Martin Bortlik - Academia.edu (original) (raw)

Papers by Martin Bortlik

Research paper thumbnail of Efficacy of Intensification Regimes of Biologic Therapy in Patients With Inflammatory Bowel Disease and Secondary Non-Response: Experience of a Single Referral Centre

Research paper thumbnail of Telemedicine and inflammatory bowel disease – results of the IBD Assistant pilot project

Gastroenterologie a hepatologie, 2020

Research paper thumbnail of Tofacitinib induction efficacy and safety in ulcerative colitis at week 8 – results from clinical practice

Gastroenterologie a hepatologie, 2020

Research paper thumbnail of The efficacy of a non-leaching antibacterial central venous catheter - a prospective, randomized, double-blind study

Biomedical Papers, 2019

Background. Antimicrobial coatings of central venous catheters (CVC) have the potential to reduce... more Background. Antimicrobial coatings of central venous catheters (CVC) have the potential to reduce the risk of infectious complications. The aim of this study was to examine the efficacy of a catheter with a non-leaching antimicrobial coating against catheter colonization and bloodstream infections (BSI). Methods. The study was conducted in two centers using a prospective, randomized, double-blind and controlled design (680 intensive care patients; a protective CVC (Certofix® protect) or a standard CVC (Certofix®). Primary objectives were the rates of catheter colonization and BSI in the two groups. Other baseline demographics, APACHE II score, insertion site, location of CVC placement (ICU or theatre), indwelling time and length of ICU stay were comparable for both groups. Results. While the rate of catheter colonization between the coated and uncoated CVC (17.4% vs. 18.7%, P=0.7477) and the rate of microbiologically confirmed catheter associated infections were similar (1.4% vs. 1.9%, P=0.7521), the coated CVC showed a significantly lower incidence of BSI (2.0% vs. 6.5%, P=0.0081) and a significantly lower mean incidence of BSI per 1000 catheter days (3.2 vs. 8.3, P=0.0356). Conclusion. The non-leaching antibacterial coating of the protective catheter was effective in reducing the incidence of BSI but not the rate of catheter colonization. However, the incidence of BSI is a better surrogate marker for the risk of developing clinical signs of infection suggesting that use of the non-leaching protective catheter is effective in this regard. Trial number: ClinicalTrials.gov (ID: NCT00555282), https://clinicaltrials.gov/show/NCT00555282

Research paper thumbnail of Natural disease course of Crohn's disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study

Gut, Jan 23, 2018

The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with... more The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn's disease (CD). Patients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis. In total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Eu...

Research paper thumbnail of Deficiency of Adenomatous Polyposis Coli protein in sporadic colorectal adenomas and its associations with clinical phenotype and histology

World Journal of Gastroenterology, 2006

AIM: To evaluate the frequency of the loss of the Adenomatous Polyposis Coli (APC) protein and to... more AIM: To evaluate the frequency of the loss of the Adenomatous Polyposis Coli (APC) protein and to compare the APC status with the characteristics of colorectal adenomas. METHODS: Immunohistochemical analysis of the APC protein was performed on 118 adenomas and the results were compared with parameters of malignant potential, location of adenomas, macroscopic appearance and age of the patients. RESULTS: A complete loss of the APC protein was found in 28 (24%) adenomas, while 90 (76%) were APC positive. The mean size of adenomas was 13.5 ± 14.2 mm (95% CI 10.5-16.5) in APC-positive, and 13.8 ± 15.5 mm (95% CI 7.8-19.8) in APC-negative adenomas (P = 0.364). Statistical analysis revealed no difference between APC-positive and negative adenomas as to the histological type (P = 0.327) and grade of dysplasia (P =0.494). We found that even advanced adenomas did not differ in their APC status from the non-advanced tumors (P = 0.414). Finally, no difference was found when the location (P = 0.157), macroscopic appearance (P = 0.571) and age of patients (P = 0.438) were analysed and compared between both APC positive and negative adenomas.

Research paper thumbnail of Fecal zonulin is elevated in Crohn’s disease and in cigarette smokers

Practical Laboratory Medicine, 2017

Objectives: Human zonulin is a protein that increases permeability in the epithelial layer of the... more Objectives: Human zonulin is a protein that increases permeability in the epithelial layer of the small intestine by reversibly modulating the intercellular tight junctions. There is not sufficient information available about zonulin's participation in inflammatory bowel diseases (IBD). The aim of this study was therefore to investigate fecal and serum zonulin in IBD patients and its relation to the disease localization, behavior and smoking status. Design and methods: Forty IBD patients and forty healthy persons were examined for fecal and serum zonulin concentrations by competitive ELISA (DRG International Inc). Values were correlated to IBD type, localization and behavior, and smoking. Results: Serum and fecal zonulin were significantly higher in patients with Crohn's disease compared to ulcerative colitis (p = 0.038 for fecal zonulin, and p = 0.041 for serum zonulin concentrations). No association of serum or fecal zonulin was found with respect to IBD localization and behavior. The only difference was found with respect to smoking. Both the IBD cohort and healthy smokers showed significantly higher fecal zonulin levels (median 203 ng/mL) compared to non-smokers (median 35.8 ng/mL), p < 0.001. Conclusions: Fecal and serum zonulin levels are elevated in patients with active Crohn's disease but not with ulcerative colitis. High fecal zonulin levels in smokers irrespective of IBD point to the significant and undesirable up-regulation of gut permeability in cigarette smokers.

