Trends in management and outcomes of pulmonary embolism with a multidisciplinary response team

Journal of Thrombosis and Thrombolysis - Multidisciplinary pulmonary embolism (PE) response teams have garnered widespread adoption given the complexities of managing acute PE and provide a...     

Maximizing Breast Cancer Therapy with Awareness of Potential Treatment-Related Blood Disorders

In this review we summarize the impact of the various modalities of breast cancer therapy coupled with intrinsic patient factors on incidence of subsequent treatment-induced myelodysplasia and acute myelogenous leukemia (t-MDS/AML). It is clear that risk is increased for patients treated with radiation and chemotherapy at younger ages. Radiation is associated with modest risk, whereas chemotherapy, particularly the combination of an alkylating agent and an anthracycline, carries higher risk and radiation and chemotherapy combined increase the risk markedly. Recently, treatment with granulocyte colony-stimulating factor (G-CSF), but not pegylated G-CSF, has been identified as a factor associated with increased t-MDS/AML risk. Two newly identified associations may link homologous DNA repair gene deficiency and poly (ADP-ribose) polymerase inhibitor treatment to increased t-MDS/AML risk. When predisposing factors, such as young age, are combined with an increasing number of potentially leukemogenic treatments that may not confer large risk singly, the risk of t-MDS/AML appears to increase. Patient and treatment factors combine to form a biological cascade that can trigger a myelodysplastic event. Patients with breast cancer are often exposed to many of these risk factors in the course of their treatment, and triple-negative patients, who are often younger and/or BRCA positive, are often exposed to all of them. It is important going forward to identify effective therapies without these adverse associated effects and choose existing therapies that minimize the risk of t-MDS/AML without sacrificing therapeutic gain.

Implications for Practice

Breast cancer is far more curable than in the past but requires multimodality treatment. Great care must be taken to use the least leukemogenic treatment programs that do not sacrifice efficacy. Elimination of radiation and anthracycline/alkylating agent regimens will be helpful where possible, particularly in younger patients and possibly those with homologous repair deficiency (HRD). Use of colony-stimulating factors should be limited to those who truly require them for safe chemotherapy administration. Further study of a possible leukemogenic association with HRD and the various forms of colony-stimulating factors is badly needed.

     

Primary Care Physician Attitudes and Intentions Toward the Use of HIV Pre-exposure Prophylaxis in Adolescents in One Metropolitan Region

Purpose

Understanding the attitudes of physicians toward the use of pre-exposure prophylaxis (PrEP) for HIV prevention among youth is critical to improving access to PrEP. We examined PrEP-related attitudes among physicians who provide primary care to 13- to 21-year-old adolescents.

The Role of the Medical Expert in the Retrospective Assessment of Testamentary Capacity

Objectives:Physicians and other mental health experts are increasingly called on to assist the courts with the determination of testamentary capacity. We aim to improve the understanding of the retrospective assessment of testamentary capacity for medical experts in order to provide more useful reports for the court’s determinations and to provide a methodology for the retrospective assessment of testamentary capacity.Method:Medical experts with experience in the retrospective assessment of testamentary capacity collaborated with lawyers who practice estate litigation. The medical literature on the assessment of testamentary capacity was reviewed and integrated. The medical experts provided a clinical perspective, while the lawyers ensured that the case law and legal perspective were integrated into this review.Results:The focus and limitations of the medical expert are outlined including the need to be objective, nonpartisan, and fair. For the benefit of the court, the medical expert should describe the nature and severity of relevant medical, psychiatric, and cognitive disorders, and how they may impact on the specific criteria for testamentary capacity as defined by the leading case of Banks v Goodfellow. Medical experts should opine only on the issue of vulnerability to influence and defer to the court to determine the facts of the case regarding any influence that may have been exerted.Conclusions:Although the ultimate determination of testamentary capacity is a legal one, medical experts can help the court achieve the most informed legal decision by providing relevant information on clinical issues that may impact the criteria for testamentary capacity.     

In Utero Exposure to Benzo[a]pyrene Induces Ovarian Mutations at Doses That Deplete Ovarian Follicles in Mice

Polycyclic aromatic hydrocarbons like benzo[a]pyrene (BaP) are ubiquitous environmental contaminants formed during incomplete combustion of organic materials. Our prior work showed that transplacental exposure to BaP depletes ovarian follicles and increases prevalence of epithelial ovarian tumors later in life. We used the MutaMouse transgenic rodent model to address the hypothesis that ovarian mutations play a role in tumorigenesis caused by prenatal exposure to BaP. Pregnant MutaMouse females were treated with 0, 10, 20, or 40 mg/(kg day) BaP orally on gestational days 7–16, covering critical windows of ovarian development. Female offspring were euthanized at 10 weeks of age; some ovaries with oviducts were processed for follicle counting; other ovaries/oviducts and bone marrow were processed for determination of lacZ mutant frequency (MF). Mutant plaques were pooled within dose groups and sequenced to determine the mutation spectrum. BaP exposure caused highly significant dose-related decreases in ovarian follicles and increases in ovarian/oviductal and bone marrow mutant frequencies at all doses. Absence of follicles, cell packets, and epithelial tubular structures were observed with 20 and 40 mg/(kg day) BaP. Depletion of ovarian germ cells was inversely associated with ovarian MF. BaP induced primarily G > T and G > C transversions and deletions in ovaries/oviducts and bone marrow cells and produced a mutation signature highly consistent with that of tobacco smoking in human cancers. Overall, our results show that prenatal BaP exposure significantly depletes ovarian germ cells, causes histopathological abnormalities, and increases the burden of ovarian/oviductal mutations, which may be involved in pathogenesis of epithelial ovarian tumors. Environ. Mol. Mutagen. 60:410–420, 2019. © 2018 Her Majesty the Queen in Right of Canada