Drug-related macular edema: a real-world FDA Adverse Event Reporting System database study.

Purpose: This study aims to assess the risks associated with drug-induced macular edema and to examine the epidemiological characteristics of this condition.

Methods: This study analyzed data from the U.S.

Investigation of the total anticholinergic load of reported anticholinergic drug-related adverse events using the Japanese adverse drug event report database: a retrospective pharmacovigilance study.

Background: The Anticholinergic Risk Scale and Total Anticholinergic Load were developed to assess the risks associated with anticholinergic drugs. Recently, the Japan Anticholinergic Risk Scale was introduced; however, the total anticholinergic load for adverse events has not been clarified, and the criteria for risk assessment in clinical practice have not been established. In this study, we used data from the Japanese Adverse Drug Event Report (JADER) database provided by the Pharmaceuticals and Medical Devices Agency to determine the total anticholinergic load associated with reported adverse events related to anticholinergic syndrome.

Development and experimental validation of a machine learning model for the prediction of new antimalarials.

A large set of antimalarial molecules (N ~ 15k) was employed from ChEMBL to build a robust random forest (RF) model for the prediction of antiplasmodial activity. Rather than depending on high throughput screening (HTS) data, molecules tested at multiple doses against blood stages of Plasmodium falciparum were used for model development. The open-access and code-free KNIME platform was used to develop a workflow to train the model on 80% of data (N ~ 12k).

Direct oral anticoagulants versus warfarin for venous thromboembolism prophylaxis in nephrotic syndrome patients: a retrospective study.

Background: Nephrotic syndrome (NS) is associated with an increased risk of venous thromboembolism (VTE). Anticoagulants are widely used in the prevention of VTE in NS patients. The use of direct oral anticoagulants (DOACs) has not been studied intensively in NS patients.

Serum cardiac and inflammatory biomarker levels following chemotherapy among female patients with breast cancer attending at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia.

Background: Chemotherapy is a well-established therapeutic approach for several malignancies, including breast cancer (BCa). However, the clinical efficacy of this drug is limited by cardiotoxicity. Assessing multiple cardiac biomarkers can help identify patients at risk of adverse outcomes from chemotherapy.

CircUCK2(2,3) promotes cancer progression and enhances synergistic cytotoxicity of lenvatinib with EGFR inhibitors via activating CNIH4-TGFα-EGFR signaling.

Background: Circular (circ)RNAs have emerged as crucial contributors to cancer progression. Nonetheless, the expression regulation, biological functions, and underlying mechanisms of circRNAs in mediating hepatocellular carcinoma (HCC) progression remain insufficiently elucidated.

Methods: We identified circUCK2(2,3) through circRNA sequencing, RT-PCR, and Sanger sequencing.

Clinical characteristics, treatment, and outcomes of nivolumab-induced uveitis.

Nivolumab has been linked to occurrences of uveitis, yet the clinical features associated with these episodes remain unclear. This study aimed to explore the clinical characteristics of uveitis induced by nivolumab and to offer guidance for its prevention, diagnosis, and treatment. We conducted a retrospective analysis by gathering case reports related to nivolumab-induced uveitis from both Chinese and English databases, covering the period from inception until September 30, 2024.

Essential oils modulate virulence phenotypes in a multidrug-resistant pyomelanogenic Pseudomonas aeruginosa clinical isolate.

Pyomelanogenic P. aeruginosa, frequently isolated from patients with urinary tract infections and cystic fibrosis, possesses the ability to withstand oxidative stress, contributing to virulence and resulting in persistent infections. Whole genome sequence analysis of U804, a pyomelanogenic, multidrug-resistant, clinical isolate, demonstrates the mechanism underlying pyomelanin overproduction.

Dihydropyrimidine Dehydrogenase Deficiency (DPYD) Genotyping-Guided Fluoropyrimidine-Based Adjuvant Chemotherapy for Breast Cancer. A Cost-Effectiveness Analysis.

Background And Objective: While standard doses of adjuvant fluoropyrimidine-based chemotherapies are generally safe for most patients, the risk of severe adverse drug reactions (ADRs) is increased for those with dihydropyrimidine dehydrogenase deficiency (DPYD), a genetic variation that affects drug metabolism. The objective of this study was to examine the cost effectiveness of offering DPYD pharmacogenetic-guided care, where genetic testing informs personalized dosing versus the current standard of care (SoC), which involves administering fluoropyrimidine-based therapies without prior genetic screening, for local or metastatic breast cancer patients in Qatar.