Research paper thumbnail of 515 Biosimilar Infliximab Is Effective and Safe in Inflammatory Bowel Disease Patients Naïve to Anti-TNF Therapy: A Tertiary Center Experience

Research paper thumbnail of P046 Pregnancy in Ibd Patients

Journal of Crohn's and Colitis Supplements, 2007

Background: Creating the patient' s database is necessary for availability of up to date informat... more Background: Creating the patient' s database is necessary for availability of up to date informations on the large group of IBD patients. Aim and method: 1. elucidate a current situation in the field of IBD in the Czech Republic; 2. ensure a prospective follow-up of patients; 3. allow a high-level cooperation with international institutions (e.g. ECCO); 4. offer a posibility to create compatible databases in each cooperating center. The database was set up on the basis of a cooperation between centers participating in the Czech IBD Working Group. In order to avoid many drawbacks that could arise during creation of a database, a well-proven Danish system (DCCD) was adopted and modified for our conditions. Results: The fundamentals of the Registry are as follows: 1. Every patient fulfilling the criteria of IBD can be entered. Simultaneously, retrospective data are collected. 2. Subsequently, all visits are documented using the standardized forms. Disease activity and therapy are the essential informations that are taken. Occasional events (e.g. surgery) are reported if happen. 3. The data are collected in a written and then digitalized. The identity of each patient can not be disclosed. 4. Each center can arbitrarily use it' s own data. When data from more centers will be used, each center must agree. 5. The Registry is funded by contributions from pharmaceutical companies. Another sources, like grants, or contributions from the Czech Society of Gastroenterology, will be requested. The Registry started in April 2006; since then, 388 IBD patients have been enrolled in 9 centers out of 18 planned. The descriptive data from the Registry will be presented biannually at the meetings of the Working Group. Conclusion: The Czech IBD Registry has recently been established. It is believed that it improves cooperation between Czech centers and extends possibilities of collaboration with foreign and international institutions.

Research paper thumbnail of 283 Deep Remission in Crohn's Disease Does Not Prevent Disease Relapse After Withdrawal of Anti-TNFa Therapy

Gastroenterology, 2015

the induction phase (0-2-6 weeks) are contradicting. Furthermore, the evolution of serum TNF duri... more the induction phase (0-2-6 weeks) are contradicting. Furthermore, the evolution of serum TNF during IFX induction has been sparsely studied. We investigated if serum markers of inflammation or drug exposure help in understanding what is driving PNR. Methods: We studied a cohort of 201 anti-TNF naive Crohn's disease (CD) patients who received IFX induction and had serum samples drawn at weeks 0, 2, 6 and 14. In all samples CRP, albumin, TNF, ATI (homogeneous mobility shift assay, Prometheus Laboratories Inc.) and TL (inhouse-developed ELISA) were assessed. PNR was defined as complete absence of clinical improvement at week 14 (physician global assessment). Results: The incidence of PNR was 8% (n=16). In univariate analysis, low albumin at w6 was associated with PNR (P=0.01, Mann Whitney test). We observed a significant increase of serum TNF after each IFX infusion (see figure 1) with medians at w0 and w14 of 1.6 pg/ml (IQR 0.9-2.7) and 7.7 pg/ml (IQR 4.5-11.5) respectively (P<0.0001, Kruskal-Wallis test). In patients with PNR, this rise in TNF (w14-w0) was significantly lower than in responders (P=0.03, Mann Whitney test). In an attempt to classify inflammation driven by TNF relative to the overall inflammation, we compared TNF/CRP ratio between both groups. A stepwise multiple logistic regression model identified albumin at w6 and TNF/CRP at w0 to be independent significant predictors (P<0.01) of PNR to infliximab at w14, with OR (95% CI) of 0.08 (0.02–0.37) and 3.10 (1.54–6.25) respectively. Conclusions: A high disease burden (represented by low albumin, high CRP and serum TNF) and not IFX TL or ATI (detectable in 21% of patients at w14) are the most important factors driving PNR to IFX. TNF and CRP separately did not predict primary response but a higher TNF/CRP ratio before start of IFX was predictive for PNR, contradicting the theorem that PNR might be due to 'nonTNF-driven' disease. Although the median TL at w14 between both groups did not differ significantly (P=0.48), this ratio indicates that the contribution of TNF in inflammation might even be higher in PNR before IFX start, and possibly demanding a higher loading dose. We further observed an increase of serum TNF after IFX and this was less in PNR. The mechanism behind this increase remains unclear. These results warrant further investigation for the role of disease burden in PNR to IFX.

