Journal of internal medicine
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Osteoarthritis (OA) is a chronic joint disease caused by disruption of joint homeostasis by a variety of systemic and biomechanical factors. The disease is characterized by degradation of cartilage and other joint tissues, and low-grade inflammation which may result in pain, reduced function, and disability. The disease appears to have ancient origins, with findings of OA recognized in fossilized bones from birdlike dinosaurs living some 130 million years ago. ⋯ Current development of drug candidates, aimed to restore joint homeostasis, is mainly targeting either inhibition of catabolic factors or stimulation of anabolic factors. However, there is yet no breakthrough in stage III clinical trials. Earlier diagnosis, better knowledge of endotypes-for example, by new insights into soluble biomarkers, and compositional imaging-and more careful selection of patients into clinical trials are possible tools to aid development of future therapies.
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Sarcoidosis is characterized by noncaseating granulomas which form in almost any part of the body, primarily in the lungs and/or thoracic lymph nodes. Environmental exposures in genetically susceptible individuals are believed to cause sarcoidosis. There is variation in incidence and prevalence by region and race. ⋯ However, there is still much left to be discovered. The pervading challenge is how to account for patient variability. Future studies should focus on how to optimize current tools and develop new approaches so that treatment and follow-up can be targeted to individuals with more precision.
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Findings of liver enzyme elevations in recent cannabidiol studies have raised concerns over liver safety. This study aimed to determine the association between cannabidiol use, liver enzyme elevation, and drug-induced liver injury (DILI). ⋯ Cannabidiol-associated liver enzyme elevations and DILI meet the criteria of common adverse drug events. Clinicians are encouraged to screen for cannabidiol use and monitor liver function in patients at increased risk.
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Alcohol use is a major cause of disability and death globally. These negative consequences disproportionately affect people who develop alcohol addiction, a chronic relapsing condition characterized by increased motivation to use alcohol, choice of alcohol over healthy, natural rewards, and continued use despite negative consequences. Available pharmacotherapies for alcohol addiction are few, have effect sizes in need of improvement, and remain infrequently prescribed. ⋯ Two mechanisms in this category, antagonism at corticotropin-releasing factor type 1, and neurokinin 1/substance P receptors, have been subject to initial evaluation in humans. A third, kappa-opioid receptor antagonism, has been evaluated in nicotine addiction and could soon be tested for alcohol. This paper discusses findings with these mechanisms to date, and their prospects as future targets for novel medications.
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Sodium-glucose transport inhibitors (SGLT2i) are effective in heart failure (HF) with ejection fraction (EF) <40% (referred to as HF with reduced EF - HFrEF) and left ventricular EF (LVEF) >40%. Current evidence suggests that SGLT2i should be initiated across a large spectrum of EFs and renal function in patients with HF and with and without diabetes. We reviewed the benefits of SGLT2i in the entire spectrum of HF and provided some clues that may guide physicians in their strategy of initiating and maintaining SGLT2i (with or without SGLT1i effect) therapy. ⋯ SGLT2i appear to be effective and well-tolerated drugs in the majority of clinical HF scenarios, regardless of LVEF, estimated glomerular filtration rate, diabetic status or the level of the acuteness of the clinical setting. Therefore, most patients with HF should be treated with SGLT2i. However, in the face of the therapeutic inertia that has been observed in HF over the past decades, the actual implementation of SGLT2i in routine practice remains the most significant challenge.