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Publikacije (112)

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L. Vork, Z. Mujagic, M. Drukker, D. Keszthelyi, J. Conchillo, M. Hesselink, J. van os, A. Masclee et al.

Confirming treatment response in clinical trials for irritable bowel syndrome (IBS) is challenging, due to the lack of biomarkers and limitations of the currently available symptom assessment tools. The Experience Sampling Method (ESM) might overcome these limitations by collecting digital assessments randomly and repeatedly during daily life. This study evaluated differences in change in abdominal pain between real‐time (ie, ESM) and retrospective (ie, Gastrointestinal Symptom Rating Scale [GSRS] and an end‐of‐day symptom diary) measurements, using data of an RCT on escitalopram vs placebo in patients with IBS and comorbid panic disorder.

L. Vork, D. Keszthelyi, Z. Mujagic, J. Kruimel, C. Leue, I. Pontén, H. Törnblom, M. Simrén et al.

End‐of‐day questionnaires, which are considered the gold standard for assessing abdominal pain and other gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS), are influenced by recall and ecological bias. The experience sampling method (ESM) is characterized by random and repeated assessments in the natural state and environment of a subject, and herewith overcomes these limitations. This report describes the development of a patient‐reported outcome measure (PROM) based on the ESM principle, taking into account content validity and cross‐cultural adaptation.

N. Srabović, A. Softič, Samra Hasanbašić, Adi Rifatbegović, Jasminka Mustedanagić, A. Smajlović, E. Dautović, Z. Muminović et al.

Due to better understanding complex immune-inflammatory responses following surgical injury, the aim of present study was to investigate the changes of VEGF and IL-6 levels in serum and seroma of invasive breast cancer patients after surgery and their correlation with breast cancer tumour expression of VEGF Samples from 20 breast cancer patients and 15 benign breast disease patients were included in the study. Immunohistochemical staining was used for determining VEGF expression in tissue samples from tumour, stromal and normal breast. Measuring VEGF and IL-6 levels was conducted by ELISA. Differences in VEGF expression between tumour and stroma (p=0,007) and between tumour and normal breast tissue were significant (p=0,0001), as well as differences in VEGF expression between stromal and normal breast tissue (p=0,004). Serum level of VEGF was higher in patients with breast cancer then in patients with benign breast disease, before surgery (p=0,023).VEGF was significantly elevated postoperatively in serum (p=0,009) and seroma (p=0,0001) in patients with breast cancer. Level of IL-6 was elevated after surgery in serum (p=0,015) and seroma (p=0,0001) in patients with breast cancer, as well as in serum of patients with benign breast disease (p=0,018). Significant correlation was found between seroma levels of VEGF and IL-6 in breast cancer patients (p=0,009). The findings suggest involvement of VEGF and IL-6 in physiological changes after breast cancer surgery. Normal 0 21 false false false BS-LATN-BA X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

L. Vork, Z. Z. Weerts, Z. Mujagic, J. Kruimel, M. Hesselink, J. Muris, D. Keszthelyi, D. Jonkers et al.

The Rome criteria for irritable bowel syndrome (IBS) have been revised and are expected to apply only to the subset of Rome III IBS subjects with abdominal pain as predominant symptom, occurring at least once a week. The aim of this study was to determine the percentage of Rome III IBS subjects that fulfills Rome IV criteria and to evaluate differences between Rome IV‐positive and Rome IV‐negative subjects.

A. V. Vila, F. Imhann, V. Collij, S. Jankipersadsing, Thomas Gurry, Z. Mujagic, A. Kurilshikov, M. Bonder et al.

E. Tigchelaar, Z. Mujagic, A. Zhernakova, M. Hesselink, Saskia Meijboom, C.W.M. Perenboom, A. Masclee, C. Wijmenga et al.

Diet is considered to be a key factor in symptom generation in Irritable Bowel Syndrome (IBS) and patients tend to exclude food products from their diet in pursue of symptom relief, which may impair diet quality.

Z. Mujagic, D. Jonkers, S. Ludidi, D. Keszthelyi, M. Hesselink, Z. Z. Weerts, R. N. Kievit, J. F. Althof et al.

Increased visceral sensitivity is observed in up to 60% of patients with Irritable Bowel Syndrome (IBS). Mucosal inflammation, altered neuroendocrine activity and intraluminal metabolic processes may contribute to the development of visceral hypersensitivity. Previously, we demonstrated that biomarkers, indicative for these biological processes, were altered in IBS patients compared to healthy controls. However, how these processes relate to visceral hypersensitivity is unknown.

