Predictive Modeling of Tacrolimus Dose Requirement Based on High-Throughput Genetic Screening.

Any biochemical reaction underlying drug metabolism depends on individual gene-drug interactions and on groups of genes interacting together. Based on a high-throughput genetic approach, we sought to identify a set of covariant single-nucleotide polymorphisms predictive of interindividual tacrolimus (Tac) dose requirement variability. Tac blood concentrations (Tac C0 ) of 229 kidney transplant recipients were repeatedly monitored after transplantation over 3 mo. Given the high dimension of the genomic data in comparison to the low number of observations and the high multicolinearity among the variables (gene variants), we developed an original predictive approach that integrates an ensemble variable-selection strategy to reinforce the stability of the variable-selection process and multivariate modeling. Our predictive models explained up to 70% of total variability in Tac C0 per dose with a maximum of 44 gene variants (p-value <0.001 with a permutation test). These models included molecular networks of drug metabolism with oxidoreductase activities and the multidrug-resistant ABCC8 transporter, which was found in the most stringent model. Finally, we identified an intronic variant of the gene encoding SLC28A3, a drug transporter, as a key gene involved in Tac metabolism, and we confirmed it in an independent validation cohort.

Mycotic arterial aneurysm secondary to BCG intravesical instillation: A review.

OBJECTIVE: Mycotic aortic aneurysm is a rare and life-threatening pathology. The first case of mycotic aneurysm induced by immunotherapy with bacille Calmette-Guérin for malignancy was published in 1988. The main objective of this review is to characterize this rare pathology. MATERIALS AND METHODS: Since then, 60 cases of arterial aneurysm following intra vesical BCG instillation have been described in the literature. All cases have been included, and characteristics have been collected retrospectively, with simple statistical analyses of the cases. RESULTS: We present a brief review from 1988 to 2022 enhancing the contemporary understanding of this arterial infection. Mycotic aneurysm secondary to BCG instillation has a poor prognosis, up to 50% complication and 15% mortality at 1 month, whether managed by open repair or endovascular means. CONCLUSION: BCG mycotic aneurysm is an extremely serious condition, the diagnosis of which must be considered at an early stage in order to adapt diagnostic and therapeutic strategies.

A case of a 15-year evolution of a coral reef aortic lesion.

We are reporting here the 15-year history of a patient affected by a chronic and evolutive coral reef aorta successfully treated by repeated revascularization.

Validation of a simple method assessing nitric oxide and nitrogen dioxide concentrations.

Monitoring of nitric oxide (NO) and nitrogen dioxide (NO2) is a prerequisite for the clinical use of NO. Chemiluminescence, the reference method, cannot be used as a routine in clinical practice in view of its cost and other restraints. This study was performed to evaluate a device using an electrochemical method (Polytrons NO and NO2, Dräger). Forty-nine simultaneous measurements of NO and various oxides of nitrogen (NOx) concentrations by the two apparatus were performed. NO measurements by means of these two methods are very well correlated (r = 0.96; p < 10(-5)). The mean difference according to the method of Bland and Altman was 2.8 +/- 1.7 ppm, with the limits of agreement at -0.6 and +6.2 ppm (confidence interval of 95%). There was also a good correlation between measurements of NO2 obtained via Polytrons and NOx via chemiluminescence (r = 0.84; p < 10(-5)). However, NO2 measurements obtained via Polytrons may be insufficient to exclude potential toxicity of NO2 due to the inability to detect measurements in the ppb-range. This study demonstrates that devices designed for industrial purposes (Polytrons NO and NO2, Dräger) can be used for clinical purposes.

[Physical modeling of inhalation anesthesia]. / Modélisation physique de l'anesthésie par inhalation.

A new physical model simulating the pharmacokinetics of volatile anaesthetics is presented. It consists in a ventilator connected to a water manometer. Gas is removed from the gaseous part of this manometer with a constant rate pump. This gas flow is directed thereafter into three capacitances with valves and pumps: one capacitance only contains air, representing the lungs, and the other two olive oil, representing the visceral and muscle compartments. Halothane, enflurane and isoflurane (1 vol%) were administered to this model with different values of cardiac output and alveolar ventilation. There was good concordance between the values of FA/FI that were measured in this model and those calculated by computer simulation. No correction factor was required. Such a physical model may therefore be used to test new techniques of administration of volatile agents.