Pulmonary vein dose and risk of atrial fibrillation in patients with non-small cell lung cancer following definitive radiotherapy: An NI-HEART analysis.

BACKGROUND AND PURPOSE: Symptomatic arrhythmia is common following radiotherapy for non-small cell lung cancer (NSCLC), frequently resulting in morbidity and hospitalization. Modern treatment planning technology theoretically allows sparing of cardiac substructures. Atrial fibrillation (AF) comprises the majority of post-radiotherapy arrhythmias, but efforts to prevent this cardiotoxicity have been limited as the causative cardiac substructure is not known. In this study we investigated if incidental radiation dose to the pulmonary veins (PVs) is associated with AF. MATERIAL AND METHODS: A single-centre study of patients completing contemporary (chemo)radiation for NSCLC, with modern planning techniques. Oncology, cardiology and death records were examined, and AF events were verified by a cardiologist. Cardiac substructures were contoured on planning scans for retrospective dose analysis. RESULTS: In 420 eligible patients with NSCLC treated with intensity-modulated (70%) or 3D-conformal (30%) radiotherapy with a median OS of 21.8 months (IQR 10.8-35.1), there were 26 cases of new AF (6%). All cases were grade 3 except two cases of grade 4. Dose metrics for both the left (V55) and right (V10) PVs were associated with the incidence of new AF. Metrics remained statistically significant after accounting for the competing risk of death and cardiovascular covariables for both the left (HR 1.02, 95%CI 1.00-1.03, p = 0.005) and right (HR 1.01 (95%CI 1.00-1.02, p = 0.033) PVs. CONCLUSION: Radiation dose to the PVs during treatment of NSCLC was associated with the onset of AF. Actively sparing the PVs during treatment planning could reduce the incidence of AF during follow-up, and screening for AF may be warranted for select cases.

The Additional Value of Endolymphatic Hydrops Imaging With Intratympanic Contrast for Diagnostic Work-Up-Experience From a Neurotology Center in Austria.

Objective: To illustrate the merit of hydrops imaging during clinical workup of dizziness and balance disorders. Background: Ever since the first description of in-vivo endolymphatic hydrops imaging in 2007, this diagnostic tool has been implemented in an increasing number of centers. The more experience in its clinical application is gathered, the more it is possible to critically assess its potential value for the diagnostic workup. This article intends to provide information about the experience of handling and utilization of endolymphatic hydrops imaging in one of the first centers in Austria. Methods: Retrospective analysis and review of clinical cases. Results: Based on our experience of endolymphatic hydrops imaging (EHI), which was established in cooperation between our departments of radiology and otorhinolaryngology in 2017, we have exclusively used intratympanic application of a contrast agent prior to magnetic resonance imaging, as this approach provides high quality imaging results. In 42.6% of cases, EHI could lead to the diagnosis of MD or HED. Since precise vestibular examination is still necessary, EHI is not a tool to replace the clinical examination but rather to add significantly to the interpretation of the results. Conclusion: Endolymphatic hydrops imaging represents a valuable, safe and well-applicable tool for evaluating cases with inconclusive clinical results. However, its potential additional diagnostic benefits rely on a correct indication based on prior thorough vestibular investigations.

The influence of care place and diagnosis on care communication at the end of life: bereaved family members' perspective.

OBJECTIVE: To investigate the influence of care place and diagnosis on care communication during the last 3 months of life for people with advanced illness, from the bereaved family members' perspective. METHOD: A retrospective survey design using the VOICES(SF) questionnaire with a sample of 485 bereaved family members (aged: 20-90 years old, 70% women) of people who died in hospital was employed to meet the study aim. RESULTS: Of the deceased people, 79.2% had at some point received care at home, provided by general practitioners (GPs) (52%), district nurses (36.7%), or specialized palliative home care (17.9%), 27.4% were cared for in a nursing home and 15.7% in a specialized palliative care unit. The likelihood of bereaved family members reporting that the deceased person was treated with dignity and respect by the staff was lowest in nursing homes (OR: 0.21) and for GPs (OR: 0.37). A cancer diagnosis (OR: 2.36) or if cared for at home (OR: 2.17) increased the likelihood of bereaved family members reporting that the deceased person had been involved in decision making regarding care and less likely if cared for in a specialized palliative care unit (OR: 0.41). The likelihood of reports of unwanted decisions about the care was higher if cared for in a nursing home (OR: 1.85) or if the deceased person had a higher education (OR: 2.40). SIGNIFICANCE OF RESULTS: This study confirms previous research about potential inequalities in care at the end of life. The place of care and diagnosis influenced the bereaved family members' reports on whether the deceased person was treated with respect and dignity and how involved the deceased person was in decision making regarding care.

Dimethylsulfoxide Inhibits Oligodendrocyte Fate Choice of Adult Neural Stem and Progenitor Cells.

