Anticoagulation in patients with atrial fibrillation (AF) should be guided by considerations of the risk of thromboembolism, stroke, and bleeding as well as the patient's preference. Well-recognized scores have been developed to help the clinician in daily risk assessment, but there are several special patient populations for whom scores are not developed or validated. Furthermore, these patients were not adequately represented in the pivotal randomized trials for non-vitamin K antagonist oral anticoagulants (NOACs). In patients with cancer, the intrinsic hypercoagulable state has to be balanced against an increased risk of bleeding, and a dynamic concept should be applied, taking into account the cancer type, current disease state, therapeutic strategy, and patient-related factors, with NOACs playing an increasingly larger role. In women with planned pregnancy or already pregnant, NOACs should be avoided. However, accidental exposure during pregnancy should not lead to recommendations for pregnancy termination in view of current observational data. Whether patients on dialysis with AF benefit from anticoagulation at all is questionable. But if the decision for anticoagulation is made, NOACs may contribute to a more favorable risk-benefit profile than vitamin- K antagonists. Finally, patients on the ward deserve special considerations regarding periprocedural management of anticoagulation. Although for the majority of procedures a short discontinuation of oral anticoagulation seems appropriate, there are some low-bleeding-risk procedures that do not require cessation. The aim of the present review is to discuss the major particularities of these four patient subgroups and thus to facilitate the clinical decision-making.
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http://dx.doi.org/10.1007/s00059-021-05042-1 | DOI Listing |
Background: There is an urgent need for new therapeutic and diagnostic targets for Alzheimer's disease (AD). Dementia afflicts roughly 55 million individuals worldwide, and the prevalence is increasing with longer lifespans and the absence of preventive therapies. Given the demonstrated heterogeneity of Alzheimer's disease in biological and genetic components, it is critical to identify new therapeutic approaches.
View Article and Find Full Text PDFBackground: Our previous study identified that Sildenafil (a phosphodiesterase type 5 [PDE5] inhibitor) is a candidate repurposable drug for Alzheimer's Disease (AD) using in silico network medicine approach. However, the clinically meaningful size and mechanism-of-actions of sildenafil in potential prevention and treatment of AD remind unknown.
Method: We conducted new patient data analyses using both the MarketScan® Medicare with Supplemental database (n = 7.
Alzheimers Dement
December 2024
EQT Life Sciences Partners, Amsterdam, 1071 DV Amsterdam, Netherlands.
Background: Alzheimer's disease (AD) trials report a high screening failure rate (potentially eligible trial candidates who do not meet inclusion/exclusion criteria during screening) due to multiple factors including stringent eligibility criteria. Here, we report the main reasons for screening failure in the 12-week screening phase of the ongoing evoke (NCT04777396) and evoke+ (NCT04777409) trials of semaglutide in early AD.
Method: Key inclusion criteria were age 55-85 years; mild cognitive impairment due to AD (Clinical Dementia Rating [CDR] global score of 0.
Alzheimers Dement
December 2024
NYU Grossman School of Medicine, New York, NY, USA; NYU, New York City, NY, USA.
Background: Astrocytes, a major glial cell in the central nervous system (CNS), can become reactive in response to inflammation or injury, and release toxic factors that kill specific subtypes of neurons. Over the past several decades, many groups report that reactive astrocytes are present in the brains of patients with Alzheimer's disease, as well as several other neurodegenerative diseases. In addition, reactive astrocyte sub-types most associated with these diseases are now reported to be present during CNS cancers of several types.
View Article and Find Full Text PDFBackground: Convergent evidence indicates that deficits in the endosomal recycling pathway underlies pathogenesis of Alzheimer's disease (AD). SORL1 encodes the retromer-associated receptor SORLA that plays an essential role in recycling of AD-associated cargos such as the amyloid precursor protein and the glutamatergic AMPA receptor. Importantly, loss of function pathogenic SORL1 variants are associated with AD.
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