Research paper thumbnail of DNA repair genetic polymorphisms and risk of colorectal cancer in the Czech Republic

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2008

This article was published in an Elsevier journal. The attached copy is furnished to the author f... more This article was published in an Elsevier journal. The attached copy is furnished to the author for non-commercial research and education use, including for instruction at the author's institution, sharing with colleagues and providing to institution administration. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit:

Research paper thumbnail of Endoscopic Evaluation of Surgically Altered Bowel in Patients with Inflammatory Bowel Diseases

Inflammatory Bowel Diseases, 2015

Patients with inflammatory bowel diseases often undergo surgical procedures for medically refract... more Patients with inflammatory bowel diseases often undergo surgical procedures for medically refractory disease or colitis associated dysplasia. Endoscopic evaluation of the surgically altered bowel is often needed to assess for disease recurrence, its severity, and for therapy. It is important to obtain and review the operative report and abdominal imaging before performing the endoscopy. Diagnostic and therapeutic endoscopy can be safely performed in most patients with inflammatory bowel disease with altered bowel anatomy under conscious sedation without fluoroscopy. Carefully planned stricture therapy with balloon dilation or needle knife stricturotomy can be performed for simple, short, and fibrotic strictures. A multidisciplinary approach involving a team of endoscopist, endoscopy nurse, colorectal surgeon, gastrointestinal pathologist, and gastrointestinal radiologist is important for a safe and effective endoscopy. We attempt to review the aspects that need consideration before the endoscopy, the technique of endoscopy, and briefly the therapies that can be performed during endoscopy of the bowel through an ileostomy, a colostomy, in the diverted large bowel or ileal pouch, and small bowel after stricturoplasty and bowel bypass surgery in patients with inflammatory bowel diseases.

Research paper thumbnail of P123 Risk Factors for Subsequent Intestinal Resections in Patients with Crohn's Disease

Journal of Crohn's and Colitis Supplements, 2008

years) underwent 85 ballon dilations for 65 symptomatic strictures which were located as follows:... more years) underwent 85 ballon dilations for 65 symptomatic strictures which were located as follows: colonic (15), ileocoecal valve (7), terminal ileum (26), ileocolonic anastomosis (17) and duodenum (1). Hydrostatic through the scope balloons were used with a diameter of 18 mm on inflation (Microvasive Rigiflex Ballons, Boston Scientific, Boston, MA, USA). Results: In 47 (94%) out of the 50 patients, balloon dilation was technically successfull. 12 (24%) patients needed surgery within a median period of 1,5 (0-20) months. Indications were procedure related perforation of the terminal ileum (1, uneventfull recovery), technical failure of the procedure (2), persistent or recurrent obstructive symptoms (4), newly developped enteroenteric or enterovesical fistula during follow-up (3) and patient' s wish despite of successfull endoscopic dilation (2). All patients who required surgery had de novo strictures at the ileocoecal valve (1) and in the terminal ileum (11). This means, that 14% of the strictures at the ileocoecal valve and 42% of the strictures in the terminal ileum needed surgical treatment. Strictures at all other locations were dilated successfully with a median observation period of 37 (1-96) months. During the follow-up period, 15 patients had a second, 8 patients a third and 1 patient a fifth balloon dilation. Conclusion: Endoscopic hydrostatic balloon dilation is an effective treatment of Crohn' s symptomatic strictures with a low complication rate. However, long term success seems to depend on the location of the stricture. In our study, only patients with strictures in the terminal ileum and at the ileocoecal valve required surgery.

Research paper thumbnail of Biological therapy in inflammatory bowel diseases: Access in Central and Eastern Europe

World Journal of Gastroenterology, 2015

Author contributions: Gulácsi L and Lakatos PL equally contributed to the paper and were involved... more Author contributions: Gulácsi L and Lakatos PL equally contributed to the paper and were involved in all activities including the design, epidemilogy and antTNF acess data collection, data analysis and drafting and revising the manuscript; Renz F and Péntek M were involved in data analysis and drafting and revising the manuscript; all other authors were involved in drafting and revising the manuscript.

