Annals of medicine
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Tirofiban is a small non-peptide ligand-mimetic Glycoprotein (GP) IIb/IIIa inhibitor which can reversibly bind to the arginine-glycine-aspartic acid (RGD) recognition site of GP IIb/IIIa to prevent platelet aggregation. It reduces the incidence of thrombotic cardiovascular events in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). ⋯ This side effect caused by tirofiban is especially concerning given how frequently it is used in the practice of contemporary cardiovascular care. The present review provides an overview of the pathophysiology, clinical presentation, management, and risk factors associated with tirofiban-induced thrombocytopenia.
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Persons with diabetes and chronic kidney disease (CKD) have a high residual risk of developing cardiovascular (CV) complications despite treatment with renin-angiotensin system blockers and sodium-glucose cotransporter type 2 inhibitors. Overactivation of mineralocorticoid receptors plays a key role in the progression of renal and CV disease, mainly by promoting inflammation and fibrosis. Finerenone is a nonsteroidal selective mineralocorticoid antagonist. ⋯ Key messages:Despite inhibition of renin-angiotensin system and sodium-glucose cotransporter type 2, persons with type 2 diabetes (T2D) and chronic kidney disease (CKD) remain on high cardiovascular (CV) residual risk. Overactivation of mineralocorticoid receptors plays a key role in the progression of renal and CV disease, mainly by promoting inflammation and fibrosis that is not targeted by traditional treatments. Finerenone is a nonsteroidal selective mineralocorticoid antagonist that decreases not only albuminuria, but also the risk of CKD progression, and CV risk in subjects with T2D and CKD.
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Tumour-associated endothelial cells (TECs) are a critical stromal cell type in the tumour microenvironment and play central roles in tumour angiogenesis. Notably, TECs have phenotypic plasticity, as they have the potential to transdifferentiate into cells with a mesenchymal phenotype through a process termed endothelial-to-mesenchymal transition (EndoMT). ⋯ In this review, we comprehensively explore the phenomenon of EndoMT in the tumour microenvironment and identify influencing factors and molecular mechanisms responsible for EndoMT induction. Furthermore, the pathological functions of EndoMT in tumour progression and potential therapeutic strategies for targeting EndoMT in tumour treatment are also discussed to highlight the pivotal roles of EndoMT in tumour progression and therapy.
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Metastases to the central nervous system (CNS) in patients with non-small cell lung cancer constitute an extremely difficult clinical problem, and their occurrence is associated with a poor prognosis. Due to the existence of the blood-brain barrier (BBB) and the action of proteins responsible for the transport of drugs, e.g. P-glycoprotein (P-gp), the penetration of drugs into the CNS is insufficient. ⋯ This was achieved by modifying the structure of individual molecules, which became, inter alia, less substrates for P-gp. These modifications caused that less than 10% of patients experience progression in CNS during new ALK inhibitors treatment. This review summarizes the knowledge about the action of BBB, the pharmacodynamics and pharmacokinetics of ALKi, with particular emphasis on their ability to penetrate the CNS and the intracranial activity of individual drugs from different generations of ALK inhibitors.
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Antimicrobial resistance results from the widespread use of antimicrobial agents and is a significant obstacle to the effectiveness of these agents. Numerous methods are used to overcome this problem with moderate success. Besides efforts of antimicrobial stewards, several artificial intelligence (AI)-based technologies are being explored for preventing resistance development. ⋯ IMPORTANCE SECTIONThe paper presents the establishment of a second-generation AI chronobiology-based approach to help in preventing further resistance and possibly overcome existing resistance. Key messagesAntimicrobial resistance results from the widespread use of antimicrobial agents and is a significant obstacle to the effectiveness of these agents. We present the establishment of a second-generation AI chronobiology-based approach to help in preventing further resistance and possibly overcome existing resistance.