Several clinical trials address demyelinating diseases via transplantation of mesenchymal stromal cells (MSCs). Published reports detail that administration of MSCs in patients may provide a beneficial immunomodulation, and that factors secreted by MSCs are potent inducers of oligodendrogenesis. Dimethylsulfoxide (DMSO) is widely used in life science and medicine as solvent, vehicle or cryoprotectant for cells used in transplantation. Importantly, most transplantation protocols do not include the removal of DMSO before injecting the cell suspension into patients. This indifferent application of DMSO is coming under increasing scrutiny following reports investigating its potential toxic side-effects. While the impact of DMSO on the central nervous system (CNS) has been partially studied, its effect on oligodendrocytes and oligodendrogenesis has not been addressed yet. Consequently, we evaluated the influence of DMSO on oligodendrogenesis, and on the pro-oligodendrogenic effect of MSCs' secreted factors, using adult rat neural stem and progenitor cells (NSPCs). Here, we demonstrate that a concentration of 1% DMSO robustly suppressed oligodendrogenesis and drove the fate of differentiating NSPCs toward astrogenesis. Furthermore, the pro-oligodendrogenic effect of MSC-conditioned medium (MSCCM) was also nearly completely abolished by the presence of 1% DMSO. In this condition, inhibition of the Erk1/2 signal transduction pathway and high levels of Id2 expression, a specific inhibitor of oligodendrogenic differentiation, were detected. Furthermore, inflammatory demyelinating diseases may even potentiate the impact of DMSO on oligodendrogenesis. Our results demonstrate the imperative of considering the strong anti-oligodendrogenic activity of DMSO when designing future clinical trial protocols.

Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that leads to severe neurological deficits. Due to their immunomodulatory and neuroprotective activities and their ability to promote the generation of oligodendrocytes, mesenchymal stem cells (MSCs) are currently being developed for autologous cell therapy in MS. As aging reduces the regenerative capacity of all tissues, it is of relevance to investigate whether MSCs retain their pro-oligodendrogenic activity with increasing age. We demonstrate that MSCs derived from aged rats have a reduced capacity to induce oligodendrocyte differentiation of adult CNS stem/progenitor cells. Aging also abolished the ability of MSCs to enhance the generation of myelin-like sheaths in demyelinated cerebellar slice cultures. Finally, in a rat model for CNS demyelination, aging suppressed the capability of systemically transplanted MSCs to boost oligodendrocyte progenitor cell (OPC) differentiation during remyelination. Thus, aging restricts the ability of MSCs to support the generation of oligodendrocytes and consequently inhibits their capacity to enhance the generation of myelin-like sheaths. These findings may impact on the design of therapies using autologous MSCs in older MS patients.

Bereaved Family Members' Satisfaction with Care during the Last Three Months of Life for People with Advanced Illness.

BACKGROUND: Studies evaluating the end-of-life care for longer periods of illness trajectories and in several care places are currently lacking. This study explored bereaved family members' satisfaction with care during the last three months of life for people with advanced illness, and associations between satisfaction with care and characteristics of the deceased individuals and their family members. METHODS: A cross-sectional survey design was used. The sample was 485 family members of individuals who died at four different hospitals in Sweden. RESULTS: Of the participants, 78.7% rated the overall care as high. For hospice care, 87.1% reported being satisfied, 87% with the hospital care, 72.3% with district/county nurses, 65.4% with nursing homes, 62.1% with specialized home care, and 59.6% with general practitioners (GPs). Family members of deceased persons with cancer were more likely to have a higher satisfaction with the care. A lower satisfaction was more likely if the deceased person had a higher educational attainment and a length of illness before death of one year or longer. CONCLUSION: The type of care, diagnoses, length of illness, educational attainment, and the relationship between the deceased person and the family member influences the satisfaction with care.

Hippocampal neurogenesis and antidepressive therapy: shocking relations.

Speculations on the involvement of hippocampal neurogenesis, a form of neuronal plasticity, in the aetiology of depression and the mode of action of antidepressive therapies, started to arise more than a decade ago. But still, conclusive evidence that adult neurogenesis contributes to antidepressive effects of pharmacological and physical therapies has not been generated yet. This review revisits recent findings on the close relation between the mode(s) of action of electroconvulsive therapy (ECT), a powerful intervention used as second-line treatment of major depression disorders, and the neurogenic response to ECT. Following application of electroconvulsive shocks, intricate interactions between neurogenesis, angiogenesis, and microglia activation, the hypothalamic-pituitary-adrenal axis and the secretion of neurotrophic factors have been documented. Furthermore, considering the fact that neurogenesis strongly diminishes along aging, we investigated the response to electroconvulsive shocks in young as well as in aged cohorts of mice.