Effect of mucosal healing (Mayo 0) on clinical relapse in patients with ulcerative colitis in clinical remission

Objective: The aim of this study was to identify the effect of mucosal healing (MH) on clinical relapse in patients with ulcerative colitis (UC) who are in clinical remission, with special reference to Mayo endoscopic subscore 0.

Methods: Between November 2005 and December 2013, medical records from a total of 215 patients with UC who underwent colonoscopic examination at the time of clinical remission were retrospectively reviewed. Endoscopic MH was defined as a ‘0 point’ of Mayo endoscopic subscore (Mayo 0). Patients were categorized into two groups according to Mayo endoscopic subscore and then analyzed.

Results: The baseline characteristics of both groups (MH vs. no-MH), including age at diagnosis, gender, and initial clinical and colonoscopic findings, were not significantly different. The median follow-up duration was 80 (12–118) months. Factors predictive of longer clinical remission duration were age ≥30 years at diagnosis (≥30 years vs. <30 years; hazard ratio [HR] 3.16, 95% CI 1.88–5.30, p?p?=?0.015), and presence of MH at clinical remission (HR 1.95, 95% CI 1.15–3.32, p?=?0.014). With a Cox regression model, patients with MH at clinical remission were more likely to have longer duration of clinical remission than patients without MH.

Conclusion: The achievement of MH, Mayo 0 in particular, in patients with UC who are in clinical remission is important in predicting a favorable disease course prognosis.     

Class II (HLA-DR, -DP,and -DQ) antigens on intestinal epithelia in ulcerative colitis,Crohn’s disease,colorectal cancer and normal small intestine

Class II antigens in involved colonic epithelia of ulcerative colitis (UC), Crohn’s disease (CD), colorectal cancer, and epithelia of normal small intestine were investigated using an immunoperoxidase method. Ten normal colonic mucosa served as normal controls. Ten specimens were studied for each group. Normal colonie epithelia did not express class II antigens. In colonie diseases; (1) with regard to the frequency and extent of class II antigens on epithelia, HLA-DR antigens were the most highly and greatly expressed, followed by HLA-DP and then HLA-DQ antigens. (2) The extent of HLA-DR and -DP, but not HLA-DQ, expression on epithelia of UC and colorectal cancer seemed to be positively correlated with the degree of mononuclear cell infiltration in the lesion. (3) The extent of class II antigen expression on colonie epithelia in CD was not related to the degree of mononuclear cell infiltration in the lesion. (4) The extent of HLA-DR and -DP expression on epithelia of colorectal cancer seemed to be positively correlated with increasing undifferentiation. In the normal small intestine, where HLA-DR antigens were physiologically expressed on epithelia, HLA-DQ antigens were not expressed. The heterogeneity among colonie diseases, and between the physiological and pathological status, may reflect differences in immunoregulation. This work was partly supported by a grant from the Research Committee for Intractable Intestinal Diseases (Member; Osamu Masamune), Ministry of Health and Welfare, Japan.     

Correlation of serum biomarkers with clinical severity and mucosal inflammation in Chinese ulcerative colitis patients

OBJECTIVE: Serum biomarkers are commonly used for diagnosing and monitoring the disease activity of ulcerative colitis (UC) patients. However, their role in predicting active mucosal inflammation on Chinese patients is unknown. Our aim was to determine the sensitivity and correlation of these biomarkers with clinical severity and mucosal inflammation. METHODS: Patients who had been newly diagnosed or who had developed a clinical relapse were identified. Active mucosal inflammation was confirmed by colonoscopy and histology. Those patients who had routine serum biomarkers (C‐reactive protein [CRP], erythrocyte sedimentation rate [ESR], white cell count, hemoglobin, platelet count and albumin) checked within 14 days of the index colonoscopy were recruited for a retrospective analysis. The disease severity was graded clinically and the positive rate of each marker was determined. The correlation of these markers with the clinical severity and extent of colitis were assessed by the Mann–Whitney U‐test or the Kruskal–Wallis test. For the categorical variable, χ² or the Fisher's exact test were adopted. RESULTS: From January 2001 to December 2006, 49 Chinese UC patients fulfilled the inclusion criteria. There were 78 acute mucosal inflammatory episodes (24 at diagnosis and 54 clinical relapses). Abnormal CRP, ESR, white cell count, hemoglobin, platelet count and albumin occurred in 42.3%, 55.1%, 23.1%, 21.8%, 32.1% and 25.6% of these mucosal inflammatory episodes, respectively. For the severity of the clinical disease, all serum biomarkers demonstrated a good correlation with the severity grading. On the other hand, the serum biomarkers correlated well with endoscopic extensive colitis but not with proctitis or left‐sided colitis. CONCLUSION: Routine serum biomarkers are not sensitive in predicting mucosal inflammation. However, they are helpful in identifying patients with extensive colitis or clinically severe disease.     

