https://hdl.handle.net/20.500.14178/905 2026-10-01T18:22:26Z 2026-10-01T18:22:26Z Kroupa, Josef Radvan, Martin Mrózek, Jan Sluka, Martin Jirouš, Štěpán Hlinomaz, Ota Plíva, Milan Pudil, Jan Voběrková, Hana Bartošková, Karolína Poloczek, Martin Kameník, Martin Brabec, Michal Lichnerová, Eva Hutyra, Martin Bernat, Ivo Novák, Martin Horáková, Johana Jelínková, Lucie Kníže, Tomáš Toušek, Petr Štěchovský, Cyril Varhaník, Filip Coufal, Zdeněk Jarkovský, Jiří Kočka, Viktor https://hdl.handle.net/20.500.14178/3959 2026-09-17T01:00:32Z 2026-01-01T00:00:00Z

Catheter-Directed Thrombolysis in Intermediate-High-Risk Pulmonary Embolism Kroupa, Josef; Radvan, Martin; Mrózek, Jan; Sluka, Martin; Jirouš, Štěpán; Hlinomaz, Ota; Plíva, Milan; Pudil, Jan; Voběrková, Hana; Bartošková, Karolína; Poloczek, Martin; Kameník, Martin; Brabec, Michal; Lichnerová, Eva; Hutyra, Martin; Bernat, Ivo; Novák, Martin; Horáková, Johana; Jelínková, Lucie; Kníže, Tomáš; Toušek, Petr; Štěchovský, Cyril; Varhaník, Filip; Coufal, Zdeněk; Jarkovský, Jiří; Kočka, Viktor BACKGROUND: Whether catheter-directed thrombolysis improves clinical outcomes in patients with intermediate-high-risk pulmonary embolism, as compared with anticoagulation alone, is uncertain. METHODS: In this multicenter, open-label, randomized trial, we randomly assigned patients with intermediate-high-risk acute pulmonary embolism (defined by hemodynamic stability, a simplified Pulmonary Embolism Severity Index score of >=1, and right ventricular dysfunction plus an elevated level of cardiac troponin or natriuretic peptide) in a 1:1 ratio to receive catheter-directed thrombolysis with alteplase plus anticoagulation therapy (thrombolysis group) or anticoagulation therapy alone (standard-care group). The primary outcome was a composite of death from any cause, recurrence of pulmonary embolism, or cardiorespiratory decompensation or collapse within 7 days after randomization. Secondary outcomes included clinically relevant bleeding as defined by the Bleeding Academic Research Consortium, major bleeding as defined in the Global Use of Strategies to Open Occluded Coronary Arteries guidelines, and intracranial hemorrhage. RESULTS: A total of 558 patients underwent randomization; 280 were assigned to the thrombolysis group, and 278 to the standard-care group. The median age was 64 years, and 40.9% were female. A primary-outcome event occurred in 2 patients (0.7%) in the thrombolysis group and in 19 patients (6.8%) in the standard-care group (relative risk, 0.10; 95% confidence interval, 0.02 to 0.44; P<0.001); this difference was driven mainly by the lower incidence of cardiorespiratory decompensation or collapse in the thrombolysis group. By day 7, clinically relevant bleeding had occurred in 13 patients (4.6%) in the thrombolysis group and in 14 patients (5.0%) in the standard-care group (P = 0.85); major bleeding in 4 (1.4%) and 6 (2.2%), respectively (P = 0.54); and intracranial hemorrhage in 2 (0.7%) and none. One patient in the thrombolysis group died within 30 days, and 4 patients in the standard-care group died within 7 days. CONCLUSIONS: Among patients with intermediate-high-risk acute pulmonary embolism, catheter-directed thrombolysis with alteplase plus anticoagulation therapy led to a lower risk of death from any cause, recurrent pulmonary embolism, or cardiorespiratory decompensation or collapse within 7 days after randomization than anticoagulation therapy alone. (Funded by the Ministry of Health of the Czech Republic and others; PRAGUE-26 ClinicalTrials.gov number, NCT05493163; EudraCT number, 2022-002218-18; European Union Clinical Trials number, 2024-516144-25-00.).