Research paper thumbnail of Impaired Deoxyribonuclease I Activity in Patients with Inflammatory Bowel Diseases

Autoimmune Diseases, 2011

Background and Aims. Deoxyribonuclease I (DNaseI) is an endonuclease that facilitates chromatin b... more Background and Aims. Deoxyribonuclease I (DNaseI) is an endonuclease that facilitates chromatin breakdown and promotes susceptibility to autoimmune disorders. The aim of current study was to investigate serum DNase I activity in patients with inflammatory bowel diseases (IBD).Patients and Methods. A cohort of 110 IBD patients was evaluated, aged 35±12 years, 77 with Crohn's disease (CD) and 33 with ulcerative colitis (UC). 50 SLE patients and 50 healthy blood donors were examined as control groups.Results. DNase I activity in IBD patients was significantly lower than in healthy individuals, but higher than in SLE patients (P<.0001). Patients with UC showed higher DNase I activity than CD patients,P=.21. DNase I activity in female patients with IBD was significantly lower than in males,P=.024; however, no differences in DNase I activity were found in relation to gender in healthy individuals. DNase I activity has shown a strong negative correlation with the serum concentration...

Research paper thumbnail of P042 Pouch Surgery Offers a Good Quality of Life Despite Ongoing Problems

Journal of Crohn's and Colitis Supplements, 2007

Research paper thumbnail of NKX2-3 and IRGM variants are associated with disease susceptibility to IBD in Eastern European patients

World Journal of Gastroenterology, 2010

carried out genetic analysis and data analysis, collection and validation of patients, and manusc... more carried out genetic analysis and data analysis, collection and validation of patients, and manuscript preparation; Leniček M and Vítek L provided the DNA samples for the Czech patients and controls, and helped with manuscript preparation;

Research paper thumbnail of Variants of CARD15, TNFA and PTPN22 and susceptibility to Crohn’s disease in the Czech population: high frequency of the CARD15 1007fs

Tissue Antigens, 2008

Crohn's disease (CD) has been shown to be associated with the variants in the CARD15 gene as well... more Crohn's disease (CD) has been shown to be associated with the variants in the CARD15 gene as well as in other genes involved in the immune response. The frequencies of the variants profoundly differ among populations and so does the associated risk. We examined the associations of variants in the CARD15, TNFA and PTPN22 genes with pediatric-onset and adult-onset CD in the Czech population. Genotype, phenotype and allelic frequencies were compared between 345 patients with CD (136 pediatric-onset and 209 adult-onset patients) and 501 unrelated healthy controls. At least one minor allele of the CARD15 gene was carried by 46% patients and only 21% control subjects (OR ¼ 3.2, 95% CI 2.4-4.4). In a multiple logistic regression model, the strongest association with CD was found for the 1007fs variant (OR ¼ 4.6, 95% CI 3.0-7.0), followed by p.G908R (OR ¼ 2.9, 95% CI 1.5-5.7) and p.R702W (OR ¼ 1.7, 95% CI 1.0-2.9), while no independent association was found for the remaining variants in the CARD15 gene (p.268S, p.955I and p.289S), for the p.R620W variant in the PTPN22 gene or for the g.2308G>A variant in the TNFA gene. The age at CD onset was strongly modified by positivity for the 1007fs allele: it was present in 42% pediatric-onset and only 25% adult-onset patients. In conclusion, we report a high frequency of the minor allele of the CARD15 1007fs polymorphism in the Czech population and a strong effect of this allele on the age at disease onset.

Research paper thumbnail of P198 - Anti-infliximab antibodies in routine clinical practice – is it worth to assess them?

Journal of Crohn's and Colitis, 2009

Research paper thumbnail of P145 - Adalimumab in a clinical practice – experience with human anti TNF-α therapy in tertiary clinical center

Journal of Crohn's and Colitis, 2009

Patients and methods: Data of all patients with UC or CD on treatment with AZA due to steroid-dep... more Patients and methods: Data of all patients with UC or CD on treatment with AZA due to steroid-dependency for at least 12 months were recorded. Response was described as clinical remission free of steroids for at least 6 months during the first 12 months of starting AZA. Clinical data at diagnosis, at the beginning of AZA and during the follow-up were recorded. Smoking status was obtained from clinical story or for telephonic recall. Results: 163 patients (103 CD, 60 UC) were included. 55% of CD and 16% of UC patients were active smokers at the onset of AZA therapy. AZA was withdrawn for intolerance in 15% of them (20% of CD, 6% of UC). 72% of CD and 61% of UC patients achieved initial response. Tobacco did not influence on the time elapsed from diagnosis to AZA therapy, the initial response to AZA, the need for rescue therapies, or the development of penetrating or structuring complications (CD) or proximal extension (UC). However, CD patients who continued smoking required more courses of steroids during the follow-up. UC patients showed a lower incidence of AZA intolerance as compared to CD patients. Conclusions: Active smoking does not seem to influence AZA efficacy in steroid-dependent IBD.