Methods: We developed a two-stage decision analysis, with an analytic tree model over a 6-month period, followed by a life-table Markov model over a lifetime horizon.

Efflux transporters in drug disposition during pregnancy.

Evidence-based dose selection of drugs in pregnant women has been lacking because of challenges in studying maternal-fetal pharmacokinetics. Hence, many drugs are administered off-label during pregnancy based on data obtained from nonpregnant women. During pregnancy, drug transporters play an important role in drug disposition along with known gestational age-dependent changes in physiology and drug-metabolizing enzymes.

Impact of genetic polymorphisms and drug-drug interactions mediated by carboxylesterase 1 on remimazolam deactivation.

Remimazolam (Byfavo, Acacia Pharma), a recent Food and Drug Administration-approved ester-linked benzodiazepine, offers advantages in sedation, such as rapid onset and predictable duration, making it suitable for broad anesthesia applications. Its favorable pharmacological profile is primarily attributed to rapid hydrolysis, the primary metabolism pathway for its deactivation. Thus, understanding remimazolam hydrolysis determinants is essential for optimizing its clinical use.

Uncovering the impact of COVID-19-mediated bidirectional dysregulation of cytochrome P450 3A4 on systemic and pulmonary drug concentrations using physiologically based pharmacokinetic modeling.

Several clinical studies have shown that COVID-19 increases the systemic concentration of drugs in hospitalized patients with COVID-19. However, it is unclear how COVID-19-mediated bidirectional dysregulation of hepatic and pulmonary cytochrome P450 (CYP) 3A4 affects drug concentrations, especially in the lung tissue, which is most affected by the disease. Herein, physiologically based pharmacokinetic modeling was used to demonstrate the differences in systemic and pulmonary concentrations of 4 respiratory infectious disease drugs when CYP3A4 is concurrently downregulated in the liver and upregulated in the lung based on existing clinical data on COVID-19-CYP3A4 interactions at varying severity levels including outpatients, non-intensive care unit (ICU), and ICU patients.

Efficacy and safety of anti-thrombotic therapy after surgical mitral valve repair: a scoping review.

Background: Mitral valve repair (MVr) is the gold standard treatment for degenerative mitral regurgitation, yet there is ongoing controversy regarding optimal anti-thrombotic therapy post-MVr. This scoping review aimed to summarise current evidence on the safety and efficacy of anti-thrombotic therapy after MVr, identify knowledge gaps and propose a future study design.

Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Clinicaltrials.

ConciliaMed: an interactive mobile and web tool to reconcile chronic medications of patients undergoing elective surgery.

Objective: The last decade has seen exponential growth in electronic health tools. However, only a limited number of electronic medication reconciliation tools have been developed and implemented in healthcare settings. Here, we present ConciliaMed, a mobile and web-based tool for healthcare professionals to reconcile the chronic medications of patients undergoing elective surgery.

Risk and prognosis of post-transplant lymphoproliferative disease in Epstein-Barr virus-seronegative kidney transplant recipients - An observational cohort study from Norway and western Denmark.

Post-transplant lymphoproliferative disorder (PTLD) poses a serious challenge in kidney transplant recipients. Epstein-Barr virus (EBV)-seronegative recipients have a significantly increased risk of PTLD, but few studies have investigated risk factors for PTLD in EBV-seronegative recipients in the current era of immunosuppression. This cohort study from Norway and western Denmark included first-time kidney transplant recipients between 2007-2021, and estimated the cumulative incidence, risk and prognosis of PTLD.

Efficacy and Safety of Dapagliflozin Compared to Pioglitazone in Diabetic and Non-Diabetic Patients with Non-alcoholic Steatohepatitis: A Randomized Clinical Trial.

Background: Non-alcoholic steatohepatitis (NASH) is a serious end-stage spectrum of non-alcoholic fatty liver disease (NAFLD) with associated high risk of hepatic and extrahepatic complications. Several studies showed the significant beneficial effect of dapagliflozin on body composition, hepatic and metabolic parameters on NAFLD/NASH patients. The study aimed to investigate the efficacy and safety of dapagliflozin in both diabetic and non-diabetic biopsy-proven NASH patients; compared to pioglitazone.

Assessing the Utilization of HIV Genotype Resistance Testing: Insight from Italian Infectious Diseases Units.

Purpose: We aimed to assess the utilization of Genotype Resistance Testing (GRT) by Infectious Diseases Units across Italy.

