Gutenberg Open Science

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ZeitschriftenaufsatzAccess status: Open Access ,
Burden and long-term impact of pulmonary embolism on health-related quality of life : a matched cohort study
(2025) Valerio, Luca; Grochtdreis, Thomas; Mavromanoli, Anna C.; Farmakis, Ioannis T.; Abele, Christina; Neusius, Thomas; Mohr, Katharina; Christodoulou, Konstantinos C.; Hobohm, Lukas; Keller, Karsten; Konnopka, Alexander; Barco, Stefano; Konstantinides, Stavros V.
Aims It has not been conclusively established whether and to what extent pulmonary embolism (PE) affects health-related quality of life (HrQoL). We aimed to assess the long-term independent association of PE with HrQoL to provide reference values for interventional studies and support quantification of the burden of PE in terms of quality- or disability-adjusted life years (QALYs and DALYs). Methods and results A total of 1005 patients from a prospective multicenter study, followed 3 and 12 months after PE, were successfully matched to 3058 individuals from the general population of the same country based on age, sex, and key comorbidities. Differences between acute PE survivors and matched controls in the ordinal EQ-5D-5L HrQoL dimensions were assessed using multivariable ordinal regression, in the HrQoL index (reflecting overall HrQoL) using multivariable-adjusted mixed linear regression. Both multiple imputation and complete case analysis were performed. Compared with controls, patients reported worse HrQoL in the dimensions self-care, usual activities, and anxiety/depression, and worse HrQoL index at both 3 [adjusted difference −0.04 (95% CI: −0.06, −0.039) in a range from 0 to 1] and 12 months [−0.02 (95% CI: −0.04, −0.01)] in the imputation analysis. Complete case analysis showed similar results. The annual disability weight of PE for DALY calculation was conservatively estimated at 0.03 (95% CI: 0.02, 0.04). Conclusion PE was independently associated with a moderate decrease in HrQoL, which persisted 12 months after the acute episode despite partial recovery over time. This degree of impairment is comparable to that imposed by several other cardiopulmonary diseases.
ZeitschriftenaufsatzAccess status: Open Access ,
Coagulation proteases modulate nucleic acid uptake and cGAS- STING-IFN induction in the tumor microenvironment
(2025) Wilgenbus, Petra; Pott, Jennifer; Pagel, Sven; Witzler, Claudius; Royce, Jennifer; Marini, Federico; Reyda, Sabine; Madhusudhan, Thati; Kindler, Thomas; Hausen, Anne; Gaida, Matthias M.; Weiler, Hartmut; Ruf, Wolfram; Graf, Claudine
Malignancies increase the risk for thrombosis and metastasis dependent on complex interactions of innate immune cells, platelets, and the coagulation system. Immunosuppressive functions of platelets and macrophage-derived coagulation factors in the tumor microenvironment (TME) drive tumor growth. Here, we show that patients with malignancies and tumor-bearing mice have increased levels of coagulation factor (F) X–expressing circulating monocytes engaged in platelet aggregate formation. This interaction and resulting thrombin generation on platelets interferes with monocyte differentiation and antigen uptake of antigen-presenting cells (APCs). Myeloid cell–specific deletion of FX or abrogated FXa signaling via protease activated receptor 2 (PAR2) averts the suppressive activity of platelets on tumor cell debris uptake and promotes the immune stimulatory activity of APCs in the TME. Myeloid cell FXa-PAR2 signaling deficiency specifically enhances activation of the cGAS-STING-IFN-I pathway with a resulting expansion of antigen experienced progenitor exhausted CD8+ T cells. Pharmacological blockade of FXa with direct oral anticoagulants expands T cell priming–competent immune cells in the TME and synergizes with the reactivation of exhausted CD8+ T cells by immune checkpoint inhibitors for improved antitumor responses. These data provide mechanistic insights into the emerging clinical evidence demonstrating the translational potential of FXa inhibition to synergize with immunotherapy.
ZeitschriftenaufsatzAccess status: Open Access ,
On the relation between approaches for boundary feedback control of hyperbolic systems
(2025) Herty, Michael; Thein, Ferdinand
Stabilization of partial differential equations is a topic of utmost importance in mathematics as well as in engineering sciences. Concerning one dimensional problems there exists a well developed theory. Due to numerous important applications the interest in boundary feedback control of multi-dimensional hyperbolic systems is increasing. In the present work we want to discuss the relation between some of the most recent results available in the literature. The key result of the present work is to show that the type of system discussed in Yang and Yong (2024) identifies a particular class which falls into the framework presented in Herty and Thein (2024).