[Fish odor syndrome: A socially disabling disorder]. / Le « Fish odor syndrome ¼ : une maladie socialement invalidante.

INTRODUCTION: Fish odor syndrome (FOS) is a rare metabolic disorder that manifests as "rotten fish" body odor and is caused by the excretion of trimethylamine (TMA) in body fluids. This disease can have a negative impact on the social life of affected patients. CASE REPORTS: We report the case of two female patients complaining about unpleasant body odor. The diagnosis of FOS was confirmed by the demonstration of trimethylaminuria by NMR spectroscopy and by molecular analysis of the FMO3 gene. A restrictive choline diet combined with digestive decontamination reduced odor symptoms and improved the social life of these 2 patients. CONCLUSIONS: Fish odor syndrome is a rare and unrecognized disease that can affect the quality of life of affected persons. Following laboratory diagnosis, treatment is often effective.

Traces pilot pharmacokinetic study dataset.

The dataset displays the pharmacokinetics data obtained from the TRACES pilot study. The nine patients included were undergoing haemorrhagic caesarean section (blood loss > 800 mL) and receiving a single i.v dose of tranexamic acid (0.5, 1 or 2 g over 1 min). The dataset gathers the tranexamic acid blood and urinary concentrations. With these first elements, a pharmacokinetic compartment model was built as described in Gilliot et al. and the individual pharmacokinetic parameters were estimated. In parallel, the patients anthropometric, biological, and clinical characteristics were collected. The correlation between the patient data and the estimated individual pharmacokinetic parameters were tested. The correlation tests revealed that the dose, the height, the body weight, and the ideal bodyweight had and impact on the volume of distribution of tranexamic acid. According to these results, these latter covariates were explored using a multi-regression analysis in Gilliot et al.

Hypothesis for a partially non urinary elimination of tranexamic acid in haemorrhagic caesarean section: Traces pilot pharmacokinetic study: Pharmacokinetics of tranexamic acid in obstetrics.

BACKGROUND: In previous studies, the choice of doses of tranexamic acid was empirically defined as no pharmacokinetic study had been conducted in haemorrhagic caesarean section. OBJECTIVE: The objective was to build a pharmacokinetic model in patients receiving a single 0.5, 1 or 2 g intravenous bolus. METHOD: A preliminary monocentric open study was performed in the Lille centre. Blood samples and one urinary sample were collected in the 6 h following the injection. Nine patients were included. Tranexamic acid concentration was measured using liquid chromatography system coupled with tandem mass spectrometry. We used Monolix 2019R1 for population pharmacokinetic modelling. A structural model was constructed followed by the investigation of potential covariates. RESULTS: Data were best described with a two-compartment model with a double first-order elimination from the central compartment. The model was improved when the variable ideal weight per dose was affected as a covariate for the apparent volume of distribution. Assuming a dose of 1 g and a height of 160 cm, the pharmacokinetic parameters were estimated at 10.26 L.h-1 for total clearance, 11.5 L for the volume of the central compartment, 15.8 L for the volume of the second compartment, a diffusional clearance of 30.36 L.h-1 , and a urinary excretion fraction of 25.8%. CONCLUSIONS: The population pharmacokinetic model of tranexamic acid in haemorrhagic caesarean section was successfully established in our tiny sample of patients. The results of this preliminary TRACES pharmacokinetic study suggested that elimination of tranexamic acid is partially non urinary in contrast with healthy patients.

Characterization of the in vivo immune network of IDO, tryptophan metabolism, PD-L1, and CTLA-4 in circulating immune cells in melanoma.

In melanoma, both the induction of immunosuppression by tumor cells and the inflammatory antitumor response can induce an upregulation of counter-regulatory mechanisms such as indoleamine 2,3-dioxygenase (IDO), programmed death-ligand 1 (PD-L1) and CTLA-4+ regulatory T-cells (Tregs) in the tumor microenvironment. Even though these immunosuppressive mediators are targets for immunotherapy, research investigating their expression in the peripheral blood is lacking. We therefore, performed flow cytometry on PBMCs of stage I-IV melanoma patients. IDO expression was detected in plasmacytoid dendritic cells (pDC) and monocytic myeloid-derived suppressor cells (mMDSC), and increased in advanced disease stage (p = 0.027). Tryptophan breakdown confirmed the functional activity of IDO and was linked with increased PD-L1+ cytotoxic T-cells (p = 0.009), relative lymphopenia (p = 0.036), and a higher mDC/pDC ratio (p = 0.002). High levels of circulating PD-L1+ cytotoxic T-cells were associated with increased CTLA-4 expression by Tregs (p = 0.005) and MDSC levels (p = 0.033). This illustrates that counter-regulatory immune mechanisms in melanoma should be considered as one interrelated signaling network. Moreover, both increased PD-L1+ T-cells and CTLA-4 expression in Tregs conferred a negative prognosis, indicating their in vivo relevance. Remarkably, circulating CTLA-4, IDO, and pDC levels were altered according to prior invasion of the sentinel lymph node and IDO expression in the sentinel was associated with more IDO+ PBMCs. We conclude that the expression of IDO, PD-L1, and CTLA-4 in the peripheral blood of melanoma patients is strongly interconnected, associated with advanced disease and negative outcome, independent of disease stage. Combination treatments targeting several of these markers are therefore likely to exert a synergistic response.