Lipidomic profiling of exosomes from colorectal cancer cells and patients reveals potential biomarkers.

Strong evidence suggests that differences in the molecular composition of lipids in exosomes depend on the cell type and has an influence on cancer initiation and progression. Here, we analyzed by liquid chromatography-mass spectrometry (LC-MS) the lipidomic signature of exosomes derived from the human cell lines normal colon mucosa (NCM460D), and colorectal cancer (CRC) nonmetastatic (HCT116) and metastatic (SW620), and exosomes isolated from the plasma of nonmetastatic and metastatic CRC patients and healthy donors. Analysis of this exhaustive lipid study highlighted changes in some molecular species that were found in the cell lines and confirmed in the patients. For example, exosomes from primary cancer patients and nonmetastatic cells compared with healthy donors and control cells displayed a common marked increase in phosphatidylcholine (PC) 34 : 1, phosphatidylethanolamine (PE) 36 : 2, sphingomyelin (SM) d18 : 1/16 : 0, hexosylceramide (HexCer) d18 : 1/24 : 0 and HexCer d18 : 1/24 : 1. Interestingly, these same lipids species were decreased in the metastatic cell line and patients. Further, levels of PE 34 : 2, PE 36 : 2, and phosphorylated PE p16 : 0/20 : 4 were also significantly decreased in metastatic conditions when compared to the nonmetastatic counterparts. The only molecule species found markedly increased in metastatic conditions (in both patients and cells) when compared to controls was ceramide (Cer) d18 : 1/24 : 1. These decreases in lipid species in the extracellular vesicles might reflect function-associated changes in the metastatic cell membrane. Although these potential biomarkers need to be validated in a larger cohort, they provide new insight toward the use of clusters of lipid biomarkers rather than a single molecule for the diagnosis of different stages of CRC.

Sodium citrate versus saline catheter locks for non-tunneled hemodialysis central venous catheters in critically ill adults: a randomized controlled trial.

PURPOSE: Sodium citrate has antibacterial and anticoagulant properties that are confined to the catheter when used as a catheter lock. Studies of its use as a catheter lock in chronic hemodialysis patients suggest it may be efficacious in preventing infection and thrombotic complications. We compared sodium citrate with saline catheter locks for non-tunneled hemodialysis central venous catheters in critically ill adult patients. Primary endpoint was catheter life span without complication. METHODS: This was a randomized, controlled, open-label trial involving intensive care patients with acute renal failure requiring hemodialysis. Events were defined as catheter-related bloodstream infection and catheter malfunction. RESULTS: Seventy-eight patients were included. Median catheter life span without complication was 6 days (saline group) versus 12 days (citrate group) [hazard ratio (HR) 2.12 (95% CI 1.32-3.4), p = 0.0019]. There was a significantly higher rate of catheter malfunction in the saline group compared with in the citrate group (127 catheter events/1,000 catheter-days, saline group vs. 26 events/1,000 catheter-days, citrate group, p < 0.00001). There was no significant difference in incidence of infections between groups. We observed a significantly longer time to occurrence of infection in the citrate group (20 days vs. 14 days, HR 2.8, 95% CI 1.04-7.6, p = 0.04). By multivariate analysis, age and citrate group were the only independent factors that influenced catheter life span. CONCLUSIONS: This study shows for the first time that citrate lock reduced catheter complications and increased catheter life span as compared to saline lock in critically ill adults requiring hemodialysis.