1. Emerging therapies and new directions in the treatment of pulmonary arterial hypertensionGrzegorz Kopec, Andris Skride, Egle Ereminiene, Iveta Šimkova, Roxana Enache, Miroslav Samaržija, Barbara Salobir, Pavel Jansa, 2025, review article Abstract: Pulmonary arterial hypertension (PAH) is a severe and progressive disease with limited survival prospects under currently available therapies. Since the 2022 edition of the European Society of Cardiology and European Respiratory Society guidelines on pulmonary hypertension, substantial clinical evidence has emerged, supporting a new treatment algorithm for PAH as presented at the 7th World Symposium on Pulmonary Hypertension 2024 and the following proceeding papers. Key updates include the introduction of sotatercept as a second-line therapy leading to a revised definition of maximal medical therapy now encompassing agents from four therapeutic groups (phosphodiesterase-5 inhibitors/soluble guanylate cyclase stimulators, endothelin receptor antagonists, prostacyclin pathway agents, and sotatercept), instead of three (phosphodiesterase-5 inhibitors/soluble guanylate cyclase stimulators, endothelin receptor antagonists, prostacyclin pathway agents). Other novelties include the elimination of a distinct pathway for patients with cardiopulmonary comorbidities in favor of an individualized approach, a reduction in the initial patient assessment risk categories from three to two, and a follow-up interval shortened from 3–6 months to 3–4 months post-treatment initiation. This review presents these advancements and emphasizes the need for their widespread implementation in clinical practice. At the end, we present new opportunities and challenges in the treatment of pulmonary arterial hypertension in eight Central and Eastern European countries.
Keywords: activin signaling inhibitors, novel therapies, risk assessment, treatment strategy, sotatercept
Published in DiRROS: 15.12.2025; Views: 280; Downloads: 244
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2. Efficacy and safety of nintedanib and docetaxel in patients with previously treated lung non-squamous non-small cell lung cancer : a multicenter retrospective real-world analysisLidija Ljubicic, Urška Janžič, Mojca Unk, Ana Sophie Terglav, Katja Mohorčič, Fran Seiwerth, Lela Bitar, Sonja Badovinac, Sanja Pleština, Marta Koršić, Suzana Kukulj, Miroslav Samaržija, Marko Jakopović, 2023, original scientific article Published in DiRROS: 25.07.2024; Views: 1113; Downloads: 614
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3. High burden of clonal mast cell disorders and hereditary ▫$α-tryptasemia$▫ in patients who need Hymenoptera venom immunotherapyPeter 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: 1369; Downloads: 816
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4. Comparative analysis of prognostic histopathologic parameters in subtypes of epithelioid pleural mesotheliomaAgnes Bilecz, Paul Stockhammer, Dirk Theegarten, Izidor Kern, Marko Jakopović, Miroslav Samaržija, Thomas Klikovits, Mir Alireza Hoda, Balazs Dome, Felicitas Oberndorfer, 2020, original scientific article Abstract: Malignant pleural mesothelioma (MPM) is a rare malignancy with a dismal prognosis. While the
epithelioid type is associated with a more favourable outcome, additional factors are needed to further stratify prognosis and to identify patients who can benefit from multimodal treatment. As epithelioid MPM shows remarkable morphological variability, the prognostic role of the five defined morphologies, the impact of the nuclear grading system and the mitosis-necrosis score were investigated in this study. Methods and results: Tumour specimens of 192 patients with epithelioid MPM from five European centres were histologically subtype d. Nuclear grading
and mitosis–necrosi s score were determined and correlated with clinicopathological parameters and overall survival (OS). Digital slides of 55 independent cases from The Cancer Genome Atlas (TCGA) database were evaluated for external validation. Histological subtypes were collapsed into three groups based on their overlapping survival curves. The tubulopapillary/microcystic group had a significantly longer OS than the solid/trabecular group (732 days versus 397 days, P = 0.0013). Pleomorphic tumours had the shortest OS (173 days). The solid/trabecular variants showed a significant association with high nuclear grade and mitosis – necrosis score. The mitosis–necrosis score was a robust and independent prognostic factor in our patient cohort. The prognos-
tic significance of all three parameters was externally validated in the TCGA cohort. Patients with tubulopapillary or microcystic tumours showed a greater improvement in OS after receiving multimodal therapy than those with solid or trabecular tumours. Conclusions: Histological subtypes of epithelioid MPM have a prognostic impact, and might help to select patients for intensive multimodal treatment approaches.
Keywords: epithelioid malignant pleural mesothelioma, histological subtypes
Published in DiRROS: 08.07.2020; Views: 3345; Downloads: 2115
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