Analysis of cytotoxic T lymphocyte associated antigen 4 gene polymorphisms in patients with ulcerative colitis

BACKGROUND AND AIM: Ulcerative colitis (UC) is a multifactorial disease associated with dysregulated immunity. Recently, cytotoxic T lymphocyte associated antigen 4 (CTLA-4) gene polymorphisms have been reported in association with several autoimmune diseases in several populations. In the present study, the possible implication of the CTLA-4 gene as a risk factor for UC in the Iranian population was investigated. METHODS: One hundred UC patients and 100 healthy subjects were studied. CTLA-4 exon 1 position 49 (A/G: codon 17: Thr/Ala) polymorphisms were investigated by polymerase chain reaction single strand confirmation polymorphism method. Four of the patients and one of the healthy controls were excluded from the study because of incomplete DNA extraction. RESULTS: The allele frequencies of A and G in 96 patients (A: 66.1%; G: 33.9%) were not significantly different from the 99 control subjects (A: 63.1%; G: 36.9%, P > 0.05). No significant differences in the distribution of genotype frequencies were observed between A + 49G gene polymorphisms and UC in the Iranian population (P > 0.05). CONCLUSION: CTLA-4 polymorphism is not associated with UC in the Iranian population.     

Characterisation of mucosal lymphoid aggregates in ulcerative colitis: immune cell phenotype and TcR-gammadelta expression

BACKGROUND AND AIMS: A histopathological feature considered indicative of ulcerative colitis (UC) is the so-called basal lymphoid aggregates. Their relevance in the pathogenesis of UC is, however, unknown. We have performed a comprehensive analysis of the immune cells in these aggregates most likely corresponding to the lymphoid follicular hyperplasia also described in other colitides. METHODS: Resection specimens of UC and normal colon were analysed by immunomorphometry, immunoflow cytometry, and immunoelectron microscopy, using a large panel of monoclonal antibodies. RESULTS: (1) In all cases of UC, colonic lamina propria contained numerous basal aggregates composed of lymphocytes, follicular dendritic cells, and CD80/B7.1 positive dendritic cells. (2) CD4(+)CD28(-) alphabeta T cells and B cells were the dominant cell types in the aggregates. (3) The aggregates contained a large fraction of cells that are normally associated with the epithelium: that is, gammadelta T cells (11 (7)%) and alpha(E)beta(7)(+) cells (26 (13)%). The gammadelta T cells used Vdelta1 and were CD4(-)CD8(-). Immunoelectron microscopy analysis demonstrated TcR-gammadelta internalisation and surface downregulation, indicating that the gammadelta T cells were activated and engaged in the disease process. (4) One third of cells in the aggregates expressed the antiapoptotic protein bcl-2. CONCLUSIONS: Basal lymphoid aggregates in UC colon are a consequence of anomalous lymphoid follicular hyperplasia, characterised by abnormal follicular architecture and unusual cell immunophenotypes. The aggregates increase in size with severity of disease, and contain large numbers of apoptosis resistant cells and activated mucosal gammadelta T cells. The latter probably colonise the aggregates as an immunoregulatory response to stressed lymphocytes or as a substitute for defective T helper cells in B cell activation. gammadelta T cells in the aggregates may be characteristic of UC.     

