1. Priporočila za nadomeščanje holekalciferola (vitamina D3) v obdobjih respiratornih okužb in za nadomeščanje holekalciferola pri posameznikih s COVID-19Marija Pfeifer, Darko Siuka, Igor Pravst, Alojz Ihan, 2020, elaborat, predštudija, študija Ključne besede: vsebnost vitaminov pri ljudeh, vitamin D, vpliv pomanjkanja na respiratorna obolenja, priporočila
Objavljeno v DiRROS: 15.12.2025; Ogledov: 142; Prenosov: 51
 Celotno besedilo (790,07 KB)
Gradivo ima več datotek! Več... |
2. Gene therapy of rare diseases as a milestone in medicine : overview of the field and report on initial experiences in SloveniaUrh Grošelj, Marko Kavčič, Ana Drole Torkar, Jan Kafol, Duško Lainšček, Roman Jerala, Matjaž Sever, Samo Zver, Gregor Serša, Maja Čemažar, Primož Strojan, Aleš Grošelj, Mojca Žerjav-Tanšek, Špela Miroševič, Simona Ivančan, Tomaž Prelog, David Gosar, Jasna Oražem, Matej Mlinarič, Sara Bertok, Jernej Kovač, Jana Kodrič, Saba Battelino, Marko Pokorn, Alojz Ihan, Janez Jazbec, Tadej Battelino, Damjan Osredkar, 2025, pregledni znanstveni članek Povzetek: Gene therapy has transitioned from a long-awaited promise to a clinical reality, offering transformative treatments for rare congenital diseases and certain cancers, which have a significant impact on patients’ lives. Current approaches focus on gene replacement therapy, either in vivo or ex vivo, mostly utilizing viral vectors to deliver therapeutic genes into target cells. However, refining these techniques is essential to overcome challenges and complications associated with gene therapy to ensure long-term safety and efficacy. Slovenia has witnessed significant advancements in this field since 2018, marked by successful gene therapy trials and treatments for various rare diseases. Significant strides have been made in the field of gene therapy in Slovenia, treating patients with spinal muscular atrophy and rare metabolic disorders, including the pioneering work on CTNNB1 syndrome. Additionally, immune gene therapy, exemplified by IL-12 adjuvant therapy for cancer, has been a focus of research in Slovenia. Through patient-centred initiatives and international collaborations, researchers in Slovenia are advancing preclinical research and clinical trials, paving the way for accessible gene therapies. Establishing clinical infrastructure and genomic diagnostics for rare diseases is crucial for gene therapy implementation. Efforts in this regard in Slovenia, including the establishment of a Centre for Rare Diseases, Centre for the Technologies of Gene and Cell Therapy, and rapid genomic diagnostics, demonstrate a commitment to comprehensive patient care. Despite the promises of gene therapy, challenges remain, including cost, distribution, efficacy, and long-term safety. Collaborative efforts are essential to address these challenges and ensure equitable access to innovative therapies for patients with rare diseases.
