Articles: function.
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Randomized Controlled Trial
Soluble Nogo-Receptor-Fc decoy (AXER-204) in patients with chronic cervical spinal cord injury in the USA: a first-in-human and randomised clinical trial.
Spinal cord injury (SCI) causes neural disconnection and persistent neurological deficits, so axon sprouting and plasticity might promote recovery. Soluble Nogo-Receptor-Fc decoy (AXER-204) blocks inhibitors of axon growth and promotes recovery of motor function after SCI in animals. This first-in-human and randomised trial sought to determine primarily the safety and pharmacokinetics of AXER-204 in individuals with chronic SCI, and secondarily its effect on recovery. ⋯ Wings for Life Foundation, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences, National Institute on Drug Abuse, and ReNetX Bio.
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Critical care medicine · Aug 2023
Long-Term Prognosis Following Early Rehabilitation in the ICU: A Retrospective Cohort Study.
Critically ill patients often have residual functional disabilities. Studies have shown that early rehabilitation improves short-term physical function. However, it remains unknown whether early rehabilitation affects long-term prognosis and healthcare resource utilization. ⋯ Starting rehabilitation within 3 days of ICU admission was associated with shorter durations of future hospitalization and lower healthcare costs. Early rehabilitation for ICU patients might be associated with reduced healthcare resource utilization.
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Practice Guideline
Respiratory Management of Patients with Neuromuscular Weakness: An American College of Chest Physicians Clinical Practice Guideline and Expert Panel Report.
Respiratory failure is a significant concern in neuromuscular diseases (NMDs). This CHEST guideline examines the literature on the respiratory management of patients with NMD to provide evidence-based recommendations. ⋯ Evidence of best practices for respiratory management in NMD is limited and is based primarily on observational data in amyotrophic lateral sclerosis. The panel found that pulmonary function testing every 6 months may be beneficial and may be used to initiate noninvasive ventilation (NIV) when clinically indicated. An individualized approach to NIV settings may benefit patients with chronic respiratory failure and sleep-disordered breathing related to NMD. When resources allow, polysomnography or overnight oximetry can help to guide the initiation of NIV. The panel provided guidelines for mouthpiece ventilation, transition to home mechanical ventilation, salivary secretion management, and airway clearance therapies. The guideline panel emphasizes that NMD pathologic characteristics represent a diverse group of disorders with differing rates of decline in lung function. The clinician's role is to add evaluation at the bedside to shared decision-making with patients and families, including respect for patient preferences and treatment goals, considerations of quality of life, and appropriate use of available resources in decision-making.
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Induced pluripotent stem cells (iPSCs) have enabled the generation of various difficult-to-access cell types such as human nociceptors. A key challenge associated with human iPSC-derived nociceptors (hiPSCdNs) is their prolonged functional maturation. While numerous studies have addressed the expression of classic neuronal markers and ion channels in hiPSCdNs, the temporal development of key signaling cascades regulating nociceptor activity has remained largely unexplored. ⋯ However, effective inhibition of forskolin-induced PKA-II activation by opioid receptor agonists required 70 days of in vitro differentiation. Our results identify a pronounced time difference between early expression of functionally important ion channels and emergence of regulatory metabotropic sensitizing and desensitizing signaling only at advanced stages of in vitro cultivation, suggesting an independent regulation of ionotropic and metabotropic signaling. These data are relevant for devising future studies into the development and regulation of human nociceptor function and for defining time windows suitable for hiPSCdN-based drug discovery.
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Breathlessness is the most common symptom in individuals with pleural effusion and is often disabling. The pathophysiology of breathlessness associated with pleural effusion is complex. ⋯ Impaired hemidiaphragm function and a compensatory increase in respiratory drive to maintain ventilation appear to be an important mechanism of breathlessness associated with pleural effusion. Thoracocentesis reduces diaphragm distortion and improves its movement; these changes appear to reduce respiratory drive and associated breathlessness by improving the neuromechanical efficiency of the diaphragm.