Fecal calprotectin (FC), as determined by the enzyme-linked immunoassay (ELISA) test, has been proposed as a promising biomarker of endoscopic activity in Crohn's disease (CD). However data on its ...accuracy in predicting endoscopic remission according to location and postoperative recurrence (POR) is scarce.
Our objective was to evaluate the ability of FC determined by a new quantitative point-of-care test (FC-QPOCT) to predict endoscopic remission and POR in CD patients.
FC was determined simultaneously by an enzyme-linked immunoassay test (FC-ELISA) and a FC-QPOCT in CD patients undergoing colonoscopy. Clinical disease activity was assessed according to the Crohn's Disease Activity Index (CDAI). Endoscopic results were assessed according to the Crohn's Disease Endoscopic Activity Index of Severity (CDEIS) and postoperative recurrence according to the Rutgeerts' score.
A total of 115 ileocolonoscopies were performed (29 on patients with ileocolonic resection). FC levels correlated more closely with the CDEIS than leucocytes, platelets or CRP. The prediction of “endoscopic remission” (CDEIS<3), using FC-QPOCT (cut-off 272μg/g) and FC-ELISA (cut-off 274μg/g) presented an AUC of 0.933 and 0.935 respectively. FC-QPOCT results correlated better with endoscopic activity in the ileocolonic location (Pearson's correlation, r=0.879; P<0.001), than the colonic (r=0.725; P<0.001) or the ileal location (r=0.437; P=0.016). Median FC-QPOCT levels discriminated Rutgeerts' score i0–i1 from i2–i4 (98 (range 30–306)μg/g vs. 234.5 (range 100–612)μg/g respectively, P=0.012).
FC determined by rapid quantitative test predicts “endoscopic remission” and endoscopic postoperative recurrence in CD patients.
While indirect comparison of infliximab (IFX) and vedolizumab (VDZ) in adults with Crohn's disease (CD) or ulcerative colitis (UC) shows that IFX has better effectiveness during induction, and ...comparable efficacy during maintenance treatment, comparative data specific to subcutaneous (SC) IFX (i.e., CT-P13 SC) versus VDZ are limited.
Pooled analysis of randomised studies to compare efficacy and safety with IFX SC and VDZ in moderate-to-severe inflammatory bowel disease.
Parallel-group, randomised studies evaluating IFX SC and VDZ in patients with moderate-to-severe CD or UC were identified. Eligible studies reported ≥ 1 prespecified outcome of interest at Week 6 (reflecting treatment during the induction phase) and/or at 1 year (Weeks 50-54; reflecting treatment during the maintenance phase). Prespecified efficacy and safety outcomes considered in this pooled analysis included the proportions of patients achieving disease-specific clinical responses, clinical remission, or discontinuing due to lack of efficacy, and the proportions of patients experiencing adverse events (AEs), serious AEs, infections, serious infections, or discontinuing due to AEs. Data from multiple studies or study arms were extracted and pooled using a random-effect model; comparative analyses were performed separately for patients with CD and UC.
We identified three eligible CD trials and four eligible UC trials that assigned over 1200 participants per disease cohort to either IFX SC or VDZ. In patients with CD, intravenous induction therapy with IFX demonstrated better efficacy (non-overlapping 95% confidence intervals CIs) compared with VDZ; during the maintenance phase, IFX SC showed numerically better efficacy (overlapping 95% CIs) than VDZ. A lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In patients with UC, efficacy profiles were similar with IFX SC and VDZ during the induction and maintenance phases, and a lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In both cohorts, safety profiles for IFX SC and VDZ were generally comparable during 1 year.
IFX SC demonstrated better efficacy than VDZ in patients with CD, and similar efficacy to VDZ in patients with UC; 1-year safety was comparable with IFX SC and VDZ.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fecal calprotectin (FC) determined by the enzyme-linked immunosorbent assay (ELISA) test has been proposed as a promising biomarker of endoscopic activity in ulcerative colitis (UC). However, data on ...its accuracy in predicting endoscopic activity is scarce. Besides, FC determined by the quantitative-point-of-care test (FC-QPOCT) that provides rapid and individual results could optimize its use in clinical practice. The aims of our study were to evaluate the ability of FC to predict endoscopic activity according to the Mayo score in patients with UC when determined by FC-QPOCT and to compare it with the ELISA test (FC-ELISA).
