Journal of internal medicine
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11-beta-hydroxysteroid dehydrogenases (11β-HSDs) catalyse the conversion of active 11-hydroxy glucocorticoids (cortisol, corticosterone) and their inert 11-keto forms (cortisone, 11-dehydrocorticosterone). They were first reported in the body and brain 70 years ago, but only recently have they become of interest. 11β-HSD2 is a dehydrogenase, potently inactivating glucocorticoids. In the kidney, 11β-HSD2 generates the aldosterone-specificity of intrinsically non-selective mineralocorticoid receptors. 11β-HSD2 also protects the developing foetal brain and body from premature glucocorticoid exposure, which otherwise engenders the programming of neuropsychiatric and cardio-metabolic disease risks. ⋯ Transgenic models show this rise contributes to age-related cognitive decline, at least in mice. 11β-HSD1 inhibition robustly improves memory in healthy and pathological ageing rodent models and is showing initial promising results in phase II studies of healthy elderly people. Larger trials are needed to confirm and clarify the magnitude of effect and define target populations. The next decade will be crucial in determining how this tale ends - in new treatments or disappointment.
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Review Meta Analysis
Long-term glucocorticoids in relation to the metabolic syndrome and cardiovascular disease: A systematic review and meta-analysis.
The striking link of Cushing's syndrome with the metabolic syndrome (MetS) and cardiovascular disease (CVD) suggests that long-term exposure to extremely high cortisol levels catalyzes cardiometabolic deterioration. However, it remained unclear whether the findings from the extreme glucocorticoid overabundance observed in Cushing's syndrome could be translated into more subtle variations in long-term glucocorticoid levels among the general population, for example, due to chronic stress. Here, we performed a systematic review (PROSPERO: CRD42023425541) of evidence regarding the role of subtle variations in long-term biological stress, measured as levels of scalp hair cortisol (HairF) and cortisone (HairE), in the context of MetS and CVD in adults. ⋯ Results regarding the associations of HairF and HairE with MetS were inconsistent. Altogether, long-term biological stress, measured as HairF and HairE, is associated with the presence of CVD, and less consistently with MetS. Prospective studies need to evaluate the directionality of this relationship and determine whether HairF and HairE can be used in addition to standard risk factors in predicting future cardiometabolic deterioration.
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Review Meta Analysis
Long-term glucocorticoids in relation to the metabolic syndrome and cardiovascular disease: A systematic review and meta-analysis.
The striking link of Cushing's syndrome with the metabolic syndrome (MetS) and cardiovascular disease (CVD) suggests that long-term exposure to extremely high cortisol levels catalyzes cardiometabolic deterioration. However, it remained unclear whether the findings from the extreme glucocorticoid overabundance observed in Cushing's syndrome could be translated into more subtle variations in long-term glucocorticoid levels among the general population, for example, due to chronic stress. Here, we performed a systematic review (PROSPERO: CRD42023425541) of evidence regarding the role of subtle variations in long-term biological stress, measured as levels of scalp hair cortisol (HairF) and cortisone (HairE), in the context of MetS and CVD in adults. ⋯ Results regarding the associations of HairF and HairE with MetS were inconsistent. Altogether, long-term biological stress, measured as HairF and HairE, is associated with the presence of CVD, and less consistently with MetS. Prospective studies need to evaluate the directionality of this relationship and determine whether HairF and HairE can be used in addition to standard risk factors in predicting future cardiometabolic deterioration.
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Sarcoma subtype classification is currently mainly based upon histopathological morphology. Molecular analyses have emerged as an efficient addition to the diagnostic workup and sarcoma care. Knowledge about the sarcoma genome increases, and genetic events that can either support a histopathological diagnosis or suggest a differential diagnosis are identified, as well as novel therapeutic targets. ⋯ With the exploding availability of sequencing technologies, it becomes increasingly important to understand the strengths and limitations of those methods and their context in sarcoma diagnostics. It is reasonable to believe that most sarcoma treatment centers will increase the use of massive-parallel sequencing soon. We conclude that the context in which the genetic findings are interpreted is of importance, and the interpretation of genomic findings requires considering tumor histomorphology.
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Cardiovascular and thromboembolic risks are increasing in the population as a whole and therefore also in inflammatory bowel disease (IBD) patients. Obesity is a worldwide challenge also affecting the IBD population, and a causal association with Crohn's disease may exist. IBD itself, particularly when active, is also associated with a significant risk of thromboembolic and cardiovascular events such as myocardial infarction and stroke. ⋯ In this context, IBD healthcare providers need to be alert to the assessment of cardiovascular risk - particularly as cardiovascular events appear to be confined to specific patient groups with pre-existing risk factors. In addition, the potential for S1P modulator drug interactions requires a higher level of vigilance in patients with polypharmacy compared to biologics. Cardiovascular risk is not static, and updated assessment will need to become part of the routine in many IBD units.