BACKGROUND: Ulcerative colitis (UC) with concomitant primary sclerosing cholangitis (PSC) represents a distinct disease entity (PSC-UC). Mayo endoscopic subscore (MES) is a standard tool for assessing disease activity in UC but its relevance in PSC-UC remains unclear. AIM: To assess the accuracy of MES in UC and PSC-UC patients, we performed histological scoring using Nancy histological index (NHI). METHODS: MES was assessed in 30 PSC-UC and 29 UC adult patients during endoscopy. NHI and inflammation were evaluated in biopsies from the cecum, rectum, and terminal ileum. In addition, perinuclear anti-neutrophil cytoplasmic antibodies, fecal calprotectin, body mass index, and other relevant clinical characteristics were collected. RESULTS: The median MES and NHI were similar for UC patients (MES grade 2 and NHI grade 2 in the rectum) but were different for PSC-UC patients (MES grade 0 and NHI grade 2 in the cecum). There was a correlation between MES and NHI for UC patients (Spearman's r = 0.40, P = 0.029) but not for PSC-UC patients. Histopathological examination revealed persistent microscopic inflammation in 88% of PSC-UC patients with MES grade 0 (46% of all PSC-UC patients). Moreover, MES overestimated the severity of active inflammation in an additional 11% of PSC-UC patients. CONCLUSION: MES insufficiently identifies microscopic inflammation in PSC-UC. This indicates that histological evaluation should become a routine procedure of the diagnostic and grading system in both PSC-UC and PSC.

• Klíčová slova
• Diagnosis, Mayo endoscopic subscore, Nancy histological index, Primary sclerosing cholangitis, Ulcerative colitis,
• Publikační typ
• časopisecké články MeSH

Advances in diagnostics of inflammatory bowel diseases (IBD) and improved treatment strategies allowed the establishment of new therapeutic endpoints. Currently, it is desirable not only to cease clinical symptoms, but mainly to achieve endoscopic remission, a macroscopic normalization of the bowel mucosa. However, up to one-third of IBD patients in remission exhibit persisting microscopic activity of the disease. The evidence suggests a better predictive value of histology for the development of clinical complications such as clinical relapse, surgical intervention, need for therapy escalation, or development of colorectal cancer. The proper assessment of microscopic inflammatory activity thus became an important part of the overall histopathological evaluation of colonic biopsies and many histopathological scoring indices have been established. Nonetheless, a majority of them have not been validated and no scoring index became a part of the routine bioptic practice. This review summarizes a predictive value of microscopic disease activity assessment for the subsequent clinical course of IBD, describes the most commonly used scoring indices for Crohn's disease and ulcerative colitis, and comments on current limitations and unresolved issues.

• Klíčová slova
• Crohn’s disease, Microscopy, Predictor, Score, Ulcerative colitis,
• MeSH
• Crohnova nemoc * farmakoterapie   MeSH
• endoskopie škodlivé účinky   MeSH
• idiopatické střevní záněty * komplikace   MeSH
• lidé MeSH
• střevní sliznice diagnostické zobrazování   patologie   MeSH
• ulcerózní kolitida * patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND AND AIMS: Histological scoring plays a key role in the assessment of disease activity in ulcerative colitis [UC] and is also important in Crohn´s disease [CD]. Currently, there is no common scoring available for UC and CD. We aimed to validate the Inflammatory Bowel Disease [IBD]-Distribution [D], Chronicity [C], Activity [A] score [IBD-DCA score] for histological disease activity assessment in IBD. METHODS: Inter- and intra-rater reliability were assessed by 16 observers on biopsy specimens from 59 patients with UC and 25 patients with CD. Construct validity and responsiveness to treatment were retrospectively evaluated in a second cohort of 30 patients. RESULTS: Inter-rater reliability was moderate to good for the UC cohort (intraclass correlation coefficients [ICCs] = 0.645, 0.623, 0.767 for D, C, and A, respectively) and at best moderate for the CD cohort [ICC = 0.690, 0.303, 0.733 for D, C, and A, respectively]. Intra-rater agreement ranged from good to excellent in both cohorts. Correlation with the Nancy Histological Index [NHI] was moderate and strong with the Simplified Geboes Score [SGS] and a Visual Analogue Scale [VAS], respectively. Large effect sizes were obtained for all three parameters. External responsiveness analysis revealed correlated changes between IBD-DCA score and NHI, SGS and VAS. CONCLUSIONS: The IBD-DCA score is a simple histological activity score for UC and CD, agreed and validated by a large group of IBD specialists. It provides reliable information on treatment response. Therefore, it has potential value for use in routine diagnostics as well as clinical studies.

