Can aortic valve calcium score predict a need for permanent pacemaker implantation after transcatheter aortic valve implantation?

Introduction: Conductive disturbances requiring permanent pacemaker (PPM) implantation remain a major concern after transcatheter aortic valve implantation (TAVI).

Aims: To assess the impact of aortic valve calcium score (AVCS) on conductive disturbances requiring PPM after TAVI.

Methods: All patients who underwent TAVI with accessible AVCS from the preprocedural CT scan report were included in this retrospective single-centre study.

Cathinone metabolism and biliary excretion in an ex-vivo pig liver model: Example of 4-Cl-PVP and eutylone.

Objective: Recently, the pig liver model perfused ex vivo using a normothermic machine perfusion (NMP) has been proposed as a suitable model to study xenobiotic metabolism and biliary excretion. The aim of our study is to describe the metabolism of NPS such as cathinones (with a focus on 4-Cl-PVP and eutylone) in blood and bile, using a normothermic perfused pig liver model.

Methods: Livers (n = 4) from male large white pigs, 3-4 months of age and weighing approximately 75-80 kg, were harvested and reperfused onto an NMP (LiverAssist®, XVIVO) using autologous whole blood at 38 °C.

One Concentration Does Not Fit All: It is Time to Personalize the Therapeutic Range of Infliximab in Crohn Disease.

Background: Therapeutic drug monitoring of infliximab is commonly performed based on trough concentration. However, doses and dosing intervals may be adapted to patient outcomes, and this trough concentration target may correspond to a large range of exposures in terms of the area under the concentration-time curve (AUC). The objectives of this study were to assess the real-life exposure to intravenous infliximab in patients with Crohn disease in remission at year 1 and to assess the evolution of exposure in patients who switched to subcutaneous infliximab.

A biological pharmacology network to secure the risk of drug-drug interaction with nirmatrelvir/ritonavir.

Nirmatrelvir/ritonavir is a protease inhibitor antiviral drug indicated in the treatment of severe acute respiratory syndrome coronavirus-2 infections in high-risk patients for a severe disease. Unfortunately, ritonavir, used to boost nirmatrelvir pharmacokinetics, can also inhibit or induce the metabolism of other co-administered drugs substrates. This may lead to a subsequent risk of adverse drug reaction and lack of efficacy.

Phenotypic clustering of patients hospitalized in intensive cardiac care units: Insights from the ADDICT-ICCU study.

Background: Intensive cardiac care units (ICCUs) were created to manage ventricular arrhythmias after acute coronary syndromes, but have diversified to include a more heterogeneous population, the characteristics of which are not well depicted by conventional methods.

Aims: To identify ICCU patient subgroups by phenotypic unsupervised clustering integrating clinical, biological, and echocardiographic data to reveal pathophysiological differences.

Methods: During 7-22 April 2021, we recruited all consecutive patients admitted to ICCUs in 39 centers.

Follow the Area Under the Curve Not the Trough Concentration: A Case Study of Tacrolimus Monitoring in a Kidney Transplant Recipient Cotreated With Phenobarbital.

The authors described tacrolimus dosing in a kidney transplant patient concurrently treated with phenobarbital, where measuring the tacrolimus area under the curve was necessary to achieve adequate drug exposure and improve kidney function.

Can we predict the influence of inflammation on voriconazole exposure? An overview.

Voriconazole is a triazole antifungal indicated for invasive fungal infections that exhibits a high degree of inter-individual and intra-individual pharmacokinetic variability. Voriconazole pharmacokinetics is non-linear, making dosage adjustments more difficult. Therapeutic drug monitoring is recommended by measurement of minimum plasma concentrations.

Impact of Prosthesis-Patient Mismatch After Transcatheter Aortic Valve Replacement.

Background: Data on the long-term impact of prosthesis-patient mismatch (PPM) on outcomes after transcatheter aortic valve replacement (TAVR) remain sparse. We therefore aimed to investigate the incidence, predictive factors, and long-term prognostic impact of PPM on bioprosthesis durability and mortality.

Methods: This was a single-centre retrospective study including 2117 patients who underwent TAVR for aortic stenosis from 2002 to 2022.

Area under the curve of tacrolimus using microsampling devices: towards precision medicine in solid organ transplantation?

Purpose: Therapeutic drug monitoring of tacrolimus using trough concentration (C) is mandatory to ensure drug efficacy and safety in solid organ transplantation. However, C is just a proxy for the area under the curve of drug concentrations (AUC) which is the best pharmacokinetic parameter for exposure evaluation. Some studies suggest that patients may present discrepancies between these two parameters.