Research paper thumbnail of Efficacy of Intensification Regimes of Biologic Therapy in Patients With Inflammatory Bowel Disease and Secondary Non-Response: Experience of a Single Referral Centre

Research paper thumbnail of Telemedicine and inflammatory bowel disease – results of the IBD Assistant pilot project

Gastroenterologie a hepatologie, 2020

Research paper thumbnail of Tofacitinib induction efficacy and safety in ulcerative colitis at week 8 – results from clinical practice

Gastroenterologie a hepatologie, 2020

Research paper thumbnail of The efficacy of a non-leaching antibacterial central venous catheter - a prospective, randomized, double-blind study

Biomedical Papers, 2019

Background. Antimicrobial coatings of central venous catheters (CVC) have the potential to reduce... more Background. Antimicrobial coatings of central venous catheters (CVC) have the potential to reduce the risk of infectious complications. The aim of this study was to examine the efficacy of a catheter with a non-leaching antimicrobial coating against catheter colonization and bloodstream infections (BSI). Methods. The study was conducted in two centers using a prospective, randomized, double-blind and controlled design (680 intensive care patients; a protective CVC (Certofix® protect) or a standard CVC (Certofix®). Primary objectives were the rates of catheter colonization and BSI in the two groups. Other baseline demographics, APACHE II score, insertion site, location of CVC placement (ICU or theatre), indwelling time and length of ICU stay were comparable for both groups. Results. While the rate of catheter colonization between the coated and uncoated CVC (17.4% vs. 18.7%, P=0.7477) and the rate of microbiologically confirmed catheter associated infections were similar (1.4% vs. 1.9%, P=0.7521), the coated CVC showed a significantly lower incidence of BSI (2.0% vs. 6.5%, P=0.0081) and a significantly lower mean incidence of BSI per 1000 catheter days (3.2 vs. 8.3, P=0.0356). Conclusion. The non-leaching antibacterial coating of the protective catheter was effective in reducing the incidence of BSI but not the rate of catheter colonization. However, the incidence of BSI is a better surrogate marker for the risk of developing clinical signs of infection suggesting that use of the non-leaching protective catheter is effective in this regard. Trial number: ClinicalTrials.gov (ID: NCT00555282), https://clinicaltrials.gov/show/NCT00555282

Research paper thumbnail of Natural disease course of Crohn's disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study

Gut, Jan 23, 2018

The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with... more The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn's disease (CD). Patients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis. In total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Eu...

Research paper thumbnail of Deficiency of Adenomatous Polyposis Coli protein in sporadic colorectal adenomas and its associations with clinical phenotype and histology

World Journal of Gastroenterology, 2006

AIM: To evaluate the frequency of the loss of the Adenomatous Polyposis Coli (APC) protein and to... more AIM: To evaluate the frequency of the loss of the Adenomatous Polyposis Coli (APC) protein and to compare the APC status with the characteristics of colorectal adenomas. METHODS: Immunohistochemical analysis of the APC protein was performed on 118 adenomas and the results were compared with parameters of malignant potential, location of adenomas, macroscopic appearance and age of the patients. RESULTS: A complete loss of the APC protein was found in 28 (24%) adenomas, while 90 (76%) were APC positive. The mean size of adenomas was 13.5 ± 14.2 mm (95% CI 10.5-16.5) in APC-positive, and 13.8 ± 15.5 mm (95% CI 7.8-19.8) in APC-negative adenomas (P = 0.364). Statistical analysis revealed no difference between APC-positive and negative adenomas as to the histological type (P = 0.327) and grade of dysplasia (P =0.494). We found that even advanced adenomas did not differ in their APC status from the non-advanced tumors (P = 0.414). Finally, no difference was found when the location (P = 0.157), macroscopic appearance (P = 0.571) and age of patients (P = 0.438) were analysed and compared between both APC positive and negative adenomas.

Research paper thumbnail of Fecal zonulin is elevated in Crohn’s disease and in cigarette smokers

Practical Laboratory Medicine, 2017

Objectives: Human zonulin is a protein that increases permeability in the epithelial layer of the... more Objectives: Human zonulin is a protein that increases permeability in the epithelial layer of the small intestine by reversibly modulating the intercellular tight junctions. There is not sufficient information available about zonulin's participation in inflammatory bowel diseases (IBD). The aim of this study was therefore to investigate fecal and serum zonulin in IBD patients and its relation to the disease localization, behavior and smoking status. Design and methods: Forty IBD patients and forty healthy persons were examined for fecal and serum zonulin concentrations by competitive ELISA (DRG International Inc). Values were correlated to IBD type, localization and behavior, and smoking. Results: Serum and fecal zonulin were significantly higher in patients with Crohn's disease compared to ulcerative colitis (p = 0.038 for fecal zonulin, and p = 0.041 for serum zonulin concentrations). No association of serum or fecal zonulin was found with respect to IBD localization and behavior. The only difference was found with respect to smoking. Both the IBD cohort and healthy smokers showed significantly higher fecal zonulin levels (median 203 ng/mL) compared to non-smokers (median 35.8 ng/mL), p < 0.001. Conclusions: Fecal and serum zonulin levels are elevated in patients with active Crohn's disease but not with ulcerative colitis. High fecal zonulin levels in smokers irrespective of IBD point to the significant and undesirable up-regulation of gut permeability in cigarette smokers.

