Lancet
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Remodelling is a response of the myocardium and vasculature to a range of potentially noxious haemodynamic, metabolic, and inflammatory stimuli. Remodelling is initially functional, compensatory, and adaptive but, when sustained, progresses to structural changes that become self-perpetuating and pathogenic. Remodelling involves responses not only of the cardiomyocytes, endothelium, and vascular smooth muscle cells, but also of interstitial cells and matrix. In this Review we characterise the remodelling processes in atherosclerosis, vascular and myocardial ischaemia-reperfusion injury, and heart failure, and we draw attention to potential avenues for innovative therapeutic approaches, including conditioning and metabolic strategies.
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Atrial septal defects are the third most common type of congenital heart disease. Included in this group of malformations are several types of atrial communications that allow shunting of blood between the systemic and the pulmonary circulations. Most children with isolated atrial septal defects are free of symptoms, but the rates of exercise intolerance, atrial tachyarrhythmias, right ventricular dysfunction, and pulmonary hypertension increase with advancing age and life expectancy is reduced in adults with untreated defects. ⋯ Surgical closure is safe and effective and when done before age 25 years is associated with normal life expectancy. Transcatheter closure offers a less invasive alternative for patients with a secundum defect who fulfil anatomical and size criteria. In this Seminar we review the causes, anatomy, pathophysiology, treatment, and outcomes of atrial septal defects in children and adult patients in whom this defect is the primary cardiac anomaly.
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At least 10% of adults and nearly all children who receive renal-replacement therapy have an inherited kidney disease. These patients rarely die when their disease progresses and can remain alive for many years because of advances in organ-replacement therapy. ⋯ In this review, we discuss the nature of rare inherited kidney diseases, the challenges they pose, and opportunities from technological advances, which are well suited to target the kidney. Mechanistic insights from rare disorders are relevant for common disorders such as hypertension, kidney stones, cardiovascular disease, and progression of chronic kidney disease.
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Review
Epidemiology, contributors to, and clinical trials of mortality risk in chronic kidney failure.
Patients with chronic kidney failure--defined as a glomerular filtration rate persistently below 15 mL/min per 1·73 m(2)--have an unacceptably high mortality rate. In developing countries, mortality results primarily from an absence of access to renal replacement therapy. ⋯ Characterisation of the key pathophysiological contributors to increased mortality and cardiorenal risk staging systems are needed for the rational design of clinical trials aimed at decreasing mortality. Policy changes to improve access to renal replacement therapy should be combined with research into low-cost renal replacement therapy and optimum clinical care, which should include multifaceted approaches simultaneously targeting several of the putative contributors to increased mortality.
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Vaccine probe studies have emerged in the past 15 years as a useful way to characterise disease. By contrast, traditional studies of vaccines focus on defining the vaccine effectiveness or efficacy. The underlying basis for the vaccine probe approach is that the difference in disease burden between vaccinated and unvaccinated individuals can be ascribed to the vaccine-specific pathogen. ⋯ For instance, even when a vaccine has a seemingly low efficacy, a high baseline disease incidence can lead to a large vaccine-preventable disease burden and thus that population-based vaccine introduction would be justified. So far, vaccines have been used as probes to characterise disease syndromes caused by Haemophilus influenzae type b, pneumococcus, rotavirus, and early infant influenza. However, vaccine probe studies have enormous potential and could be used more widely in epidemiology, for example, to define the vaccine-preventable burden of malaria, typhoid, paediatric influenza, and dengue, and to identify causal interactions between different pathogens.