Determination of tranexamic acid in human plasma by UHPLC coupled with tandem mass spectrometry targeting sub-microgram per milliliter levels

Tranexamic acid (TXA) is an antifibrinolytic drug, with the ability to inhibit lysine binding at plasminogen receptors, used in adult trauma patients with on-going or at risk of significant haemorrhage. To understand the pharmacokinetics and pharmacodynamics of this drug in variable age groups undergoing surgeries with high blood loss, effective methods for determination of TXA in biological samples at sub-μg mL−1 are still required. We describe herein the development and validation of a method based on ultra-high performance liquid chromatography coupled to triple quadrupole-tandem mass spectrometry to quantify TXA in human plasma. An inexpensive, simple and efficient sample clean-up was implemented, not requiring matrix-matching calibration. Sample preparation consisted in protein precipitation using acetonitrile containing 0.5% (v/v) formic acid, followed by hydrophilic interaction based chromatographic separation, with elution in isocratic mode using a combination of acetonitrile and water (75:25, v/v), with quantification of TXA based on selected reaction monitoring. Good linearity was achieved (r2 > 0.997) for TXA concentrations ranging from 30 to 600 ng mL−1, with LOD of 18 ng mL−1 in plasma. The developed method proved to be selective, sensitive, accurate (96.4–105.7% of nominal values) and precise (RSD ≤ 4.5%). TXA was found to be stable in plasma extracts standing 24 h at room temperature (20 °C) or in the autosampler, and after three freeze-thawing cycles. Mean recovery values of TXA spiked plasma samples were ≥91.9%. No significant matrix effects were observed. The proposed methodology was successfully applied to the clinical study of plasma samples recovered during scoliosis surgery of pediatric patients pretreatment with TXA.info:eu-repo/semantics/publishedVersio

Cerebral Gaseous Microemboli are Detectable During Continuous Venovenous Hemodialysis in Critically Ill Patients: An Observational Pilot Study

BACKGROUND Continuous venovenous hemodialysis (CVVHD) may generate microemboli that cross the pulmonary circulation and reach the brain. The aim of the present study was to quantify (load per time interval) and qualify (gaseous vs. solid) cerebral microemboli (CME), detected as high-intensity transient signals, using transcranial Doppler ultrasound. MATERIALS AND METHODS Twenty intensive care unit (ICU group) patients requiring CVVHD were examined. CME were recorded in both middle cerebral arteries for 30 minutes during CVVHD and a CVVHD-free interval. Twenty additional patients, hospitalized for orthopedic surgery, served as a non-ICU control group. Statistical analyses were performed using the Mann-Whitney U test or the Wilcoxon matched-pairs signed-rank test, followed by Bonferroni corrections for multiple comparisons. RESULTS In the non-ICU group, 48 (14.5-169.5) (median [range]) gaseous CME were detected. In the ICU group, the 67.5 (14.5-588.5) gaseous CME detected during the CVVHD-free interval increased 5-fold to 344.5 (59-1019) during CVVHD (P<0.001). The number of solid CME was low in all groups (non-ICU group: 2 [0-5.5]; ICU group CVVHD-free interval: 1.5 [0-14.25]; ICU group during CVVHD: 7 [3-27.75]). CONCLUSIONS This observational pilot study shows that CVVHD was associated with a higher gaseous but not solid CME burden in critically ill patients. Although the differentiation between gaseous and solid CME remains challenging, our finding may support the hypothesis of microbubble generation in the CVVHD circuit and its transpulmonary translocation toward the intracranial circulation. Importantly, the impact of gaseous and solid CME generated during CVVHD on brain integrity of critically ill patients currently remains unknown and is highly debated

Analyse de l’attachement et de son lien avec l’alliance de travail

Attachment theorists propose that attachment styles affect the development of relationships inside and outside of therapy. By integrating attachment theory into their work with clients, therapists may strengthen the working alliance and lower the risk of clients prematurely ending therapy. Attachment theory is reviewed, and methods of integrating it into counselling practice are discussed. Daly and Mallinckrodt’s (2009) model of adapting therapeutic distance to establish safety in the therapy relationship is presented. Also reviewed is how therapists can integrate client culture into the adjustment of therapeutic distance.Les théoriciens de l’attachement avancent que les styles d’attachement influencent le développement de relations à l’intérieur et à l’extérieur de la thérapie. En intégrant la théorie de l’attachement dans leur travail auprès des clients, les thérapeutes peuvent renforcer l’alliance de travail et réduire les risques que le client n’interrompe prématurément la thérapie. On passe en revue la théorie de l’attachement, tout en discutant des méthodes permettant de l’intégrer dans la pratique de counseling. On présente le modèle de Daly et Mallinckrodt (2009) d’adaptation de la distance thérapeutique pour sécuriser la relation de thérapie. On examine également la façon dont les thérapeutes peuvent intégrer la culture du client au réglage de la distance thérapeutique