Prevalence, risk factors, and prediction of inappropriate use of non-vitamin K antagonist oral anticoagulants in elderly Chinese patients with atrial fibrillation: A study protocol.

Background: Atrial fibrillation (AF) is an arrhythmia that is prevalent globally, and its incidence grows exponentially with aging. Non-vitamin K antagonist oral anticoagulants (NOACs) have been developed in recent years, and it challenges the supremacy of warfarin for thromboembolism prophylaxis in AF. Nevertheless, there are limited data specifically evaluating the real-life use of NOACs in elderly patients with AF in China. Methods: This is a national, multicenter, non-interventional, cross-sectional study that enrolls patients with AF aged 75 years and above from 31 institutions across China. Data were collected using the Hospital Information System. The primary outcomes include (1) profiles of NOAC use in the elderly; (2) frequency of inappropriate NOAC use based on guidelines and approved labeling recommendations; (3) exploring potential risk factors related to NOACs inappropriate use; and (4) creating a prediction tool for inappropriate NOACs use. Conclusion: The results of this study reveal the prevalence, risk factors, and corresponding prediction tool of inappropriate NOACs use in older patients with AF in China, as well as provide valuable insights into the clinical application of NOACs in high-risk populations in the real-world setting. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT05361889.

Antithrombotic Management for Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention or With Acute Coronary Syndrome: An Evidence-Based Update.

Combined antithrombotic regimens for atrial fibrillation (AF) patients with coronary artery disease, particularly for those who have acute coronary syndrome (ACS) and/or are undergoing percutaneous coronary intervention (PCI), presents a great challenge in the real-world clinical scenario. Conventionally, a triple antithrombotic therapy (TAT), which consists of combined oral anticoagulant therapy to prevent systemic embolism or stroke along with dual antiplatelet therapy to prevent coronary arterial thrombosis (CAT), is used. However, TAT has been associated with a significantly increased risk of bleeding. With the emergence of non-vitamin K antagonist oral anticoagulants (NOACs), randomized controlled trials have demonstrated a better risk-to-benefit ratio of dual antithrombotic therapy (DAT) in combination of a NOAC and with a P2Y12 inhibitor than vitamin K antagonist-based TAT. The results of these studies have impacted the recommendations of current international guidelines, which favor a DAT with a NOAC and P2Y12 inhibitor (especially clopidogrel) in this clinical setting. Additionally, aspirin can be administered during the periprocedural period, while the treatment duration of TAT should be as short as possible. In this article, we summarize the up-to-date evidence regarding antithrombotic regimens for AF patients with PCI or ACS, with a specific focus on the optimal approach and critical discussions of key scientific data and future developments for antithrombotic management in these patients.

Appropriate Dosing Regimens of Non-Vitamin K Antagonist Oral Anticoagulants for Treatment of Patients With Non-Valvular Atrial Fibrillation: An Evidence-Based Consideration.

Patients with non-valvular atrial fibrillation (NVAF) exhibit a high risk of stroke, which is associated with high mortality. Thus, stroke prevention is crucial for the overall management of NVAF. Two categories of drugs, vitamin K antagonist warfarin and non-vitamin K antagonist oral anticoagulants (NOACs), are clinically used to prevent NVAF-related stroke. In some circumstances, NOACs are superior to warfarin. However, NOACs selection for NVAF patients is affected by many factors, including individual patient characteristics, comorbidities, risk factors, or laboratory variables. This article summarizes the discrepancy in NOACs management with emphasis on the dosing regimens and influencing factors, such as stroke risk, age, body weight, renal function, gastrointestinal bleeding (GIB) risk, and combination of antiplatelet therapy, in order to identify individual groups with particular clinical characteristics who may obtain more benefit from a certain dosing regimen of NOACs. Determination of a particular subset of patient populations for the appropriate dose regimen of NOACs will help to achieve desired clinical outcomes. Furthermore, to compensate clinical evidence, we should place more emphasis on the findings of current clinical trials and supplement real-world data.

Circular RNA expression profile of Alzheimer's disease and its clinical significance as biomarkers for the disease risk and progression.