Genetic control of immune response to a purified Schistosoma mansoni antigen. I. Effect of MHC class II antigens on the cellular, humoral and protective responses

The influence of the I region of the major histocompatibility complex (MHC) on T-dependent immune responses against a purified schistosome antigen (9B antigen) was investigated. H-2 congenic mice expressing both I-A and I-E antigens (I-E+) showed a higher in-vitro proliferation to 9B antigen as compared to the recombinant strains expressing only I-A (I-E-). These two strains of mice differed both qualitatively and quantitatively in the humoral responses elicited by the purified antigen. Furthermore, in-vivo protection experiments showed that mice which do not express I-E molecules can be partially protected against the disease by prior immunization with the 9B antigen in contrast to their I-E expressing counterparts. The possible role of the I-E molecule in the immune responses elicited during Schistosoma mansoni infection is discussed.     

Treatment of patients with acute ulcerative colitis: Conventional corticosteroid therapy (MP) versus granulocytapheresis (GMA): A pilot study

AIM: The aim of our pilot study is to report the efficacy of granulocytapheresis in patients with acute ulcerative colitis with respect to the use of conventional corticosteroids such as methylprednisolone. METHODS: The activity of disease was evaluated by clinical activity index and endoscopic index. Forty patients with acute ulcerative colitis were randomly divided in two groups of 20 subjects each: one group was treated with five sessions of granulocytapheresis, the other one with methylprednisolone for 5 weeks. Complete response was defined as clinical activity index lower than 6 and endoscopic index lower than 4 after 6 weeks of follow-up. Partial response was defined as clinical activity index lower than 6 but endoscopic index more than 4 after 6 weeks of follow-up. All the conditions not included are classified as nonresponders. RESULTS: All the patients completed the trial. Complete clinical response was observed in 70% of patients treated with granulocytapheresis versus 60% of patients treated with methylprednisolone. A partial response was observed in 20% of patients treated with granulocytapheresis versus 15% of patients treated with methylprednisolone. During the sessions of granulocytapheresis only a transient mild headache was recorded in 10% of patients, while side effects were more common (50%) in the patients treated with methylprednisolone. CONCLUSION: Granulocytapheresis represents a new and promising approach to active ulcerative colitis. In fact, even if more expensive than conventional corticosteroids, it seems slightly more effective and, above all, with side effects much less frequent and serious. Thus, granulocytapheresis cycles could be prolonged or repeated, if necessary, in more severe diseases without significant risks for the patients.     

Genetic polymorphisms of CD14 and Toll-like receptor-2 (TLR2) in patients with ulcerative colitis

BACKGROUND AND AIM: Ulcerative colitis (UC) is a multifactorial disease resulting from a complex interaction of genetic and environmental factors. Identifying genetic variants that alter the innate immune response is highly relevant to understanding the pathogenesis of UC. The aim of this study was to investigate the association between CD14 and Toll-like receptor-2 (TLR2) genetic polymorphisms and chronic UC in Japanese patients. METHODS: The study population consisted of 102 chronic UC patients and 146 healthy control subjects. Polymorphisms in the promoter at C-260T of CD14 gene were investigated by PCR restriction fragment length polymorphism, and -196 to -174 del of TLR2 was investigated by allele-specific PCR. RESULTS: The frequencies of CD14 TT and T carrier were significantly higher in UC patients than in controls (TT: OR = 3.98, 95% CI 1.82-8.71, P = 0.0005; T carrier: OR = 2.98, 95% CI 1.47-6.01, P = 0.002). In addition, TT and T carrier were more closely associated with distal colitis phenotype (TT: OR = 7.78, 95% CI 2.14-28.28, P = 0.0007; T carrier: OR = 6.30, 95% CI 2.71-14.58, P = 0.005), onset after 20 years of age (TT: OR = 5.28, 95% CI 2.18-12.79; T carrier: OR = 3.79, 95% CI 1.67-8.59), chronic continuous type (TT: OR = 4.26, 95% CI 1.56-11.64; T carrier: OR = 3.09, 95% CI 1.33-7.82), and fewer than two hospitalizations (TT: OR = 4.44, 95% CI 1.81-10.89; T carrier: OR = 3.26, 95% CI 1.43-7.27). There was no significant difference in TLR2 -196 to -174 del/del and del/ins carrier frequencies between UC patients and healthy controls. However, these frequencies were significantly higher in steroid-dependant patients than in controls (del/del: OR = 6.08, 95% CI 1.41-26.21; del carrier: OR = 3.00, 95% CI 1.13-7.98). CONCLUSION: The results suggest that existence of a mutation in the CD14 gene is associated with an increased susceptibility to developing UC, especially chronic continuous distal colitis phenotypes that develop after 20 years of age. Furthermore, polymorphism of TLR2 may be related to an increased risk of intensive types such as steroid-dependent patients.     

