Lancet neurology
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Randomized Controlled Trial Multicenter Study
Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study.
Given burdensome side-effects and long latency for efficacy with conventional agents, there is a continued need for generalised myasthenia gravis treatments that are safe and provide consistently sustained, long-term disease control. Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with generalised myasthenia gravis in a phase 2 study. We aimed to assess the safety and efficacy of nipocalimab in a phase 3 study. ⋯ Janssen Research & Development, LLC, a Johnson & Johnson company.
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Randomized Controlled Trial Multicenter Study
Safety and efficacy of satralizumab in patients with generalised myasthenia gravis (LUMINESCE): a randomised, double-blind, multicentre, placebo-controlled phase 3 trial.
Evidence from preclinical studies suggests that IL-6 signalling has the potential to modulate immunopathogenic mechanisms upstream of autoantibody effector mechanisms in patients with generalised myasthenia gravis. We aimed to assess the safety and efficacy of satralizumab, a humanised monoclonal antibody targeting the IL-6 receptor, in patients with generalised myasthenia gravis. ⋯ F Hoffmann La Roche.
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Review
Unique considerations in the assessment and management of traumatic brain injury in older adults.
The age-specific incidence of traumatic brain injury in older adults is rising in high-income countries, mainly due to an increase in the incidence of falls. The severity of traumatic brain injury in older adults can be underestimated because of a delay in the development of mass effect and symptoms of intracranial haemorrhage. Management and rehabilitation in older adults must consider comorbidities and frailty, the treatment of pre-existing disorders, the reduced potential for recovery, the likelihood of cognitive decline, and the avoidance of future falls. ⋯ Although prognostication is uncertain, unsubstantiated nihilism (eg, early withdrawal decisions from the assumption that old age necessarily leads to poor outcomes) should be avoided. The absence of management recommendations for older adults highlights the need for stronger evidence to enhance prognostication. In the meantime, decision making should be multidisciplinary, transparent, personalised, and inclusive of patients and relatives.
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Autosomal dominant mutations in the gene encoding the DNA and RNA binding protein FUS are a cause of amyotrophic lateral sclerosis (ALS), and about 0·3-0·9% of patients with ALS are FUS mutation carriers. FUS-mutation-associated ALS (FUS-ALS) is characterised by early onset and rapid progression, compared with other forms of ALS. However, different pathogenic mutations in FUS can result in markedly different age at symptom onset and rate of disease progression. ⋯ FUS also forms inclusions in around 5% of patients with the related neurodegenerative condition frontotemporal dementia. However, there are key differences between the two diseases at the genetic and neuropathological level, which suggest distinct pathogenic processes. Experimental models have uncovered potential pathogenic mechanisms in FUS-ALS and informed therapeutic strategies that are currently in development, including the silencing of FUS expression using an intrathecally administered antisense oligonucleotide.