Clinical medicine (London, England)
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Multidrug-resistant tuberculosis (MDR TB) is a significant threat to global health estimated to account for nearly half a million new cases and over 200,000 deaths in 2013. The number of MDR TB cases in the UK has risen over the last 15 years, with ever more complex clinical cases and associated challenging public health and societal implications. In this review, we provide an overview of the epidemiology of MDR TB globally and in the UK, outline the clinical management of MDR TB and summarise recent advances in diagnostics and prospects for new treatment.
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Chronic hepatitis caused by hepatitis C virus infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma globally. Over the last few years, there have been significant advances in our understanding of the immunopathogenesis of this infection, as well as revolutionary developments in the therapeutic armamentarium. ⋯ Nonetheless, a number of clinical scenarios remain challenging and research is ongoing in these areas. In this update, we review developments in both basic as well as translational research in the field.
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Since the advent of modern molecular tools, researchers have extensively shown that essential cellular machineries have robust circadian (roughly 24 hours) variations in their pace. This molecular rhythmicity translates directly into time-of-day-dependent variation in physiology in most organ systems, which in turn provides the mechanistic rationale for why timing on a daily basis should matter in many aspects of human health. ⋯ Therefore, it has not been clear how physicians should incorporate knowledge of natural 24-hour rhythms into routine practice. This review is a brief summary of results from recently completed clinical studies on hypertension, myocardial infarction, diabetes mellitus, and adrenal dysfunction that highlights new evidence for the emerging importance of circadian rhythms in diagnosis, prognosis and treatment of disease.
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Systemic sclerosis is the most severe disease within the scleroderma spectrum and is a major medical challenge with high mortality and morbidity. There have been advances in understanding of pathogenesis that reflect the interplay between immune-inflammatory processes and vasculopathy and fibrosis. ⋯ Treatment is available for many aspects of the disease although the available therapies are not curative and some complications remain very challenging, especially non-lethal manifestations such as fatigue, calcinosis and anorectal dysfunction. Immunosuppression is now established as a beneficial approach but balancing risk and benefit is vital, especially for powerful approaches such as autologous stem cell transplantation.
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There is a growing understanding of the epigenetic mechanisms that regulate gene expression in healthy conditions and a realisation that dysregulation of these mechanisms is an underlying factor in many human diseases. We discuss studies demonstrating that small molecule inhibitors of epigenetic regulatory proteins can block pathogenic mechanisms associated with rheumatoid arthritis, focusing on the effects of these inhibitors on synovial fibroblasts-fibroblast-like synoviocytes.