RESUMO
OBJECTIVES: The non-oncological population is relatively under-represented among end-of-life (EOL) patients managed by palliative care (PC) services, and the effects of different PC delivery models are understudied in this population.This retrospective observational study on routinely collected data aimed at evaluating the effects of the extension from workday-only to 24/7 mixed hands-on and advisory home PC service on emergency department (ED) access and emergency medical services (EMS) interventions needed by non-oncological patients during their last 90 days of life, and their probability to die in hospital. METHODS: A before-and-after design was adopted comparing preimplementation and postimplementation periods (2018-2019 and 2021-22).We used a difference-in-differences approach to estimate changes in ED access and EMS intervention rates in the postintervention period through binomial negative regression. The oncological population, always exposed to 24/7 PC, was used as a control. A robust Poisson regression model was adopted to investigate the differences regarding hospital mortality. The analyses were adjusted for age, sex and disease grouping by the system involved. Results were reported as incidence rate ratios (IRRs) and ORs. RESULTS: A total of 2831 patients were enrolled in the final analysis.After the implementation of 24/7 home PC, both ED admissions (IRR=0.390, p<0.001) and EMS interventions (IRR=0.413, p<0.001) dropped, as well as the probability to die in hospital (OR=0.321, p<0.001). CONCLUSIONS: The adoption of a 24/7 mixed hands-on and advisory model of home PC could have relevant effects in terms of ED access and EMS use by non-oncological EOL patients under PC. TRIAL REGISRATION NUMBER: NCT05640076.
RESUMO
Bone metastasis (BM) is a dismal complication of cancer that frequently occurs in patients with advanced carcinomas and that often manifests as an osteolytic lesion. In bone, tumor cells promote an imbalance in bone remodeling via the release of growth factors that, directly or indirectly, stimulate osteoclast resorption activity. However, carcinoma cells are also characterized by an altered metabolism responsible for a decrease of extracellular pH, which, in turn, directly intensifies osteoclast bone erosion. Here, we speculated that tumor-derived acidosis causes the osteoblast-osteoclast uncoupling in BM by modulating the pro-osteoclastogenic phenotype of osteoblasts. According to our results, a low pH recruits osteoclast precursors and promotes their differentiation through the secretome of acid-stressed osteoblasts that includes pro-osteoclastogenic factors and inflammatory mediators, such as RANKL, M-CSF, TNF, IL-6, and, above the others, IL-8. The treatment with the anti-IL-6R antibody tocilizumab or with an anti-IL-8 antibody reverted this effect. Finally, in a series of BM patients, circulating levels of the osteolytic marker TRACP5b significantly correlated with IL-8. Our findings brought out that tumor-derived acidosis promotes excessive osteolysis at least in part by inducing an inflammatory phenotype in osteoblasts, and these results strengthen the use of anti-IL-6 or anti-IL-8 strategies to treat osteolysis in BM.