https://hdl.handle.net/20.500.14178/903 2026-10-02T08:03:29Z https://hdl.handle.net/20.500.14178/3959 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 https://hdl.handle.net/20.500.14178/3895 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 https://hdl.handle.net/20.500.14178/3890 Implementation and First Results of the Czech Nationwide Prostate Cancer Screening Pilot Program Koudelková, Marcela; Hejcmanová, Katerina; Babjuk, Marek; Zachoval, Roman; Ferda, Jiří; Bratt, Ola; Chloupková, Renata; Ngo, Ondřej; Hejduk, Karel; Válek, Vlastimil; Dušek, Ladislav; Májek, Ondřej Background: In 2022, the European Union recommended piloting organized prostate cancer screening. Subsequently, the Czech Republic launched a nationwide pilot program fully reimbursed by public health insurance in January 2024 to reduce the high incidence of late-stage prostate cancer and the widespread unorganized prostate-specific antigen (PSA) testing. Objective: To describe the strategy, methodology, and first results of the Czech nationwide prostate cancer screening pilot program. Design, setting, and participants: We analyzed data from the first 12 mo of the program targeting men aged 50-69 yr without a previous diagnosis of prostate cancer. General practitioners and urologists offer men an initial PSA test. Those with PSA >= 3.0 lg/l are referred to certified urologists. Based on urology assessment, selected for magnetic resonance imaging (MRI) and, if indicated, targeted biopsy. Outcome measurements and statistical analysis: Reported key indicators are PSA testing coverage and overall use of prebiopsy MRI. Results and limitations: Screening was offered to 150 498 men; PSA results were available for 146 109 (97.1%) men, 8.8% of whom had PSA >= 3.0 lg/l. Within 6 mo, 67.2% of the men with PSA >= 3.0 lg/l underwent urological evaluation. From 2023 to 2024, the 2-yr PSA testing rate rose from 47.4% to 53.3%, and pre-biopsy MRI use increased from 28.0% to 38.3% (10.3 percentage-point difference, 95% confidence interval 8.3-12.2). Data on diagnostic outcomes are not yet analyzed. 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3699 Determinants of Implantation Success in Pancreatic Cancer Patient-Derived Xenografts: Role of Matrigel Application, Histological Subtype, and Time Management Gayibov, Emin; Sychra, Tomáš; Spálenková, Alžběta; Šeborová, Karolína; Koucká, Kamila; Tesařová, Tereza; Kočí, Kamila; Vícha, Matěj; Szabó, Arpád; Václavíková, Radka; Šubrt, Zdeněk; Souček, Pavel; Oliverius, Martin Pancreatic cancer (PC) is a growing global health concern, highlighting the need for improved preclinical models. Patient-derived xenografts (PDXs) closely replicate tumor biology and serve as a vital link between preclinical and clinical research. This study investigated the key factors influencing the success of PDX implantation in PC. We compared Matrigel-assisted implantation versus Matrigel-free implantation. We also evaluated the impact of histological subtype on implantation success, analyzing pancreatic ductal adenocarcinoma (PDAC), adenosquamous carcinoma (ASPC), and acinar cell carcinoma (ACC). Additionally, we assessed whether the tumor specimen culture-to-implantation period affected both the take rate and tumor growth rate. A significance threshold of p < 0.05 was applied (95% confidence interval), and multivariable regression analysis was conducted to identify independent predictors of implantation success. In both NOD/SCID and NU/NU (nude) strains, Matrigel-assisted PDAC implantations achieved significantly higher take rates (75% vs. 90%) compared to direct implantations (25% vs. 0%) in the second generation (p = 0.02). The ASPC subtype was a significant predictor of success in the NOD/SCID strain (p = 0.04). The culture-to-implantation period did not affect take rates. The nude strain significantly prolonged ACC engraftment (p = 0.02). In direct ACC implantations, earlier generations (F1-F5) required shorter engraftment growth duration (p < 0.0001). For ASPC, later generations demonstrated longer growth duration (p < 0.04). These findings emphasize critical variables in optimizing PC PDX protocols, particularly Matrigel use, mouse strain selection, and consideration of histological and generation-specific effects. Such refinements can optimize PDX efficiency and translational relevance. 2025-01-01T00:00:00Z