Ključne besede: gene therapy, rare genetic diseases, Slovenia, CAR-T cells, cancer, immune gene therapy
Objavljeno v DiRROS: 04.12.2025; Ogledov: 160; Prenosov: 124
Celotno besedilo (2,18 MB)
Gradivo ima več datotek! Več... |
3. Sequencing of chemotherapy in total neoadjuvant treatment for rectal cancer does not predict radiation-induced lymphopeniaMiha Oražem, Vaneja Velenik, Alojz Ihan, 2025, izvirni znanstveni članek Povzetek: Radiation-induced lymphopenia (RIL) is associated with an increased risk of death in solid tumors, including rectal cancer. The aim of this study was to determine whether the sequencing of chemotherapy in total neoadjuvant treatment (TNT) for rectal cancer predicts the development of RIL. Patients and methods We analyzed acute hematologic toxicity data from 53 patients who underwent TNT for locally or locoregionally advanced rectal cancer between July 2022 and April 2023. Twenty-eight patients received induction chemotherapy with capecitabine and oxaliplatin [CAPOX], and 25 received consolidation chemotherapy (6 cycles of CAPOX in both groups). The chemoradiation protocol consisted of Volumetric Modulated Arc Therapy with Simultaneous Integrated Boost Radiotherapy (VMAT-SIB RT) up to 48.4 Gy in 22 fractions, concomitantly with capecitabine twice a day (lat. bis in die, BID). The Mann-Whitney U test was performed to compare RIL between the two patient groups. Pelvic bone marrow was contoured as a non-limiting organ-at-risk to assess the received dose, and binary logistic regression was used to determine whether RIL depends on V5Gy~V42Gy or the planning target volume (PTV) size. Results Thirty-four patients (64.2%) developed RIL of any grade, which was not significantly associated with either the induction or consolidation chemotherapy TNT regimen (Wald = 3.159, p = 0.076). No significant differences were found in neutrophil counts or the neutrophil-to-lymphocyte ratio. In the logistic regression model predicting the likelihood of RIL, two variables were statistically significant: V10Gy (Wald = 4.366, p = 0.037) and V30Gy (Wald = 6.084, p = 0.014). These results indicate that V10Gy< 71% and V30Gy< 26.6% may reduce the likelihood of developing RIL. Conclusions In our study, the sequencing of chemotherapy in TNT for rectal cancer did not predict the development of RIL. However, the incidence of RIL may be reduced by applying RT dosimetric constraints to the pelvic bone marrow.
Ključne besede: radiation-induced lymphopenia, rectal cancer, total neoadjuvant treatment
Objavljeno v DiRROS: 26.11.2025; Ogledov: 155; Prenosov: 47
Celotno besedilo (508,29 KB) |
4. Safety, long-term effectiveness, and immunogenicity of varicella vaccination in children with juvenile idiopathic arthritis treated with biologic therapyMaša Bizjak, Jakob Peterlin, Tadej Avčin, Miroslav Petrovec, Alojz Ihan, Mojca Zajc Avramovič, Gašper Markelj, Tina Vesel, Veronika Osterman, Jerneja Ahčan, Helena Mole, Katja Dejak Gornik, Alenka Biteznik, Sara Jevnikar, Larisa Janžič, Miha Bajc, Andreja Nataša Kopitar, Nataša Toplak, 2025, izvirni znanstveni članek Povzetek: Objective: To evaluate safety, long-term effectiveness and immunogenicity of varicella vaccination in children with JIA, treated with biologic disease-modifying antirheumatic drugs (bDMARDs). Methods: This is a prospective case-control study. VZV-naive patients with JIA on selected bDMARDs (TNFi, IL-6 and IL-1 inhibitors), who were at risk for contracting varicella, had stable disease and normal values of immunoglobulins and lymphocyte populations, were vaccinated against varicella. Adverse events (AEs) and disease activity were followed after vaccination. VZV-specific humoral (VZV-IgG) and cell-mediated immunity (VZV-CMI) were measured at predetermined time points after vaccination by Liaison and intracellular cytokine staining, respectively. Two healthy control (HC) groups comprised 52 healthy children after varicella vaccination and 69 healthy children after varicella infection. Results: 17 patients were vaccinated against varicella (12 on TNFi, 4 on IL-6 inhibitors and 1 on IL-1 inhibitor), of whom 14 patients received both the first and second dose on bDMARDs. No vaccine-strain infections or other serious AEs occurred after vaccination. Disease activity increased in 3/17 (18 %) patients following vaccination. Four out of 17 (24 %) patients developed mild breakthrough varicella (BV) 4 months-4.5 years after vaccination, and none of the HC. Fourteen out of 17 (82 %) patients and 50/52 (96 %) vaccinated HC were seropositive after second vaccination and 8/11 (72 %) patients and 42/43 (98 %) vaccinated HC developed VZV-CMI, which persisted longer compared to VZV-IgG. Patients presented lower antibody levels compared to HC. The rate of VZV-IgG decline was comparable between patients and HC after vaccination or infection. Five patients received the third vaccine dose due to primary or secondary vaccine failure, and none of them developed BV. Conclusions: Varicella vaccination was safe and largely immunogenic in our cohort of JIA patients treated with bDMARDs. Although the vaccination was not always fully effective, it prevented severe disease in all vaccinated patients.