An unexplored angle: T cell antigen discoveries reveal a marginal contribution of proteasome splicing to the immunogenic MHC class I antigen pool

In the current era of T cell–based immunotherapies, it is crucial to understand which types of MHC-presented T cell antigens are produced by tumor cells. In addition to linear peptide antigens, chimeric peptides are generated through proteasome-catalyzed peptide splicing (PCPS). Whether such spliced peptides are abundantly presented by MHC is highly disputed because of disagreement in computational analyses of mass spectrometry data of MHC-eluted peptides. Moreover, such mass spectrometric analyses cannot elucidate how much spliced peptides contribute to the pool of immunogenic antigens. In this Perspective, we explain the significance of knowing the contribution of spliced peptides for accurate analyses of peptidomes on one hand, and to serve as a potential source of targetable tumor antigens on the other hand. Toward a strategy for mass spectrometry independent estimation of the contribution of PCPS to the immunopeptidome, we first reviewed methodologies to identify MHC-presented spliced peptide antigens expressed by tumors. Data from these identifications allowed us to compile three independent datasets containing 103, 74, and 83 confirmed T cell antigens from cancer patients. Only 3.9%, 1.4%, and between 0% and 7.2% of these truly immunogenic antigens are produced by PCPS, therefore providing a marginal contribution to the pool of immunogenic tumor antigens. We conclude that spliced peptides will not serve as a comprehensive source to expand the number of targetable antigens for immunotherapies.     

Antineutrophil antibodies associated with ulcerative colitis interact with the antigen(s) during the process of apoptosis

BACKGROUND: Cell death by apoptosis seems to be an important mechanism for translocation to the cell surface of a variety of intracellular components capable of inducing autoantibody production. AIMS: To identify the cellular location of antigen (Ag)-antineutrophil cytoplasmic antibodies (ANCA) in non-apoptotic human neutrophils, and to assess if ANCA associated with ulcerative colitis reacts with neutrophil antigen(s) during neutrophil apoptosis. The cellular distribution of Ag-ANCA in apoptotic neutrophils was also investigated. METHODS: Sera from 18 ulcerative colitis patients known to be positive for perinuclear IgG-ANCA (titre > or =1/320), as assessed by indirect immunofluorescence (IIF), were analysed by immunofluorescent confocal laser scanning microscopy. ANCA were identified with fluorescein isothiocyanate (FITC) and tetramethylrhodamine isothiocyanate (TRITC) in non-apoptotic and apoptotic neutrophils, respectively. Apoptotic and non-apoptotic DNA was labelled with FITC and propidium iodide, respectively. Cycloheximide was added to polymorphonuclear leucocyte culture to induce apoptosis. RESULTS: Three patterns of scanning laser immunofluorescence microscopy in non-apoptotic neutrophils were observed with respect to cellular ulcerative colitis associated ANCA distribution: (1) diffuse nuclear localisation (16.7%); (2) nuclear localisation in the nuclear periphery (50%); and (3) mixed nuclear and cytoplasmic localisation (33.4%). In all sera ANCA fluorescence colocalised almost completely with apoptotic DNA, with persistence of a diffuse and intense fluorescence. No significant changes in ANCA titres were found in non-apoptotic neutrophils. CONCLUSIONS: The antigen(s) of ANCA associated with ulcerative colitis seems to be localised in most cases in the neutrophil nucleus. The almost identical colocalisation of ANCA and apoptotic cleaved DNA suggests that intracellular DNA redistribution during neutrophil apoptosis may play a role in antigen exposure to the immune system and ANCA production in ulcerative colitis.     

