https://hdl.handle.net/20.500.14178/904 Tue, 22 Sep 2026 21:52:52 GMT 2026-09-22T21:52:52Z https://hdl.handle.net/20.500.14178/3960 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. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3960 2026-01-01T00:00:00Z 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.). Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3959 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3924 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. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3924 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3912 GWAS meta-analysis provides new insights into uveal melanoma risk D'Mellow, Matthew; Wang, Huanwei; Palmer, Jane M; Hemminki, Kari Jussi; Cebulla, Colleen M; Beasley, Aaron B; Bechrakis, Nikolaos E; Pritchard, Antonia L; Wadt, Karin W; Johansson, Peter A; Mobuchon, Lenha; Barlow, Samantha; Brooks, Kelly; Beckman, Timothy; Olsen, Catherine M; Warrier, Sunil K; Byrne, Lindsey; Kalirai, Helen; Mustard, Colette; Ingold, Nathan; Försti, Asta; Isaacs, Timothy; Jayasinghe, G J M Shanika R; Glasson, William J; Williamson, Gayle; McGrath, Lindsay A; Le, Ngoc-Quynh; Chadha, Vikas; Gray, Elin S; Brown, Kevin M; Cauchi, Paul; Thomsen, Hauke; Connolly, Julie; MacGregor, Stuart; Whiteman, David C; Kiilgaard, Jens F; Stern, Marc-Henri; Coupland, Sarah E; Abdel-Rahman, Mohamed H; Zeschnigk, Michael; Hayward, Nick; Law, Matthew H OBJECTIVE: The aim of this research is to identify germline genetic variants that predispose to uveal melanoma (UM) using data from nine studies involving 5839 individuals with UM (3853 novel) and 349,863 healthy controls. METHODS: Five novel UM genome-wide association studies (GWAS) were performed and included for meta-analysis with four previously published UM GWAS. A fixed-effects inverse-variance weighted (IVW) meta-analysis was performed by combining data from these nine UM case-control cohorts. A follow-up transcriptome-wide association study (TWAS) was conducted to identify candidate target genes at UM risk loci. Genetic correlations with melanoma-related phenotypes were measured to elucidate UM's genetic architecture. RESULTS: We identify nine linkage disequilibrium (LD)-independent loci (three novel) with an IVW P value of less than 5 x 10(-8). TWAS analysis indicates five potential target genes, including MOB3B, RBAK, and MTSS1, which have established links to multiple cancer types. We note a significant genetic correlation (rg = 0.31, P = 0.01) between UM and cutaneous melanoma (CM), and a non-significant but consistent correlation with naevus count (rg = 0.25, P = 0.08). CONCLUSIONS: This meta-analysis offers new insights into the genetic architecture of UM, highlights potential therapeutic targets, and explores the genetic relationship with CM and skin pigmentation. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3912 2026-01-01T00:00:00Z