Pharmacokinetics of baricitinib in critically ill COVID-19 patients.

Background: The use of the selective Janus Kinase 1/2 inhibitor baricitinib has shown a survival benefit in mechanically ventilated COVID-19 patients but this is not without adverse drug reactions. Although critically ill patients are at risk of altered drug exposure, data on baricitinib pharmacokinetics (PK) are scarce. This study describes real-life baricitinib plasma exposure in critically ill COVID-19 patients.

Impact of coronary artery disease on clinical outcomes after TAVR: Insights from the BRAVO-3 randomized trial.

Objective: To determine the prognostic impact of coronary artery disease (CAD) in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR).

Background: CAD is a common comorbidity among patients undergoing TAVR and studies provide conflicting data on its prognostic impact.

Methods: The Bivalirudin on Aortic Valve Intervention Outcomes-3 (BRAVO-3) randomized trial compared the use of bivalirudin versus UFH in 802 high-surgical risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis.

The concomitant use of proton pump inhibitors and BRAF/MEK inhibitors in metastatic melanoma.

Background: Proton-pump inhibitors (PPIs) are commonly used by patients with cancer, although they could reduce the absorption of oral anticancer targeted therapies. The US Food and Drug Administration states that the effect of PPIs on the efficacy of dabrafenib use by patients with metastatic melanoma is unknown. As a precautionary measure, the European Society for Medical Oncology recommends avoiding PPIs for patients receiving dabrafenib.

Contribution of voriconazole N-oxide plasma concentration measurements to voriconazole therapeutic drug monitoring in patients with invasive fungal infection.

Background: Voriconazole (VRC), a widely used triazole antifungal, exhibits significant inter- and intra-individual pharmacokinetic variability. The main metabolite voriconazole N-oxide (NOX) can provide information on the patient's drug metabolism capacity.

Objectives: Our objectives were to implement routine measurement of NOX concentrations and to describe the metabolic ratio (MR), and the contribution of the MR to VRC therapeutic drug monitoring (TDM) by proposing a suggested dosage-adjustment algorithm.

Comparison of different equations for renal function evaluation as proxies for antibiotic drug clearance: The examples of amoxicillin and cloxacillin.

The most appropriate renal function estimation equation to predict drug clearance is a matter of debate. In this study, we compare the Modification of Diet in Renal Disease (MDRD), the Chronic Kidney Disease Epidemiology collaboration (CKD-EPI) and the Cockroft-Gault (CG) equations to predict amoxicillin and cloxacillin clearance among hospitalized patients receiving high doses of these antibiotic treatments. This study aimed to compare different equations used to predict amoxicillin and cloxacillin clearance among hospitalized patients receiving amoxicillin or cloxacillin treatments outside the intensive care unit.

Quantitative impact of pre-analytical process on plasma uracil when testing for dihydropyrimidine dehydrogenase deficiency.

Aims: Determining dihydropyrimidine dehydrogenase (DPD) activity by measuring patient's uracil (U) plasma concentration is mandatory before fluoropyrimidine (FP) administration in France. In this study, we aimed to refine the pre-analytical recommendations for determining U and dihydrouracil (UH ) concentrations, as they are essential in reliable DPD-deficiency testing.

Methods: U and UH concentrations were collected from 14 hospital laboratories.

Blood, Cellular, and Tissular Calcineurin Inhibitors Pharmacokinetic-Pharmacodynamic Relationship in Heart Transplant Recipients: The INTRACAR Study.

Background: After heart transplantation, calcineurin inhibitors (CNI) (cyclosporin A and tacrolimus) are key immunosuppressive drugs to prevent graft rejection. Whole-blood concentration (C blood )-guided therapeutic drug monitoring (TDM) is systematically performed to improve graft outcomes. However, some patients will still experience graft rejection and/or adverse events despite CNI C blood within the therapeutic range.

A Robust and Fast/Multiplex Pharmacogenetics Assay to Simultaneously Analyze 17 Clinically Relevant Genetic Polymorphisms in , , , , , , and Genes.

In the field of pharmacogenetics, the trend is to analyze a panel of several actionable genetic polymorphisms. It may require the use of high-throughput sequencing which demands expensive reagents/instruments and specific skills to interpret results. As an alternative, the aim of this work was to validate an easy, fast, and inexpensive multiplex pharmacogenetics assay to simultaneously genotype a panel of 17 clinically actionable variants involved in drug pharmacokinetics/pharmacodynamics.