Ključne besede: varicella vaccination, juvenile idiopathic arthritis, biologic therapy, anti-cytokine therapy
Objavljeno v DiRROS: 13.11.2025; Ogledov: 200; Prenosov: 92
Celotno besedilo (2,05 MB)
Gradivo ima več datotek! Več... |
5. Exhausted natural killer cells in adult IgA vasculitisMatija Bajželj, Emanuela Senjor, Nika Boštic, Matjaž Hladnik, Snežna Sodin-Šemrl, Milica Perišić, Janko Kos, Alojz Ihan, Alojzija Hočevar, Andreja Nataša Kopitar, Katja Lakota, 2025, izvirni znanstveni članek Povzetek: Introduction. IgA vasculitis nephritis (IgAVN) manifests in up to 84% of adult patients with IgA vasculitis (IgAV) and is associated with an elevated risk of progression to chronic kidney failure. The underlying pathogenic mechanism of adult IgAVN in leukocytes remain largely uncharacterised. Although natural killer (NK) cells were investigated in paediatric IgAV, their specific role in the pathogenesis of adult IgAV has yet to be elucidated. Methods. RNA sequencing of leukocytes from adult IgAV patients and healthy controls (HC) was performed. NK cells’ cytotoxicity was assessed using calcein-AM stained K562 cells, and exocytosis was measured by LAMP-1/CD107a expression. Intracellular perforin and granzyme B were analyzed via flow cytometry, and cytokine secretion was measured by Luminex xMAP. Interferon-induced genes were validated with qPCR. Results. Principal component analysis (PCA) of leukocyte gene expression profiles distinguished IgAV patients from HC. Pathway enrichment analysis showed differences in patients’ subsets - Interferon signalling Reactome pathway was observed only in sample from patients with skin-limited IgAV (sl-IgAV) and was confirmed by increased expression of interferon-induced genes using qPCR. Only in samples from IgAVN patients enrichment of NK cell-mediated cytotoxicity KEGG pathway was found. NK cells from IgAVN patients showed significantly decreased cytotoxicity compared to samples from sl-IgAV patients (p = 2.53 × 10− 2). The % of CD107a+-NK cells significantly increased after stimulation in HC (p = 9.7 × 10− 3) and in sl-IgAV patient samples (p = 2.21 × 10− 2) while only a minor increase was observed in samples of IgAVN patients. IgAVN patients exhibited a decreased % of perforin+ NK cells compared to HC. Following phytohemagglutinin (PHA)/interleukin (IL)-2 stimulation, a significant reduction in intracellular perforin level was observed in HC (p = 2.53 × 10− 2), but not in IgAVN patients NK cells. Interferon (IFN)-ϒ and macrophage inflammatory protein (MIP)-1β were significantly decreased in NK cell culture supernatants from IgAVN patients (p = 2.64 × 10− 2 and p = 2.65 × 10− 2 respectively). Conclusion. Patients with IgAVN exhibited impaired cytotoxic and immunomodulatory functions of NK cells, along with a marked absence of interferon signaling in PBMCs. Further studies are needed to confirm if discrimination of patient subsets based on leukocyte samples might be of clinical use and if deregulated NK function might contribute to the pathogenesis of nephritis in adult IgAV.
Ključne besede: immunoglobulin A, IgAVN, IgA vasculitis, RNA sequencing, kidney diseases, immunoglobulins, killer cells, adults
Objavljeno v DiRROS: 12.11.2025; Ogledov: 214; Prenosov: 91
Celotno besedilo (1,65 MB)
Gradivo ima več datotek! Več... |
6. |
7. 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, izvirni znanstveni članek Povzetek: 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.
Objavljeno v DiRROS: 04.03.2025; Ogledov: 542; Prenosov: 579
Celotno besedilo (558,83 KB)
Gradivo ima več datotek! Več... |
8. 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, izvirni znanstveni članek Povzetek: 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.
