1. First-line anti-TNF agents, ustekinumab and vedolizumab perform similarly in Crohn' disease, but not in ulcerative colitisEva Supovec, Jurij Hanžel, Gregor Novak, Damjan Manevski, Borut Štabuc, David Drobne, 2025, original scientific article Abstract: Background: Real-word comparisons between first-line biologicals in inflammatory bowel disease (IBD) are scarce. Aims: The aim of this study is to compare drug persistence and patient reported outcome-2 (PRO-2) remission rates of first-line biological classes [anti-tumor necrosis factor (TNF) agents vs anti-integrin vedolizumab vs IL-12/23 inhibitor ustekinumab] in real life cohort. Methods: Individual level data of 946 adults (588 Crohn's disease and 358 ulcerative colitis) were retrieved from UR-CARE IBD platform. Adjusted drug survival curves using a pooled logistic model and PRO-2 remission rates for each class of biologicals were calculated and compared. Results: In Crohn's disease, no differences in drug survival were observed for anti-TNF agents vs vedolizumab vs ustekinumab as estimated survival with 95% confidence intervals were 0.81 (0.77-0.84) vs 0.89 (0.82-0.96) vs 0.88 (0.79-0.97) at year 1 and 0.52 (0.46-0.58) vs 0.58 (0.37-0.78) vs 0.58 (0.39-0.77) at year 4. In ulcerative colitis, however, anti-TNF agents had shorter drug survival than vedolizumab with estimated drug survival with 95% confidence intervals 0.60 (0.52-0.67) vs 0.76 (0.67-0.84) at year 1 and 0.37 (0.30-0.44) vs 0.50 (0.36-0.64) at year 4. No differences in PRO-2 remission rates were observed between drug classes in Crohn's disease (P = 0.95), but more patients enjoyed PRO-2 remission in ulcerative colitis treated with anti-TNF agents compared to vedolizumab (94.8 vs 78.9%, P = 0.002). Conclusion: Our real-world data suggest similar drug persistence and efficacy of first-line treatments with anti-TNF agents, vedolizumab and ustekinumab in Crohn's disease. In ulcerative colitis, however, drug persistence was higher for vedolizumab compared to anti-TNF agents, but on the cost of lower PRO-2 remission rates.
Keywords: anti-TNF agents, ustekinumab, vedolizumab
Published in DiRROS: 01.12.2025; Views: 290; Downloads: 99
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2. Free and bioavailable vitamin D are correlated with disease severity in acute pancreatitis : a single-center, prospective studyDarko Siuka, Matej Rakuša, Aleš Vodenik, Lana Vodnik Klun, Borut Štabuc, David Štubljar, David Drobne, Helena Matelič, Joško Osredkar, 2025, original scientific article Abstract: Acute pancreatitis (AP) is primarily caused by inflammation and immunological responses, both of which are regulated by vitamin D. The purpose of this study was to examine the correlation between the severity of AP and vitamin D levels, including its total, free, and bioavailable forms. Eighty individuals with AP were enrolled in this study. Serum levels of free 25(OH)D3, bioavailable 25(OH)D3, and total 25-hydroxyvitamin D 25(OH)D3 were assessed. The severity of the disease course was assessed by scoring systems (Revised Atlanta classification, Ranson score, CTSI). Vitamin D deficiency was common in AP patients, with 31.3% being categorized as deficient (<50 nmol/L) and 27.5% having a severe deficiency (<30 nmol/L). Compared to patients with adequate vitamin D status, those with lower vitamin D levels had a significantly higher risk of developing moderate-to-severe AP (44.7% vs. 14.3%, p = 0.029). Patients with severe vitamin D insufficiency were the only ones who experienced severe AP. Clinical outcomes showed similar correlations: patients with significant vitamin D deficiency had longer hospital stays (mean of 12.1 ± 5.3 days vs. 7.8 ± 3.4 days, p = 0.018) and higher rates of ICU admission (31.8% vs. 8.0%, p = 0.007). Low levels of total, free, and bioavailable vitamin D were significantly associated with the severity of AP and ICU admission. Free, bioavailable, and total vitamin D were correlated with the severity of acute pancreatitis. All severe cases occurred in patients with severe vitamin D deficiency. Given the observational design, these associations require confirmation in interventional or mechanistic studies.
