@article{HerzbergScherlingStahletal.2021, author = {Herzberg, Moritz and Scherling, Korbinian and Stahl, Robert and Tiedt, Steffen and Wollenweber, Frank A. and K{\"u}pper, Clemens and Feil, Katharina and Forbrig, Robert and Patzig, Maximilian and Kellert, Lars and Kunz, Wolfgang G. and Reidler, Paul and Zimmermann, Hanna and Liebig, Thomas and Dieterich, Marianne and Dorn, Franziska}, title = {Late Thrombectomy in Clinical Practice: Retrospective Application of DAWN/DEFUSE3 Criteria within the German Stroke Registry}, series = {Clinical Neuroradiology}, volume = {31}, journal = {Clinical Neuroradiology}, number = {3}, doi = {10.1007/s00062-021-01033-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264765}, pages = {799-810}, year = {2021}, abstract = {Background and Purpose To provide real-world data on outcome and procedural factors of late thrombectomy patients. Methods We retrospectively analyzed patients from the multicenter German Stroke Registry. The primary endpoint was clinical outcome on the modified Rankin scale (mRS) at 3 months. Trial-eligible patients and the subgroups were compared to the ineligible group. Secondary analyses included multivariate logistic regression to identify predictors of good outcome (mRS ≤ 2). Results Of 1917 patients who underwent thrombectomy, 208 (11\%) were treated within a time window ≥ 6-24 h and met the baseline trial criteria. Of these, 27 patients (13\%) were eligible for DAWN and 39 (19\%) for DEFUSE3 and 156 patients were not eligible for DAWN or DEFUSE3 (75\%), mainly because there was no perfusion imaging (62\%; n = 129). Good outcome was not significantly higher in trial-ineligible (27\%) than in trial-eligible (20\%) patients (p = 0.343). Patients with large trial-ineligible CT perfusion imaging (CTP) lesions had significantly more hemorrhagic complications (33\%) as well as unfavorable outcomes. Conclusion In clinical practice, the high number of patients with a good clinical outcome after endovascular therapy ≥ 6-24 h as in DAWN/DEFUSE3 could not be achieved. Similar outcomes are seen in patients selected for EVT ≥ 6 h based on factors other than CTP. Patients triaged without CTP showed trends for shorter arrival to reperfusion times and higher rates of independence.}, language = {en} } @article{WelkerKerstenMuelleretal.2021, author = {Welker, Armin and Kersten, Christian and M{\"u}ller, Christin and Madhugiri, Ramakanth and Zimmer, Collin and M{\"u}ller, Patrick and Zimmermann, Robert and Hammerschmidt, Stefan and Maus, Hannah and Ziebuhr, John and Sotriffer, Christoph and Schirmeister, Tanja}, title = {Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2}, series = {ChemMedChem}, volume = {16}, journal = {ChemMedChem}, number = {2}, doi = {10.1002/cmdc.202000548}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225700}, pages = {340 -- 354}, year = {2021}, abstract = {Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PL\(^{pro}\)) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide (2 b), which is known to bind into the S3 and S4 pockets of the SARS-CoV PL\(^{pro}\). Moreover, we report the discovery of isoindolines as a new class of potent PL\(^{pro}\) inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PL\(^{pro}\) are valuable starting points for the development of new pan-coronaviral inhibitors.}, language = {en} }