FC was determined simultaneously by FC-ELISA and FC-QPOCT in patients with UC undergoing colonoscopy. Clinical disease activity and endoscopy were assessed according to the Mayo score. Blood tests were taken to analyze serological biomarkers.
A total of 146 colonoscopies were performed on 123 patients with UC. FC-QPOCT correlated more closely with the Mayo endoscopic subscore (Spearman's correlation coefficient rank r = 0.727, P < 0.001) than clinical activity (r = 0.636, P < 0.001), platelets (r = 0.381, P < 0.001), leucocytes (r = 0.300, P < 0.001), and C-reactive protein (r = 0.291, P = 0.002). The prediction of "endoscopic remission" (Mayo endoscopic subscore ≤1) with FC-QPOCT (280 µg/g) and FC-ELISA (250 µg/g) presented an area under the curve of 0.906 and 0.924, respectively. The interclass correlation index between both tests was 0.904 (95% confidence interval, 0.864-0.932; P < 0.001).
FC determined by QPOCT was an accurate surrogate marker of "endoscopic remission" in UC and presented a good correlation with the FC-ELISA test.
Background
Patients with inflammatory bowel disease (IBD) may present extraintestinal manifestations (EIMs) that affect the joints, skin, eyes, and hepatobiliary area, among others.
Aims
Our aim was ...to analyse the prevalence and characteristics of EIMs in patients with IBD and to identify the possible risk factors associated with the development of EIMs in the largest series published to date.
Methods
Observational, cross-sectional study including patients from the Spanish ENEIDA registry promoted by GETECCU. We retrospectively identified all cases of EIMs in the ENEIDA registry until January 2018.
Results
The study included 31,077 patients, 5779 of whom had at least one EIM (global prevalence 19%; 95% CI 18.2–19.0). Among the different types of EIMs, rheumatic manifestations had a prevalence of 13% (95% CI 12.9–13.7; 63% of EIMs), with a prevalence of 5% (95% CI 4.7–5.2) for mucocutaneous manifestations, 2.1% (95% CI 1.9–2.2) for ocular manifestations, and 0.7% (95% CI 0.6–0.8) for hepatobiliary manifestations. The multivariable analysis showed that the type of IBD (Crohn’s disease,
p
< 0.001), gender (female,
p
< 0.001), the need for an immunomodulator (
p
< 0.001) or biologic drugs (
p
< 0.001), a previous family history of IBD (
p
< 0.001), and an extensive location of IBD (
p
< 0.001) were risk factors for the presence of EIMs.
Conclusions
One-fifth of patients with IBD may have associated EIMs, with rheumatic manifestations as the most frequent (> 60% of EIMs). Female patients with severe Crohn’s disease represent the group with the highest risk of developing EIMs. These patients should therefore be specially monitored and referred to the corresponding specialist when suggestive symptoms appear.
The most recent and promising therapeutic strategies for inflammatory bowel disease (IBD) have engaged biologics targeting single effector components involved in major steps of the ...immune-inflammatory processes, such as tumor necrosis factor, interleukins or integrins. Nevertheless, these molecules have not yet met expectations regarding efficacy and safety, resulting in a significant percentage of refractory or relapsing patients. Thus, novel treatment options are urgently needed. The minor isoform of the complement inhibitor C4b-binding protein, C4BP(β-), has been shown to confer a robust anti-inflammatory and immunomodulatory phenotype over inflammatory myeloid cells. Here we show that C4BP(β-)-mediated immunomodulation can significantly attenuate the histopathological traits and preserve the intestinal epithelial integrity in dextran sulfate sodium (DSS)-induced murine colitis. C4BP(β-) downregulated inflammatory transcripts, notably those related to neutrophil activity, mitigated circulating inflammatory effector cytokines and chemokines such as CXCL13, key in generating ectopic lymphoid structures, and, overall, prevented inflammatory immune cell infiltration in the colon of colitic mice. PRP6-HO7, a recombinant curtailed analogue with only immunomodulatory activity, achieved a similar outcome as C4BP(β-), indicating that the therapeutic effect is not due to the complement inhibitory activity. Furthermore, both C4BP(β-) and PRP6-HO7 significantly reduced, with comparable efficacy, the intrinsic and TLR-induced inflammatory markers in myeloid cells from both ulcerative colitis and Crohn's disease patients, regardless of their medication. Thus, the pleiotropic anti-inflammatory and immunomodulatory activity of PRP6-HO7, able to "reprogram" myeloid cells from the complex inflammatory bowel environment and to restore immune homeostasis, might constitute a promising therapeutic option for IBD.
