Kidney Function Worsening Is Linked to Parenteral-Nutrition-Dependent Survival in Palliative Care Patients

Background. Parenteral nutrition (PN) is frequently administered in palliative care patients suffering from cachexia. The evidence regarding the use of PN in terminally ill patients is scarce. Routine laboratory parameters might help to decide whether to start or forgo PN, which could decrease overtreatment at the end of life. Kidney failure was frequently associated with survival. However, a relation between kidney function parameters and parenteral nutrition has not been observed thus far. The aim of this retrospective cohort study was to analyze kidney function parameters in palliative care patients under PN, as well as the relation between these parameters and overall survival. Methods. Patients who were admitted to the Department of Palliative Medicine at the Medical University of Vienna were screened for PN treatment. Whether kidney function parameters at baseline or their dynamics over the course of two weeks were associated with survival was assessed with descriptive and interferential statistics. Results. In total, 113 of 443 palliative care patients were administered parenteral nutrition for the first time. The overall survival (OS) for all patients with increased kidney function parameters at baseline was lower (creatinine: hazard ratio (HR) = 1.808, p < 0.001; urea: HR = 1.033, p < 0.001; uric acid HR = 1.055, p = 0.015). No significant increase in creatinine blood levels was observed in the first 2 weeks after the initiation of PN when compared to the non-PN group (p = 0.86). However, if creatinine blood levels increased within the PN group, lower overall survival was found (HR = 2.046, p = 0.007). Conclusion. Increased kidney function parameters, such as creatinine, urea and uric acid, might be used as negative prognostic markers in palliative care patients under PN. Moreover, an increase in creatinine during the administration of parenteral nutrition in the first 2 weeks is linked to worse outcomes. These findings may help future studies to establish objective markers for clinicians to determine whether to start or end PN in palliative cancer patients and decrease potential overtreatment at the end of life

The human placenta shapes the phenotype of decidual macrophages

During human pregnancy, placenta-derived extravillous trophoblasts (EVTs) invade the decidua and commu-nicate with maternal immune cells. The decidua distinguishes into basalis (decB) and parietalis (decP). The latter remains unaffected by EVT invasion. By defining a specific gating strategy, we report the accumulation of macrophages in decB. We describe a decidua basalis-associated macrophage (decBAM) population with a differential transcriptome and secretome compared with decidua parietalis-associated macrophages (dec-PAMs). decBAMs are CD11chi and efficient inducers of Tregs, proliferate in situ, and secrete high levels of CXCL1, CXCL5, M-CSF, and IL-10. In contrast, decPAMs exert a dendritic cell-like, motile phenotype char-acterized by induced expression of HLA class II molecules, enhanced phagocytosis, and the ability to acti-vate T cells. Strikingly, EVT-conditioned media convert decPAMs into a decBAM phenotype. These findings assign distinct macrophage phenotypes to decidual areas depending on placentation and further highlight a critical role for EVTs in the induction of decB-associated macrophage polarization.Funding Agencies|Clinical biomarker facility at SciLifeLab Sweden; Austrian Science Fund [P33485]; Austrian National Bank [17613ONB]</p

Metabolic support by macrophages sustains colonic epithelial homeostasis

The intestinal epithelium has a high turnover rate and constantly renews itself through proliferation of intestinal crypt cells, which depends on insufficiently characterized signals from the microenvironment. Here, we showed that colonic macrophages were located directly adjacent to epithelial crypt cells in mice, where they metabolically supported epithelial cell proliferation in an mTORC1-dependent manner. Specifically, deletion of tuberous sclerosis complex 2 (Tsc2) in macrophages activated mTORC1 signaling that protected against colitis-induced intestinal damage and induced the synthesis of the polyamines spermidine and spermine. Epithelial cells ingested these polyamines and rewired their cellular metabolism to optimize proliferation and defense. Notably, spermine directly stimulated proliferation of colon epithelial cells and colon organoids. Genetic interference with polyamine production in macrophages altered global polyamine levels in the colon and modified epithelial cell proliferation. Our results suggest that macrophages act as "commensals"that provide metabolic support to promote efficient self-renewal of the colon epithelium.Peer reviewe