2026-01-01T00:00:00Z Mihályová, Jana Panovská, Anna Šimkovič, Martin Smolej, Lukáš Špaček, Martin Shokralla, Tereza Kubová, Zuzana Zuchnická, Jana Arpáš, Tomáš Vodárek, Pavel Turcsányi, Peter Polcerová, Lenka Chrápavá, Marika Lysák, Daniel Brejcha, Martin Móciková, Heidi Doubek, Michael https://hdl.handle.net/20.500.14178/3895 2026-08-21T01:00:55Z 2026-01-01T00:00:00Z

Comparable outcomes of BTK inhibitors and fixed-duration venetoclax plus rituximab in second-line treatment of chronic lymphocytic leukaemia: a real-world analysis by the Czech CLL study group Mihályová, Jana; Panovská, Anna; Šimkovič, Martin; Smolej, Lukáš; Špaček, Martin; Shokralla, Tereza; Kubová, Zuzana; Zuchnická, Jana; Arpáš, Tomáš; Vodárek, Pavel; Turcsányi, Peter; Polcerová, Lenka; Chrápavá, Marika; Lysák, Daniel; Brejcha, Martin; Móciková, Heidi; Doubek, Michael In relapsed/refractory (RR) chronic lymphocytic leukaemia (CLL), Bruton tyrosine kinase inhibitors (BTKi) are administered as monotherapy until disease progression. In contrast, venetoclax, a B-cell lymphoma 2 (BCL-2) protein inhibitor, is typically combined with rituximab (VenR) as a time-limited regimen. To date, neither randomized nor retrospective trials have directly compared these approaches in RR CLL, and only limited data are available comparing venetoclax plus obinutuzumab (VenObi) to BTKi in the first-line setting. We retrospectively analysed 352 patients receiving second-line therapy: 93 VenR and 259 BTKi (ibrutinib: n = 222; acalabrutinib: n = 37). Baseline characteristics were well balanced, except for a higher incidence of TP53 mutation and trisomy 12 in BTKi-treated patients. At a median follow-up of 13.8 months (VenR) and 22.1 months (BTKi), 12-month progression-free survival (PFS) and overall survival (OS) were comparable (PFS: 85.1% vs. 82.2%, p = 0.265; OS: 87.6% vs. 88.4%, p = 0.291). Estimated median PFS (45.4 vs. 37.9 months, p = 0.265) and OS (83.6 vs. 74.2 months, p = 0.291) also showed no significant differences between the VenR and BTKi cohorts. Treatment discontinuation due to adverse events before month 24 was more frequent with BTKi (22.5% with VenR vs. 34.3% with BTKi), primarily due to infections (10.6% vs. 28.6%) and disease progression (14.3% vs. 22.5%). These preliminary data suggest comparable outcomes and manageable toxicity profiles for both regimens.

2026-01-01T00:00:00Z Houngbedji, Priam-Amedeo Bachtíková, Andrea Boháčová, Jarmila Tabarestani, Parinaz Janďourek, Ondřej Konečná, Klára Ősterreicher, Jan Paterová, Pavla Novák, Martin Bárta, Pavel Záhorszká, Monika Korduláková, Jana Mori, Matteo Meneghetti, Fiorella Zitko, Jan https://hdl.handle.net/20.500.14178/3889 2026-08-05T01:00:16Z 2026-01-01T00:00:00Z

