European journal of clinical investigation
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Eur. J. Clin. Invest. · Oct 2022
ReviewModulation of cellular redox environment as a novel therapeutic strategy for Parkinson's Disease.
Parkinson's disease (PD) is an incurable neurodegenerative movement disorder. PD affects 2% of the population above 65 years old; however, with the growing number of senior citizens, PD prevalence is predicted to increase in the following years. Pathologically, PD is characterized by dopaminergic cell neurodegeneration in the substantia nigra, resulting in decreased dopamine levels in the nigrostriatal pathway, triggering motor symptoms. ⋯ Although most mitochondria-targeted antioxidants with beneficial effects in PD-associated models have failed to show any therapeutic benefit in clinical trials, several questions remain to be clarified. Hereby, we review the role played by oxidative stress in PD pathogenesis, emphasizing mitochondria as reactive oxygen species (ROS) producers and as targets for oxidative stress-related dysfunctional mechanisms. In addition, we also describe the importance of using dietary-based mitochondria-targeted antioxidants as a valuable strategy to counteract the deleterious effects of ROS in pre-clinical and/or clinical trials of PD, pointing out their significance to slow, and possibly halt, the progression of PD.
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Eur. J. Clin. Invest. · Oct 2022
Review Meta AnalysisOff-label underdosing of four individual NOACs in patients with non-valvular atrial fibrillation: a systematic review and meta-analysis of observational studies.
Although several meta-analyses have examined the effects of off-label underdosing of nonvitamin K antagonist oral anticoagulants (NOACs) compared with their recommended doses in patients with atrial fibrillation (AF), they combined different kinds of NOACs in their primary analyses. Herein, we first conducted a meta-analysis to separately assess the effects of off-label underdosing versus on-label dosing of four individual NOACs on adverse outcomes in the AF population. ⋯ Off-label underdosing of rivaroxaban may increase the risk of stroke or systematic embolism, whereas off-label underdosing of apixaban may heighten the incidence of all-cause death.
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Eur. J. Clin. Invest. · Oct 2022
Microvascular disease increases the risk of lower limb amputation - a Western Danish cohort study.
Peripheral artery disease is the leading cause of nontraumatic lower limb amputation. Microvascular disease (MVD) increases the risk of lower limb amputation in patients with peripheral artery disease (PAD). We estimated the risk of lower limb amputation associated with MVD and PAD in a Danish cohort. ⋯ Microvascular disease and PAD are independently associated with a threefold and sevenfold increase of amputation risk, respectively. Combined, they had an additive effect constituting a 12-fold amputation risk. The amputation risk was higher in men than women, and 3 in 10 amputations were attributed to the male sex.