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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.

Most practicing anesthesiologists are involved in the care of multisystem injured patients at some time in their careers; others specialize in trauma management. In addition to providing anesthesia for trauma patients requiring surgery, anesthetic training and skills naturally lend themselves to the ongoing monitoring, resuscitation, and critical care that these challenging patients require. An understanding of the mechanisms of injury and the resultant patterns of injury is essential for the management of every traumatized patient. This knowledge allows clinicians to formulate perioperative management plans that optimize safety for patients and to anticipate complications that may arise later from missed or occult injuries. As an integral part of the team caring for these complex patients, it is unacceptable for anesthesiologists to merely provide intraoperative anesthetic care in isolation. This article discusses those mechanisms of injury in commonly seen types of blunt and penetrating trauma and reviews the patterns of injury resulting from them.

Background Because the ultimate purpose of new medical knowledge is to achieve improved health outcomes, physicians need to possess and use this knowledge in their practice. The authors introduced enhanced education and individualized feedback to reduce postoperative nausea and vomiting (PONV). The primary objective was to increase anesthesiologists' use of preventive measures to reduce PONV, and the secondary objective was to determine whether patient outcomes were improved. Methods After obtaining hospital ethics committee approval, the effect of education and feedback on anesthesiologist performance and the rate of PONV in major surgery elective inpatients during a 2-yr period was assessed. After baseline data collection (6 months), anesthesiologists at the study hospital received enhanced education (8 months) and individualized feedback (10 months). Parallel data collection was performed at a control hospital at which practice was continued as usual. The education promoted preventive measures (antiemetic premedication, nasogastric tubes, droperidol, metoclopramide). Individualized feedback provided the number of patients receiving promoted measures and the rate of PONV. The mean percentage of anesthesiologists' patients receiving at least one promoted measure and the rate of PONV were compared with baseline levels. Results At the study hospital, there was a significant increase in the mean percentage of the anesthesiologists' female patients receiving a preventive measure as well as a significant increase in the use of droperidol > or = 1 mg (P < 0.05) for all patients. The use of other promoted measures was unaffected. Absolute rates of PONV were unaffected at the study hospital until the post-feedback period (decrease of 8.8% between baseline and post-feedback (P = 0.015)). Conclusion It was demonstrated that enhanced education and individualized feedback can change anesthesiologists' practice patterns. The actual benefit to patients from use of preventive measures was limited when used in the everyday clinical situation. Therefore, only modest decreases in PONV were achieved, despite the use of preventive measures.

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,...

e22107 Background: Although a rare peripheral cell population, circulating tumor cells (CTCs) represent a potential alternative to serial invasive biopsies as a source of tissue in monitoring clinical states of non-hematological malignancies. CTCs harvested from a single patient are a heterogeneous mixture of cells differing in their transcriptome expressional profiles, metastatic potential and drug resistance properties. Mere identification and enumeration of CTCs are unable to provide qualitative information about individual CTC biology. The presence of a few highly malignant, metastasis-capable CTCs and cancer stem cells among the other less aggressive CTCs in the circulating population will not be apparent from CTC counts alone. Methods: We developed a high-throughput size-exclusion microsieve device (CellSievo, Singapore) to isolate CTCs (defined as DAPI-positive, CD45-negative cells), regardless of the cell surface receptors expressed, from 74 breast cancer patients. Using CTCs eluted from the microsieve post-capture, we performed microRNA expression profiling to further characterize breast cancer CTCs. Results: Using CellSievo’s microsieve device, we obtained an average mean CTC count of 21.2 (+/- 31.8; range=0-112.5) per 7.5ml peripheral blood, for breast cancer patients, as opposed to 1.3 (+/-1.6, range 0-5.0) for healthy subjects. Viable CTCs from breast cancer patients were successfully harvested for downstream microRNA profiling. CTCs from breast cancer patients were routinely found to express microRNA profiles mediating epithelial-to-mesenchymal transition, tumor invasion, and regulation of chemotherapeutic drug resistance to tamoxifen, anthracyclines, taxanes, and trastuzumab. Serial monitoring of microRNA expression pattern of CTCs could identify emergence of novel tumor populations with distinct microRNA expression patterns during or after anticancer therapy (detailed microRNA expression data to be presented). Conclusions: Our results suggest that microRNA biomarkers derived from peripheral CTCs can yield highly useful information and offer prognostic and predictive applications for therapeutics and companion diagnostic development.

To record, tabulate and report problems associated with anaesthesia, we have developedan information collection system and computer software to follow all patients attended by an anaesthetist at a teaching hospital in Canada. For the last 15 mo, data for 17,000 patients have been collected and the system is ongoing. Data collection is from three sources: carbonless copies of the handwritten Operating Room (OR) and Post Anaesthetic Care Unit (PACU) records, other hospital databases, and postoperative visits. Adverse events (observations which differ from specific physiological variables, or require an intervention and do not normally occur during the routine conduct of anaesthesia), are defined directly on each OR and PA CU record. These events are recorded when they occur by the attending anaesthetist or the PACU nurse. All data are verified by a research nurse and an anaesthetist. Computer software, developed from DBase IV, is used to track 95 individual items on preoperative status and anaesthetic technique and another possible 1,450 selections for drugs, physicians, airways, surgical procedures and events for each patient. Data are analyzed with SAS software and reports generated to link the casemix and process with outcome. Comparison of data entered into the computer programme to a retrospective chart review revealed discrepancies of less than 0.5%. Collection, verification and computer entry takes five minutes per patient and the on-going cost is estimated at $4 per patient record. Analysis of the information collected in this database has been useful for research of adverse outcome following anaesthesia, resident expertise profiles, and the administrative management of an anaesthesia department.

Background : Because the ultimate purpose of new medical knowledge is to achieve improved health outcomes, physicians need to possess and use this knowledge in their practice. The authors introduced enhanced education and individualized feedback to reduce postoperative nausea and vomiting (PONV). The primary objective was to increase anesthesiologists' use of preventive measures to reduce PONV, and the secondary objective was to determine whether patient outcomes were improved. Methods : After obtaining hospital ethics committee approval, the effect of education and feedback on anesthesiologist performance and the rate of PONV in major surgery elective inpatients during a 2-yr period was assessed. After baseline data collection (6 months), anesthesiologists at the study hospital received enhanced education (8 months) and individualized feedback (10 months). Parallel data collection was performed at a control hospital at which practice was continued as usual. The education promoted preventive measures (antiemetic premedication, nasogastric tubes, droperidol, metoclopramide). Individualized feedback provided the number of patients receiving promoted measures and the rate of PONV. The mean percentage of anesthesiologists' patients receiving at least one promoted measure and the rate of PONV were compared with baseline levels. Results : At the study hospital, there was a significant increase in the mean percentage of the anesthesiologists' female patients receiving a preventive measure as well as a significant increase in the use of droperidol ≥1 mg (P < 0.05) for all patients. The use of other promoted measures was unaffected. Absolute rates of PONV were unaffected at the study hospital until the postfeedback period (decrease of 8.8% between baseline and postfeedback (P = 0.015)). Conclusion : It was demonstrated that enhanced education and individualized feedback can change anesthesiologists' practice patterns. The actual benefit to patients from use of preventive measures was limited when used in the everyday clinical situation. Therefore, only modest decreases in PONV were achieved, despite the use of preventive measures.