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1.
Sorafenib for the treatment of hepatocellular carcinoma : a single-centre real-world study
Jurij Hanžel, Tajda 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: 22; Downloads: 17
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2.
Synergetic boost of functional properties near critical end points in antiferroelectric systems
Vida Jurečič, Lovro Fulanović, Jurij Koruza, Vid Bobnar, Nikola Novak, 2023, original scientific article

Abstract: The increase of the dielectric permittivity with an electric field and enhanced energy storage properties make antiferroelectrics very attractive for high-power electronic applications needed in emerging green energy technologies and neuromorphic computing platforms. Their exceptional functional properties are closely related to the electric field-induced antiferroelectric↔ferroelectric phase transition, which can be driven toward a critical end point by manipulation with an external electric field. The critical fluctuation of physical properties at the critical end point in ferroelectrics is a promising approach to improve their functional properties. Here, we demonstrate the existence of two critical end points in antiferroelectric ceramics with a ferroelectric-antiferroelectric-paraelectric phase sequence, using the model system Pb 0.99 Nb 0.02 [ ( Zr 0.57 Sn 0.43 ) 0.92 Ti 0.08 ] 0.98 O 3 . The critical fluctuation of the dielectric permittivity in the proximity of the antiferroelectric-to-paraelectric critical end point is responsible for the strong enhancement of the dielectric tunability (by a factor of > 2 ) measured at ≈ 395 K. The enhancement of the energy storage density at ≈ 370 K is related to the proximity of the ferroelectric-to-antiferroelectric critical end point. These findings open possibilities for material design and pave the way for the next generation of high-energy storage materials.
Keywords: electronic applications, high-power electronic, green energy, electric field
Published in DiRROS: 10.07.2024; Views: 38; Downloads: 28
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Exploring the safety of cannabidiol (CBD) : a comprehensive in vitro evaluation of the genotoxic and mutagenic potential of a CBD isolate and extract from Cannabis sativa L
Alja Štern, Matjaž Novak, Katja Kološa, Jurij Trontelj, Sonja Žabkar, Tjaša Šentjurc, Metka Filipič, Bojana Žegura, 2024, original scientific article

Abstract: Cannabidiol (CBD), a naturally occurring cyclic terpenoid found in Cannabis sativa L., is renowned for its diverse pharmacological benefits. Marketed as a remedy for various health issues, CBD products are utilized by patients as a supplementary therapy or post-treatment failure, as well as by healthy individuals seeking promised advantages. Despite its widespread use, information regarding potential adverse effects, especially genotoxic properties, is limited. The present study is focused on the mutagenic and genotoxic activity of a CBD isolate (99.4 % CBD content) and CBD-rich Cannabis sativa L extract (63.6 % CBD content) in vitro. Both CBD samples were non-mutagenic, as determined by the AMES test (OECD 471) but exhibited cytotoxicity for HepG2 cells (~IC50 (4 h) 26 µg/ml, ~IC50 (24 h) 6–8 µg/ml, MTT assay). Noncytotoxic concentrations induced upregulation of genes encoding metabolic enzymes involved in CBD metabolism, and CBD oxidative as well as glucuronide metabolites were found in cell culture media, demonstrating the ability of HepG2 cells to metabolize CBD. In this study, the CBD samples were found non-genotoxic. No DNA damage was observed with the comet assay, and no influence on genomic instability was observed with the cytokinesis block micronucleus and the γH2AX and p-H3 assays. Furthermore, no changes in the expression of genes involved in genotoxic stress response were detected in the toxicogenomic analysis, after 4 and 24 h of exposure. Our comprehensive study contributes valuable insights into CBD’s safety profile, paving the way for further exploration of CBD’s therapeutic applications and potential adverse effects.
Keywords: cannabidiol, CBD, metabolism, cytotoxicity, genotoxicity, mutagenicity
Published in DiRROS: 09.07.2024; Views: 35; Downloads: 23
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High burden of clonal mast cell disorders and hereditary ▫$α-tryptasemia$▫ in patients who need Hymenoptera venom immunotherapy
Peter Korošec, Gunter Sturm, Jonathan J. Lyons, Tinkara Pirc Marolt, Manca Svetina, Mitja Košnik, Mihaela Zidarn, Mark Kačar, Nina Frelih, Nika Lalek, Ajda Demšar Luzar, Samo Zver, Matevž Škerget, Ewa Czarnobilska, Wojciech Dyga, Sanja Popović-Grle, Miroslav Samaržija, Lisa Arzt-Gradwohl, Urban Čerpes, Grzegorz Porebski, Branko Pevec, Eva Schadelbauer, Peter Kopač, Julij Šelb, Matija Rijavec, 2024, original scientific article