In this study, we aim to identify the genes responsible for colorectal cancer risk behind the loci identified in genome-wide association studies (GWAS). These genes may be candidate targets for ...developing new strategies for prevention or therapy. We analyzed the association of genotypes for 26 GWAS single nucleotide polymorphisms (SNPs) with the expression of genes within a 2 Mb region (cis-eQTLs). Affymetrix Human Genome U219 expression arrays were used to assess gene expression in two series of samples, one of healthy colonic mucosa (n = 47) and other of normal mucosa adjacent to colon cancer (n = 97, total 144). Paired tumor tissues (n = 97) were also analyzed but did not provide additional findings. Partial Pearson correlation (r), adjusted for sample type, was used for the analysis. We have found Bonferroni-significant cis-eQTLs in three loci: rs3802842 in 11q23.1 associated to C11orf53, COLCA1 (C11orf92) and COLCA2 (C11orf93; r = 0.60); rs7136702 in 12q13.12 associated to DIP2B (r = 0.63) and rs5934683 in Xp22.3 associated to SHROOM2 and GPR143 (r = 0.47). For loci in chromosomes 11 and 12, we have found other SNPs in linkage disequilibrium that are more strongly associated with the expression of the identified genes and are better functional candidates: rs7130173 for 11q23.1 (r = 0.66) and rs61927768 for 12q13.12 (r = 0.86). These SNPs are located in DNA regions that may harbor enhancers or transcription factor binding sites. The analysis of trans-eQTLs has identified additional genes in these loci that may have common regulatory mechanisms as shown by the analysis of protein-protein interaction networks.
Guidelines recommend routine screening for colorectal cancer (CRC) in asymptomatic adults starting at age 50. The most extensively used noninvasive test for CRC screening is the fecal immunochemical ...test (FIT), which has an overall sensitivity for CRC of approximately 61.0%-91.0%, which drops to 27.0%-67.0% for advanced adenomas. These figures contain a high false-positive rate and a low positive predictive value. This work aimed to develop a new, noninvasive CRC screening tool based on fecal bacterial markers capable of decreasing FIT false-positive rates in a FIT-positive population. We defined a fecal bacterial signature (RAID-CRC Screen) in a proof-of-concept with 172 FIT-positive individuals and validated the obtained results on an external cohort of 327 FIT-positive subjects. All study participants had joined the national CRC screening program. In the clinical validation of RAID-CRC Screen, a sensitivity of 83.9% and a specificity of 16.3% were obtained for the detection of advanced neoplasm lesions (advanced adenomas and/or CRC). FIT 20 μg/g produced 184 false-positive results. Using RAID-CRC Screen, this value was reduced to 154, thus reducing the false-positive rate by 16.3%. The RAID-CRC Screen test could be implemented in CRC screening programs to allow a significant reduction in the number of colonoscopies performed unnecessarily for FIT-positive participants of CRC screening programs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There are limited comparative data for infliximab and vedolizumab in inflammatory bowel disease patients.
We conducted a systematic review and meta-analysis to compare the efficacy and safety of ...infliximab and vedolizumab in adult patients with moderate-to-severe Crohn's disease or ulcerative colitis.
