von Maja Krech ; Amos Muench ; Daniel Teichmann ; Peter Kuzman ; Abigail Kora Suwala ; Franziska M. Ippen ; Michael Müther ; Katharina J. Weber ; Katharina Wenger-Alakmeh ; Julia Onken ; Peter Vajkoczy ; Felix Behling ; Sven-Axel May ; Georgios Ntoulias ; Joachim K. Krauss ; Oday Atallah ; Majid Esmaeilzadeh ; Wolf C. Mueller ; Frank L. Heppner ; Helena Radbruch ; Carsten Dittmayer ; Werner Stenzel ; Arend Koch ; David Capper ; David Kaul ; Werner Paulus ; Karl Plate ; Joachim P. Steinbach ; Markus Czabanka ; Rudi Beschorner ; Andreas von Deimling ; Michael Bockmayr ; Julia E. Neumann ; Sebastian Brandner ; Teresa Krieger ; Christian Hartmann ; Christian Thomas ; Leonille Schweizer
Veröffentlicht: 11. Juni 2025 ; Gesehen am 29.10.2025
DNA methylation profiling; FGFR3; Neurocytoma; Progression-free survival; Radiotherapy
Central neurocytomas (CN) are intraventricular brain tumors predominantly occurring in young adults. Although prognosis is usually favorable, tumor recurrence is common, particularly following subtotal resection (STR). Currently, the risk of progression is evaluated using atypical features and an elevated Ki67 proliferation index. However, these markers lack consistent definitions, raising the need for objective criteria. Genome-wide DNA methylation profiles were examined in 136 tumors histologically classified as CN. Clinical/histopathological characteristics were assessed in 93/90 cases, and whole-exome sequencing was conducted in 12 cases. Clinical and molecular characteristics were integrated into a survival model to predict progression-free survival (PFS). A diagnosis of CN was epigenetically confirmed in 125 of 136 cases (92%). No DNA methylation subgroups were identified, but global DNA hypomethylation emerged as a hallmark feature of CN associated with higher recurrence risk. Risk stratification based on histological features of atypia and Ki67 proliferation index was not reproducible across neuropathologists. Hypomethylation at the FGFR3 locus, accompanied by increased FGFR3 protein expression, was observed in 97% of cases. Gross total resection was associated with significantly improved PFS compared to STR, while patients undergoing STR receiving radiotherapy had a better outcome (p = 0.0001). Younger patients were identified as having a higher risk of recurrence (p = 0.026). Patient age and treatment strategy were key factors associated with survival outcomes in this cohort. These findings underscore the importance of closer follow-up for younger patients and radiotherapy for STR cases. Furthermore, FGFR3 represents a hallmark feature and potential therapeutic target, warranting further investigation.
Acta neuropathologica Berlin : Springer, 1961 149(2025), Artikel-ID 61, Seite 1-16 Online-Ressource
von Hans-Josef Feistritzer ; Alexander Jobs ; Uwe Zeymer ; Steffen Schneider ; Philipp Lauten ; Miroslaw Ferenc ; Maren Weferling ; Regine Brinkmann ; Sebastian Winkler ; Ulf Landmesser ; Tobias Daniel Trippel ; Christoph Stellbrink ; Harm Wienbergen ; Georg Fürnau ; Helge Möllmann ; Axel Linke ; Christian Jung ; Alexander Lauten ; Stephan Achenbach ; Tienush Rassaf ; Thomas Schmitz ; Sebastian Cremer ; Christoph Olivier ; Volker Schächinger ; Samuel Tobias Sossalla ; Karl Toischer ; Christian Templin ; Daniel Sedding ; Peter Clemmensen ; Eike Philipp Tigges ; Felix Meincke ; Haitham Abu Sharar ; Saarraaken Kulenthiran ; Paul Christian Schulze ; Claudius Jacobshagen ; Derk Frank ; Stephan Baldus ; Ralf Lehmann ; Christian Spies ; Norbert Klein ; Ingo Eitel ; Ralf Zahn ; Alexander Schmeisser ; Tommaso Gori ; Philipp Lurz ; Ibrahim Akın ; Georgios Chatzis ; Konstantinos Rizas ; Thorsten Keßler ; Fadil Ademaj ; Albrecht Elsässer ; Lars Siegfried Maier ; Alper Öner ; Alexander Staudt ; Nikos Werner ; Tobias Geisler ; Mirjam Keßler ; Markus Ferrari ; Melchior Seyfarth ; Peter Johann Nordbeck ; Sebastian Ewen ; Christian Bietau ; Arash Haghikia ; Sebastian J. Reinstadler ; Alexander Geppert ; Nadine Hösler ; Gabor Toth-Gayor ; Björn Ulrich Nicolas Billmann ; Ramon Tschierschke ; Christian Schmidt ; Stephan Fichtlscherer ; Holger Thiele
Online verfügbar: 8. April 2025, Artikelversion: 1. Mai 2025 ; Gesehen am 19.08.2025