Methods: A cross-sectional study was conducted involving a questionnaire distributed to the Infectious Diseases Unit in Italy. A web-based survey using Google Forms software was utilized and spread via email or cellphone.

Efficacy of surgical ablation and left atrial appendage occlusion in patients with AF undergoing coronary artery bypass grafting: A network meta-analysis.

Background: Atrial fibrillation (AF) is a prevalent cardiac arrhythmia that greatly elevates the risk of stroke. This risk increases both during and after cardiac procedures, such as coronary artery bypass grafting (CABG). There is an increasing interest in non-pharmacological treatments such as left atrial appendage occlusion (LAAO) and surgical ablation, intending to enhance both immediate and long-term postoperative results.

The impact of operational trial approaches on representativeness: Comparison of decentralized clinical trial participants, conventional trial participants, and patients in daily practice.

Decentralized clinical trial (DCT) approaches - in which trial activities are conducted at participants' homes - have the potential to improve representativeness. We present a study that compared the demographics and cardiovascular risk factors of participants from a DCT (ASCEND) and a conventional trial with a similar trial objective (POPADAD) to those of patients in daily practice. We adjudicate that there are relevant differences when comparing the participants of the conventional trial and the DCT, with the latter providing better representativeness in terms of age, insulin use, smoking status, and body mass index, whereas conventional trial participants were more representative in terms of biological sex.

Cellular heterogeneity and communication networks in gastric cancer: Single-cell analysis reveals β-hydroxybutyrylation-associated genes and immune infiltration characteristics.

Gastric cancer is characterized by high heterogeneity, with its complex microenvironment and intercellular communications playing critical roles in disease progression and treatment responses. In this study, we utilized single-cell sequencing to dissect the intricate landscape of gastric cancer, identifying diverse cell populations and their interactions. We focused on the role of β-hydroxybutyrylation (Kbhb)-associated genes and their impact on the tumor microenvironment.

Exploring acemannan-loaded nanogel formulation for the treatment of IMQ-induced psoriasis-like inflammation: In vitro characterization and in vivo efficacy assessment.

This study aimed to explore a nanogel formulation containing acemannan as a carrier for the treatment of psoriasis-like skin inflammation. Several acemannan concentrations, such as F1 (2.5 %) and F2 (5 %), were used to prepare the nanogel formulation by homogenization.

Targeting RNA splicing modulation: new perspectives for anticancer strategy?

The excision of introns from pre-mRNA is a crucial process in the expression of the majority of genes. Alternative splicing allows a single gene to generate diverse mRNA and protein products. Aberrant RNA splicing is recognized as a molecular characteristic present in almost all types of tumors.

Concurrent inhibition of p300/CBP and FLT3 enhances cytotoxicity and overcomes resistance in acute myeloid leukemia.

FMS-like tyrosine kinase-3 (FLT3), a class 3 receptor tyrosine kinase, can be activated by mutations of internal tandem duplication (FLT3-ITD) or point mutations in the tyrosine kinase domain (FLT3-TKD), leading to constitutive activation of downstream signaling cascades, including the JAK/STAT5, PI3K/AKT/mTOR and RAS/MAPK pathways, which promote the progression of leukemic cells. Despite the initial promise of FLT3 inhibitors, the discouraging outcomes in the treatment of FLT3-ITD-positive acute myeloid leukemia (AML) promote the pursuit of more potent and enduring therapeutic approaches. The histone acetyltransferase complex comprising the E1A binding protein P300 and its paralog CREB-binding protein (p300/CBP) is a promising therapeutic target, but the development of effective p300/CBP inhibitors faces challenges due to inherent resistance and low efficacy, often exacerbated by the absence of reliable clinical biomarkers for patient stratification.

Predictors of Mortality in Venoarterial Extracorporeal Membrane Oxygenation Regardless of Early Left Ventricular Unloading: A National Experience.

Objective: The use of an intra-aortic balloon pump (IABP) has been suggested to unload the left ventricle while on venoarterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock (CS), leading to possibly improved in-hospital mortality. However, the predictors of mortality on dual mechanical circulatory support have not yet been evaluated, especially in real-world clinical settings. Therefore, a case-control study was conducted to determine the rate of all-cause mortality associated with VA-ECMO use regardless of left ventricular (LV) unloading, and with early LV unloading in the setting of CS, and to identify the predictors of mortality associated with VA-ECMO, with concurrent early LV unloading.