Clinical effectiveness of probiotics therapy (BIO-THREE) in patients with ulcerative colitis refractory to conventional therapy

Objective. Intestinal microflora has been implicated in the etiology of ulcerative colitis (UC). Over the past few years, the use of probiotics in UC has gained attention. The aim of this study was to evaluate the efficacy of probiotics therapy for mild to moderate distal UC refractory to conventional therapies. Material and methods. Twenty patients with mild to moderate distal UC took 9 BIO-THREE tablets per day for 4 weeks. Clinical symptoms and endoscopic findings were evaluated as ulcerative colitis disease activity index (UCDAI) scores before and after administration of BIO-THREE. Fecal samples were collected from all patients before and after probiotics administration, and fecal microflora was analyzed by the terminal restriction fragment length polymorphism (T-RFLP) method. Results. Remission (UCDAI score≤2) was observed in 45% (9/20) of the patients; response (decrease in UCDAI≥3, but final score≥3) in 10% (2/20); no response in 40% (8/20); and worsening (UCDAI>3) in 5% (1/20). T-RFLP analysis indicated that the principal alteration in microflora was an increase in bifidobacteria. Conclusions. This study showed that administration of BIO-THREE improved the clinical symptoms and endoscopic findings in patients with UC, indicating that administration of BIO-THREE is safe and efficacious for the treatment of UC.     

Disrupted mucosal barrier in quiescent ulcerative colitis: effect of metronidazole and of a symbiotic preparation in a pilot cross‐over study

OBJECTIVES: The aims of the present study were to investigate the plasma concentration of endotoxin in patients with inflammatory bowel disease (IBD), the effect of metronidazole (MNZ) and of symbiotics on that concentration, and the relationship to IBD activity. METHODS: The study group comprised 26 patients with quiescent ulcerative colitis (UC), all of whom were on maintenance mesalazine treatment (1200? 2400 mg/day). The control group comprised 15 subjects. Blood samples were taken from all study subjects to measure: routine blood chemistry, endotoxin concentration, lipopolysaccharide binding protein (LBP) and macrophage‐colony stimulating factor (M‐CSF). All the IBD patients were randomly enrolled for a 2‐week oral daily treatment regimen with either MNZ (250 mg t.i.d.) or the symbiotic mixture SCM‐III (Lactobacillus acidophilus, L. helveticus and Bifidobacteria brevis in an ion‐ and vitamin‐enriched medium; 3 mL t.i.d.). Following a 6‐week washout period during which the patients continued their maintenance treatment, the cross‐over study of the new treatments was begun. Blood parameters were checked at entry and 2 weeks after each treatment schedule. RESULTS: The concentration of endotoxin level in the UC patients, as a whole, was comparable with that of the control subjects. However, a separate group of patients with long‐standing disease and pancolitis showed a statistically significant increase in toxin. SCM‐III, but not MNZ, normalized this parameter. There was no statistical change in LBP and plasma endotoxin‐inhibiting capacity in the IBD patients. The M‐CSF concentration was increased in the UC group, particularly in the pancolitis subgroup. SCM‐III, but not MNZ, significantly decreased the M‐CSF concentration in the UC patients, but there was only an insignificant trend toward decrease in the subgroup. There was a significant correlation between M‐CSF and endotoxin in the pancolitis subgroup (r: 0.74, P < 0.05). CONCLUSIONS: Although these preliminary results need to be treated with caution, they suggest the effectiveness of long‐term administration of probiotics/symbiotics in conjunction with standard treatment in patients with UC, even if there is not gross disease activity.     

Expression of the CD11/CD18 cell surface adhesion glycoprotein family and MHC class II antigen on blood monocytes and alveolar macrophages in interstitial lung diseases

The expression of molecules of the CD 11/CD18 cell surface adhesion glycoprotein family and HLA/DR antigen was studied on peripheral blood monocytes (PBM) and alveolar macrophages (AM) in bronchoalveolar lavage (BAL) fluid from patients with sarcoidosis, idiopathic pulmonary fibrosis (IPF), and extrinsic allergic alveolitis (EAA). Patients with these interstitial lung diseases showed increased numbers of macrophages in BAL fluid. This was probably caused by an increased influx of PBM to the alveoli since the numbers of cells with a monocytic morphology were also significantly increased in BAL samples from patients with interstitial lung disease, most prominently in IPF and EAA.The increased influx of PBM into the alveoli in patients with interstitial lung diseases was not reflected by an increased expression of the CD11/CD18 leukocyte function antigens on PBM.In healthy volunteers as well as in those with sarcoidosis, IPF, and EAA, the percentages of AM positive for CD11b (the C3bi complement receptor) and CD11c were lower than among PBM. This indicates that the expression of these cell surface adhesion molecules is downregulated during maturation and migration of PBM to the alveoli. The absolute numbers of AM positive for CD11b were increased in BAL fluid of IPF and EAA patients compared to healthy volunteers. EAA patients also showed increased absolute numbers of AM positive for CD11a and CD11c. This differentially increased expression of these leukocyte function antigens on AM suggests the influence of locally produced cytokines. Offprint requests to: H. C. Hoogsteden     