We identified six eligible Crohn's disease and seven eligible ulcerative colitis trials that randomised over 1900 participants per disease cohort to infliximab or vedolizumab. In the Crohn's disease and ulcerative colitis cohorts, infliximab yielded better efficacy than vedolizumab for all analysed outcomes (CDAI-70, CDAI-100 responses, and clinical remission for Crohn's disease and clinical response and clinical remission for ulcerative colitis) during the induction phase, with non-overlapping 95% confidence intervals. In the maintenance phase, similar proportions of infliximab- or vedolizumab-treated patients achieved clinical response, clinical remission, or mucosal healing in both Crohn's disease and ulcerative colitis. For the safety outcomes, rates of adverse events, serious adverse events, and discontinuations due to adverse events were similar in infliximab- and vedolizumab-treated patients in both diseases. The infection rate was higher in infliximab for Crohn's disease and higher in vedolizumab when treating patients with ulcerative colitis. There was no difference between the treatments in the proportions of patients who reported serious infections in both indications.
Indirect comparison of infliximab and vedolizumab trials in adult patients with moderate-to severe Crohn's disease or ulcerative colitis demonstrated that infliximab has better efficacy in the induction phase and comparable efficacy during the maintenance phase and overall safety profile compared to vedolizumab.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The faecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening and for the detection of advanced colorectal neoplasia (AN) in symptomatic patients, but its accuracy could be ...improved. Our objective was to assess the impact of proton pump inhibitors (PPI) on the accuracy of the FIT in the detection of AN, namely advanced colorectal adenoma and CRC.
We performed a prospective study of 1002 individuals referred for a diagnostic colonoscopy at Bellvitge University Hospital from September 2011 through to October 2012. An exhaustive interview was performed by a gastroenterologist, prescription drug dispensing database was reviewed and the patient was given a FIT prior to colonoscopy. The positivity threshold of FIT used was ≥ 20 μg Hb/g feces and the main outcome was AN. AN was detected in 13.2% (133) of patients. The accuracy of FIT for detecting AN in the PPI users and non-PPI users were: sensitivity 43.0% vs 65.6%, P = 0.009; specificity 86.9% vs 92.3%, P = 0.010; and, predictive positive value 34.4% vs 55.5%, P = 0.007, respectively. In multivariate analysis, adjusting for potential confounders, PPIs were associated with false positives in AN detection by FIT (OR 1.63 CI 95% 1.02-2.59, P < 0.037). The ROC curve for the FIT in the detection of AN in the PPI users and non-PPI users was 0.68 (CI 95% 0.61-0.76) and 0.85 (CI 95% 0.79-0.90).
PPI therapy reduces the accuracy of FIT for detecting AN in symptomatic patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic gut inflammation in Crohn’s disease (CD) is associated with an increase in oxidative stress and an imbalance of antioxidant enzymes. We have previously shown that catalase (CAT) activity is ...permanently inhibited by CD. The purpose of the study was to determine whether there is any relationship between the single nucleotide polymorphisms (SNPs) in the CAT enzyme and the potential risk of CD associated with high levels of oxidative stress. Additionally, we used protein and regulation analyses to determine what causes long-term CAT inhibition in peripheral white mononuclear cells (PWMCs) in both active and inactive CD. We first used a retrospective cohort of 598 patients with CD and 625 age-matched healthy controls (ENEIDA registry) for the genotype analysis. A second human cohort was used to study the functional and regulatory mechanisms of CAT in CD. We isolated PWMCs from CD patients at the onset of the disease (naïve CD patients). In the genotype-association SNP analysis, the CAT SNPs rs1001179, rs475043, and rs525938 showed a significant association with CD (p < 0.001). Smoking CD patients with the CAT SNP rs475043 A/G genotype had significantly more often penetrating disease (p = 0.009). The gene expression and protein levels of CAT were permanently reduced in the active and inactive CD patients. The inhibition of CAT activity in the PWMCs of the CD patients was related to a low concentration of CAT protein caused by the downregulation of CAT-gene transcription. Our study suggests an association between CAT SNPs and the risk of CD that may explain permanent CAT inhibition in CD patients together with low CAT gene and protein expression.
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