Research paper thumbnail of 515 Biosimilar Infliximab Is Effective and Safe in Inflammatory Bowel Disease Patients Naïve to Anti-TNF Therapy: A Tertiary Center Experience

Research paper thumbnail of P046 Pregnancy in Ibd Patients

Journal of Crohn's and Colitis Supplements, 2007

Background: Creating the patient' s database is necessary for availability of up to date informat... more Background: Creating the patient' s database is necessary for availability of up to date informations on the large group of IBD patients. Aim and method: 1. elucidate a current situation in the field of IBD in the Czech Republic; 2. ensure a prospective follow-up of patients; 3. allow a high-level cooperation with international institutions (e.g. ECCO); 4. offer a posibility to create compatible databases in each cooperating center. The database was set up on the basis of a cooperation between centers participating in the Czech IBD Working Group. In order to avoid many drawbacks that could arise during creation of a database, a well-proven Danish system (DCCD) was adopted and modified for our conditions. Results: The fundamentals of the Registry are as follows: 1. Every patient fulfilling the criteria of IBD can be entered. Simultaneously, retrospective data are collected. 2. Subsequently, all visits are documented using the standardized forms. Disease activity and therapy are the essential informations that are taken. Occasional events (e.g. surgery) are reported if happen. 3. The data are collected in a written and then digitalized. The identity of each patient can not be disclosed. 4. Each center can arbitrarily use it' s own data. When data from more centers will be used, each center must agree. 5. The Registry is funded by contributions from pharmaceutical companies. Another sources, like grants, or contributions from the Czech Society of Gastroenterology, will be requested. The Registry started in April 2006; since then, 388 IBD patients have been enrolled in 9 centers out of 18 planned. The descriptive data from the Registry will be presented biannually at the meetings of the Working Group. Conclusion: The Czech IBD Registry has recently been established. It is believed that it improves cooperation between Czech centers and extends possibilities of collaboration with foreign and international institutions.

Research paper thumbnail of 283 Deep Remission in Crohn's Disease Does Not Prevent Disease Relapse After Withdrawal of Anti-TNFa Therapy

Gastroenterology, 2015

the induction phase (0-2-6 weeks) are contradicting. Furthermore, the evolution of serum TNF duri... more the induction phase (0-2-6 weeks) are contradicting. Furthermore, the evolution of serum TNF during IFX induction has been sparsely studied. We investigated if serum markers of inflammation or drug exposure help in understanding what is driving PNR. Methods: We studied a cohort of 201 anti-TNF naive Crohn's disease (CD) patients who received IFX induction and had serum samples drawn at weeks 0, 2, 6 and 14. In all samples CRP, albumin, TNF, ATI (homogeneous mobility shift assay, Prometheus Laboratories Inc.) and TL (inhouse-developed ELISA) were assessed. PNR was defined as complete absence of clinical improvement at week 14 (physician global assessment). Results: The incidence of PNR was 8% (n=16). In univariate analysis, low albumin at w6 was associated with PNR (P=0.01, Mann Whitney test). We observed a significant increase of serum TNF after each IFX infusion (see figure 1) with medians at w0 and w14 of 1.6 pg/ml (IQR 0.9-2.7) and 7.7 pg/ml (IQR 4.5-11.5) respectively (P<0.0001, Kruskal-Wallis test). In patients with PNR, this rise in TNF (w14-w0) was significantly lower than in responders (P=0.03, Mann Whitney test). In an attempt to classify inflammation driven by TNF relative to the overall inflammation, we compared TNF/CRP ratio between both groups. A stepwise multiple logistic regression model identified albumin at w6 and TNF/CRP at w0 to be independent significant predictors (P<0.01) of PNR to infliximab at w14, with OR (95% CI) of 0.08 (0.02–0.37) and 3.10 (1.54–6.25) respectively. Conclusions: A high disease burden (represented by low albumin, high CRP and serum TNF) and not IFX TL or ATI (detectable in 21% of patients at w14) are the most important factors driving PNR to IFX. TNF and CRP separately did not predict primary response but a higher TNF/CRP ratio before start of IFX was predictive for PNR, contradicting the theorem that PNR might be due to 'nonTNF-driven' disease. Although the median TL at w14 between both groups did not differ significantly (P=0.48), this ratio indicates that the contribution of TNF in inflammation might even be higher in PNR before IFX start, and possibly demanding a higher loading dose. We further observed an increase of serum TNF after IFX and this was less in PNR. The mechanism behind this increase remains unclear. These results warrant further investigation for the role of disease burden in PNR to IFX.

