Ethics of Practicing Medical Procedures on Newly Dead and Nearly Dead Patients

OBJECTIVE: To examine the ethical issues raised by physicians performing, for skill development, medically nonindicated invasive medical procedures on newly dead and dying patients. DESIGN: Literature review; issue analysis employing current normative ethical obligations, and evaluation against moral rules and utilitarian assessments manifest in other common perimortem practices. RESULTS: Practicing medical procedures for training purposes is not uncommon among physicians in training. However, empiric information is limited or absent evaluating the effects of this practice on physician competence and ethics, assessing public attitudes toward practicing medical procedures and requirements for consent, and discerning the effects of a consent requirement on physicians' clinical competence. Despite these informational gaps, there is an obligation to secure consent for training activities on newly and nearly dead patients based on contemporary norms for informed consent and family respect. Paradigms of consent-dependent societal benefits elsewhere in health care support our determination that the benefits from physicians practicing procedures does not justify setting aside the informed consent requirement. CONCLUSION: Current ethical norms do not support the practice of using newly and nearly dead patients for training in invasive medical procedures absent prior consent by the patient or contemporaneous surrogate consent. Performing an appropriately consented training procedure is ethically acceptable when done under competent supervision and with appropriate professional decorum. The ethics of training on the newly and nearly dead remains an insufficiently examined area of medical training

Snail regulates BMP and TGF beta pathways to control the differentiation status of glioma-initiating cells

Glioblastoma multiforme is a brain malignancy characterized by high heterogeneity, invasiveness, and resistance to current therapies, attributes related to the occurrence of glioma stem cells (GSCs). Transforming growth factor beta (TGF beta) promotes self-renewal and bone morphogenetic protein (BMP) induces differentiation of GSCs. BMP7 induces the transcription factor Snail to promote astrocytic differentiation in GSCs and suppress tumor growth in vivo. We demonstrate that Snail represses stemness in GSCs. Snail interacts with SMAD signaling mediators, generates a positive feedback loop of BMP signaling and transcriptionally represses the TGFB1 gene, decreasing TGF beta 1 signaling activity. Exogenous TGF beta 1 counteracts Snail function in vitro, and in vivo promotes proliferation and re-expression of Nestin, confirming the importance of TGFB1 gene repression by Snail. In conclusion, novel insight highlights mechanisms whereby Snail differentially regulates the activity of the opposing BMP and TGF beta pathways, thus promoting an astrocytic fate switch and repressing stemness in GSCs.Andra och tredje författare delar andra författarskapet.</p

Prevention and treatment of the post-thrombotic syndrome and of the chronic thromboembolic pulmonary hypertension

none2noPost-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (CTEPH) are late complications of venous thromboembolism. The purpose of this review is to present and discuss recently published studies that have improved our knowledge of PTS and CTEPH. The current understanding of the pathophysiology of PTS and CTEPH is discussed as well as the importance of chronic residual venous thrombosis, some polymorphisms of plasminogen activator inhibitor-1, and the current concept of misguided thrombus resolution. The surprising finding that elastic compression stockings may not be effective in preventing PTS and the novel medical treatment in CTEPH are discussed in detail. Novel direct oral anticoagulants show potential for prevention of PTS. No firm conclusions can be drawn on the efficacy of elastic stockings. Novel treatments of CTEPH for inoperable patients and those with persistent pulmonary hypertension after surgery have become available and further research on wider indication for their use is urgently needed.nonePesavento, Raffaele; Prandoni, PaoloPesavento, Raffaele; Prandoni, Paol