Guidelines for the management of ulcerative colitis. Recommendations of the Polish Society of Gastroenterology and the Polish National Consultant in Gastroenterology.

This paper is an update of the diagnostic and therapeutic recommendations of the National Consultant for Gastroenterology and the Polish Society of Gastroenterology from 2013. It contains 49 recommendations for the diagnosis and treatment, both pharmacological and surgical, of ulcerative colitis in adults. The guidelines were developed by a group of experts appointed by the Polish Society of Gastroenterology and the National Consultant in the field of Gastroenterology. The methodology related to the GRADE methodology was used to assess the quality of available evidence and the strength of therapeutic recommendations. The degree of expert support for the proposed statements was assessed on a 6-point Likert scale. Voting results, together with comments, are included with each statement.

Guidelines for the management of patients with Crohn's disease. Recommendations of the Polish Society of Gastroenterology and the Polish National Consultant in Gastroenterology.

This paper is an update of the diagnostic and therapeutic recommendations of the National Consultant for Gastroenterology and the Polish Society of Gastroenterology from 2012. It contains 46 recommendations for the diagnosis and treatment, both pharmacological and surgical, of Crohn's disease in adults. The guidelines were developed by a group of experts appointed by the Polish Society of Gastroenterology and the National Consultant in the field of Gastroenterology. The methodology related to the GRADE methodology was used to assess the quality and strength of the available recommendations. The degree of expert support for the proposed statement, assessment of the quality of evidence and the strength of the recommendation was assessed on a 6-point Likert scale. Voting results, quality and strength ratings with comments are included with each statement.

Redefining the Practical Utility of Blood Transcriptome Biomarkers in Inflammatory Bowel Diseases.

BACKGROUND AND AIMS: The study investigates the practical utility of whole-blood gene expression profiling to diagnose inflammatory bowel diseases [IBDs]. METHODS: The discovery cohorts included 102 and 51 paediatric IBD patients and controls, and 95 and 46 adult IBD patients and controls, respectively. The replication cohorts included 447 and 76 paediatric IBD patients and controls, and 271 and 108 adult IBD patients and controls, respectively. In the discovery phase, RNA samples extracted from whole peripheral blood were analysed using RNA-Seq, and the predictive values of selected biomarkers were validated using quantitative polymerase chain reaction [qPCR]. RESULTS: In all, 15 differentially expressed transcripts [adjusted p ≤0.05] were selected from the discovery sequencing datasets. The receiver operating characteristic curves and area under the curve [ROC-AUC] in replication analyses showed high discriminative power [AUC range, 0.91-0.98] for 11 mRNAs in paediatric patients with active IBD. By contrast, the AUC-ROC values ranged from 0.63 to 0.75 in comparison among inactive paediatric IBDs and active/inactive adult IBDs, indicating a lack of discriminative power. The best multi-mRNA diagnostic classifier showed moderate discriminative power [AUC = 0.81] for paediatric inactive IBD, but was not able to discriminate active or inactive adult IBD patients from controls. The AUC-ROC values did not confirm an ability of the mRNAs abundances to discriminate between active ulcerative colitis and active Crohn's disease in paediatric or adult populations. CONCLUSIONS: This study identifies and validates blood transcriptional biomarkers that could be used in clinical settings as diagnostic predictors of IBD clinical activity in paediatric, but not adult, IBD patients.

miR-508 Defines the Stem-like/Mesenchymal Subtype in Colorectal Cancer.

Colorectal cancer includes an invasive stem-like/mesenchymal subtype, but its genetic drivers, functional, and clinical relevance are uncharacterized. Here we report the definition of an altered miRNA signature defining this subtype that includes a major genomic loss of miR-508. Mechanistic investigations showed that this miRNA affected the expression of cadherin CDH1 and the transcription factors ZEB1, SALL4, and BMI1. Loss of miR-508 in colorectal cancer was associated with upregulation of the novel hypoxia-induced long noncoding RNA AK000053. Ectopic expression of miR-508 in colorectal cancer cells blunted epithelial-to-mesenchymal transition (EMT), stemness, migration, and invasive capacity in vitro and in vivo In clinical colorectal cancer specimens, expression of miR-508 negatively correlated with stemness and EMT-associated gene expression and positively correlated with patient survival. Overall, our results showed that miR-508 is a key functional determinant of the stem-like/mesenchymal colorectal cancer subtype and a candidate therapeutic target for its treatment.Significance: These results define a key functional determinant of a stem-like/mesenchymal subtype of colorectal cancers and a candidate therapeutic target for its treatment. Cancer Res; 78(7); 1751-65. ©2018 AACR.

Genetic architecture differences between pediatric and adult-onset inflammatory bowel diseases in the Polish population.

