Personalized Dosing of Linezolid to Reduce the Risk of Thrombocytopenia: A Systematic Review and Meta-Analysis.

Background: Linezolid-induced thrombocytopenia (LIT) occurs in a dose-dependent manner. There is no consensus regarding personalized dosing of linezolid in the real world. This study investigated the usefulness of personalized dosing for the potential mitigation of LIT compared with standard dosing.

Teicoplanin 24-h loading dose regimen using a decision tree model to target serum trough concentration of 15-30 μg/mL: A retrospective study.

Introduction: Teicoplanin (TEIC) is typically administered as a loading dose over 36-48 h. Achieving an effective concentration quickly is expected to treat severe infections, such as sepsis and methicillin-resistant Staphylococcus aureus infections. We aimed to identify the TEIC loading dose to be completed within 24 h, targeting the concentration of 15-30 μg/mL and factors affecting the loading dose by utilizing the decision tree (DT) model.

Thiamylal serum concentration for refractory convulsive status epilepticus while associated decreased concentrations of concomitant antiepileptics: a case report.

Background: Treating refractory status epilepticus (RSE) remains a challenge. Thiamylal can be used as a second- or third-line treatment; however, its potential to induce cytochrome P450 (CYP) activity may reduce the concentration of antiepileptic drugs (AEDs) administered prior to thiamylal. This report details a case of RSE patient treated with thiamylal, with monitored concentrations of thiamylal and other AEDs.

Effect of concomitant use of yokukansan on steady-state blood concentrations of donepezil and risperidone in real-world clinical practice.

Aim: Yokukansan is one of the most frequently used herbal medicines that can improve the behavioral and psychological symptoms of dementia. In this exploratory study, we investigated whether yokukansan affects the steady-state blood concentrations of donepezil, risperidone, and the major metabolites of both drugs in a real-world clinical setting.

Methods: A non-randomized, open-label, single-arm study examining drug-drug interactions was conducted.

Optimizing Cefiderocol Dosing Through Population Pharmacokinetic/Pharmacodynamic Simulation: An Assessment of Drug Cost Reductions.

Background: Cefiderocol is a siderophore cephalosporin antibiotic with bactericidal activity against carbapenem-resistant Enterobacterales. However, an efficient dosing strategy is yet to be developed. This study aimed to evaluate efficient lower-dose regimens and estimate potential drug cost reductions.

Characterization of heterozygous ATTR Tyr114Cys amyloidosis-specific induced pluripotent stem cells.

Hereditary transthyretin (TTR) amyloidosis (ATTRv amyloidosis) is autosomal dominant and caused by mutation of gene. Heterozygous ATTR Tyr114Cys (p.Tyr134Cys) amyloidosis is a lethal disease with a life expectancy of about 10 years after onset of the disease.

Silencing of ocular transthyretin, a gene responsible for hereditary transthyretin amyloidosis, by intravitreal injection of an siRNA conjugate into rabbit eyes.

The first small interfering RNA (siRNA) therapeutic received approval for hereditary transthyretin (ATTRv) amyloidosis, and the patients' lifespan extension by specific inhibition of hepatic synthesis of transthyretin (TTR) is expected. However, ocular amyloidosis in these patients has been a crucial issue. This study aims to evaluate the efficacy and safety of intravitreal TTR siRNA conjugate injection into rabbit eyes.

Dose Individualization of Cefepime for Febrile Neutropenia in Patients With Lymphoma or Multiple Myeloma: Implications for Therapeutic Drug Monitoring.

Background: Optimal cefepime dosing is a challenge because of its dose-dependent neurotoxicity. This study aimed to determine individualized cefepime dosing for febrile neutropenia in patients with lymphoma or multiple myeloma.

Methods: This prospective study enrolled 16 patients receiving cefepime at a dose of 2 g every 12 hours.

Model-informed precision dosing of vancomycin for rapid achievement of target area under the concentration-time curve: A simulation study.

In this study, we aimed to evaluate limited sampling strategies for achieving the therapeutic ranges of the area under the concentration-time curve (AUC) of vancomycin on the first and second day (AUC , AUC , respectively) of therapy. A virtual population of 1000 individuals was created using a population pharmacokinetic (PopPK) model, which was validated and incorporated into our model-informed precision dosing tool. The results were evaluated using six additional PopPK models selected based on a study design of prospective or retrospective data collection with sufficient concentrations.

Suppression of Indoxyl Sulfate Accumulation Reduces Renal Fibrosis in Sulfotransferase 1a1-Deficient Mice.

Renal fibrosis is the final manifestation of chronic kidney disease (CKD); its prevention is vital for controlling CKD progression. Indoxyl sulfate (IS), a typical sulfate-conjugated uremic solute, is produced in the liver via the enzyme sulfotransferase (SULT) 1A1 and accumulates significantly during CKD. We investigated the toxicopathological role of IS in renal fibrosis using -KO mice and the underlying mechanisms.

Model-Informed Precision Dosing of Vancomycin in Adult Patients Undergoing Hemodialysis.

Model-informed precision dosing (MIPD) maximizes the probability of successful dosing in patients undergoing hemodialysis. In these patients, area under the concentration-time curve (AUC)-guided dosing is recommended for vancomycin. However, this model is yet to be developed.

Bayesian prediction-based individualized dosing of anti-methicillin-resistant Staphylococcus aureus treatment: Recent advancements and prospects in therapeutic drug monitoring.