OBJECTIVE: To investigate circular RNA (circRNA) expression profile via microarray, and further assess the potential of candidate circRNAs as biomarkers in Alzheimer's disease (AD). METHODS: CircRNA expression profile in cerebrospinal fluid from 8 AD patients and 8 control (Ctrl) subjects was assessed by microarray. Subsequently, 10 candidate circRNAs from microarray were validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in cerebrospinal fluid from 80 AD patients and 40 Ctrl subjects. RESULTS: By microarray, 112 circRNAs were upregulated and 51 circRNAs were downregulated in AD patients compared with Ctrl subjects, and these circRNAs were enriched in AD related pathways such as neurotrophin signaling pathway, natural killer cell mediated cytotoxicity and cholinergic synapse. By RT-qPCR, circ-LPAR1, circ-AXL and circ-GPHN were increased, whereas circ-PCCA, circ-HAUS4, circ-KIF18B and circ-TTC39C were decreased in AD patients compared with Ctrl subjects, and these circRNAs were disclosed to predict AD risk by receiver operating characteristics curve analysis. Further forward-stepwise multivariate logistic regression revealed that circ-AXL, circ-GPHN, circ-ITPR3, circ-PCCA and cic-TTC39C were independent predictive factors for AD risk. Besides, in AD patients, circ-AXL and circ-GPHN negatively correlated, while circ-PCCA and circ-HAUS4 positively correlated with mini-mental state examination score; Circ-AXL negatively correlated, while circ-PCCA, circ-HAUS4 and circ-KIF18B positively correlated with Aß42; Circ-AXL and circ-GPHN positively correlated, whereas circ-HAUS4 negatively correlated with t-tau; Circ-AXL positively correlated with p-tau. CONCLUSION: Our study provides an overview of circRNA expression profile in AD, and identifies that circ-AXL, circ-GPHN and circ-PCCA hold clinical implications for guiding disease management in AD patients.

Visible-light-mediated photocatalytic cross-coupling of acetenyl ketones with benzyl trifluoroborate.

In this report, we describe a simple visible light-triggered Barbier-type reaction by employing acetenyl ketones with benzyl trifluoroborates. Through a radical-radical cross-coupling process, this photocatalytic protocol furnished a wide range of tertiary propargyl alcohols. Mechanistic investigation indicated that proton-coupled electron transfer (PCET) might be involved in the photochemical transformations.

Current Evidence for Pharmacologic Reversal Using Direct Oral Anticoagulants: What's New?

Direct oral anticoagulants are increasingly used in clinical practice and have addressed many of the issues related to vitamin K antagonists. However, the lack of reversal in life-threatening situations raises concerns regarding patient safety. Thus, current research is aimed at developing reversal agents that can safely neutralize the effects of anticoagulants. We present the design and mechanisms of action of and the animal models, clinical trials, and current evidence supporting the use of these emerging reversal agents. Idarucizumab is approved in many countries, and andexanet alfa has been approved by the US FDA, whereas others are in clinical trials. In view of the results of clinical studies to date, the problems of safety, price and accessibility remain. Therefore, these antidotes are a significant step towards improving the field of urgent and emergency reversal. From a practical perspective, post-market surveillance will be crucial to monitor the safety and effectiveness of these agents.

Fidgetin-like 1 is a ciliogenesis-inhibitory centrosome protein.

Fidgetin-like 1 (FIGL-1) is a homolog of fidgetin, an AAA protein that was identified as the protein encoded by the gene mutated in fidget mice. Because the phenotypes of fidget mice are reminiscent of the phenotypes of ciliopathy diseases, and because fidgetin has microtubule-severing activity, we hypothesize that these proteins participate in cilia-related processes. Indeed, overexpression of FIGL-1 interfered with ciliogenesis in cultured cells. In particular, overexpressed FIGL-1 strongly accumulated at the centrosome, and, when highly expressed, perturbed the localization of centrosomal proteins such as pericentrin, CP110, and centrin. Using a polyclonal antibody against human FIGL-1, we found that endogenous FIGL-1 localized preferentially around the mother centriole. Consistently, depletion of FIGL-1 by shRNA treatment enhanced ciliogenesis in HEK293T cells. By checking the integrity of the cytoplasmic microtubule network in FIGL-1-overexpressing cells, we found that FIGL-1 probably has microtubule-severing activity, as suggested by its sequence homology with other microtubule-severing proteins. Furthermore, we showed that overexpression of FIGL-1 in zebrafish embryo decreased the length of cilia and perturbed the heart laterality. Taken together, these results demonstrate that FIGL-1 is a new centrosomal protein and inhibits ciliogenesis. These results extend the already long list of centrosomal proteins and provide new insights into the regulation of ciliogenesis.