We reviewed 318 patients consecutively registered over three months (sub-study). Disease activity, organ damage, flares and healthcare resource utilization were recorded. Costs were assessed from the third-party payer perspective. Severe SLE patients had chronic active disease more frequently (22.4% vs 4.7%), higher average SLE disease activity index (SLEDAI) (10.5 vs 6.1) and systemic lupus international collaborating clinics (SLICC) damage index (1.1 vs 0.6) than non-severe patients. The mean annual direct medical cost was €3741 for severe vs €1225 for non-severe patients. Severe flares, active renal disease and organ damage were independent cost predictors. In the sub-study, 19% of unselected patients were classified as severe SLE, and 30% of them had chronic active disease. In conclusion, this is the first study to demonstrate the significant clinical and financial burden of Greek SLE patients with active major organ disease. Among them, 30% display chronic activity, in spite of standard care, which represents a significant unmet medical need.

Association of GATA2 Deficiency With Severe Primary Epstein-Barr Virus (EBV) Infection and EBV-associated Cancers.

Most patients infected with Epstein-Barr virus (EBV) are asymptomatic, have nonspecific symptoms, or have self-limiting infectious mononucleosis. EBV, however, may result in severe primary disease or cancer. We report EBV diseases associated with GATA2 deficiency at one institution and describe the hematology, virology, and cytokine findings. Seven patients with GATA2 deficiency developed severe EBV disease. Three presented with EBV infectious mononucleosis requiring hospitalization, 1 had chronic active EBV disease (B-cell type), 1 had EBV-associated hydroa vacciniforme-like lymphoma with hemophagocytic lymphohistiocytosis, and 2 had EBV-positive smooth muscle tumors. Four of the 7 patients had severe warts and 3 had disseminated nontuberculous mycobacterial infections. All of the patients had low numbers of monocytes, B cells, CD4 T cells, and natural killer cells. All had elevated levels of EBV in the blood; 2 of 3 patients tested had expression of the EBV major immediate-early gene in the blood indicative of active EBV lytic infection. Mean plasma levels of tumor necrosis factor α, interferon γ, and interferon gamma-induced protein 10 were higher in patients with GATA2 deficiency than in controls. GATA2 is the first gene associated with EBV hydroa vacciniforme-like lymphoma. GATA2 deficiency should be considered in patients with severe primary EBV infection or EBV-associated cancer, especially in those with disseminated nontuberculous mycobacterial disease and warts.

Mature T- and NK-cell non-Hodgkin lymphoma in children and young adolescents.

Mature T/Natural killer (NK)-cell neoplasms of children and the young adolescent population exhibit higher prevalence in Central and South American and Asian populations and many are associated with Epstein-Barr virus (EBV). They are represented in large part by extranodal T/NK cell lymphomas- nasal-type or extra nasal-type, chronic lymphoproliferative disorders of T/NK cells or chronic active EBV disease, systemic EBV-positive lymphoproliferative disorders of childhood, hydroa vacciniforme-like lymphoma, hepatosplenic T-cell lymphoma and primary cutaneous gamma/delta T-cell lymphoma among others. Many T/NK cell neoplasms in this age group are derived from cells of the innate immune system, in contrast to adults where they are predominantly from the adaptive immune system. The genetic basis of T/NK cell lymphomas in children and young adolescents remains largely unknown. Anthracycline-based regimens and haematopoietic stem cell transplants (allogeneic and autologous) are current treatment modalities, however it is anticipated that novel targeted therapeutic agents will be available in the near future.

Diagnostic values for the viral load in peripheral blood mononuclear cells of patients with chronic active Epstein-Barr virus disease.

Chronic active Epstein-Barr virus disease (CAEBV) is a distinct EBV-associated lymphoproliferative disease with a poor prognosis. Although the viral load in blood samples has been widely used for diagnosing CAEBV, well-defined viral load thresholds to guide clinicians are currently lacking. The aim of the present study was to determine standardized diagnostic values for EBV load in blood samples of CAEBV patients using the World Health Organization international standard for reporting. Levels of EBV DNA in 103 peripheral blood mononuclear cells (PBMCs) and 95 plasma/serum samples from 107 cases with CAEBV were quantified and expressed in international units. Receiver operating characteristic curves were analyzed to assess the most appropriate cut-off values for levels of EBV DNA to distinguish CAEBV from EBV-associated infectious mononucleosis (IM) and controls with past EBV infection. Levels of EBV DNA in PBMCs were significantly higher in the CAEBV group (median, 10(4.2)IU/μgDNA) compared to the IM (median, 10(2.1)IU/μgDNA) and control groups. An inconsistent qualitative result was seen in 13 of 86 CAEBV patients; in these, EBV-DNA was positive in PBMCs, but negative in plasma. Diagnostic cut-off values for viral load in PBMCs from CAEBV patients, as compared to those of healthy controls and IM patients, were 10(2.0)IU/μgDNA and 10(3.2)IU/μgDNA, respectively. For diagnostic purposes, the viral load of PBMCs was better than of plasma/serum. A diagnostic cut-off EBV load for CAEBV may be useful for the management of CAEBV patients.

Chronic active disease pattern predicts early damage in juvenile systemic lupus erythematosus.