Research paper thumbnail of DNA repair genetic polymorphisms and risk of colorectal cancer in the Czech Republic

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2008

This article was published in an Elsevier journal. The attached copy is furnished to the author f... more This article was published in an Elsevier journal. The attached copy is furnished to the author for non-commercial research and education use, including for instruction at the author's institution, sharing with colleagues and providing to institution administration. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit:

Research paper thumbnail of Endoscopic Evaluation of Surgically Altered Bowel in Patients with Inflammatory Bowel Diseases

Inflammatory Bowel Diseases, 2015

Patients with inflammatory bowel diseases often undergo surgical procedures for medically refract... more Patients with inflammatory bowel diseases often undergo surgical procedures for medically refractory disease or colitis associated dysplasia. Endoscopic evaluation of the surgically altered bowel is often needed to assess for disease recurrence, its severity, and for therapy. It is important to obtain and review the operative report and abdominal imaging before performing the endoscopy. Diagnostic and therapeutic endoscopy can be safely performed in most patients with inflammatory bowel disease with altered bowel anatomy under conscious sedation without fluoroscopy. Carefully planned stricture therapy with balloon dilation or needle knife stricturotomy can be performed for simple, short, and fibrotic strictures. A multidisciplinary approach involving a team of endoscopist, endoscopy nurse, colorectal surgeon, gastrointestinal pathologist, and gastrointestinal radiologist is important for a safe and effective endoscopy. We attempt to review the aspects that need consideration before the endoscopy, the technique of endoscopy, and briefly the therapies that can be performed during endoscopy of the bowel through an ileostomy, a colostomy, in the diverted large bowel or ileal pouch, and small bowel after stricturoplasty and bowel bypass surgery in patients with inflammatory bowel diseases.

Research paper thumbnail of P123 Risk Factors for Subsequent Intestinal Resections in Patients with Crohn's Disease

Journal of Crohn's and Colitis Supplements, 2008

years) underwent 85 ballon dilations for 65 symptomatic strictures which were located as follows:... more years) underwent 85 ballon dilations for 65 symptomatic strictures which were located as follows: colonic (15), ileocoecal valve (7), terminal ileum (26), ileocolonic anastomosis (17) and duodenum (1). Hydrostatic through the scope balloons were used with a diameter of 18 mm on inflation (Microvasive Rigiflex Ballons, Boston Scientific, Boston, MA, USA). Results: In 47 (94%) out of the 50 patients, balloon dilation was technically successfull. 12 (24%) patients needed surgery within a median period of 1,5 (0-20) months. Indications were procedure related perforation of the terminal ileum (1, uneventfull recovery), technical failure of the procedure (2), persistent or recurrent obstructive symptoms (4), newly developped enteroenteric or enterovesical fistula during follow-up (3) and patient' s wish despite of successfull endoscopic dilation (2). All patients who required surgery had de novo strictures at the ileocoecal valve (1) and in the terminal ileum (11). This means, that 14% of the strictures at the ileocoecal valve and 42% of the strictures in the terminal ileum needed surgical treatment. Strictures at all other locations were dilated successfully with a median observation period of 37 (1-96) months. During the follow-up period, 15 patients had a second, 8 patients a third and 1 patient a fifth balloon dilation. Conclusion: Endoscopic hydrostatic balloon dilation is an effective treatment of Crohn' s symptomatic strictures with a low complication rate. However, long term success seems to depend on the location of the stricture. In our study, only patients with strictures in the terminal ileum and at the ileocoecal valve required surgery.

Research paper thumbnail of Biological therapy in inflammatory bowel diseases: Access in Central and Eastern Europe

World Journal of Gastroenterology, 2015

Author contributions: Gulácsi L and Lakatos PL equally contributed to the paper and were involved... more Author contributions: Gulácsi L and Lakatos PL equally contributed to the paper and were involved in all activities including the design, epidemilogy and antTNF acess data collection, data analysis and drafting and revising the manuscript; Renz F and Péntek M were involved in data analysis and drafting and revising the manuscript; all other authors were involved in drafting and revising the manuscript.

