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.

Aberrant gene expression is often linked to the progression of various cancers, making the targeting of oncogene transcriptional activation a potential strategy to control tumor growth and development. The RET proto-oncogene’s gain-of-function mutation is a major cause of medullary thyroid carcinoma (MTC), which is part of multiple endocrine neoplasia type 2 (MEN2) syndrome. In this study, we used a cell-based bioluminescence reporter system driven by the RET promoter to screen for small molecules that potentially suppress the RET gene transcription. We identified adefovir dipivoxil as a transcriptional inhibitor of the RET gene, which suppressed endogenous RET protein expression in MTC TT cells. Adefovir dipivoxil also interfered with STAT3 phosphorylation and showed high affinity to bind to STAT3. Additionally, it inhibited RET-dependent TT cell proliferation and increased apoptosis. These results demonstrate the potential of cell-based screening assays in identifying transcriptional inhibitors for other oncogenes.

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.

Background: Brucellosis is a major zoonotic infection that warrants treatment with antibiotic therapy. Current treatment recommendations include using either dual or triple therapy with antibiotics active against brucella species. This study aims to evaluate the effectiveness and safety of dual and triple antibiotic therapy for treating brucellosis. Methods: This is a retrospective cohort study for patients with confirmed Brucellosis infection from 2015 to 2024. The primary outcome was the achievement of a favorable response. Secondary outcomes were treatment failure, 90-day mortality, relapse of brucella infection, hospital re-admission, and adverse drug reactions (ADRs). Baseline characteristics were reported as means with standard deviations. All the statistical tests are shown as odds ratios (ORs) with 95% confidence intervals (CIs). Results: In total, 966 patients were screened and 287 met the inclusion criteria: 164 patients in the dual therapy group and 123 patients in the triple therapy group. Achievement of a favorable response was not statistically different between the dual therapy and triple therapy groups; 87.3% vs. 90.5%, OR 1.2 (0.48–3.02, p = 0.42). No patient died in either treatment group. Treatment failure, mean duration of hospitalization, brucella relapse, hospital re-admission, and the mean time to defervescence were not statistically different between dual and triple therapy groups. Adverse drug reactions were numerically higher in the triple therapy group. Conclusions: Dual therapy was equally effective for the treatment of patients with brucellosis compared to the triple therapy regimens. Although not statistically significant, there more ADRs in the triple therapy group compared to those receiving dual therapy. Thus, dual antibiotic therapy is efficacious, less costly, and associated with fewer ADRs compared to triple antibiotic therapy.

Rationale: Management of coronavirus disease 2019 (COVID-19) has been the subject of extensive research and study, leading to the development of strategies and treatments. Nonetheless, there remains a dearth of information concerning patients who require mechanical circulatory system support. This case report presents one of the first documented cases of successful utilization of nirmatrelvir/ritonavir (Paxlovid) and dexamethasone in the treatment of a patient with a total artificial heart. Patient concerns: The patient in this case study was a 28-year-old male who had been experiencing severe heart failure. In need of a heart transplant, he underwent a procedure for implantation of a total artificial heart as a bridge to transplantation. Diagnoses: Unfortunately, after the surgical intervention, the patient contracted COVID-19, as confirmed by polymerase chain reaction. Interventions: The therapeutic approach involved a 5-day regimen of nirmatrelvir/ritonavir at a dosage of 300/100 mg administered twice daily, along with a daily dosage of 6 mg of dexamethasone. Outcomes: Remarkably, the patient oxygenation level improved on the second day of therapy. Consequently, he was transferred from the intensive care unit to the general floor. After 71 days with the total artificial heart, the patient successfully underwent heart transplantation. Lessons: This case report provides a compelling example of the successful application of nirmatrelvir/ritonavir and dexamethasone in the treatment of a COVID-19 patient with a total artificial heart. The positive outcome observed in this case underscores the potential use of these therapeutic agents in this specific patient population. However, it is imperative to conduct further research to corroborate and validate these initial findings. This study lays the foundation for further exploration of the efficacy of these drugs in patients with mechanical circulatory support systems.

This systematic review and meta-analysis evaluated the clinical efficacy and safety of carbapenems vs noncarbapenem antibiotics in adult hospitalized patients with AmpC-producing Enterobacterales infections across various infection sites. A comprehensive search of PubMed, Embase, and Cochrane Library databases was conducted for observational studies and randomized controlled trials comparing carbapenems with alternative agents. Primary outcomes included 30-day all-cause mortality, microbiological failure, infection recurrence, and adverse drug reactions (ADRs). Seventeen studies met the inclusion criteria. There was no significant difference in 30-day mortality (odds ratio [OR] = 1.29; 95% CI: 0.91-1.82; P = 0.16) or infection recurrence (OR = 0.98; 95% CI: 0.32-2.97; P = 0.97) between carbapenems and noncarbapenems. Microbiological failure rates were also comparable. However, carbapenems were associated with a higher incidence of ADRs (OR = 4.32; 95% CI: 1.73-10.79; P = 0.03). Clinical success trended in favor of noncarbapenem agents, though the difference did not reach statistical significance (OR = 0.56, 95% CI: 0.29-1.08; P = 0.08). While carbapenems remain effective for AmpC-producing infections, noncarbapenem alternatives offer comparable outcomes with fewer adverse events. These findings support IDSA guidance recommending agents such as cefepime when the minimum inhibitory concentration is ≤2 µg/ml and highlight the need for individualized, susceptibility-guided therapy.