Pyrazinamide-derived 1,2,3-triazoles: Antimicrobial evaluation, selective antimycobacterial activity and mechanism of action insights Houngbedji, Priam-Amedeo; Bachtíková, Andrea; Boháčová, Jarmila; Tabarestani, Parinaz; Janďourek, Ondřej; Konečná, Klára; Ősterreicher, Jan; Paterová, Pavla; Novák, Martin; Bárta, Pavel; Záhorszká, Monika; Korduláková, Jana; Mori, Matteo; Meneghetti, Fiorella; Zitko, Jan A series of pyrazinamide-derived 1,2,3-triazoles featuring systematic chlorination of the pyrazine ring and diverse aryl substituents was synthesized and evaluated for antimycobacterial activity. Biological activity screening revealed broad-spectrum antimycobacterial activity and good selectivity toward mycobacteria over other pathogens, with 11 of the prepared compounds showing activity against Mycobacterium tuberculosis (Mtb) H37Ra and/or Mtb H37Rv (MIC <= 62.5 mu g/mL). Structure-activity relationship analysis showed that 5-Cl substitution on the pyrazine ring was associated with improved antimycobacterial activity, with the best MIC values observed for compound 7 against Mtb H37Ra (MIC =1.98 mu g/mL) and compound 37 against Mtb H37Rv (MIC =1.56 mu g/mL). The tested compounds retained activity against drug-resistant Mtb isolates and partially against naturally resistant Mycobacterium abscessus, while showing low in vitro cytotoxicity in the HepG2 cell line and favorable selectivity indices. During advanced cytotoxicity testing, both compounds 7 and 37 displayed substantially lower hemolytic activity than bedaquiline, indicating a favorable erythrocyte safety profile within the tested concentration ranges. In vivo toxicity testing on Galleria mellonella showed low acute toxicity for both compounds. Mechanistic studies on compounds 7, 27, 31, and 37 revealed reduced biosynthesis of fatty acids and derived lipids, a phenotype consistent with interference with the Fatty Acid Synthase I (FAS I) system.

2026-01-01T00:00:00Z Skálová, Alena Laco, Jan Thompson, Lester D R Bradová, Martina Vander Poorten, Vincent Araújo, Anna Luíza Damaceno Stenman, Göran Leivo, Ilmo Agaimy, Abbas Ferlito, Alfio https://hdl.handle.net/20.500.14178/3807 2026-07-21T01:00:22Z 2026-01-01T00:00:00Z

Recent developments in salivary gland pathology after the WHO 2024 classification: new developments in existing entities and evolving new entities Skálová, Alena; Laco, Jan; Thompson, Lester D R; Bradová, Martina; Vander Poorten, Vincent; Araújo, Anna Luíza Damaceno; Stenman, Göran; Leivo, Ilmo; Agaimy, Abbas; Ferlito, Alfio Parallel to and after publication of the WHO 2024 classification of head and neck tumors, several developments concerning known existing salivary gland tumor entities, but also proposing new evolving tumor entities have been published. This review article describes the most important new developments in salivary gland pathology published through 2022-2025, that were not included in the 5th edition of the WHO Classification of Head and Neck Tumours 2024. This review summarizes these recent developments in both the benign and the malignant tumor categories. Among the recently proposed entities are palisading adenocarcinoma, microcribriform adenocarcinoma, fenestrating adenocarcinoma and skin-analogue poroid carcinoma. Developments in existing carcinoma entities include recognition of mucoacinar carcinoma as subtype of mucoepidermoid carcinoma (MAML2-fused), mucoepidermoid carcinoma without squamous cell differentiation, metatypical adenoid cystic carcinoma, and adenoid cystic carcinoma with prominent tubular hypereosinophilia. In the benign tumor category, recognition of pleomorphic adenoma with canalicular/trabecular phenotype driven by HMGA2 fusions, triphasic basal cell adenoma with S100 protein-positive "stroma", characterized by CTNNB1 mutations, metaplastic Warthin tumor with KRAS mutations and delineation of thymus-like phenotype in non-sebaceous lymphadenoma with recurrent CYLD mutations are the main highlights. Emerging concepts include benign tumor with ductal and papillary morphology (sialadenopapillary ductal tumor). Finally, new grading schemes have been developed/ proposed for acinic cell carcinoma and secretory carcinoma.

2026-01-01T00:00:00Z