Research paper thumbnail of Impaired Deoxyribonuclease I Activity in Patients with Inflammatory Bowel Diseases

Autoimmune Diseases, 2011

Background and Aims. Deoxyribonuclease I (DNaseI) is an endonuclease that facilitates chromatin b... more Background and Aims. Deoxyribonuclease I (DNaseI) is an endonuclease that facilitates chromatin breakdown and promotes susceptibility to autoimmune disorders. The aim of current study was to investigate serum DNase I activity in patients with inflammatory bowel diseases (IBD).Patients and Methods. A cohort of 110 IBD patients was evaluated, aged 35±12 years, 77 with Crohn's disease (CD) and 33 with ulcerative colitis (UC). 50 SLE patients and 50 healthy blood donors were examined as control groups.Results. DNase I activity in IBD patients was significantly lower than in healthy individuals, but higher than in SLE patients (P<.0001). Patients with UC showed higher DNase I activity than CD patients,P=.21. DNase I activity in female patients with IBD was significantly lower than in males,P=.024; however, no differences in DNase I activity were found in relation to gender in healthy individuals. DNase I activity has shown a strong negative correlation with the serum concentration...

Research paper thumbnail of P042 Pouch Surgery Offers a Good Quality of Life Despite Ongoing Problems

Journal of Crohn's and Colitis Supplements, 2007

Research paper thumbnail of NKX2-3 and IRGM variants are associated with disease susceptibility to IBD in Eastern European patients

World Journal of Gastroenterology, 2010

carried out genetic analysis and data analysis, collection and validation of patients, and manusc... more carried out genetic analysis and data analysis, collection and validation of patients, and manuscript preparation; Leniček M and Vítek L provided the DNA samples for the Czech patients and controls, and helped with manuscript preparation;

Research paper thumbnail of Variants of CARD15, TNFA and PTPN22 and susceptibility to Crohn’s disease in the Czech population: high frequency of the CARD15 1007fs

Tissue Antigens, 2008

Crohn's disease (CD) has been shown to be associated with the variants in the CARD15 gene as well... more Crohn's disease (CD) has been shown to be associated with the variants in the CARD15 gene as well as in other genes involved in the immune response. The frequencies of the variants profoundly differ among populations and so does the associated risk. We examined the associations of variants in the CARD15, TNFA and PTPN22 genes with pediatric-onset and adult-onset CD in the Czech population. Genotype, phenotype and allelic frequencies were compared between 345 patients with CD (136 pediatric-onset and 209 adult-onset patients) and 501 unrelated healthy controls. At least one minor allele of the CARD15 gene was carried by 46% patients and only 21% control subjects (OR ¼ 3.2, 95% CI 2.4-4.4). In a multiple logistic regression model, the strongest association with CD was found for the 1007fs variant (OR ¼ 4.6, 95% CI 3.0-7.0), followed by p.G908R (OR ¼ 2.9, 95% CI 1.5-5.7) and p.R702W (OR ¼ 1.7, 95% CI 1.0-2.9), while no independent association was found for the remaining variants in the CARD15 gene (p.268S, p.955I and p.289S), for the p.R620W variant in the PTPN22 gene or for the g.2308G>A variant in the TNFA gene. The age at CD onset was strongly modified by positivity for the 1007fs allele: it was present in 42% pediatric-onset and only 25% adult-onset patients. In conclusion, we report a high frequency of the minor allele of the CARD15 1007fs polymorphism in the Czech population and a strong effect of this allele on the age at disease onset.

Research paper thumbnail of P198 - Anti-infliximab antibodies in routine clinical practice – is it worth to assess them?

Journal of Crohn's and Colitis, 2009

Research paper thumbnail of P145 - Adalimumab in a clinical practice – experience with human anti TNF-α therapy in tertiary clinical center

Journal of Crohn's and Colitis, 2009

Patients and methods: Data of all patients with UC or CD on treatment with AZA due to steroid-dep... more Patients and methods: Data of all patients with UC or CD on treatment with AZA due to steroid-dependency for at least 12 months were recorded. Response was described as clinical remission free of steroids for at least 6 months during the first 12 months of starting AZA. Clinical data at diagnosis, at the beginning of AZA and during the follow-up were recorded. Smoking status was obtained from clinical story or for telephonic recall. Results: 163 patients (103 CD, 60 UC) were included. 55% of CD and 16% of UC patients were active smokers at the onset of AZA therapy. AZA was withdrawn for intolerance in 15% of them (20% of CD, 6% of UC). 72% of CD and 61% of UC patients achieved initial response. Tobacco did not influence on the time elapsed from diagnosis to AZA therapy, the initial response to AZA, the need for rescue therapies, or the development of penetrating or structuring complications (CD) or proximal extension (UC). However, CD patients who continued smoking required more courses of steroids during the follow-up. UC patients showed a lower incidence of AZA intolerance as compared to CD patients. Conclusions: Active smoking does not seem to influence AZA efficacy in steroid-dependent IBD.