Online verfügbar: 13. Februar 2025 ; Gesehen am 10.09.2025
Background - In the ESCAPE-NA1 trial, treatment with nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, was associated with improved functional outcome among patients with acute ischaemic stroke due to large vessel occlusion undergoing endovascular thrombectomy without co-treatment with an intravenous thrombolytic agent. There was no benefit when intravenous thrombolytic agent co-treatment was used. We sought to confirm the clinical benefit of nerinetide in the absence of previous intravenous thrombolytic drug treatment. - Methods - In this multicentre, randomised, double-blind, placebo-controlled study, done in 77 centres in Canada (16), the USA (16), Germany (21), Italy (four), the Netherlands (three), Norway (four), Switzerland (three), Australia (eight), and Singapore (two), we enrolled patients with acute ischaemic stroke due to anterior circulation large vessel occlusion within 12 h from onset. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation (baseline National Institutes of Health Stroke Scale [NIHSS] score >5), who had been functioning independently in the community (Barthel Index score >90) before the stroke, had Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and who were not treated with a plasminogen activator. Patients were randomly allocated (1:1) to receive intravenous infusion of nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, based upon estimated or actual weight (if known) or saline placebo using a real-time, dynamic, internet-based, stratified randomised minimisation procedure. All patients underwent endovascular thrombectomy. The primary outcome was a favourable functional outcome 90 days from randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. The analysis was by intention to treat and adjusted for time from stroke onset to randomisation (≤4·5 h [yes or no]), age, sex, baseline NIHSS score, occlusion location, time from qualifying imaging to randomisation, baseline ASPECTS, and region. Secondary outcomes were measures of mortality, worsening of stroke, improved functional independence, and measures of neurological disability. This trial is registered with ClinicalTrials.gov, NCT04462536. - Findings - From Dec 6, 2020, to Jan 31, 2023, 850 patients were assigned to receive nerinetide (n=454) or placebo (n=396). 206 (45%) participants in the nerinetide group and 181 (46%) participants in the placebo group achieved an mRS score of 0-2 at 90 days (odds ratio 0·97, 95% CI 0·72-1·30; p=0·82). Serious adverse events occurred equally between groups. - Interpretation - While nerinetide did not improve outcomes in patients with acute ischaemic stroke, it was not associated with excess adverse events. Further study is needed to identify the ideal timing of treatment and the sub-population of stroke patients who might benefit from treatment combined with current reperfusion therapies. - Funding - Canadian Institutes for Health Research and NoNO.
The lancet London [u.a.] : Elsevier, 1823 405(2025), 10478 vom: Feb., Seite 560-570 Online-Ressource
von Patrik Greguletz ; Maria Plötz ; Carolin Baade-Büttner ; Christian G. Bien ; Katharina Eisenhut ; Christian Geis ; Robert Handreka ; Jaqueline Klausewitz ; Péter Körtvélyessy ; Stjepana Kovać ; Andrea Kraft ; Jan Lewerenz ; Michael Peter Malter ; Michael Nagel ; Felix von Podewils ; Harald Prüß ; Anna Rada ; Johanna Maria Helena Rau ; Sebastian Rauer ; Rosa Rößling ; Thomas Seifert-Held ; Kai Siebenbrodt ; Kurt-Wolfram Sühs ; Simone Constanze Tauber ; Franziska Thaler ; Judith Wagner ; Jonathan Wickel ; Frank Leypoldt ; Heike Rittner ; Claudia Sommer ; Carmen Villmann ; Kathrin Janina Doppler ; Karsten Witt
von Julie George ; Lukas Maas ; Nima Abedpour ; Maria Cartolano ; Laura Kaiser ; Rieke Nila Fischer ; Andreas H. Scheel ; Jan-Philipp Weber ; Martin Hellmich ; Graziella Bosco ; Caroline Volz ; Christian Müller ; Ilona Dahmen ; Felix John ; Cleidson Padua Alves ; Lisa Werr ; Jens Peter Panse ; Martin Kirschner ; Walburga Engel-Riedel ; Jessica Jürgens ; Erich Stoelben ; Michael Brockmann ; Stefan Grau ; Martin Sebastian ; Jan Alexander Stratmann ; Jens Kern ; Horst-Dieter Hummel ; Balazs Hegedus ; Martin Schuler ; Till Plönes ; Clemens Aigner ; Thomas Elter ; Karin Toepelt ; Yon-Dschun Ko ; Sylke Kurz ; Christian Grohé ; Monika Serke ; Katja Anne Höpker ; Lars Gerd Hagmeyer ; Fabian Doerr ; Khosro Hekmath ; Judith Strapatsas ; Karl-Otto Kambartel ; Geothy Chakupurakal ; Annette Hülsmeyer ; Franz-Georg Bauernfeind ; Frank Griesinger ; Anne Lüers ; Wiebke Dirks ; Rainer Gerhard Wiewrodt ; Andrea Luecke ; Ernst Michael Rodermann ; Andreas Diel ; Volker Hagen ; Kai Severin ; Roland Ullrich ; Christian Reinhardt ; Alexander Quaas ; Magdalena Bogus ; Cornelius Courts ; Peter Nürnberg ; Kerstin Becker ; Viktor Achter ; Reinhard Büttner ; Jürgen Wolf ; Martin Peifer ; Roman Thomas
Der Artikel Revision of the “Guideline of the German Medical Association on Quality Assurance in Medical Laboratory Examinations - Rili-BAEK” wurde am 1. Dezember 2024 in der Zeitschrift Journal of Laboratory Medicine (Band 48, Heft 6) veröffentlicht.