• Klíčová slova
• Histological index, IBD-DCA, inflammatory bowel disease,
• MeSH
• biopsie MeSH
• Crohnova nemoc patologie   MeSH
• lidé MeSH
• reprodukovatelnost výsledků MeSH
• střevní sliznice patologie   MeSH
• stupeň závažnosti nemoci * MeSH
• ulcerózní kolitida patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• validační studie MeSH

• MeSH
• biopsie MeSH
• Crohnova nemoc patologie   terapie   MeSH
• delfská metoda MeSH
• klinické rozhodování MeSH
• konsensus MeSH
• lidé MeSH
• metody pro podporu rozhodování * MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• reprodukovatelnost výsledků MeSH
• střeva patologie   MeSH
• ulcerózní kolitida patologie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• směrnice pro lékařskou praxi MeSH
• systematický přehled MeSH

BACKGROUND AND AIMS: Toll-like receptors [TLRs] are potential drug targets for immunomodulation. We determined the safety and efficacy of the TLR-9 agonist DNA-based immunomodulatory sequence 0150 [DIMS0150] in ulcerative colitis [UC] patients refractory to standard therapy. METHODS: In this randomized, double-blind, placebo-controlled trial, 131 patients with moderate-to-severe active UC were randomized to receive two single doses of the oligonucleotide DIMS0150 [30 mg] or placebo administered topically during lower GI endoscopy at baseline and Week 4. The primary endpoint was clinical remission, defined as Clinical Activity Index [CAI] ≤4, at Week 12. Secondary endpoints included mucosal healing and symptomatic remission of key patient-reported outcomes [absence of blood in stool and weekly stool frequency <35]. RESULTS: There was no statistical significant difference between the groups in the induction of clinical remission at Week 12, with 44.4% in the DIMS0150 group vs. 46.5% in the placebo group. However, the proportion of patients who achieved symptomatic remission was 32.1% in the DIMS0150 group vs. 14.0% in the placebo group at Week 4 [p = 0.020], and 44.4% vs. 27.9% at Week 8 [p = 0.061]. More patients on DIMS0150 compared with those on placebo had mucosal healing [34.6% vs. 18.6%; p = 0.09] and histological improvement regarding the Geboes score [30.9% vs. 9.3%; p = 0.0073] at Week 4. Significantly more patients on DIMS0150 were in clinical remission with mucosal healing at Week 4: 21% vs. 4.7% in the placebo group [p = 0.02]. DIMS0150 was well tolerated, and no safety signals compared with placebo were evident. CONCLUSIONS: Therapy with the topically applied TLR-9 agonist DIMS0150 is a promising and well-tolerated novel therapeutic option for treatment-refractory, chronic active UC patients, warranting further clinical trials.

• Klíčová slova
• Toll-like receptors, therapy, ulcerative colitis,
• MeSH
• aplikace lokální MeSH
• DNA aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• endoskopie metody   MeSH
• imunologické faktory aplikace a dávkování   terapeutické užití   MeSH
• kolon účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři MeSH
• toll-like receptor 9 agonisté   MeSH
• ulcerózní kolitida farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• DIMS0150 MeSH Prohlížeč
• DNA MeSH
• imunologické faktory MeSH
• TLR9 protein, human MeSH Prohlížeč
• toll-like receptor 9 MeSH