Ključne besede: inflammatory bowel disease, dendritic cells, colon cancer
Objavljeno v DiRROS: 02.07.2024; Ogledov: 972; Prenosov: 636
Celotno besedilo (909,08 KB)
Gradivo ima več datotek! Več... |
9. Dynamic susceptibility contrast enhanced (DSC) MRI perfusion and plasma cytokine levels in patients after tonic-clonic seizuresTatjana Filipovič, Katarina Šurlan Popović, Alojz Ihan, David B. Vodušek, 2017, izvirni znanstveni članek Povzetek: Background Inflammatory events in brain parenchyma and glial tissue are involved in epileptogenesis. Blood concentration of cytokines is shown to be elevated after tonic-clonic seizures. As a result of inflammation, blood-brain barrier leakage occurs. This can be documented by imaging techniques, such is dynamic susceptibility contrast enhanced (DSC) MRI perfusion. Our aim was to check for postictal brain inflammation by studying DSC MRI perfusion and plasma level of cytokines. We looked for correlations between number and type of introducing seizures, postictal plasma level of cytokines and parameters of DSC MRI perfusion. Furthermore, we looked for correlation of those parameters and course of the disease over one year follow up. Patients and methods We prospectively enrolled 30 patients, 8%24 hours after single or repeated tonic-clonic seizures. Results 25 of them had normal perfusion parameters, while 5 had hyperperfusion. Patients with hyperperfusion were tested again, 3 months later. Two of 5 had hyperperfusion also on control measurements. Number of index seizures negatively correlated with concentration of proinflammatory cytokines IL-10, IFN-[gamma] and TNF-[alpha] in a whole cohort. In patients with hyperperfusion, there were significantly lower concentrations of antiinflammatory cytokine IL-4 and higher concentrations of proinflammatory TNF-[alpha]. Conclusions Long lasting blood- brain barrier disruption may be crucial for epileptogenesis in selected patients.
Ključne besede: cytokines, blood-brain barrier, tonic-clonic seizures
Objavljeno v DiRROS: 03.06.2024; Ogledov: 988; Prenosov: 620
Celotno besedilo (676,20 KB)
Gradivo ima več datotek! Več... |
10. Perioperative increase in neutrophil CD64 expression is an indicator for intra-abdominal infection after colorectal cancer surgeryMilena Kerin-Povšič, Bojana Beović, Alojz Ihan, 2017, izvirni znanstveni članek Povzetek: Colorectal surgery is associated with a high incidence of postoperative infections. Early clinical signs are difficult to distinguish from the systemic inflammatory response related to surgical trauma. Timely diagnosis may significantly improve the outcome. The objective of this study was to compare a new biomarker index CD64 for neutrophils (iCD64n) with standard biomarkers, white blood cell (WBC) count, neutrophil/lymphocyte ratio (NLR), C-reactive protein (CRP) and procalcitonin (PCT) for the early detection of postoperative infection. Methods. The prospective study included 200 consecutive patients with elective colorectal cancer surgery. Postoperative values of biomarkers from the postoperative day (POD) 1 to POD5 were analysed by the receiver operating characteristic (ROC) analysis to predict infection. The Cox regression model and the Kaplan-Meier method were used to assess prognostic factors and survival. Results. The increase of index CD64n (iCD64n) after surgery, expressed as the ratio iCD64n after/before surgery was a better predictor of infection than its absolute value. The best 30-day predictors of all infections were CRP on POD4 (AUC 0.72, 99% CI 0.61%0.83) and NLR on POD5 (AUC 0.69, 99% CI 0.57%0.80). The best 15-day predictors of organ/ space surgical site infection (SSI) were the ratio iCD64n on POD1 (AUC 0.72, 99% CI 0.58%0.86), POD3 (AUC 0.73, 99% CI 0.59%0.87) and CRP on POD3 (AUC 0.72, 99% CI 0.57%0.86), POD4 (AUC 0.79, 99% CI 0.64%0.93). In a multivariate analysis independent risk factors for infections were duration of surgery and perioperative transfusion while the infection itself was identified as a risk factor for a worse long-term survival. Conclusions. The ratio iCD64n on POD1 is the best early predictor of intra-abdominal infection after colorectal cancer surgery. CRP predicts the infection with the same predictive value on POD3.
Ključne besede: colorectal surgery, index CD64n, postoperative infection
Objavljeno v DiRROS: 10.05.2024; Ogledov: 1234; Prenosov: 380
Celotno besedilo (666,38 KB) |
