Lancet neurology
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Globally, up to 1·5 million individuals with ischaemic stroke or transient ischaemic attack can be newly diagnosed with atrial fibrillation per year. In the past decade, evidence has accumulated supporting the notion that atrial fibrillation first detected after a stroke or transient ischaemic attack differs from atrial fibrillation known before the occurrence of as stroke. ⋯ Patients with ischaemic stroke or transient ischaemic attack can be classified in three categories: no atrial fibrillation, known atrial fibrillation before stroke occurrence, and atrial fibrillation detected after stroke. This classification could harmonise future research in the field and help to understand the role of prolonged cardiac monitoring for secondary stroke prevention with application of a personalised risk-based approach to the selection of patients for anticoagulation.
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Randomized Controlled Trial
Safety and efficacy of factor XIa inhibition with milvexian for secondary stroke prevention (AXIOMATIC-SSP): a phase 2, international, randomised, double-blind, placebo-controlled, dose-finding trial.
People with factor XI deficiency have lower rates of ischaemic stroke than the general population and infrequent spontaneous bleeding, suggesting that factor XI has a more important role in thrombosis than in haemostasis. Milvexian, an oral small-molecule inhibitor of activated factor XI, added to standard antiplatelet therapy, might reduce the risk of non-cardioembolic ischaemic stroke without increasing the risk of bleeding. We aimed to estimate the dose-response of milvexian for recurrent ischaemic cerebral events and major bleeding in patients with recent ischaemic stroke or transient ischaemic attack (TIA). ⋯ Bristol Myers Squibb and Janssen Research & Development.
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Randomized Controlled Trial
Safety, tolerability, and efficacy of NLY01 in early untreated Parkinson's disease: a randomised, double-blind, placebo-controlled trial.
Converging lines of evidence suggest that microglia are relevant to Parkinson's disease pathogenesis, justifying exploration of therapeutic agents thought to attenuate pathogenic microglial function. We sought to test the safety and efficacy of NLY01-a brain-penetrant, pegylated, longer-lasting version of exenatide (a glucagon-like peptide-1 receptor agonist) that is believed to be anti-inflammatory via reduction of microglia activation-in Parkinson's disease. ⋯ D&D Pharmatech-Neuraly.
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Established by brain endothelial cells, the blood-brain barrier (BBB) regulates the trafficking of molecules, restricts immune cell entry into the CNS, and has an active role in neurovascular coupling (the regulation of cerebral blood flow to support neuronal activity). In the early stages of multiple sclerosis, around the time of symptom onset, inflammatory BBB damage is accompanied by pathogenic immune cell infiltration into the CNS. ⋯ Damage to brain endothelial cells leads to an influx of deleterious molecules into the CNS, accelerating leakage across the BBB. Potential future therapeutic approaches might help to prevent BBB damage (eg, monoclonal antibodies targeting cell adhesion molecules and fibrinogen) and help to repair BBB dysfunction (eg, mesenchymal stromal cells) in people with multiple sclerosis.
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Multicenter Study Observational Study
Clinical descriptors of disease trajectories in patients with traumatic brain injury in the intensive care unit (CENTER-TBI): a multicentre observational cohort study.
Patients with traumatic brain injury are a heterogeneous population, and the most severely injured individuals are often treated in an intensive care unit (ICU). The primary injury at impact, and the harmful secondary events that can occur during the first week of the ICU stay, will affect outcome in this vulnerable group of patients. We aimed to identify clinical variables that might distinguish disease trajectories among patients with traumatic brain injury admitted to the ICU. ⋯ European Union 7th Framework program, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences Corporation, and NeuroTrauma Sciences.