Journal of internal medicine
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Review
Current and emerging disease-modulatory therapies and treatment targets for multiple sclerosis.
The treatment of multiple sclerosis (MS), the most common chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS), continues to transform. In recent years, a number of novel and increasingly effective disease-modulatory therapies (DMTs) have been approved, including oral fumarates and selective sphingosine 1-phosphate modulators, as well as cell-depleting therapies such as cladribine, anti-CD20 and anti-CD52 monoclonals. Amongst DMTs in clinical development, inhibitors of Bruton's tyrosine kinase represent an entirely new emerging drug class in MS, with three different drugs entering phase III trials. ⋯ An additional aim is to review emerging therapies undergoing clinical development, including agents that interfere with disease processes believed to be important for neurodegeneration or aiming to enhance reparative responses. Notably, early trials now have shown initial evidence of enhanced remyelination both with small molecule compounds and biologicals. Finally, accumulating evidence from clinical trials and post-marketing real-world patient populations, which underscore the importance of early high effective therapy whilst maintaining acceptable tolerability, is discussed.
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Sepsis represents one of the major medical challenges of the 21st century. Despite substantial improvements in the knowledge on pathophysiological mechanisms, this has so far not translated into novel adjuvant treatment strategies for sepsis. In sepsis, both vascular tone and vascular integrity are compromised, and contribute to the development of shock, which is strongly related to the development of organ dysfunction and mortality. ⋯ We now discuss new evidence illustrating that these molecules indeed represent two distinct pathways involved in the development of septic shock. Recently, both ADM-enhancing therapies aimed at improving endothelial barrier function and vascular tone and DPP3-blocking therapies aimed at restoring systemic angiotensin responses have been shown to improve outcome in various preclinical sepsis models. Given the current lack of effective adjuvant therapies in sepsis, additional research on the therapeutic application of these peptides in humans is highly warranted.
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Observational Study
Hypoalbuminemia in COVID-19: assessing the hypothesis for underlying pulmonary capillary leakage.
Since the first observations of patients with COVID-19, significant hypoalbuminaemia was detected. Its causes have not been investigated yet. ⋯ Hypoalbuminaemia may serve as severity marker of epithelial-endothelial damage in patients with COVID-19. There are clues that pulmonary capillary leak syndrome plays a key role in the pathogenesis of COVID-19 and might be a potential therapeutic target.
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SARS-CoV-2, the COVID-19 causative agent, has infected millions of people and killed over 1.6 million worldwide. A small percentage of cases persist with prolonged positive RT-PCR on nasopharyngeal swabs. The aim of this study was to determine risk factors for prolonged viral shedding amongst patient's basal clinical conditions. ⋯ We found that chronic rhinosinusitis and atopy might be associated with increased risk of prolonged viral shedding. If confirmed in prospective trials, this finding might have clinical implications for quarantine duration due to increased risk of pandemic spread.
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Wild-type transthyretin (ATTRwt) amyloidosis is the most common systemic amyloidosis in Western countries and manifests mainly as progressive restrictive cardiomyopathy. ⋯ The prevalence of ATTR deposits in ligamentum flavum in patients with lumbar spinal stenosis was high but not associated with manifest ATTR cardiac amyloidosis. However, the findings of fibril type A, the prevalence of previous carpal tunnel syndrome and ATTR amyloid in surrounding adipose and vascular tissue indicate that amyloid deposits in ligamentum flavum may be an early manifestation of systemic ATTR disease.