Senescence Cell Induction Methods Display Diverse Metabolic Reprogramming and Reveal an Underpinning Serine/Taurine Reductive Metabolic Phenotype.

The relationship between in vitro senescence cell induction and intracellular biomolecular dysregulation is still poorly understood. In this study, we have found that a range of metabolic subphenotypes exists and is dependent on the induction method that is used. To develop understanding of these subphenotypes, we developed and employed a novel bioanalytical pipeline integrating untargeted metabolomics, label-free proteomics, and stable isotope tracing alongside cellular deformability measurements and established senescence biomarkers.

Model-Based Dose Selection of a Sphingosine-1-Phosphate Modulator, Etrasimod, in Patients with Various Degrees of Hepatic Impairment.

Etrasimod is a newly FDA-approved Sphingosine-1-Phosphate modulator indicated for moderate and severe ulcerative colitis. It is extensively metabolized in the liver via the cytochrome P450 system and may accumulate markedly in patients with hepatic dysfunction, exposing them to toxicity. The aim of the current study is to utilize a physiologically-based pharmacokinetic modeling approach to evaluate the impact of hepatic impairment on the pharmacokinetic behavior of etrasimod and to appropriately select dosage regimens for patients with chronic liver disease; Methods: PK-Sim was used to develop the etrasimod PBPK model, which was verified using clinical data from healthy subjects and subsequently adapted to reflect the physiological changes associated with varying degrees of hepatic dysfunction; Results: Simulations indicated that hepatic clearance of etrasimod is clearly reduced in patients with Child-Pugh B and C liver impairment.

A retrospective analysis of tacrolimus pharmacokinetic in Saudi paediatric patients in early post-liver transplantation period.

Background: Tacrolimus is an essential immunosuppressive medication in paediatric patients' post-liver transplantation. Achieving tacrolimus target concentration in early post-transplantation is crucial to minimise the risk of acute rejection; however, this is challenging due to inter- and intra-patient variability in tacrolimus metabolism and clearance. Therefore, our study aims to describe tacrolimus trough concentration variability and pharmacokinetics in paediatric post-liver transplantation during the first two weeks post-transplantation.

Leveraging machine learning in limited sampling strategies for efficient estimation of the area under the curve in pharmacokinetic analysis: a review.

Objective: Limited sampling strategies are widely employed in clinical practice to minimize the number of blood samples required for the accurate area under the curve calculations, as obtaining these samples can be costly and challenging. Traditionally, the maximum a posteriori Bayesian estimation has been the standard method for the area under the curve estimation based on limited samples. However, machine learning is emerging as a promising alternative for this purpose.

Evaluation of the predictive performance of an online voriconazole dose calculator in children.

Background: The dosing of voriconazole is challenging in pediatrics. One approach to improve the dosing is through the use of Bayesian concentration-guided dosing software. Our study assessed the predictive performance of a freely available online voriconazole dose calculator in pediatric patients "NextDose" ( https://www.

Evaluation of pharmacokinetic target attainment and hematological toxicity of linezolid in pediatric patients.

Background: Linezolid is commonly used to treat severe and/or resistant Gram-positive infections. Few studies have assessed its pharmacokinetic (PK) target attainment in pediatrics.

Objective: To evaluate the percentage of pediatrics achieving the PK targets of linezolid with standard dosing regimens and to assess the incidence and risk factors associated with its hematologic toxicity.

Perceptions and Behaviors Regarding Early Screening and Breast-Related Complaints Among Saudi Women.

Background Breast cancer (BC) is a global public health issue, contributing to a significant death toll among women. Breast cancer is the most common type among Saudi women, accounting for over a quarter of all new cancer cases. The current approaches for detecting BC include mammography, clinical breast exams, and breast self-examination (BSE).

How Did COVID-19 Impact Smoking Habits in the Saudi Community?

Background/aims Most countries have gone through lockdowns to varying degrees during the COVID-19 pandemic to reduce the spread of the disease. The successive pandemic waves have impacted the health system, imposing restrictions set by the government. This changed people's daily life routines and they felt more socially isolated, which in turn had an impact on their mental health.

Medial Tibial Stress Syndrome (Shin Splint): Prevalence, Causes, Prevention, and Management in Saudi Arabia.

Background/aims Medial tibial stress syndrome (MTSS), also known as "shin splint", is most often described as exertional leg pain along the shinbone (tibia), which occurs due to the inflammation of the muscles, tendons, and bone tissue in this area. This study aims to assess the prevalence, risk factors, and their association with the development of MTSS, as well as the effective treatments that reduce pain and improve functions among the Saudi general population. Materials and method The present cross-sectional study was conducted on the general population of Saudi Arabia through an electronic survey over a period of three months.

Therapeutic Drug Monitoring of Voriconazole in Critically Ill Pediatric Patients: A Single-Center Retrospective Study.

Background And Objective: Voriconazole pharmacokinetics are highly variable in pediatric patients, and the optimal dosage has yet to be determined. The purpose of this study was to describe voriconazole pharmacokinetic and pharmacodynamic targets achieved and evaluate the efficacy and safety of voriconazole for critically ill pediatrics.

Methods: This is a single-center retrospective study conducted at a pediatric intensive care unit at a tertiary/quaternary hospital.

Evaluation of pharmacokinetic pharmacodynamic target attainment of meropenem in pediatric patients.

