Targeting Tumor Associated Macrophages to Overcome Conventional Treatment Resistance in Glioblastoma.

Glioblastoma (GB) is the most common and devastating form of brain cancer. Despite conventional treatments, progression or recurrences are systematic. In recent years, immunotherapies have emerged as an effective treatment in a number of cancers, leaving the question of their usefulness also faced with the particular case of brain tumors. The challenge here is major not only because the brain is the seat of our consciousness but also because of its isolation by the blood-brain barrier and the presence of a unique microenvironment that constitutes the central nervous system (CNS) with very specific constituent or patrolling cells. Much of the microenvironment is made up of immune cells or inflammation. Among these, tumor-associated macrophages (TAMs) are of significant interest as they are often involved in facilitating tumor progression as well as the development of resistance to standard therapies. In this review, the ubiquity of TAMs in GB will be discussed while the specific case of microglia resident in the brain will be also emphasized. In addition, the roles of TAMs as accomplices in the progression of GB and resistance to treatment will be presented. Finally, clinical trials targeting TAMs as a means of treating cancer will be discussed.

An assessment of advance relatives approach for brain death organ donation.

BACKGROUND:: Advance announcement of forthcoming brain death has developed to enable intensivists and organ procurement organisation coordinators to more appropriately, and separately from each other, explain to relatives brain death and the subsequent post-mortem organ donation opportunity. RESEARCH AIM:: The aim was to assess how potentially involved healthcare professionals perceived ethical issues surrounding the strategy of advance approach. RESEARCH DESIGN:: A multi-centre opinion survey using an anonymous self-administered questionnaire was conducted in the six-member hospitals of the publicly funded East of France regional organ and tissue procurement network called 'Prélor'. PARTICIPANTS:: The study population comprised 460 physicians and nurses in the Neurosurgical, Surgical and Medical Intensive Care Units, the Stroke Units and the Emergency Departments. ETHICAL CONSIDERATIONS:: The project was approved by the board of the Lorraine University Diploma in Medical Ethics and the Prélor Network administrators. MAIN FINDINGS:: A slight majority of 53.5% of respondents had previously participated in an advance relatives approach: 83% of the physicians and 42% of the nurses. A majority of healthcare professionals (68%) think that the main justification for advance relatives approach is the comprehensive care of the dying patient and the research of his or her most likely opinion (74%). The misunderstanding of the related issues by relatives is an obstacle for 47% of healthcare professionals and 51% think that the answer given by the relatives regarding the most likely opinion of the person regarding post-mortem organ donation really corresponds to the person opinion in only 50% of the cases or less. CONCLUSION:: Time given by advance approach should be employed to help and enable relatives to authentically bear the values and interests of the potential donor in the post-mortem organ donation discussion. Nurses' attendance of advance relatives approach seems necessary to enable them to optimally support the families facing death and post-mortem organ donation issues.

Improvement of donor myocardial function after treatment of autonomic storm during brain death.

BACKGROUND: In experimental brain death models, autonomic storm (AS) triggers severe myocardial dysfunction, which can be attenuated by pharmacologic treatment. The aim of this study was to determine the incidence of AS in a cohort of human organ donors and to evaluate the potential interest of AS treatment on myocardial function, cardiac harvesting and transplantation. METHODS: The cohort consisted of 152 patients. Among them, 46 patients were initially considered as potential cardiac donors (main criteria: age < 60 years, no history of cardiac disease). AS diagnosis included increased systolic arterial pressure > 200 mm Hg associated with tachycardia >140 beats/min. Heart acceptance criteria were associated creatine kinase (CK), troponin Ic, and left ventricle ejection fraction (LVEF) estimated by echocardiography and visual inspection. RESULTS: AS was observed in 29 patients (63%). Hypertension was treated in 12 patients (esmolol n = 6, urapidil n = 5, nicardipine). Cardiac harvesting was performed in 28 donors (61%). LVEFs were significantly higher after AS treatment (no AS: 55.4 +/- 13.4%, untreated AS: 49.0 +/- 18.8%, treated AS: 63.9+ +/- 10.3%, P = 0.049). AS treatment was found to be independently associated with LVEF in > 50% of the cases (P = 0.034). Treatment of AS or the lack of AS were associated with an increased probability of successful cardiac transplantation (OR = 8.8; 95% CI 2.1-38.3, P = 0.002). CONCLUSIONS: Treatment of hypertension during AS may attenuate brain death-induced myocardial dysfunction and increase the number of available cardiac grafts.