Keywords: vitamin D deficiency, acute pancreatitis severity, free and bioavailable vitamin D, inflammation and immune response, clinical outcomes
Published in DiRROS: 25.11.2025; Views: 214; Downloads: 96
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3. A "crossomics" study analysing variability of different components in peripheral blood of health caucasoid individualsKristina Gruden, Matjaž Hren, Ana Herman, Andrej Blejec, Tanja Albrecht, Joachim Selbig, Chris Bauer, Jochannes Schuchardt, Michal Or-Guil, Klemen Zupančič, Urban Švajger, Borut Štabuc, Alojz Ihan, Andreja Nataša Kopitar, Maja Ravnikar, Miomir Knežević, Primož Rožman, Matjaž Jeras, 2012, original scientific article Abstract: Background: Different immunotherapy approaches for the treatment of cancer andautoimmune diseases are being developed and tested in clinical studies worldwide. Their resulting complex experimental data should be properly evaluated, therefore reliable normal healthy control baseline values are indispensable. Methodology/Principal Findings: To assess intra- and inter-individual variability of various biomarkers, peripheral blood of 16 age and gender equilibrated healthy volunteers was sampled on 3 different days within a period of one month. Complex ććcrossomicsćć analyses of plasma metabolite profiles, antibody concentrations and lymphocyte subset counts as well as whole genome expression profiling in CD4+T and NK cells were performed. Some of the observed age, gender and BMI dependences are in agreement with the existing knowledge, like negative correlation between sex hormone levels and age or BMI related increase in lipids and soluble sugars. Thus we can assume that the distribution of all 39.743 analysed markers is well representing the normal Caucasoid population. All lymphocyte subsets, 20% of metabolites and less than 10% of genes, were identified as highly variable in our dataset. Conclusions/Significance: Our study shows that the intra-individual variability was at least two-fold lower compared to the inter-individual one at all investigated levels, showing the importance of personalised medicine approach from yet another perspective.
Published in DiRROS: 04.03.2025; Views: 571; Downloads: 611
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4. Abbreviated 13C-mixed triglyceride breath test for detection of pancreatic exocrine insufficiency performs equally as standard 5-hour test in patients after gastrectomy performed for gastric cancerDarko Siuka, Kristina Kumer, Borut Štabuc, David Štubljar, David Drobne, Rado Janša, 2022, original scientific article Keywords: abbreviated 13C-mixed triglyceride breath test, pancreatic exocrine insufficiency, gastrectomy, faecal elastase, gastric cancer
Published in DiRROS: 25.07.2024; Views: 1128; Downloads: 329
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6. Sorafenib for the treatment of hepatocellular carcinoma : a single-centre real-world studyJurij Hanžel, Tajda Košir Božič, Borut Štabuc, Rado Janša, 2020, original scientific article Abstract: Background Sorafenib is an oral multi-kinase inhibitor used for the treatment of hepatocellular carcinoma. Its efficacy in randomised controlled trials was demonstrated in patients with well-preserved liver function and good functional status. In the real-world setting, treatment is often offered to patients outside these criteria. We therefore performed a single-centre real-world cohort study on the efficacy of sorafenib in patients with hepatocellular carcinoma. Patients and methods We identified all patients with hepatocellular carcinoma initiating treatment with sorafenib between January 2015 and January 2018. The primary endpoint was overall survival (OS) since starting sorafenib. Clinical and demographic variables associated with survival were studied. Results The median OS was 13.4 months (95% CI 8.2%18.6). Multivariable Cox%s regression identified worse ECOG performance status (HR 2.21; 95% CI 1.56%3.16; P < 0.0001), Child-Pugh class C (HR 52.4; 95% CI 3.20%859; P = 0.005) and absence of prior locoregional treatment (HR 2.30; 95% CI 1.37%3.86; P = 0.002) to be associated with increased mortality. Conclusions Careful selection of patients for treatment with sorafenib is of paramount importance to optimize outcomes.
