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 Octavia-Andreea Ciora ; Tanja Seegmüller ; Johannes S. Fischer ; Theresa Wirth ; Friederike Häfner ; Sophia Stoecklein ; Andreas W. Flemmer ; Kai Förster ; Alida Kindt ; Dirk Bassler ; Christian F. Poets ; Narges Ahmidi ; Anne Hilgendorff
Schmidt, Albrecht Extended Abstracts of the 2023 CHI Conference on Human Factors in Computing Systems New York,NY,United States : Association for Computing Machinery, 2023 (2023), Artikel-ID 477, Seite 1-5
Immersive and high-quality VR-based telepresence systems could be of great benefit in the medical field and the operating room (OR) specifically, as they allow distant experts to interact with each other and to assist local doctors as if they were physically present. Despite recent advances in VR technology, and more telepresence systems making use of it, most of the current solutions in use in health care (if any), are just video-based and don’t provide the feeling of presence or spatial awareness, which are highly important for tasks such as remote consultation, -supervision, and -teaching. Reasons still holding back VR telepresence systems are high demands regarding bandwidth and computational power, subpar visualization quality, and complicated setups. We propose an easy-to-set-up telepresence system that enables remote experts to meet in a multi-user virtual operating room, view live-streamed and 3D-visualized operations, interact with each other, and collaboratively explore medical data. Our system is based on Azure Kinect RGB-D cameras, a point cloud streaming pipeline, and fast point cloud rendering methods integrated into a state-of-the-art 3D game engine. Remote experts are visualized via personalized real-time 3D point cloud avatars. For this, we have developed a high-speed/low-latency multi-camera point cloud streaming pipeline including efficient filtering and compression. Furthermore, we have developed splatting-based and mesh-based point cloud rendering solutions and integrated them into the Unreal Engine 4. We conducted two user studies with doctors and medical students to evaluate our proposed system, compare the rendering solutions, and highlight our system’s capabilities.
Virtual Reality and Mixed Reality 1st ed. 2022. Cham : Springer International Publishing, 2022 (2022), Seite 89-110 1 Online-Ressource(XII, 219 p. 72 illus., 60 illus. in color.)
von Tim Van Damme ; Thatjana Gardeitchik ; Miski Mohamed ; Sergio Guerrero-Castillo ; Peter Freisinger ; Brecht Guillemyn ; Ariana Kariminejad ; Daisy Dalloyaux ; Sannevan Kraaij ; Dirk J. Lefeber ; Delfien Syx ; Wouter Steyaert ; Riet De Rycke ; Alexander Hoischen ; Erik-Jan Kamsteeg ; Sunnie Y. Wong ; Monique van Scherpenzeel ; Payman Jamili ; Ulrich Brandt ; Leo Nijtmans ; Christoph Korenke ; Brian H.Y. Chung ; Christopher C.Y. Mak ; Ingrid Hausser ; Uwe Kornak ; Björn Fischer-Zirnsak ; Tim M. Strom ; Thomas Meitinger ; Yasemin Alanay ; Gulem E. Utine ; Peter K.C. Leung ; Siavash Ghaderi-Sohi ; Paul Coucke ; Sofie Symoens ; Anne De Paepe ; Christian Thiel ; Tobias B. Haack ; Fransiska Malfait ; Eva Morava ; Bert Callewaert ; Ron A. Wevers
1-deoxy-sphingolipids; Charcot-Marie-Tooth disease; hereditary neuropathy; next generation sequencing; small fiber neuropathy
Hereditary neuropathies comprise a wide variety of chronic diseases associated to more than 80 genes identified to date. We herein examined 612 index patients with either a Charcot-Marie-Tooth phenotype, hereditary sensory neuropathy, familial amyloid neuropathy, or small fiber neuropathy using a customized multigene panel based on the next generation sequencing technique. In 121 cases (19.8%), we identified at least one putative pathogenic mutation. Of these, 54.4% showed an autosomal dominant, 33.9% an autosomal recessive, and 11.6% an X-linked inheritance. The most frequently affected genes were PMP22 (16.4%), GJB1 (10.7%), MPZ, and SH3TC2 (both 9.9%), and MFN2 (8.3%). We further detected likely or known pathogenic variants in HINT1, HSPB1, NEFL, PRX, IGHMBP2, NDRG1, TTR, EGR2, FIG4, GDAP1, LMNA, LRSAM1, POLG, TRPV4, AARS, BIC2, DHTKD1, FGD4, HK1, INF2, KIF5A, PDK3, REEP1, SBF1, SBF2, SCN9A, and SPTLC2 with a declining frequency. Thirty-four novel variants were considered likely pathogenic not having previously been described in association with any disorder in the literature. In one patient, two homozygous mutations in HK1 were detected in the multigene panel, but not by whole exome sequencing. A novel missense mutation in KIF5A was considered pathogenic because of the highly compatible phenotype. In one patient, the plasma sphingolipid profile could functionally prove the pathogenicity of a mutation in SPTLC2. One pathogenic mutation in MPZ was identified after being previously missed by Sanger sequencing. We conclude that panel based next generation sequencing is a useful, time- and cost-effective approach to assist clinicians in identifying the correct diagnosis and enable causative treatment considerations.
Journal of neurochemistry Oxford : Wiley-Blackwell, 1956 143(2017), 5, Seite 507-522 Online-Ressource
Defects of the V-type proton (H+) ATPase (V-ATPase) impair acidification and intracellular trafficking of membrane-enclosed compartments, including secretory granules, endosomes, and lysosomes. Whole-exome sequencing in five families affected by mild to severe cutis laxa, dysmorphic facial features, and cardiopulmonary involvement identified biallelic missense mutations in ATP6V1E1 and ATP6V1A, which encode the E1 and A subunits, respectively, of the V1 domain of the heteromultimeric V-ATPase complex. Structural modeling indicated that all substitutions affect critical residues and inter- or intrasubunit interactions. Furthermore, complexome profiling, a method combining blue-native gel electrophoresis and liquid chromatography tandem mass spectrometry, showed that they disturb either the assembly or the stability of the V-ATPase complex. Protein glycosylation was variably affected. Abnormal vesicular trafficking was evidenced by delayed retrograde transport after brefeldin A treatment and abnormal swelling and fragmentation of the Golgi apparatus. In addition to showing reduced and fragmented elastic fibers, the histopathological hallmark of cutis laxa, transmission electron microscopy of the dermis also showed pronounced changes in the structure and organization of the collagen fibers. Our findings expand the clinical and molecular spectrum of metabolic cutis laxa syndromes and further link defective extracellular matrix assembly to faulty protein processing and cellular trafficking caused by genetic defects in the V-ATPase complex.
The American journal of human genetics New York, NY [u.a.] : Cell Press, 1949 100(2017), 2, Seite 216-227