Abstract: Background In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the long-term effectiveness of VIT. Methods 1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms. Results 285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% [n = 207 of 610] with Ring-Messmer grade 3–4 vs. 11% [n = 78 of 709] with Grade 1–2; p < .0001), whereas only 1.3% (n = 2 of 152) of controls with LLR and none with asymptomatic sensitization (n = 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% [n = 207] in Grade 3–4 vs. 0.001% [n = 78] in Grade 1–2; p < .0001), and the majority had normal baseline serum tryptase levels (69% [n = 196 of 285]). All KIT p.D816V-positive individuals (n = 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p < .01), and remarkably, 31.0% (n = 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p < .01). Conclusions By employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT.
Keywords: anaphylaxis, hereditary α-tryptasemia, hypersensitivity, immunotherapy, mast cell, mastocytosis, venom
Published in DiRROS: 17.06.2024; Views: 133; Downloads: 78
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Lung scintigraphy in the diagnosis of pulmonary embolism : current methods and interpretation criteria in clinical practice
Ajda Skarlovnik, Damjana Hrastnik, Jurij Fettich, Marko Grmek, 2014, original scientific article

Keywords: pljučna embolija, diagnostika, scintigrafija
Published in DiRROS: 16.04.2024; Views: 249; Downloads: 104
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9.
Incidental uptake of 18F-fluorocholine (FCH) in the head or in the neck of patients with prostate cancer
Marina Hodolič, Jurij Fettich, 2014, original scientific article

Abstract: Background. Positron emission tomography-computed tomography (PET/CT) with 18F-fluorocholine (FCH) is routinely performed in patients with prostate cancer. In this clinical context, foci of FCH uptake in the head or in the neck were considered as incidentalomas, except for those suggestive of multiple bone metastases. Case reports. In 8 patients the incidental focus corresponded to a benign tumour. The standard of truth was histologyin two cases, correlative imaging with MRI in four cases, 99mTc-SestaMIBI scintigraphy, ultrasonography and biochemistry in one case and biochemistry including PTH assay in one case. The final diagnosis of benign tumoursconsisted in 3 pituitary adenomas, 2 meningiomas, 2 hyperfunctioning parathyroid glands and 1 thyroid adenoma. Malignancy was proven histologically in 2 other patients: 1 papillary carcinoma of the thyroid and 1 cerebellar metastasis.Conclusions. To the best of our knowledge, FCH uptake by pituitary adenomas or hyperfunctioning parathyroidglands has never been described previously. We thus discuss whether there might be a future indication for FCH PET/CT when one such tumour is already known or suspected: to detect a residual or recurrent pituitary adenoma aftersurgery, to guide surgery or radiotherapy of a meningioma or to localise a hyperfunctioning parathyroid gland. Inthese potential indications, comparative studies with reference PET tracers or with 99mTc-sestaMIBI in case of hyperparathyroidism could be undertaken.
Keywords: FCH, PET/CT, incidentaloma, meningioma, pituitary adenoma, hyperparathyroidism, thyroid adenoma
Published in DiRROS: 10.04.2024; Views: 254; Downloads: 54
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10.
Consequence of the introduction of routine FCH PET/CT imaging for patients with prostate cancer : a dual centre survey
Marina Hodolič, Laure Michaud, V. Huchet, S. Balogova, V. Nataf, K. Kerrou, M. Vereb, Jurij Fettich, Jean-Noël Talbot, 2014, original scientific article

Abstract: Background. Fluorocholine(18F) (FCH) was introduced at the beginning of April 2010 in France, Slovenia and three other EU member states for the localisation of bone metastases of prostate cancer with PET. The aim of the study was to compare the evolution of diagnostic imaging in patients with prostate cancer using a new radiopharmaceutical FCH, observed in France and in Slovenia, and to quantify the consequence of the results of new imaging modality on the detection rate of abnormal metastases and recurrences of prostate cancer.Patients and methods. In two centres (France/Slovenia), a survey of the number of nuclear medicine examinations in patients with prostate cancer was performed, covering 5 quarters of the year since the introduction of FCH. For each examination, the clinical and biological circumstances were recorded, as well as the detection of bone or soft tissue foci.Results. Six hundred and eighty-eight nuclear medicine examinations were performed impatients with prostate cancer. Nuclear medicine examinations were performed for therapy monitoring and follow-up in 23% of cases. The number of FCH PET/CT grew rapidly between the 1st and 5th period of the observation (+220%), while the number of bone scintigraphies (BS) and fluoride(18F) PET/CTs decreased (-42% and -23% respectively). Fluorodeoxyglucose(18F) (FDG) PET/CT remained limited to few cases of castrate-resistant or metastatic prostate cancer in Paris. The proportion of negative results was significantly lower with FCH PET/CT (14%) than with BS (49%) or fluoride(18F) PET/CT (54%). For bone metastases, the detection rate was similar, but FCH PET/CT was performed on average at lower prostate-specific antigen (PSA) levels and was less frequently doubtful (4% vs. 28% for BS). FCH PET/CT also showed foci in prostatic bed (53% of cases) or in soft tissue (35% of cases).Conclusions. A rapid development of FCH PET/CT was observed in both centres and led to a higher detection rate of prostate cancer lesions.
Keywords: prostate cancer, PET/CT, fluorocholine (FCH), fluoride(18F), bone scintigraphy, indication of imaging, prostata, rak (medicina), slikovna diagnostika
Published in DiRROS: 04.04.2024; Views: 601; Downloads: 458
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