https://hdl.handle.net/20.500.14178/904 2026-10-04T08:50:13Z 2026-10-04T08:50:13Z Ye, Wenjing Pavlov, Sergii Ali, Esraa Ambrożkiewicz, Filip Červenková, Lenka Vyčítal, Ondřej Hošek, Petr Daum, Ondřej Liška, Václav Hemminki, Kari Jussi Trailin, Andriy https://hdl.handle.net/20.500.14178/3982 2026-10-02T01:00:36Z 2026-01-01T00:00:00Z

Spatial Profiling and Prognostic Role of CD169+ Macrophages in Colorectal Cancer From Adjacent Nontumor Mucosa to Liver Metastasis Ye, Wenjing; Pavlov, Sergii; Ali, Esraa; Ambrożkiewicz, Filip; Červenková, Lenka; Vyčítal, Ondřej; Hošek, Petr; Daum, Ondřej; Liška, Václav; Hemminki, Kari Jussi; Trailin, Andriy BACKGROUND: CD169+ cells represent a distinct subset of macrophages with potential immunomodulatory roles, but their function in colorectal cancer (CRC) progression remains unclear. This study focuses on the spatial profiling and prognostic significance of CD169+ macrophages in adjacent nontumor mucosa (NM), primary CRC (pCRC), and synchronous or metachronous liver metastases (LM). MATERIALS AND METHODS: We enrolled into this retrospective cohort study patients who underwent resection of both pCRC with adjacent NM and synchronous LM (N = 55) or metachronous LM (N = 44). We applied immunohistochemical staining and computer-assisted image analysis to quantify CD169+ cell density in the NM, pCRC, synchronous, and metachronous LM. Correlations between CD169+ macrophages and T cells were evaluated. Associations between CD169+ cell density and overall survival (OS) of the patients were assessed. RESULTS: CD169+ cell density was greater in NM than in the tumor center (TC) of pCRC and in the peritumor (PT) region of LM compared to pCRC. The synchronous group exhibited a higher density of CD169+ cells than the metachronous group in the inner margin (IM) of pCRC, the TC, and the outer margin (OM) of LM. CD169+ cells were more abundant in the exterior than in the interior tumor areas in both pCRC and LM. Positive correlations were observed between densities of CD169+ macrophages with CD3+ and CD8+ lymphocytes. In the synchronous group, a high density of CD169+ macrophages in the TC of pCRC was associated with longer OS, whereas a high density in the PT of LM was associated with shorter OS. High density of CD169+ macrophages in the OM of metachronous LM was associated with poor survival. CONCLUSION: Our study highlights context-dependent prognostic associations of CD169+ macrophages in CRC. While high CD169+ macrophage density in the TC of pCRC was linked to favorable survival in the synchronous group, increased density in both synchronous and metachronous LM was associated with adverse outcomes. Further prospective studies and functional investigations are needed to validate these observations.

2026-01-01T00:00:00Z Zitrický, František Sundquist, Kristina Sundquist, Jan Försti, Asta Hemminki, Akseli Kaaks, Rudolf Hemminki, Kari Jussi https://hdl.handle.net/20.500.14178/3960 2026-09-22T01:01:14Z 2026-01-01T00:00:00Z

Increase in second primary lung cancers in a nation-wide cohort study from Sweden Zitrický, František; Sundquist, Kristina; Sundquist, Jan; Försti, Asta; Hemminki, Akseli; Kaaks, Rudolf; Hemminki, Kari Jussi Background: We describe the occurrence of second primary lung cancers (SPLCs) and their determinant in Sweden. Methods: Nation-wide cancer registry from years 1961 to 2021 identified a total of 853 SPLCs. Results: The incidence of SPLCs increased almost linearly from 1980 onwards, equally for women and men and approximately equally after the four main histological types. SPLC included adenocarcinoma 63.9%, squamous cell carcinoma (SCC) 19.4%, small cell carcinoma 9.6% and large cell carcinoma 9.1%. The female cumulative probability (CumP) of SPLC after first adenocarcinoma in 10 years reached 0.019, after SCC 0.015 and after small and large cell carcinoma 2 0.008. The respective CumP for men were 0.013, 0.012, 0.002 and 0.005. While adenocarcinoma was often followed by second adenocarcinoma, after first non-adenocarcinoma SPLCs presented in diverse histologies. Relative risk of SPLC compared to first lung cancer was overall 3.59, higher for women (4.16) than for men (2.99) and approximately equally high after adenocarcinoma and SCC. In patients diagnosed before age 55 years, the relative risk was 6.68 for all, but after female adenocarcinoma it was 9.95 compared to 6.77 for males. The highest relative risks, up to 20-fold, were found after early onset female adenocarcinoma diagnosed after defined T stages. Conclusions: Although SPLCs are still rare their number is increasing rapidly and the relative risks compared to first lung cancer are substantial, qualifying selected groups of high-risk patients, such as early onset adenocarcinoma patients for early detection by CT screening when/if such tests become available.

2026-01-01T00:00:00Z 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 Dvořák, Pavel Tonar, Zbyněk https://hdl.handle.net/20.500.14178/3924 2026-09-11T01:00:24Z 2026-01-01T00:00:00Z

Estimating clinical manifestations in cell biology teaching is a suitable active element for teaching beginning medical students Dvořák, Pavel; Tonar, Zbyněk Objective: Cell biology courses in medical education often emphasize molecular detail without sufficient clinical integration, which can reduce student motivation and hinder application of knowledge. Embedding diagnostic reasoning into basic science teaching may enhance engagement and relevance. We developed short, task-based exercises in which students are actively encouraged to infer potential clinical symptoms of genetically determined diseases from cellular mechanisms. Methods: Each task followed three steps: (1) introduction to a specific cellular process, (2) guided prediction of clinical manifestations resulting from dysfunction of key proteins, and (3) verification of hypotheses through published literature. Tasks were implemented into first-year medical student seminars of Medical Biology in both face-to-face and online formats. Evaluation was based on assessments by experienced teachers and a student questionnaire at the end of the course. Results: Two illustrative tasks were presented: role of adhesion proteins in leukocyte extravasation, linked to leukocyte adhesion deficiency syndromes, and sarcolemma-cytoskeleton interactions, associated with various muscular dystrophies. Teachers as well as students consistently rated the tasks positively in surveys conducted. Better understanding of the connection between cellular mechanisms and clinical symptoms, greater confidence in diagnostic reasoning, and an increased ability to search and interpret scientific literature were reported. Based on the evaluation, modifications to the learning outcomes were proposed to place greater emphasis on the ability to draw conclusions from cellular processes. Conclusion: Integrating short, clinically anchored exercises into cell biology teaching provides an effective means of activating student learning and fostering early diagnostic reasoning. This approach strengthens the perceived relevance of basic science, supports critical thinking, and offers a scalable model for enhancing preclinical medical curricula.

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