Azodisalicylate (Olsalazine) in the treatment of active ulcerative colitis. A placebo controlled clinical trial and assessment of drug disposition

Abstract The efficacy, safety and disposition of azodisalicylate, (ADS, Olsalazine) was assessed in patients with left-sided ulcerative colitis (UC) or proctitis in a double-blind placebo controlled trial. Thirty patients with a mild-to-moderate attack of UC were randomly allocated to ADS capsules 1 g (b.d.) or placebo for 6 weeks; other therapy was ceased. Patients were reviewed weekly and plasma, urine and faecal concentrations of ADS and its metabolites were determined by high performance liquid chromatography (HPLC). Sigmoidoscopy and biopsy were repeated at 6 weeks.
Four patients receiving placebo and two receiving ADS were withdrawn because of diarrhoea. Five patients known to be allergic to sulphasalazine had no adverse reactions to ADS. Good clinical response was found in six patients receiving ADS and in two receiving placebo ( P = 0.11). Improvement in sigmoidoscopic findings and histological appearance of rectal biopsies was also seen more frequently in ADS-treated patients. Plasma concentrations of ADS were significantly higher in patients who improved. Faecal ADS, 5-ASA and acetyl-5-ASA varied widely and showed no correlation with response. ADS showed an advantage over placebo which needs to be confirmed by further studies; it was safe in sulphasalazine-sensitive patients but appeared to cause watery diarrhoea in two patients.     

Anti-tumour necrosis factor alpha (Infliximab) in the treatment of severe ulcerative colitis: result of an open study on 13 patients

BACKGROUND: Conventional treatment options for patients with severe steroid-refractory ulcerative colitis include intravenous cyclosporine, which is frequently burdened by toxicity, or colectomy. Preliminary data suggest a benefit from anti-tumour necrosis factor alpha (Infliximab) therapy in patients with steroid refractory ulcerative colitis. AIM: To evaluate the efficacy of Infliximab in the treatment of severe ulcerative colitis refractory to conventional therapy PATIENTS AND METHODS: A series of 13 patients with severe ulcerative colitis, refractory to therapy with methyl-prednisolone, 60 mg daily for seven or more days, were treated with a single intravenous infusion of Infliximab 5 mg/kg. RESULTS AND CONCLUSIONS: Of these 13 patients, 10 (77%) had a clinical response to therapy defined by a clinical activity index 10 on two consecutive days. In 2 patients (15%) total colectomy was necessary on account of clinical worsening whilst one patient refused surgery and was lost to follow-up. All patients who responded showed very rapid clinical improvement, within 2 to 3 days of infusion. Infusion with Infliximab produced no significant adverse events. The mean time of follow-up was 10.1 months (range 5-12; during this time, 9 out of 10 patients (90%) maintained clinical remission and were able to discontinue corticosteroid therapy. Infliximab appears to be an effective agent for inducing long-standing remission in refractory patients with severe ulcerative colitis.     

Infliximab in ulcerative colitis: real-life analysis of factors predicting treatment discontinuation due to lack of response or colectomy: ECIA (ACAD Colitis and Infliximab Study)

