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In this Continuing Professional Development module, we review the practical pharmacology of tranexamic acid and its clinical use in trauma, obstetrics, and major orthopedic surgery.Tranexamic acid is a synthetic drug that inhibits fibrinolysis. Multiple clinical trials in various clinical settings have shown that it can reduce blood loss, transfusion rates, and bleeding-associated mortality. In trauma and obstetrical bleeding, early tranexamic acid administration (three hours) may have greater clinical benefits. Overall, tranexamic acid use appears safe with no significant increase of thromboembolic or seizure events. Nevertheless, current evidence has limitations related to wide heterogeneity in dose, route, and timing of drug administration, as well as generalizability of the large-scale trial findings to higher income nations.Tranexamic acid is an efficacious and safe pharmacological-based blood conservation technique in the management of clinically significant hemorrhage. All anesthesiologists should have a good understanding of the pharmacotherapeutic properties and perioperative role of tranexamic acid therapy both inside and outside of the operating room. The use of tranexamic acid is likely to continue to rise with endorsement by various clinical guidelines and healthcare organizations. Further quantitative research is needed to evaluate optimal dosing and drug efficacy in these clinical scenarios.RéSUMé: OBJECTIF: Dans ce module de Développement professionnel continu, nous passons en revue la pharmacologie pratique de l’acide tranexamique et son utilisation clinique dans le trauma, l’obstétrique, et les chirurgies orthopédiques majeures. CONSTATATIONS PRINCIPALES: L’acide tranexamique est un médicament synthétique inhibant la fibrinolyse. Plusieurs essais cliniques dans divers contextes cliniques ont montré qu’il peut réduire les pertes de sang, les taux de transfusion et la mortalité associée aux saignements. Dans les cas de saignement traumatologique et obstétrical, l’administration précoce d’acide tranexamique (trois heures) pourrait avoir de plus grands bienfaits cliniques. Globalement, l’utilisation d’acide tranexamique semble sécuritaire et n’entraîne pas d’augmentation significative des complications thromboemboliques ou de convulsions. Néanmoins, les données probantes actuelles comportent des limites liées à une grande hétérogénéité dans la posologie, la voie et le moment d’administration du médicament, ainsi qu’à l’aspect généralisable des résultats des études à grande échelle pour les pays à revenu élevé. CONCLUSION: L’acide tranexamique est une technique pharmacologique de conservation du sang efficace et sécuritaire pour la prise en charge de l’hémorragie cliniquement significative. Les anesthésiologistes devraient tous posséder une bonne compréhension des propriétés pharmacothérapeutiques et du rôle périopératoire de la thérapie par acide tranexamique, tant à l’intérieur qu’à l’extérieur de la salle d’opération. L’utilisation de l’acide tranexamique continuera vraisemblablement à augmenter au fur et à mesure de l’obtention de son approbation par diverses lignes directrices cliniques et organismes de soins de santé. D’autres recherches quantitatives sont nécessaires pour évaluer le dosage optimal et l’efficacité du médicament dans ces scénarios cliniques.

Circulating tumor cells (CTCs) are cells shed from tumors or metastatic sites and are a potential biomarker for cancer diagnosis, management, and prognostication. The majority of current studies use single or infrequent CTC sampling points. This strategy assumes that changes in CTC number, as well as phenotypic and molecular characteristics, are gradual with time. In reality, little is known today about the actual kinetics of CTC dissemination and phenotypic and molecular changes in the blood of cancer patients. Herein, we show, using clinical case studies and hypothetical simulation models, how sub-optimal CTC sampling may result in misleading observations with clinical consequences, by missing out on significant CTC spikes that occur in between sampling times. Initial studies using highly frequent CTC sampling are necessary to understand the dynamics of CTC dissemination and phenotypic and molecular changes in the blood of cancer patients. Such an improved understanding will enable an optimal, study-specific sampling frequency to be assigned to individual research studies and clinical trials and better inform practical clinical decisions on cancer management strategies for patient benefits.

e13032Background: Recent advances in NGS increase the accessibility and affordability of germline genomic diagnostic testing in cancer care. Singapore, a multi-ethnic society, is a destination for patients with medical needs across Asia. Despite the availability of NGS testing, questions remain about the interpretation of results in patients from the developing world. Methods: A total of 91 patients were seen at a Singapore based centre. All patients provided a 3-generation pedigree and received pre/post test counselling. After informed consent, patients provided samples for NGS multiplexed panels. Samples were analyzed in a US-based CAP & CLIA certified laboratory for assessment of germline variants. Results: All 91 patients (22 male/69 female; median age 45) were successfully sequenced. Pathogenic variants (PV) were identified in 11.0% (10/91) of patients and variants of uncertain significance (VUS) were reported in 39.6% (36/91). PV’s seen include BRCA1 (3), BRCA2 (2) and 1 each for BRIP1, MUTYH, MLH1,...