Keywords: hepatocellular carcinoma, survival, sorafenib
Published in DiRROS: 12.07.2024; Views: 1086; Downloads: 617
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7. Dendritic cell profiles in the inflamed colonic mucosa predict the responses to tumor necrosis factor alpha inhibitors in inflammatory bowel diseaseNataša Smrekar, David Drobne, Lojze Šmid, Ivan Ferkolj, Borut Štabuc, Alojz Ihan, Andreja Nataša Kopitar, 2018, original scientific article Abstract: Background Dendritic cells play crucial roles in the control of inflammation and immune tolerance in the gut. We aimed to investigate the effects of tumor necrosis factor alpha (TNFa) inhibitors on intestinal dendritic cells in patients with inflammatory bowel disease and the potential role of intestinal dendritic cells in predicting the response to treatment. Patients and methods Intestinal biopsies were obtained from 30 patients with inflammatory bowel disease before and after treatment with TNFa inhibitors. The proportions of lamina propria dendritic cell phenotypes were analysed using flow cytometry. Disease activity was endoscopically assessed at baseline and after the induction treatment. Results At baseline, the proportion of conventional dendritic cells was higher in the inflamed mucosa (7.8%) compared to the uninflamed mucosa (4.5%) (p = 0.003), and the proportion of CD103+ dendritic cells was lower in the inflamed mucosa (47.1%) versus the uninflamed mucosa (57.3%) (p = 0.03). After 12 weeks of treatment, the proportion of conventional dendritic cells in the inflamed mucosa decreased from 7.8% to 4.5% (p = 0.014), whereas the proportion of CD103+ dendritic cells remained unchanged. Eighteen out of 30 (60%) patients responded to their treatment by week 12. Responders had a significantly higher proportion of conventional dendritic cells (9.16% vs 4.4%, p < 0.01) with higher expression of HLA-DR (median fluorescent intensity [MFI] 12152 vs 8837, p = 0.038) in the inflamed mucosa before treatment compared to nonresponders. Conclusions A proportion of conventional dendritic cells above 7% in the inflamed inflammatory bowel disease mucosa before treatment predicts an endoscopic response to TNFa inhibitors.
Keywords: inflammatory bowel disease, dendritic cells, colon cancer
Published in DiRROS: 02.07.2024; Views: 1017; Downloads: 652
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9. The influence of cytokine gene polymorphisms on the risk of developing gastric cancer in patients with Helicobacter pylori infectionDavid Štubljar, Samo Jeverica, Tomislav Jukić, Miha Skvarč, Tadeja Pintar, Bojan Tepeš, Rajko Kavalar, Borut Štabuc, Alojz Ihan, 2015, original scientific article Keywords: cytokine gene, gastric cancer, Helicobacter pylori infection
Published in DiRROS: 16.04.2024; Views: 1081; Downloads: 353
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10. Microsatellite instability in colorectal cancerMatej Horvat, Borut Štabuc, 2011, review article Abstract: Background. Colorectal cancer (CRC) is the third most common cancer in the world. In 75% CRC develops sporadically, in 25% hereditary or as a consequenceof inflammatory bowel disease. CRC carcinogenesis develops over many years. The cause of CRC in 85% is chromosomal instability (CIN) and in 15% microsatellite instability (MSI-H), where hereditary nonpolyposis colorectal cancer (HNPCC) represents 10-20%. Microsatellite sequences (MS) arerepeated sequences of short stretches of DNA all over the genome. Microsatellite stability (MSS) means MS are the same in each cell of an individual, whereas microsatellite instability (MSI-H) means MS differ in normal and cancer cells of an individual. The cause of MSI-H is a damaged mismatch repair mechanism (MMR), with the most important MMR proteins being MSH2, MLH1 and MSH6. Conclusions. MSI-H seems to be an important prognostic factor in CRC and an important predictive factor of CRC chemotherapeutic treatment efficacy. Clinical trials conducted until now have shown contradictory findings in different chemotherapeutic settings, adjuvant and palliative; therefore MSI-H is going to be the object of the future research. The future of cancer treatment is in the individualized therapy based on molecular characteristics of the tumour, such as MSI-H in CRC.
Published in DiRROS: 19.03.2024; Views: 1189; Downloads: 540
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