Most inflammatory bowel diseases (IBDs) are classic complex disorders represented by common alleles. Here we aimed to define the genetic architecture of pediatric and adult-onset IBDs for the Polish population. A total of 1495 patients were recruited, including 761 patients with Crohn's disease (CD; 424 pediatric), 734 patients with ulcerative colitis (UC; 390 pediatric), and 934 healthy controls. Allelotyping employed a pooled-DNA genome-wide association study (GWAS) and was validated by individual genotyping. Whole exome sequencing (WES) was performed on 44 IBD patients diagnosed before 6 years of age, 45 patients diagnosed after 40 years of age, and 18 healthy controls. Altogether, out of 88 selected SNPs, 31 SNPs were replicated for association with IBD. A novel BRD2 (rs1049526) association reached significance of P = 5.2 × 10-11 and odds ratio (OR) = 2.43. Twenty SNPs were shared between pediatric and adult patients; 1 and 7 were unique to adult-onset and pediatric-onset IBD, respectively. WES identified numerous rare and potentially deleterious variants in IBD-associated or innate immunity-associated genes. Deleterious alleles in both groups were over-represented among rare variants in affected children. Our GWAS revealed differences in the polygenic architecture of pediatric- and adult-onset IBD. A significant accumulation of rare and deleterious variants in affected children suggests a contribution by yet unexplained genetic components.

New pharmaceuticals in inflammatory bowel disease.

This paper complements the previously published Guidelines of the Working Group of the Polish Society of Gastroenterology and former National Consultant in Gastroenterology regarding the management of patients with Crohn's disease and ulcerative colitis. Attention was focused on the new pharmaceutical recently registered for inflammatory bowel disease treatment.

Dexlansoprazole - a new-generation proton pump inhibitor.

Dexlansoprazole modified release (MR) is an R-enantiomer of lansoprazole and a new-generation proton pump inhibitor exhibiting high efficacy in the treatment of symptoms and lesions associated with erosive oesophagitis caused by gastroesophageal reflux disease (GERD). The dual release of the active ingredient - in the duodenum and the small intestine - makes it possible to achieve two peak concentrations at various times, within two and five hours of administration. Dexlansoprazole MR ensures the longest maintenance of drug concentration in the plasma of all known proton pump inhibitors, and the longest proton pump inhibitory effect. The basic indications for the drug include all forms of gastroesophageal reflux disease, especially with night-time heartburn and sleep disorders resulting from GERD. Dexlansoprazole can be taken regardless of meal times. It has a good safety profile and carries a low risk of adverse interactions with other drugs.

Iron deficiency anaemia in patients with inflammatory bowel disease: National Consultant for Gastroenterology Working Group Recommendations.

Anaemia is a common complication associated with inflammatory bowel diseases (Crohn's disease and ulcerative colitis). It substantially impairs quality of life, makes therapy more complicated, and increases costs of treatment. It seems that anaemia therapy is suboptimal in this group of patients in the Polish population. The recommendations presented below provide iron deficiency anaemia management clues in patients with inflammatory bowel disease.

Biosimilar medicines - their use in the treatment of inflammatory bowel diseases. Position statement of the Working Group of the Polish National Consultant in Gastroenterology.

Biological medical products are drugs whose active components are produced only by living, genetically modified organisms or live cell cultures. Patents and exclusivity for most biopharmaceuticals has either expired or will expire soon, which enables biotechnological companies to introduce similar biological products. The problem of replacing a biological medicine with a biosimilar in the course of therapy remains open. In this statement, the Working Group of the Polish National Consultant in Gastroenterology, in the absence of data regarding bioequivalence in patients with inflammatory bowel disease, does not recommend switching from original biological medicine to its biosimilar analogue in the course of treatment in inflammatory disease patients; however, this may change after receiving the results of controlled studies regarding bioequivalence in this group.

IL-17+ regulatory T cells in the microenvironments of chronic inflammation and cancer.

Foxp3(+)CD4(+) regulatory T (Treg) cells inhibit immune responses and temper inflammation. IL-17(+)CD4(+) T (Th17) cells mediate inflammation of autoimmune diseases. A small population of IL-17(+)Foxp3(+)CD4(+) T cells has been observed in peripheral blood in healthy human beings. However, the biology of IL-17(+)Foxp3(+)CD4(+) T cells remains poorly understood in humans. We investigated their phenotype, cytokine profile, generation, and pathological relevance in patients with ulcerative colitis. We observed that high levels of IL-17(+)Foxp3(+)CD4(+) T cells were selectively accumulated in the colitic microenvironment and associated colon carcinoma. The phenotype and cytokine profile of IL-17(+)Foxp3(+)CD4(+) T cells was overlapping with Th17 and Treg cells. Myeloid APCs, IL-2, and TGF-ß are essential for their induction from memory CCR6(+) T cells or Treg cells. IL-17(+)Foxp3(+)CD4(+) T cells functionally suppressed T cell activation and stimulated inflammatory cytokine production in the colitic tissues. Our data indicate that IL-17(+)Foxp3(+) cells may be "inflammatory" Treg cells in the pathological microenvironments. These cells may contribute to the pathogenesis of ulcerative colitis through inducing inflammatory cytokines and inhibiting local T cell immunity, and in turn may mechanistically link human chronic inflammation to tumor development. Our data therefore challenge commonly held beliefs of the anti-inflammatory role of Treg cells and suggest a more complex Treg cell biology, at least in the context of human chronic inflammation and associated carcinoma.

