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 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 London : Sage Publishing, 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
von Jürgen Beck ; Christian Fung ; Daniel Strbian ; Lukas Bütikofer ; Werner J. Z'Graggen ; Matthias F. Lang ; Seraina Beyeler ; Jan Gralla ; Florian Ringel ; Karl Schaller ; Nikolaus Plesnila ; Marcel Arnold ; Werner Hacke ; Peter Jüni ; Alexander David Mendelow ; Christian Stapf ; Rustam Al-Shahi Salman ; Jenny Bressan ; Stefanie Lerch ; Arsany Hakim ; Nicolas Martinez-Majander ; Anna Piippo-Karjalainen ; Peter Vajkoczy ; Stefan Wolf ; Gerrit A. Schubert ; Anke Höllig ; Michael Veldeman ; Roland Rölz ; Andreas Gruber ; Philip Rauch ; Dorothee Wachter ; Veit Rohde ; Thomas Kerz ; Eberhard Uhl ; Enea Thanasi ; Hagen B. Huttner ; Bernd Kallmünzer ; L. Jaap Kappelle ; Wolfgang Deinsberger ; Christian Roth ; Robin Lemmens ; Jan Leppert ; Jose L. Sanmillan ; Jonathan M. Coutinho ; Katharina Hackenberg ; Gernot Reimann ; Mikael Mazighi ; Claudio L. A. Bassetti ; Heinrich P. Mattle ; Andreas Raabe ; Urs Fischer ; Renán Sánchez-Porras
BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed. FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.
The lancet London [u.a.] : Elsevier, 1823 403(2024), 10442 vom: Juni, Seite 2395-2404 Online-Ressource