Background - Multivessel coronary artery disease (CAD) is present in 30% to 70% of patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) depending on varying age and risk profiles. In contrast to the STEMI cohort, there is only limited scientific evidence derived from randomized controlled trials directing the general decision for or against complete revascularization in the NSTEMI population. - Primary hypothesis - The COMPLETE-NSTEMI trial aims to investigate whether multivessel percutaneous coronary intervention (PCI) is superior over culprit-lesion only PCI in patients with NSTEMI and multivessel CAD. - Design - COMPLETE-NSTEMI is a prospective, randomized, controlled, multicenter, parallel group, open-label trial. It will enroll 3390 NSTEMI patients with multivessel CAD at 65 to 70 sites in Germany and Austria. Patients will be randomized 1:1 to either complete revascularization with PCI or culprit lesion-only PCI. - Endpoints - The primary efficacy endpoint is a composite of cardiovascular death or rehospitalization for nonfatal myocardial infarction during follow-up. The trial is event-driven and will be stopped as soon as 578 primary endpoint events and a minimal follow-up duration of 12 months for each patient are reached. - Current status - The first patient was enrolled at October 27, 2023. By April 2025, 51 sites have been activated and >500 patients have been randomized. Completion of recruitment is expected for the first half of 2027. The final results of the primary endpoint are expected in 2028. - Outlook - COMPLETE NSTEMI will be the first dedicated trial to answer the question about the optimal revascularization strategy in patients with NSTEMI and multivessel CAD. - Trial registration: ClinicalTrials.gov - NCT05786131
American heart journal Amsterdam [u.a.] : Elsevier, 1925 287(2025), Seite 94-106 Online-Ressource
von Anette Friedrichs ; Roman Wenz ; Daniel Pape ; Katharina Appel ; Thomas Bahmer ; Karsten Becker ; Sven Bercker ; Sabine Blaschke ; Josephine Braunsteiner ; Jana Butzmann ; Edgar Dahl ; Johanna Erber ; Lisa Fricke ; Ramsia Geisler ; Siri Göpel ; Andreas Güldner ; Marina Hagen ; Axel Hamprecht ; Stefan Hansch ; Peter Heuschmann ; Sina Hopff ; Björn-Erik Ole Jensen ; Nadja Käding ; Julia Koepsell ; Carolin E.M. Koll ; Marcin Krawczyk ; Thomas Lücke ; Patrick Meybohm ; Milena Milovanovic ; Lazar Mitrov ; Carolin Nürnberger ; Christoph Römmele ; Margarete Scherer ; Lena Schmidbauer ; Melanie Stecher ; Phil-Robin Tepasse ; Andreas Teufel ; Jörg Janne Vehreschild ; Christof Alexander Winter ; Oliver Witzke ; Christoph Wyen ; Frank Hanses ; Amke Caliebe
Purpose The benefit of antibiotic treatment (ABT) for patients with moderate COVID-19 is unclear and overtreatment poses the risk of adverse effects such as Clostridioides difficile infection and antibiotic resistance. This multi-center study compares health status improvement between patients with and without ABT at hospital admission. Methods Between March 2020 and May 2023, hospitalized adults with confirmed SARS-CoV-2 infection were recruited from the German National Pandemic Cohort Network (NAPKON), which includes patients from various hospitals across Germany. The study population included patients with moderate or severe COVID-19 at baseline. The primary objective was to compare health improvement or decline after two weeks between patients who received ABT at baseline and those who did not in the moderate COVID-19 population. The statistical analysis adjusted for confounders such as gender, age, vaccination status, clinical condition, and comorbidities. The severe COVID-19 population was investigated as a secondary objective. Results A total of 1,317 patients (median age 59 years; 38% women) were eligible for analysis, of whom 1,149 had moderate and 168 severe COVID-19 disease. ABT for pneumonia was administered to 467 patients with moderate and 117 with severe COVID-19. ABT at baseline was significantly associated with a higher deterioration rate after two weeks in patients with moderate COVID-19 (ABT: 292 improvement, 61 deterioration; no ABT: 429 improvement, 14 deterioration). A similar result was obtained in the multiple regression analysis where an odds ratio of 5.00 (95% confidence interval: 2.50 - 10.93) for ABT was observed. Conclusion We found no benefit of antibiotic therapy in patients with moderate COVID-19. Use of ABT was associated with a higher likelihood of clinical deterioration. Graphical abstract