As one of the efficient techniques for TDM, the population pharmacokinetic (popPK) model approach for dose individualization has been developed due to the rapidly growing innovative progress in computer technology and has recently been considered as a part of model-informed precision dosing (MIPD). Initial dose individualization and measurement followed by maximum a posteriori (MAP)-Bayesian prediction using a popPK model are the most classical and widely used approach among a class of MIPD strategies. MAP-Bayesian prediction offers the possibility of dose optimization based on measurement even before reaching a pharmacokinetically steady state, such as in an emergency, especially for infectious diseases requiring urgent antimicrobial treatment.

Population Pharmacokinetics and AUC-Guided Dosing of Tobramycin in the Treatment of Infections Caused by Glucose-Nonfermenting Gram-Negative Bacteria.

Purpose: Tobramycin (TOB) exhibits variable pharmacokinetic properties due to the clinical condition of patients. This study aimed to investigate the AUC-guided dosing of TOB based on population pharmacokinetic analysis in the treatment of infections caused by Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia.

Methods: This retrospective study was conducted between January 2010 and December 2020 after obtaining approval from our institutional review board.

Model-informed precision dosing of teicoplanin for the rapid achievement of the target area under the concentration-time curve: A simulation study.

Teicoplanin, a glycopeptide antimicrobial, is recommended for therapeutic drug monitoring, but it remains unclear how to target the area under the concentration-time curve (AUC). This simulation study purposed to demonstrate the potential of the Bayesian forecasting approach for the rapid achievement of the target AUC for teicoplanin. We generated concordant and discordant virtual populations against a Japanese population pharmacokinetic model.

Potential use of EGFR-targeted molecular therapies for tumor suppressor CYLD-negative and poor prognosis oral squamous cell carcinoma with chemoresistance.

Background: Tumor suppressor CYLD dysfunction by loss of its expression, triggers malignant transformation, especially drug resistance and tumor invasion/metastasis. Although loss of CYLD expression is significantly associated with poor prognosis in a large variety of tumors, no clinically-effective treatment for CYLD-negative cancer patients is available.

Methods: We focused on oral squamous cell carcinoma (OSCC), and sought to develop novel therapeutic agents for CYLD-negative cancer patients with poor prognosis.

Feasibility Study of Dendrimer-Based TTR-CRISPR pDNA Polyplex for Ocular Amyloidosis in Vitro.

Hereditary amyloidgenic transthyretin (ATTR) amyloidosis is caused by a genetic point-mutated transthyretin such as TTR Val30Met (TTR V30M), since it forms protein aggregates called amyloid resulting in the tissue accumulation and functional disorders. In particular, ATTR produced by retinal pigment epithelial cells often causes ATTR ocular amyloidosis, which elicits deterioration of ocular function and ultimately blindness. Therefore, development of novel therapeutic agents is urgently needed.

Multifunctional Therapeutic Cyclodextrin-Appended Dendrimer Complex for Treatment of Systemic and Localized Amyloidosis.

Amyloidosis pathologically proceeds via production of amyloidogenic proteins by organs, formation of protein aggregates through structural changes, and their deposition on tissues. A growing body of evidence demonstrates that amyloidosis generally develops through three critical pathological steps: (1) production of amyloid precursor proteins, (2) amyloid formation, and (3) amyloid deposition. However, no clinically effective therapy that is capable of targeting each pathological step of amyloidosis independently is currently available.

Ribosomal proteins induce stem cell-like characteristics in glioma cells as an "extra-ribosomal function".

The characteristic features of plasticity and heterogeneity in glioblastoma (GB) cells cause therapeutic difficulties. GB cells are exposed to various stimuli from the tumor microenvironment and acquire the potential to resist chemoradiotherapy. To investigate how GB cells acquire stem cell-like phenotypes, we focused on ribosomal proteins, because ribosome incorporation has been reported to induce stem cell-like phenotypes in somatic cells.

Assessing the Role of Ependymal and Vascular Cells as Sources of Extracellular Cues Regulating the Mouse Ventricular-Subventricular Zone Neurogenic Niche.

Neurogenesis persists in selected regions of the adult mouse brain; among them, the ventricular-subventricular zone (V-SVZ) of the lateral ventricles represents a major experimental paradigm due to its conspicuous neurogenic output. Postnatal V-SVZ neurogenesis is maintained by a resident population of neural stem cells (NSCs). Although V-SVZ NSCs are largely quiescent, they can be activated to enter the cell cycle, self-renew and generate progeny that gives rise to olfactory bulb interneurons.

Polymorphism Associates With mTOR Inhibitor-Induced Interstitial Lung Disease in Patients With Renal Cell Carcinoma.

We evaluated the association of signal transducer and activator of transcription 3 () polymorphisms with the incidence of mammalian target of rapamycin (mTOR) inhibitor-induced interstitial lung disease (ILD) in patients with renal cell carcinoma (RCC). We also used lung-derived cell lines to investigate the mechanisms of this association. Japanese patients with metastatic RCC who were treated with mTOR inhibitors were genotyped for the polymorphism, rs4796793 (1697C/G).

Glioma Cells Acquire Stem-like Characters by Extrinsic Ribosome Stimuli.

Although glioblastoma (GBM) stem-like cells (GSCs), which retain chemo-radio resistance and recurrence, are key prognostic factors in GBM patients, the molecular mechanisms of GSC development are largely unknown. Recently, several studies revealed that extrinsic ribosome incorporation into somatic cells resulted in stem cell properties and served as a key trigger and factor for the cell reprogramming process. In this study, we aimed to investigate the mechanisms underlying GSCs development by focusing on extrinsic ribosome incorporation into GBM cells.