P. de Vos, Z. Mujagic, B. de Haan, R. Siezen, P. Bron, M. Meijerink, J. Wells, A. Masclee et al.

Orally ingested bacteria interact with intestinal mucosa and may impact immunity. However, insights in mechanisms involved are limited. In this randomized placebo-controlled cross-over trial, healthy human subjects were given Lactobacillus plantarum supplementation (strain TIFN101, CIP104448, or WCFS1) or placebo for 7 days. To determine whether L. plantarum can enhance immune response, we compared the effects of three stains on systemic and gut mucosal immunity, by among others assessing memory responses against tetanus toxoid (TT)-antigen, and mucosal gene transcription, in human volunteers during induction of mild immune stressor in the intestine, by giving a commonly used enteropathic drug, indomethacin [non-steroidal anti-inflammatory drug (NSAID)]. Systemic effects of the interventions were studies in peripheral blood samples. NSAID was found to induce a reduction in serum CD4+/Foxp3 regulatory cells, which was prevented by L. plantarum TIFN101. T-cell polarization experiments showed L. plantarum TIFN101 to enhance responses against TT-antigen, which indicates stimulation of memory responses by this strain. Cell extracts of the specific L. plantarum strains provoked responses after WCFS1 and TIFN101 consumption, indicating stimulation of immune responses against the specific bacteria. Mucosal immunomodulatory effects were studied in duodenal biopsies. In small intestinal mucosa, TIFN101 upregulated genes associated with maintenance of T- and B-cell function and antigen presentation. Furthermore, L. plantarum TIFN101 and WCFS1 downregulated immunological pathways involved in antigen presentation and shared downregulation of snoRNAs, which may suggest cellular destabilization, but may also be an indicator of tissue repair. Full sequencing of the L. plantarum strains revealed possible gene clusters that might be responsible for the differential biological effects of the bacteria on host immunity. In conclusion, the impact of oral consumption L. plantarum on host immunity is strain dependent and involves responses against bacterial cell components. Some strains may enhance specific responses against pathogens by enhancing antigen presentation and leukocyte maintenance in mucosa. In future studies and clinical settings, caution should be taken in selecting beneficial bacteria as closely related strains can have different effects. Our data show that specific bacterial strains can prevent immune stress induced by commonly consumed painkillers such as NSAID and can have enhancing beneficial effects on immunity of consumers by stimulating antigen presentation and memory responses.

Z. Mujagic, D. Jonkers, A. Hungin, N. D. de Wit, K. Wensaas, M. Palka, Vico Leeters, J. Kruimel et al.

Background and objectives The majority of patients with irritable bowel syndrome (IBS) are diagnosed and treated in primary care. The aim of this study was to investigate the implementation of the Rome criteria in daily primary care clinical practice and adherence of general practitioners (GPs) to recommended diagnostic approaches for IBS. Patients and methods A survey consisting of 18 questions was distributed across 11 European countries and was used to assess GPs’ diagnostic approach of IBS, the use of Rome criteria in daily practice and GPs’ perspective on the aetiology of the disorder. Results Overall, 185 GPs completed the survey. In daily clinical practice, 32% of GPs reported that they usually make a positive diagnosis on the basis of symptoms only, whereas 36% of GPs reported regular use of the Rome criteria to diagnose IBS. Furthermore, 62% of the responders reported that they applied additional diagnostics, such as blood tests, 31% found it necessary to perform endoscopy to make a positive diagnosis of IBS and 29% referred patients with IBS to a specialist. Psychological factors were the most frequently selected potential aetiological factor of IBS (88% of GPs). Overall, 52% of GPs reported systematically including questions on psychological symptoms in the assessment of history of IBS. Conclusion Only about one-third of GPs regularly used the Rome criteria to diagnose IBS. In daily primary care practice, IBS largely remains a diagnosis of exclusion. This has implications in terms of GPs’ specialty training and questions the applicability of IBS guidelines in daily care, which advocate an early, positive, symptom-based diagnosis.

E. Wilms, D. Jonkers, D. Keszthelyi, Z. Mujagic, L. Vork, Z. Z. Weerts, J. Kruimel, F. Troost et al.

M. Bonder, A. Kurilshikov, E. Tigchelaar, Z. Mujagic, F. Imhann, A. V. Vila, Patrick Deelen, T. Vatanen et al.

Agnieszka Baranska, Z. Mujagic, A. Smolinska, J. Dallinga, Daisy Jonkers, E. Tigchelaar, J. Dekens, A. Zhernakova et al.

The diagnosis of irritable bowel syndrome (IBS) is challenging because of its heterogeneity and multifactorial pathophysiology. No reliable biomarkers of IBS have been identified so far.

Z. Mujagic, E. Tigchelaar, A. Zhernakova, Thomas Ludwig, J. Ramiro-García, A. Barańska, M. Swertz, A. Masclee et al.

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