Infection München : Urban & Vogel, 1973 53(2025), 6, Seite 2543-2555 Online-Ressource
von Jule Filler ; Marios K. Georgakis ; Daniel Janowitz ; Marco Düring ; Rong Fang ; Anna Dewenter ; Felix J. Bode ; Sebastian Stösser ; Christine Kindler ; Peter Hermann ; Christian H. Nolte ; Thomas Liman ; Lucia Kerti ; Kathleen Bernkopf ; Benno Ikenberg ; Wenzel Glanz ; Michael Wagner ; Annika Spottke ; Karin Waegemann ; Michael Görtler ; Silke Wunderlich ; Matthias Endres ; Inga Zerr ; Gabor Petzold ; Martin Dichgans
Tatjana Wittenberg; Jan Friedrich Scheitz; Harald Prüß; Pia Sperber; Alexander Heinrich Nave; Anna Kufner Ibaroule; Julius Nicolai Meißner; Taraneh Ebrahimi; Julia Nordsiek; Niklas Michael Beckonert; Matthias Schmitz; Stefan Goebel; Timothy Bunck; Julia Schütte-Schmidt; Sabine Nuhn; Corinna Volpers; Peter Dechent; Matthias Bähr; Anna Maria Kopczak; Frank Arne Wollenweber; Christiane Huber; Holger Poppert; Tony Stöcker; Katja Neumann; Oliver Speck
Background - Cancer immunotherapy has revolutionized melanoma treatment, but the high number of non-responders still emphasizes the need for improvement of therapy. One potential avenue for enhancing anti-tumor treatment is through the modulation of coagulation and platelet activity. Both have been found to play an important role in the tumor microenvironment, tumor growth and metastasis. Preclinical studies indicate a beneficial effect, clinical data has been inconsistent. - Methods - We examined a cohort of advanced, non-resectable melanoma patients (n = 2419) derived from the German prospective multicenter skin cancer registry ADOReg, who were treated with immune checkpoint inhibitors (ICI). The patients were classified based on whether it was documented that they received platelet aggregation inhibition (PAI) (n = 137) (acetylsalicylic acid (ASA) or clopidogrel), anticoagulation (AC) (n = 185) (direct oral anticoagulation (DOAC), phenprocoumon, heparins) at the start of ICI or no antithrombotic medication (n = 2097) at any point during ICI treatment. The study endpoints were best overall response (BOR), progression-free survival (PFS) and overall survival (OS). - Results - A significantly improved PFS was observed in patients documented to receive ASA (15.1 vs 6.4 months, HR 0.67, 95 % CI: 0.5 to 0.88, p = 0.0047) as well as in patients to receive AC (15.1 vs. 6.4 months, HR 0.7, 95 % CI: 0.53 to 0.91, p = 0.01) compared to patients for whom no antithrombotic medication was documented. Multivariate analysis of OS showed significant risk reduction in patients who received DOAC (HR 0.68, 95 % CI: 0.49 to 0.92, p = 0.0170) or phenprocoumon (HR: 0.44, 95 % CI: 0.19 to 0.85, p = 0.0301). - Conclusion - Our study indicates a positive prognostic effect of anticoagulant and antiplatelet concomitant medication in melanoma patients receiving ICI. Further studies are needed to confrim the cancer-related benefit of adding anticoagulation or platelet inhibition to ICI treatment.
European journal of cancer Amsterdam [u.a.] : Elsevier, 1992 214(2025) vom: Jan., Artikel-ID 115159, Seite 1-11
von Victor Schulze-Zachau ; Nikki Rommers ; Nikos Ntoulias ; Alex Brehm ; Nadja Krug ; Ioannis Tsogkas ; Matthias Anthony Mutke ; Thilo Rusche ; Amedeo Cervo ; Claudia Rollo ; Markus Alfred Möhlenbruch ; Jessica Jesser ; Kornelia Kreiser ; Katharina Althaus ; Manuel Requena ; Marc Rodrigo-Gisbert ; Tomas Dobrocky ; Bettina L. Serrallach ; Christian H. Nolte ; Christoph Paul Riegler ; Jawed Nawabi ; Errikos Maslias ; Patrik Michel ; Guillaume Saliou ; Nathan Manning ; Alexander McQuinn ; Alon Taylor ; Christoph J. Maurer ; Ansgar Berlis ; Daniel Kaiser ; Ani Cuberi ; Manuel Moreu ; Alfonso López-Frías ; Carlos Pérez-García ; Riitta Rautio ; Ylikotila Pauli ; Nicola Limbucci ; Leonardo Renieri ; Isabel Fragata ; Tania Rodriguez-Ares ; Jan Kirschke ; Julian Schwarting ; Sami Al Kasab ; Alejandro