Journal of internal medicine
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Abdominal aortic aneurysm (AAA) rupture is a common cause of death in adults. Current AAA treatment is by open surgical or endovascular aneurysm repair. Rodent model and human epidemiology, and genetic and observational studies over the last few decades have highlighted the potential of a number of drug therapies, including medications that lower blood pressure, correct dyslipidaemia, or inhibit thrombosis, inflammation or matrix remodelling, as approaches to managing small AAA. ⋯ Three further trials assessed the effect of a mast cell inhibitor, fibrate or platelet aggregation inhibition and reported no effect on AAA growth or clinical events. Past trials were noted to have a number of design issues, particularly small sample sizes and limited follow-up. Much larger trials are needed to properly test potential therapeutic approaches if a convincingly effective medical therapy for AAA is to be identified.
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Given the increasing availability of large data set, small single-institutional series raise decreasing attention. Rapid expansion of technology from electronic medical records to easily accessible internet access, and widespread use and acceptance of registries in the medical world has allowed for research and quality improvement efforts using 'big data'. Big data, although technically not defined, typically refers to large databases that can be used to investigate common or rare disease processes or outcomes, describe variation in clinical practices across and between different specialties at various practice location, whilst allowing important information about trends over time. ⋯ Within vascular surgery specifically, big data have expanded over the last decade and now includes regional, national and global registries that have major benefits of gathering specific clinical and procedural information within vascular surgery. In this review, we highlight the main vascular surgery registries and recap a few success stories of how the registries have been leveraged to benefit discovery, quality improvement and ultimately patient care. Additionally, we outline future directions that will be imperative for continued expansion, acceptance and adoption of 'big data' utilization inpatients with vascular disease.
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Multiple sclerosis (MS), a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system, is today a leading cause of unpredictable lifelong disability in young adults. The treatment of patients in progressive stages remains highly challenging, alluding to our limited understanding of the underlying pathological processes. In this review, we provide insights into the mechanisms underpinning MS progression from a perspective of epigenetics, that refers to stable and mitotically heritable, yet reversible, changes in the genome activity and gene expression. ⋯ Despite minor overlap at individual methylation sites, nearly 30% of altered genes reported in peripheral immune cells of progressive MS patients were found in brain tissue, jointly converging on alterations of neuronal functions. We further speculate about the mechanisms underlying shared epigenetic patterns between blood and brain, which likely imply the influence of internal (genetic control) and/or external (e.g. smoking and ageing) factors imprinting a common signature in both compartments. Overall, we propose that epigenetics might shed light on clinically relevant mechanisms involved in disease progression and open new avenues for the treatment of progressive MS patients in the future.
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Abdominal aortic aneurysm (AAA) is a relatively common and potentially fatal disease. The management of AAA has undergone extensive changes in the last two decades. High quality vascular surgical registries were established early and have been found to be instrumental in the evaluation and monitoring of these changes, most notably the wide implementation of minimally invasive endovascular surgical technology. ⋯ By using large-scale data over longer periods of time, the importance of centralization of care to high-volume centres was shown, particularly for open repair. Additionally, large-scale databases can offer an opportunity to assess practice and outcomes in patient subgroups (e.g. treatment of AAA in women and the elderly) as well as in rare aortic pathologies. In this review article, we point out the most important paradigm shifts in AAA management based on vascular registry data.
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Remnant cholesterol in triglyceride-rich lipoproteins is associated observationally and genetic, causally with increased risk of atherosclerotic cardiovascular disease in healthy individuals. ⋯ In individuals with a diagnosis of myocardial infarction/ischaemic stroke, a lower remnant cholesterol of 0.8 mmol L-1 (32 mg dL-1 ) was estimated to reduce recurrent MACE by 20% in secondary prevention. Our data indicate an unmet medical need for secondary prevention in individuals with high nonfasting remnant cholesterol levels.