[Impact of cigarette smoking on the clinical outcome of Crohn's disease]. / Wplyw palenia na przebieg kliniczny choroby Lesniowskiego-Crohna.

Cigarette smoking is a well known independent risk factor for a more severe course of Crohn's disease, but individual factors determining this impact are poorly known and it is not evident if smoking cessation is associated with an improvement in the disease activity. The aim of our study was to assess the factors determining the harmful impact of smoking in individuals with Crohn's disease. A total of 148 consecutive patients with Crohn's disease and Crohn's disease activity index < 200 were enrolled in a prospective 12-18 month study. Patients were classified into three groups as: current smokers, former smokers, and nonsmokers. Body mass index, alcohol consumption, oral contraceptive use and blood lipid levels were also recorded. The main outcome measure was the rate of fare-up. We observed the flare-up developement in 38% current smokers, versus 21% non-smokers and 26% former smokers. The relative risk of flare-up adjusted for confounding factors was 1.37 (1.09 +/- 1.96) in current smokers. Obesity, dyslipidaemia, and alcohol consumption had no significant effect. Current smoking, particularly heavy smoking, significantly increases the risk of flare-up in Crohn's disease patients. Former smokers have a risk similar to that of non-smokers.

Retrospective analysis of hospital admissions of patients with ulcerative colitis and Crohn's disease from semi-rural and rural regions in the Department of Gastroenterology in Lublin between 2000- 2006.

UNLABELLED: Inflammatory bowel disease (IBD), comprising of ulcerative (UC) colitis and Crohn's disease (CD), are chronic relapsing disorders of unknown etiology. The environmental factors in addition to genetic predisposition are thought to play an important role in the pathogenesis of these diseases. IBD was found to be more common in urban areas than in the rural environment. So far, there have been no reports of the frequency of IBD in Polish rural regions. The aim of the study was to describe the characteristics of IBD in patients from semi-rural and rural regions hospitalized in the Department of Gastroenterology of the Medical University of Lublin between 2000-2006. METHODS: A retrospective systematic search of clinical records, identifying cases of inflammatory bowel disease. RESULTS: In the 2000-2006 period of the study, 727 cases of IBD were recorded, of which 334 (46 % ) originated from semi-rural and rural regions. UC accounted for 69.2 % (231 patients) while CD for 30.8 % (103 patients). The total number of patients with IBD was higher in the last 3 years (435 patients), compared to 2000-2003 (292 patients). Demographic data, clinical presentation and the location of the disease in patients with IBD from rural and semi-rural regions are similar to patients from urban communities. CONCLUSION: The rise in hospital admission rates of patients with UC and CD from rural and semi-rural regions confirms the observation of an increasing incidence of IBD in areas, where these diseases were less common in the past.

[Pulmonary complications in patient with ulcerative colitis, treated with 5-aminosalicylic preparations]. / Powiklania pucne u chorego z wrzodziejacym zapaleniem jelita grubego, leczonego preparatami kwasu 5-aminosalicylowego.

Pulmonary complications in patients with ulcerative colitis treated with 5-aminosalicylic acid are infrequent adverse events. The authors present a 35-year-old man, taking sulfasalazine and mesalazine in whom pulmonary abnormalities resembling tuberculosis were observed during several months of therapy. Withdrawal of mesalazine resulted in complete resolution of lung injury. Patient is doing well on maintenance treatment with immunosuppressants

[Association of ulcerative colitis and lupus nephropathy--report of two cases]. / Skojarzenie wystepowania wrzodziejacego zapalenia jelita grubego z nefropatia toczniowa - analiza kliniczna dwóch przypadków chorobowych.

In the literature, there are descriptions of single cases of ulcerative colitis (UC) and systemic lupus erythematosus (SLE) coincidence in the same patient. The association of these two autoimmune diseases might be explained by etiopathogenetic factors that they have in common. Recently there have been two patients observed (48 and 31-year old) in whom two and three years (respectively) after diagnosing ulcerative colitis, symptoms of chronic nephropathy showed up (i.e. chronic glomerulonephritis and mild renal failure, respectively). Both of them fulfilled the ACR criteria for SLE. Clinical features and results of laboratory tests allowed the authors to recognize SLE with renal involvement (lupus nephritis in one and nephropathy in the course of secondary antyphospholipid syndrome in the other patient). In both cases drug-induced lupus like syndrome was taken into consideration in differential diagnosis (as both of the patients were previously treated with sulphasalazine) but clinical features and long lasting follow-up after sulphasalazine withdrawal allowed the authors to recognize association of SLE with concomitant nephropathy and UC. In the presented article the problems of differential diagnosis of drug-induced lupus-like syndromes from SLE coexisting with UC are discussed.