In recent years, anticoagulant and antiplatelet use have increased over the past years for the prevention and treatment of several cardiovascular conditions. Due to the rising use of antithrombotic medications and the complexity of specific clinical cases requiring such therapies, bleeding remains the primary concern among patients using antithrombotics. Direct oral anticoagulants (DOACs) include rivaroxaban, apixaban, edoxaban, and betrixaban. Direct thrombin inhibitors (DTIs) include argatroban, bivalirudin, and dabigatran. DOACs are associated with lower rates of fatal, life-threatening, and significant bleeding risks compared to those of warfarin. The immediate reversal of these agents can be indicated in an emergency setting. Antithrombotic reversal recommendations are still in development. Vitamin K and prothrombin complex concentrate (PCCs) can be used for warfarin reversal. Andexanet alfa and idarucizumab are specific reversal agents for DOACs and DTIs, respectively. Protamine sulfate is the solely approved reversal agent for unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH). However, there are no specific reversal agents for antiplatelets. This article aims to provide a practical guide for clinicians regarding the reversal of anticoagulants and antiplatelets in clinical practice based on the most recent studies.

Background: Hyperuricemia has been linked to various adverse clinical outcomes. Data on the clinical outcomes and the relationship between hyperuricemia and sepsis remain limited. The aim of this study was to evaluate the impact of hyperuricemia on clinical outcomes in sepsis patients and to identify whether it can predict the mortality in this patient population. Methods: This was a retrospective cohort study of adult patients with sepsis admitted to the intensive care unit (ICU) from 1 January 2021 to 31 December 2023. The patients were divided into hyperuricemia and non-hyperuricemia groups. Hyperuricemia was defined as a serum uric acid level > 416.4 µmol/L (7.0 mg/dL) in males or >357.0 µmol/L (6.0 mg/dL) in females based on the first serum uric acid reading within 24 h of ICU admission. The primary outcome of this study was ICU mortality. Secondary outcomes included in-hospital mortality, progression to septic shock, and ICU and hospital lengths of stay (LOSs). Results: A total of 599 patients were included in the study. Among these, 303 were in hyperuricemia group, while 296 were in the non-hyperuricemia group. The incidence of ICU and in-hospital mortality was higher in the hyperuricemia group compared to the non-hyperuricemia group (26.7% vs. 18.9% (p < 0.001) and 34.7% vs. 19.3% (p < 0.001), respectively). After adjusting for cofounders, hyperuricemia was not a predictor of ICU mortality (OR 1.52, 95% CI 0.95–2.43, p = 0.083). Most secondary outcomes were similar between the groups. However, the hyperuricemia group had a higher incidence of progression to septic shock (67.3% vs. 50.7%, p < 0.001), and hospital LOS was significantly longer in the hyperuricemia group (384 vs. 264 h, p = 0.004). Conclusions: Our findings demonstrated that hyperuricemia in sepsis patients was associated with worse clinical outcomes such as higher ICU and hospital mortality. Moreover, there was a higher incidence of septic shock progression and longer hospital LOS. The other outcomes were not statistically significantly different. Further prospective research is warranted to confirm these findings.

Background: Acetaminophen is generally considered safe when used according to the recommended guidelines. Consumption in excessive doses can lead to severe liver damage and, in critical cases, may even result in death. To reduce the effects of acetaminophen overdose, N-acetylcysteine (NAC) has been established as the preferred intervention to prevent liver damage. Objectives: The purpose of this updated systematic review and meta-analysis is to evaluate the potential benefits of a two-bag N-acetylcysteine (NAC) dosing regimen compared to the traditional three-bag protocol in the treatment of acetaminophen-induced liver toxicity. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The research team utilized the PubMed and Cochrane databases to perform a thorough and comprehensive search of the relevant literature from the inception of these databases up until January 2024. Results: Nine studies were included. The overall use of two-bag NAC was associated with lower anaphylactic reactions and gastrointestinal symptoms compared to the three-bag method. The rate of liver toxicity resolution was the same between the two treatment groups. Conclusions: The two-bag NAC regimen can be considered a safe and effective method for managing acetaminophen toxicity.

Antibiotic resistance is a critical global health concern, driven by biofilm formation and the declining effectiveness of conventional therapies. This study investigates polymer-lipid hybrid nanoparticles (PLNs) as an innovative drug delivery system to enhance the antibacterial efficacy of gentamicin (Gen) while addressing challenges related to its hydrophilicity and encapsulation. Using an optimized double-emulsification/solvent-evaporation technique, PLNs were designed to improve drug entrapment efficiency (EE%) and loading capacity (DL%). The resulting formulations were characterized for particle size, polydispersity, zeta potential, and encapsulation efficiency. Transmitted electron microscopy (TEM) provided insights into particle morphology, while antibacterial activity was tested against multiple bacterial strains, including resistant isolates. The optimized formulation (F4) demonstrated significant improvements, achieving an EE% of 42%, a DL% of 7.2%, and uniform particle sizes (~143.4 nm) with high stability (zeta potential ~-38 mV) and a monodisperse distribution. TEM analysis confirmed Gen encapsulation within the lipid-polymer matrix. F4 exhibited notably enhanced antibacterial performance, particularly against Methicillin-resistant Staphylococcus aureus (MRSA-59) and Pseudomonas aeruginosa (PA-78), with up to a 160-fold reduction in minimum inhibitory/bactericidal concentrations (MIC/MBC) compared to free Gen. These findings underscore the potential of PLNs as a robust platform for targeted drug delivery, offering a promising strategy to combat antimicrobial resistance.