Evaluations of end of life with dementia by families in Dutch and U.S. nursing homes

BACKGROUND: The End-of-Life in Dementia (EOLD) scales comprise the most specific set of instruments developed for evaluations of patients' end of life by their families. It is not known whether the EOLD scales are useful for cross-national comparisons. METHODS: We used a mortality follow-back design in multi-center studies in the Netherlands (pilot study 2005-2007) and the U.S.A. (1999), and we compared EOLD Satisfaction With Care (SWC; last three months of life), Symptom Management (SM; last three months) and Comfort Assessment in Dying (CAD) scores for 54 Dutch and 76 U.S. nursing home residents. RESULTS: SWC total scores did not differ significantly between the Dutch and U.S. studies (31.9, SD 4.7 versus 30.4, SD 6.1), but three of ten items were rated more favorable for Dutch residents, as were SM total scores (29.1, SD 9.2 versus 20.4, SD 10.6). CAD total scores did not differ (32.0, SD 5.4 versus 30.5, SD 5.9, respectively), but the "well-being" subscale was rated more favorably for Dutch residents. Results were similar after adjustment for demographics and dementia severity. CONCLUSION: The Dutch families rated end of life with dementia in nursing homes as somewhat better than did U.S. families. Although differences were small, the observed patterns were consistent. This suggests validity of the SM and CAD to assess differences in quality of dying and possible sensitivity to differences between countries or time frames. Larger, simultaneous, cross-national studies are needed to confirm usefulness of the scales and to detect areas which need improvement in the respective countrie

IgG opsonization of bacteria promotes Th17 responses via synergy between TLRs and Fc gamma RIIa in human dendritic cells

Dendritic cells (DCs) are essential in inducing adaptive immune responses against bacteria by expressing cytokines that skew T-cell responses toward protective Th17 cells. Although it is widely recognized that induction of these cytokines by DCs involves activation of multiple receptors, it is still incompletely characterized which combination of receptors specifically skews Th17-cell responses. Here we have identified a novel role for Fc gamma RIIa in promoting human Th17 cells. Activation of DCs by bacteria opsonized by serum IgG strongly promoted Th17 responses, which was Fc gamma RIIa-dependent and coincided with enhanced production of selected cytokines by DCs, including Th17-promoting IL-1 beta and IL-23. Notably, Fc gamma RIIa stimulation on DCs did not induce cytokine production when stimulated individually, but selectively amplified cytokine responses through synergy with TLR2, 4, or 5. Importantly, this synergy is mediated at 2 different levels. First, TLR-Fc gamma RIIa costimulation strongly increased transcription of pro-IL-1 beta and IL-23p19. Second, Fc gamma RIIa triggering induced activation of caspase-1, which cleaves pro-IL-1 beta into its bioactive form and thereby enhanced IL-1 beta secretion. Taken together, these data identified cross-talk between TLRs and Fc gamma RIIa as a novel mechanism by which DCs promote protective effector Th17-cell responses against bacteria. (Blood. 2012;120(1):112-121

IgG opsonization of bacteria promotes Th17 responses via synergy between TLRs and Fc gamma RIIa in human dendritic cells

Dendritic cells (DCs) are essential in inducing adaptive immune responses against bacteria by expressing cytokines that skew T-cell responses toward protective Th17 cells. Although it is widely recognized that induction of these cytokines by DCs involves activation of multiple receptors, it is still incompletely characterized which combination of receptors specifically skews Th17-cell responses. Here we have identified a novel role for Fc gamma RIIa in promoting human Th17 cells. Activation of DCs by bacteria opsonized by serum IgG strongly promoted Th17 responses, which was Fc gamma RIIa-dependent and coincided with enhanced production of selected cytokines by DCs, including Th17-promoting IL-1 beta and IL-23. Notably, Fc gamma RIIa stimulation on DCs did not induce cytokine production when stimulated individually, but selectively amplified cytokine responses through synergy with TLR2, 4, or 5. Importantly, this synergy is mediated at 2 different levels. First, TLR-Fc gamma RIIa costimulation strongly increased transcription of pro-IL-1 beta and IL-23p19. Second, Fc gamma RIIa triggering induced activation of caspase-1, which cleaves pro-IL-1 beta into its bioactive form and thereby enhanced IL-1 beta secretion. Taken together, these data identified cross-talk between TLRs and Fc gamma RIIa as a novel mechanism by which DCs promote protective effector Th17-cell responses against bacteria. (Blood. 2012;120(1):112-121

Dutch experience of monitoring euthanasia

Doctors in the United Kingdom can accompany their patients every step of the way, up until the last. The law stops them helping their patients take the final step, even if that is the patient's fervent wish. Next month's debate in the House of Lords could begin the process of changing the law. To help doctors decide where they stand we publish a range of opinion

Fc gamma receptor-TLR cross-talk elicits pro-inflammatory cytokine production by human M2 macrophages

M2 macrophages suppress inflammation in numerous disorders, including tumour formation, infection and obesity. However, the exact role of M2 macrophages in the context of several other diseases is still largely undefined. We here show that human M2 macrophages promote inflammation instead of suppressing inflammation on simultaneous exposure to complexed IgG (c-IgG) and TLR ligands, as occurs in the context of diseases such as rheumatoid arthritis (RA). c-IgG-TLR ligand co-stimulation of M2 macrophages selectively amplifies production of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 and promotes Th17 responses, which all play a critical role in RA pathology. Induction of pro-inflammatory cytokines on c-IgG co-stimulation mainly depends on Fc gamma receptor IIa (FcγRIIa), which selectively amplifies cytokine gene transcription and induces caspase-1 activation. These data indicate that FcγR-TLR cross-talk may be targeted for treatment to attenuate inflammation in RA, by restoring the anti-inflammatory function of M2 macrophage