The objective of this article is to assess disease activity patterns and their relationship to damage, death and growth failure in a cohort of juvenile lupus. Chronic active, relapsing-remitting and long quiescent activity patterns were retrospectively classified according to longitudinal scores of both the Modified SLEDAI-2K and ECLAM. The Pediatric SLICC/ACR Damage Index (Ped-SDI) was scored at the last visit in patients followed more than six months. Survival analysis was performed considering death, damage and growth failure, and stratified according to disease activity patterns. Cox model analysis identified predictors for damage and growth failure among onset clinical variables. Thirty-seven patients with 11 years mean age at diagnosis and 3.2 years mean follow-up were studied. According to the Modified SLEDAI-2K, activity pattern was 67.5% relapsing-remitting, 29.8% chronic active and 2.7% long quiescent and by ECLAM, 45.9%, 48.7% and 5.4%, respectively. The five-year survival was 90%. Damage accrued in 62.5% and growth failure in 31.3%. Chronic active cases progressed to damage earlier than relapsing-remitting (log-rank test, p < 0.05). Damage was associated with disease duration (p < 0.0001), thrombocytopenia (p < 0.05) and alopecia (p < 0.004). Growth failure was associated with disease duration (p < 0.007) and renal failure (p < 0.007). Damage was observed in nearly two-thirds of patients, and occurred earlier in the chronic active pattern. Disease duration, thrombocytopenia and alopecia at onset predicted damage.

Chronic and non-healing wounds: The story of vascular endothelial growth factor

The pathophysiology of the chronicity and non-healing status of wounds remains unknown. This paper presents the following hypothesis: abnormal patterns of vascular endothelial growth factor receptors (VEGFRs) are the culprits of wound chronicity and non-healing. More specifically, for patients with poor circulation, the decreased VEGFR-2 level is the cause of poor wound healing; for patients with non-compromised circulation, for example, patients with concurrent chronic wounds and active autoimmune diseases, the increased VEGFR-1 level is related to the non-healing status of wounds.The hypothesis is supported by the following facts. VEGFR-1 is the main contributor for inflammation and VEGFR-2 facilitates angiogenesis; soluble VEGFR-1 (sVEGFR-1) inactivates both VEGFR-1 and VEGFR-2. Patients with auto-immune disease have abnormally increased VEGFR-1 and decreased sVEGFR. Wounds in patients with active autoimmune diseases have poor response to electric stimulation which facilitates chronic wound healing in patients without active autoimmune diseases via increasing vascular endothelial growth factor (VEGF) secretion. Patients with chronic wounds (including diabetic foot ulcers and venous leg ulcers) but no active autoimmune diseases have decreased VEGFR-2 levels.We thus believe that abnormal patterns of VEGFRs are the culprits of wound chronicity and non-healing. For wounds with compromised circulation, VEGFR-2 decrease contributes to its chronicity; whereas for wounds with non-compromised circulation, VEGFR-1 increase is the leading cause of the non-healing status of chronic wounds. Treatments and research in wound care should be tailored to target these changes based on circulation status of wounds. Complete elucidation of changes of VEGFRs in chronic and non-healing wounds will enhance our understandings in tissue healing and thus better our selection of appropriate treatments for chronic and non-healing wounds.

A reappraisal of the ileo-rectal anastomosis in ulcerative colitis.

Colectomy is still frequently required in the care of ulcerative colitis. The most common indications are either non-responding colitis in the emergency setting, chronic active disease, steroid-dependent disease or neoplastic change like dysplasia or cancer. The use of the ileal pouch anal anastomosis has internationally been the gold standard, substituting the rectum with a pouch. Recently the use of the ileorectal anastomosis has increased in frequency as reconstructive method after subtotal colectomy. Data from centres using ileorectal anastomosis have shown the method to be safe, with functionality and risk of failure comparable to the ileal pouch anal anastomosis. The methods have different advantages as well as disadvantages, depending on a number of patient factors and where in life the patient is at time of reconstruction. The ileorectal anastomosis could, together with the Kock continent ileostomy, in selected cases be a complement to the ileal pouch anal anastomosis in ulcerative colitis and should be discussed with the patient before deciding on reconstructive method.

Clinical course and predictors of total colectomy in ulcerative colitis; a referral center experience from Turkey.

We aimed to describe the clinical course of Ulcerative colitis (UC) and the factors that predict the need for total colectomy in Turkish patients with severe UC receiving regular follow up. We analyzed the demographic and clinical characteristics of 612 patients with UC receiving regular follow up between 1994 and 2010 in a tertiary referral center in Ankara. Men accounted for 58% of patients (M:F ratio, 1.4:1), and the mean age at diagnosis was 37.9 years. Of these, 32% had distal colitis and 8.8% had further extension, and 39 patients (6.4%) had chronic active disease. Steroid dependency and steroid resistance rates were 7.5% and 17.2%, respectively. In multivariate analysis, steroid dependency (p=0.04), steroid resistance (p=0.002), further extension (p<0.001), presence of extensive disease (p=0.006), and chronic active disease (p<0.001) were independent predictors of the need for total colectomy. Patients with chronic active disease had lower total colectomy free survival (p<0.001). The predictors of total colectomy were comparable with those previously reported in the literature. However, we identified further extension in disease localization to predict the need for total colectomy.