Journal of laboratory medicine Berlin : De Gruyter, 2018 48(2024), 6, Seite 263-306
Royal Society (London) Proceedings. Mathematical, physical and engineering sciences London : [Verlag nicht ermittelbar], 1996 479(2023), 2275 Online-Ressource
In dieser Arbeit wurde der prognostische Einfluss von Immunzellsubpopulationen der B- und T-Lymphozyten in der direkten Tumorumgebung sowie von Treibermutationen in Abhängigkeit von Checkpointproteinen und dem klinischen Tumorstadium untersucht. Hierfür erfolgte die immunhistochemische Untersuchung von 156 Adenokarzinomen der Lunge sowie die NGS Sequenzierung von 17 therapierelevanten Genen der Tumor-DNA. Bei 100 dieser Fälle war der Vitalstatus bekannt. In der Korrelationsanalyse konnte u.a. ein signifikant geringeres Auftreten von CD8+ TILs, CD20+ B-TILs im Stadium IV nachgewiesen werden. Einen signifikanten Einfluss auf die Immunzellen der direkten Tumorumgebung wies ebenfalls ein Expressionsstatus von >50% PD-L1+ Tumorzellen sowie das Vorhandensein bestimmter Treibermutationen auf. Als prognostisch günstig für das Überleben der Patienten wurden hierbei hohe Anzahlen von CD3+ und CD20+ TILs sowie CD19+ B-Follikel identifiziert.
In this study we investigated the prognostic value of the immune cell subpopulations of B- and T-cells in the tumormicroenvironment as well as drivermutations and checkpointproteins in different clinical tumor stages. We performed immunhistochemical investigations of 156 adenocarcinomas of the Lung and NGS-sequencing of 17 therapeutic significant gene-sequences in the tumor-DNA. Survival outcome was known in 100 of these cases. Statistical analysis displayed a significant decrease in cell numbers of CD8+, CD20+ TILs as well as CD19+ B-follicles in stage IV disease. Other significant influences on the immune cells in the direct tumorenvironment were a PD-L1 expression status of >50% tumor cells and a decrease in numbers of CD19+ B-follicles and CD20+ B-TILS in the direct tumor microenvironment in case of positive mutationstatus for drivermutations. Prognostic significance could be shown for high numbers of CD3+ and CD20+ Tils as well as CD19+ B-follicles.
The aim of the dissertation was to detect rubber inflatables carrying migrants and refugees using remote sensing data. The research follows the vision of providing civilian rescue teams on the ground with situational images to support their search for boats in distress. We utilised synthetic aperture radar (SAR) to provide a search infrastructure for maritime rescue operations that is independent of the time of day and weather conditions. We carried out two measurement campaigns lasting around six months with a 12m-long inflatable boat to collect SAR images from various satellites and analysed the results. In this way, we gained a comprehensive understanding of the radar patterns of inflatable boats in SAR data and were able to show that automated detection is possible. As part of the work, existing ship detectors were systematically analysed and new detectors specially adapted to the test object were developed.
Ziel der Dissertation war es, mit MigrantInnen und Geflüchteten besetzte Schlauchboote mittels Fernerkundungsdaten zu detektieren. Die Forschung folgt der Vision, zivilen Rettungskräfte vor Ort Lagebilder zu liefern um deren Suche nach Booten in Seenot zu unterstützen. Um eine tageszeit- und witterungsunabhängige Suchinfrastruktur für die maritime Seenotrettung zu ermöglichen, nutzten wir „Synthetic Aperture Radar“ (SAR). Wir führten zwei ca. sechsmonatige Messkampagnen mit einem 12m langen Fluchtschlauchboot durch, um SAR-Bilder verschiedener Satelliten zu sammeln und werteten die Ergebnisse aus. Damit schufen wir ein umfassendes Verständnis der Radarmustern von Schlauchbooten in SAR-Daten und konnten zeigen, dass eine Detektion möglich ist. Im Rahmen der Arbeit wurden systematisch existierende Schiffsdetektoren untersucht und daraus neue, speziell auf das Testobjekt abgestimmte Detektoren entwickelt.
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