Analytical Validation of a Novel 6-Gene Signature for Prediction of Distant Recurrence in Estrogen Receptor-Positive, HER2-Negative, Early-Stage Breast Cancer.

BACKGROUND: OncoMasTR is a recently developed multigene prognostic test for early-stage breast cancer. The test has been developed in a kit-based format for decentralized deployment in molecular pathology laboratories. The analytical performance characteristics of the OncoMasTR test are described in this study. METHODS: Expression levels of 6 genes were measured by 1-step reverse transcription-quantitative PCR on RNA samples prepared from formalin-fixed, paraffin-embedded (FFPE) breast tumor specimens. Assay precision, reproducibility, input range, and interference were determined using FFPE-derived RNA samples representative of low and high prognostic risk scores. A pooled RNA sample derived from 6 FFPE breast tumor specimens was used to establish the linear range, limit of detection, and amplification efficiency of the individual gene expression assays. RESULTS: The overall precision of the OncoMasTR test was high with an SD of 0.16, which represents less than 2% of the 10-unit risk score range. Test results were reproducible across 4 testing sites, with correlation coefficients of 0.94 to 0.96 for the continuous risk score and concordance of 86% to 96% in low-/high-risk sample classification. Consistent risk scores were obtained across a > 100-fold RNA input range. Individual gene expression assays were linear up to quantification cycle values of 36.0 to 36.9, with amplification efficiencies of 80% to 102%. Test results were not influenced by agents used during RNA isolation, by low levels of copurified genomic DNA, or by moderate levels of copurified adjacent nontumor tissue. CONCLUSION: The OncoMasTR prognostic test displays robust analytical performance that is suitable for deployment by local pathology laboratories for decentralized use.

Implementation of non-vitamin K antagonist oral anticoagulants in daily practice: the need for comprehensive education for professionals and patients.

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for the prevention and treatment of venous thromboembolism and for stroke prevention in patients with atrial fibrillation. NOACs do not require routine coagulation monitoring, creating a challenge to established systems for patient follow-up based on regular blood tests. Healthcare professionals (HCPs) are required to cope with a mixture of patients receiving either a vitamin K antagonist or a NOAC for the same indications, and both professionals and patients require education about the newer drugs. A European working group convened to consider the challenges facing HCPs and healthcare systems in different countries and the educational gaps that hinder optimal patient management. Group members emphasised the need for regular follow-up and noted national, regional and local variations in set-up and resources for follow-up. Practical incorporation of NOACs into healthcare systems must adapt to these differences, and practical follow-up that works in some systems may not be able to be implemented in others. The initial prescriber of a NOAC should preferably be a true anticoagulation specialist, who can provide initial patient education and coordinate the follow-up. The long-term follow-up care of patients can be managed through specialist coagulation nurses, in a dedicated anticoagulation clinic or by general practitioners trained in NOAC use. The initial prescriber should be involved in educating those who perform the follow-up. Specialist nurses require access to tools, potentially including specific software, to guide systematic patient assessment and workflow. Problem cases should be referred for specialist advice, whereas in cases for which minimal specialist attention is required, the general practitioner could take responsibility for patient follow-up. Hospital departments and anticoagulation clinics should proactively engage with all downstream HCPs (including pharmacists) to ensure their participation in patient management and reinforcement of patient education at every opportunity. Ideally, (transmural) protocols for emergency situations should be developed. Last but not least, patients should be well-informed about their condition, the treatment, possible risk scenarios, including the consequences of non-adherence to prescribed therapy, and the organisation of follow-up care.

Aneurysm-related disseminated intravascular coagulation successfully treated by endovascular repair.

Aortic abdominal aneurysm (AAA) is an uncommon etiology of disseminated intravascular coagulation (DIC). The authors report a case of an 81-year-old male patient who presented with hematuria, intraoral hemorrhage, melaenas and ecchymosis of the lower back and of the abdominal wall, after being medicated with etoricoxib for a back pain. During the study, an abdominal aortic aneurysm, which prolonged to the left common and internal iliac artery, was discovered. The diagnosis of AAA induced DIC was made. After endovascular aneurysm repair (EVAR), the patient's hemorrhagic manifestations disappeared and the laboratory findings normalized. In conclusion, the state-of-the-art treatment of DIC is the elimination of the underlying disease; in this case, EVAR was proven to be effective in treating the aortic aneurysm and the AAA-related DIC.

[Superwarfarine Poisoning]. / Intoxicação por Supervarfarina.

The superwarfarin-type anticoagulant rodenticides are used throughout the world and distinguish themselves from warfarin for its high potency and long acting anticoagulant activity. Easy access to these products enables the accidental or deliberate human poisoning. A case of voluntary rodenticide poisoning (RATIBRONÂ) by a woman who ingested an estimated 27.5 mg of bromadiolone total quantity for two weeks, with minor bleeding episodes, whose reversal of the anticoagulant effect with the correction of the abnormal values of the clotting tests took about one month to reverse is reported here. The correction of the haemostasis defects takes usually a long time and there are no treatment guidelines, but a gradually vitamin K dosage reduction, as out patients, along with the monitoring of the International Normalized Ratio levels, allows a safe evaluation of the therapeutic response.

Os raticidas do tipo supervarfarina são usados em todo o mundo e distinguem-se da varfarina pela sua elevada potência e duração de acção anticoagulante. O fácil acesso a este produto possibilita o seu uso no envenenamento humano acidental ou deliberado. à apresentado um caso clínico de intoxicação voluntária de raticida (RATIBRON®) por uma mulher que ingeriu uma quantidade total estimada de 27,5 mg de bromadiolona durante duas semanas, com manifestações hemorrágicas ligeiras, cuja reversão do efeito anticoagulante,com correcção do estudo da coagulação, demorou cerca de um mês. A correcção dos valores da hemostase é habitualmentedemorada e não existem orientações terapêuticas para estes casos, sendo que uma diminuição gradual das doses de vitamina K, em ambulatório, acompanhada do estudo do International Normalized Ratio, permite avaliar com segurança a resposta à terapêutica.