Objective. To describe clinical practice with infliximab (IFX) in ulcerative colitis (UC); identification of predictive factors for IFX treatment discontinuation due to insufficient response and for colectomy. Material and methods. Retrospective, multicentric and observational study including every UC IFX-treated patient in 10 Spanish hospitals. Variables analyzed: epidemiological data; variables for poor prognosis; IFX prior treatments; characteristics of the IFX treatment; time from the UC diagnosis to induction with IFX; time from induction to colectomy or until data collection. Predictive and protective factors for IFX discontinuation due to lack of response and for colectomy were analyzed with binary logistic regression and Cox analysis. Results. Follow-up time from induction with IFX to the collection of data or colectomy: 36.7 ± 25.7 months. Prior treatment with immunomodulator medications (IMM): 79%; IFX + immunosuppressant therapy: 77%; discontinuation of IFX: 26%, colectomy 16%. Independent predictive or protective factors for IFX discontinuation: IMM resistance (OR: 2.9, p = 0.022, 95%CI: 1.2–7.2), prior use of leukocytapheresis (OR: 3.3, p = 0.024, 95%CI: 1.1–9.4), IFX + IMM therapy (OR: 0.3, p = 0.022, 95%CI: 0.1–0.9, and HR: 0.4, p = 0.006, 95%CI: 0.2–0.8) and corticosteroid use in induction (HR: 1.9, p = 0.049, 95%CI: 1.0–3.8). Independent predictive or protective factors for colectomy: Use of leukocytapheresis (OR: 3.0, p = 0.036, 95%CI: 1.1–8.4), IFX + IMM therapy (OR: 0.3, p = 0.022, 95%CI: 0.1–0.8, and HR: 0.3, p = 0.011, 95%CI: 0.1–0.8) and severe cortico-resistant flare-up (HR: 2.5, p = 0.032, 95%CI: 1.1–5.9). Conclusions. Prior use of IMM and leukocytapheresis, the use of corticosteroids in induction and a severe cortico-resistant flare predict a worse response to IFX and the need for colectomy. Combination therapy is a protective factor for both.     

Application of the neutrophil to lymphocyte ratio in the diagnosis and activity determination of ulcerative colitis: A meta-analysis and systematic review

Background:The neutrophil to lymphocyte ratio (NLR) may be a potential biomarker to evaluate the condition of ulcerative colitis (UC), but whether it can determine the activity of UC is still controversial. So we conducted this meta-analysis to study the relationship between them.Methods:We searched the databases of Pubmed, Embase, Cochrane, Wanfang, and CNKI to collect qualified articles. Random effect or fixed effect model is used to calculate the standard mean difference (SMD) with 95% confidence interval (CI).Results:A total of 11 articles (including 1741 participants) were included in this meta-analysis. The results showed that the level of NLR in peripheral blood of patients with UC was significantly higher than that of control group (SMD = 1.04, 95% CI = 0.71-1.36). The NLR value of active patients was significantly higher than that of inactive patients (SMD = 1.35, 95% CI = 0.87-1.83).Conclusion:NLR may be a useful index to determine the severity and activity of UC, and it is expected to be widely used in clinical practice in the future.     

Mesenteric blood flow is related to disease activity and risk of relapse in ulcerative colitis: a prospective follow up study

BACKGROUND: The diagnostic significance of increased splanchnic blood flow in ulcerative colitis is unclear. This prospective study was therefore undertaken to define the role of Doppler sonography in the assessment of disease activity and in the prediction of early relapse. SUBJECTS/METHODS: Splanchnic flowmetry was performed in 76 patients with ulcerative colitis (47 with active disease and 29 in remission), six with infectious colitis, and 13 healthy controls during fasting and 30 minutes after ingestion of a standardised meal. Twenty seven of the patients with ulcerative colitis and all patients with infectious colitis were investigated during the active state as well as in clinical remission and followed up for six months. Flow velocity and pulsatility index (PI) of the superior (SMA) and inferior (IMA) mesenteric arteries and the portal vein were related to clinical (Truelove index), laboratory (C-reactive protein), and endoscopic (Sutherland index) parameters of disease activity. RESULTS: The mean flow velocity of the IMA correlated closest with clinical activity (Truelove, r = 0.41, p<0.005), the PI with C-reactive protein (r = 0.30, p<0.05), and endoscopic activity (r = 0.45, p<0.001). All patients in remission after six months (14/14) or with infectious colitis (6/6) showed an increase in PI of the IMA compared with the initial measurement during active disease (mean increase for ulcerative colitis +36% and for infectious colitis +77%). In contrast, most patients with later relapse or surgery (11/13) had decreased PI during initial remission (mean decrease -12%). The positive predictive value of this index for maintenance of remission was 0.77. Flow variables of the SMA and portal vein displayed weaker correlations. CONCLUSIONS: Flow measurements in the IMA are closely related to clinical and endoscopic disease activity in patients with ulcerative colitis. Repeated measurement of the PI allows estimation of the risk of recurrence.