M. Spiotta ; Ahmad Abu Qdais ; Adam A. Dmytriw ; Robert W. Regenhardt ; Aman B. Patel ; Vitor Mendes Pereira ; Nicole M. Cancelliere ; Carsten Schmeel ; Franziska Dorn ; Malte Sauer ; Grzegorz Marek Karwacki ; Jane Khalife ; Ajith Thomas ; Hamza A. Shaikh ; Christian Commodaro ; Marco Pileggi ; Roland Schwab ; Flavio Bellante ; Anne Dusart ; Jeremy Hofmeister ; Paolo Machi ; Edgar A. Samaniego ; Diego J. Ojeda ; Robert M. Starke ; Ahmed Abdelsalam ; Frans van den Bergh ; Sylvie De Raedt ; Maxim Bester ; Fabian Flottmann ; Daniel Arvid Weiß ; Marius Kaschner ; Peter T. Kan ; Gautam Edhayan ; Michael R. Levitt ; Spencer L. Raub ; Mira Katan ; Urs Fischer ; Marios-Nikos Psychogios
Introduction: Thrombectomy complications remain poorly explored. This study aims to characterize periprocedural intracranial vessel perforation including the effect of thrombolysis on patient outcomes. - Patients and methods: In this multicenter retrospective cohort study, consecutive patients with vessel perforation during thrombectomy between January 2015 and April 2023 were included. Vessel perforation was defined as active extravasation on digital subtraction angiography. The primary outcome was modified Rankin Scale (mRS) at 90 days. Factors associated with the primary outcome were assessed using proportional odds models. - Results: 459 patients with vessel perforation were included (mean age 72.5 ± 13.6 years, 59% female, 41% received thrombolysis). Mortality at 90 days was 51.9% and 16.3% of patients reached mRS 0-2 at 90 days. Thrombolysis was not associated with worse outcome at 90 days. Perforation of a large vessel (LV) as opposed to medium/distal vessel perforation was independently associated with worse outcome at 90 days (aOR 1.709, p = 0.04) and LV perforation was associated with poorer survival probability (HR 1.389, p = 0.021). Patients with active bleeding >20 min had worse survival probability, too (HR 1.797, p = 0.009). Thrombolysis was not associated with longer bleeding duration. Bleeding cessation was achieved faster by permanent vessel occlusion compared to temporary measures (median difference: 4 min, p < 0.001). - Discussion and conclusion: Vessel perforation during thrombectomy is a severe and frequently fatal complication. This study does not suggest that thrombolysis significantly attributes to worse prognosis. Prompt cessation of active bleeding within 20 min is critical, emphasizing the need for interventionalists to be trained in complication management.
European stroke journal Oxford : Oxford University Press, 2016 10(2025), 1, Seite 63-73 Online-Ressource
von Ibrahim Alkatout ; Rudy Leon de Wilde ; Jörg Herrmann ; Rüdiger Klapdor ; Ivo Meinhold-Heerlein ; József Mészáros ; Alexander Mustea ; Peter Oppelt ; Julian Maria Pape ; Sebastian Daniel Schäfer ; Markus Wallwiener ; Bernhard Krämer
von Rong Fang ; Marco Düring ; Felix J. Bode ; Sebastian Stösser ; Julius Nicolai Meißner ; Peter Hermann ; Thomas Liman ; Christian H. Nolte ; Lucia Kerti ; Benno Ikenberg ; Kathleen Bernkopf ; Wenzel Glanz ; Daniel Janowitz ; Michael Wagner ; Katja Neumann ; Oliver Speck ; Emrah Düzel ; Benno Gesierich ; Anna Dewenter ; Annika Spottke ; Karin Waegemann ; Michael Görtler ; Silke Wunderlich ; Inga Zerr ; Gabor Petzold ; Matthias Endres ; Marios K. Georgakis ; Martin Dichgans
von Friederike A. Arlt ; Pia S. Sperber ; Regina von Rennenberg ; Pimrapat Gebert ; Bianca Teegen ; Marios K. Georgakis ; Rong Fang ; Anna Dewenter ; Michael Görtler ; Gabor Petzold ; Silke Wunderlich ; Inga Zerr ; Martin Dichgans ; Harald Prüß ; Matthias Endres
Thomas Liman; Christian H Nolte; Lucia Kerti; Tatjana Wittenberg; Jan Friedrich Scheitz; Alexander Heinrich Nave; Anna Kufner; Felix J Bode; Sebastian Stösser; Julius Nicolai Meißner; Taraneh Ebrahimi; Julia Nordsiek; Niklas Michael Beckonert; Peter Hermann; Matthias Schmitz; Stefan Goebel; Julia Schütte-Schmidt; Sabine Nuhn; Corinna Volpers; Peter Dechent; Matthias Bähr; Wenzel Glanz; Steffen Tiedt; Karin Waegemann; Daniel Janowitz; Benno Ikenberg; Kathleen Bermkopf; Christiane Huber; Michael Wagner; Katja Neumann; Annika Spottke; Tony Stöcker; Marco Dühring; Oliver Speck; Emrah Düzel; Peter Bartenstein
