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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The twin cycle hypothesis postulated that type 2 diabetes was a result of excess liver fat causing excess supply of fat to the pancreas with resulting dysfunction of both organs. If this was so, the condition should be able to be returned to normal by calorie restriction. The Counterpoint study tested this prediction in short-duration type 2 diabetes and showed that liver glucose handling returned to normal within 7 days and that beta-cell function returned close to normal over 8 weeks. ⋯ Remission is independent of BMI, underscoring the personal fat threshold concept that type 2 diabetes develops when an individual acquires more fat than can be individually tolerated even at a BMI which in the nonobese range. Observations on people of South Asian or Afro-American ethnicity confirm that substantial weight loss achieves remission in the same way as in the largely White Europeans studied in detail. Diagnosis of type 2 diabetes can now be regarded as an urgent signal that weight loss must be achieved to avoid a progressive decline of health.
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Ageing of the population, together with population growth, has brought along an ample increase in the number of older individuals living with dementia and disabilities. Dementia is the main cause of disability in old age, and promoting healthy brain ageing is considered as a key element in diminishing the burden of age-related disabilities. The World Health Organization recently launched the first risk reduction guidelines for cognitive impairment and dementia. ⋯ Within the World-Wide FINGERS network, the multidomain FINGER concept is now tested and adapted worldwide proving evidence and tools for effective and easily implementable preventive strategies. Close collaboration between researchers, policymakers and healthcare practitioners, involvement of older adults and utilization of new technologies to support self-management is needed to facilitate the implementation of the research findings. In this scoping review, we present the current scientific evidence in the field of dementia and disability prevention and discuss future directions in the field.
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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.