Background: Meropenem is a widely used carbapenem for treating severe pediatric infections. However, few studies have assessed its pharmacokinetics/pharmacodynamics (PK/PD) in pediatric patients. This study aimed to evaluate the proportion of Saudi pediatric patients achieving the PK/PD target of meropenem.

External Validation of Obese/Critically Ill Vancomycin Population Pharmacokinetic Models in Critically Ill Patients Who Are Obese.

Obesity combined with critical illness might increase the risk of acquiring infections and hence mortality. In this patient population the pharmacokinetics of antimicrobials vary significantly, making antimicrobial dosing challenging. The objective of this study was to assess the predictive performance of published population pharmacokinetic models of vancomycin in patients who are critically ill or obese for a cohort of critically ill patients who are obese.

Interethnic differences in drug response: projected impact of genetic variations in the Saudi population.

Ethnicity is known to have an impact on drug responses. This is particularly important for drugs that have a narrow therapeutic window, nonlinearity in pharmacokinetics and are metabolized by enzymes that demonstrate genetic polymorphisms. However, most clinical trials are conducted among Caucasians, which might limit the usefulness of the findings of such studies for other ethnicities.

Population Pharmacokinetics of Rivaroxaban in Real-World Patients.

The pharmacokinetics (PK) of rivaroxaban have been studied in different populations, and there were differences in the PK parameters. However, most of these studies were conducted on healthy subjects from different ethnic groups. Thus, this study aimed to investigate the PK of rivaroxaban in real-world patients to determine the covariates that may cause differences in the pharmacokinetics of rivaroxaban.

Evaluation of vancomycin individualized model-based dosing approach in neonates.

Background: Vancomycin is commonly used to treat methicillin-resistant staphylococcal infections in neonates. Consensus on its ideal dosing in neonates has not been achieved. Model-based dosing recently has evolved as an important tool to optimize vancomycin initial dosing.

Clinical pharmacokinetics of capecitabine and its metabolites in colorectal cancer patients.

Background: Capecitabine is one of the fluoropyrimidine anticancer agents which is extensively used in the management of colorectal cancer. We have noticed a discrepancy between the doses we are using in our patients and the recommended dosing regimen. Thus, this study aims to assess the pharmacokinetic parameters of capecitabine and its metabolites in colorectal cancer patients and report some clinical outcomes.

Successful treatment of Gustilo type 3C open tibial fracture with a massive muscles and soft tissues wasting: A case report.

Introduction And Importance: Gustilo-Anderson type 3 open tibial fractures are commonly accompanied by extensive damage and serious complications, especially in types 3B and 3C.

Case Presentation: A 25-year-old male was transferred after motor vehicle accident and the emergent choice was an above-knee amputation in other two hospital. A left open distal tibial fracture (Gustilo type 3C) with a wide and contaminated soft tissues defect, that extended from the knee to the midfoot, is accompanied by wasting of the anterior compartment muscles and ruptured of the anterior tibial artery.

Can First-Dose Therapeutic Drug Monitoring Predict the Steady State Area Under the Blood Concentration-Time Curve of Busulfan in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation?

Busulfan has high intra-individual variability and possible time-dependent changes in clearance, which complicates therapeutic drug monitoring (TDM), as first dose sampling may not predict the steady state concentrations. In this study, we aimed to use Bayesian pharmacokinetic parameters estimated from the first dose to predict the steady state AUC for busulfan. This observational study was conducted among pediatric patients at King Abdullah Specialist Children's Hospital.

Early Bactericidal Activity of Delpazolid (LCB01-0371) in Patients with Pulmonary Tuberculosis.

Delpazolid, an oxazolidinone, has been studied in non-clinical studies of efficacy and toxicity and Phase 1 clinical studies. Delpazolid has activity against Gram-positive bacteria, including Mycobacterium tuberculosis. This study evaluated the bactericidal activity, safety, and pharmacokinetics of delpazolid in patients with pulmonary tuberculosis (TB).

Assessment of Micafungin Dosage Regimens in Patients with Cancer Using Pharmacokinetic/Pharmacodynamic Modeling and Monte Carlo Simulation.

Micafungin is widely used for invasive candidiasis, especially in critically ill patients and those with cancer, and for empirical antifungal therapy in patients with neutropenic fever. This is the first study to investigate the pharmacokinetics and disposition parameters of micafungin in patients with cancer. In this observational pharmacokinetic study, blood samples were collected and analyzed using high-performance liquid chromatography.

Pharmacokinetics of meropenem in critically ill patients in Saudi Arabia.

Background: Meropenem is commonly used in the ICU to treat gram-negative infections. Due to various pathophysiological changes, critically ill patients are at higher risk of having subtherapeutic concentrations and hence have a higher risk of treatment failure-especially in regions where gram-negative drug resistance is increasing, such as Saudi Arabia. No studies have evaluated the pharmacokinetics of meropenem in critically ill patients in Saudi Arabia.

Dorsalis pedis artery pseudoaneurysm: A rare entity in the field of vascular surgery.

Introduction: Dorsalis pedis artery aneurysms (PDAA) and pseudoaneurysms are rare conditions of lower limb vasculature. The rarity of the disease increases in the pediatric age group where only 4 cases of pediatric patients with PDAA.

Presentation Of The Case: We present A case of a 2-year-old baby girl who was diagnosed with dorsalis pedis pseudoaneurysm, which was treated successfully with pseudoaneurysm dissection and anastomosis.