Mesenchymal stromal cells mitigate liver damage after extended resection in the pig by modulating thrombospondin-1/TGF-ß.

Post-surgery liver failure is a serious complication for patients after extended partial hepatectomies (ePHx). Previously, we demonstrated in the pig model that transplantation of mesenchymal stromal cells (MSC) improved circulatory maintenance and supported multi-organ functions after 70% liver resection. Mechanisms behind the beneficial MSC effects remained unknown. Here we performed 70% liver resection in pigs with and without MSC treatment, and animals were monitored for 24 h post surgery. Gene expression profiles were determined in the lung and liver. Bioinformatics analysis predicted organ-independent MSC targets, importantly a role for thrombospondin-1 linked to transforming growth factor-ß (TGF-ß) and downstream signaling towards providing epithelial plasticity and epithelial-mesenchymal transition (EMT). This prediction was supported histologically and mechanistically, the latter with primary hepatocyte cell cultures. MSC attenuated the surgery-induced increase of tissue damage, of thrombospondin-1 and TGF-ß, as well as of epithelial plasticity in both the liver and lung. This suggests that MSC ameliorated surgery-induced hepatocellular stress and EMT, thus supporting epithelial integrity and facilitating regeneration. MSC-derived soluble factor(s) did not directly interfere with intracellular TGF-ß signaling, but inhibited thrombospondin-1 secretion from thrombocytes and non-parenchymal liver cells, therewith obviously reducing the availability of active TGF-ß.

Effectiveness of a bundled approach to reduce urinary catheters and infection rates in trauma patients.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are common nosocomial infections. In 2015, the Centers for Medicare and Medicaid Services began imposing financial penalties for institutions where CAUTI rates are higher than predicted. However, the surveillance definition for CAUTI is not a clinical diagnosis and may represent asymptomatic bacteriuria. The objective of this study was to compare rates of urinary catheterization and CAUTI before and after the implementation of a bundled intervention. METHODS: This retrospective review evaluated trauma patients from January 2013-January 2015. The bundled intervention optimized the urinary catheterization process and culturing practices to reduce false positives. The CAUTI rate was defined as a positive surveillance CAUTI divided by total catheter days multiplied by 1,000 days. RESULTS: A total of 6,236 patients were included (pre: n = 5,003; post: n = 1,233). Fewer patients in the post bundle group received a urinary catheter (pre: 25% vs post: 16%; P < .001). After bundle implementation, the CAUTI rate reduced over one third (pre: 4.07 vs post: 2.56; incidence rate ratio, 0.63; 95% confidence interval, 0.19-2.07). CONCLUSIONS: Although the number of patients exposed to urinary catheters and catheter days was decreased, optimization of culturing practices was essential to prevent the CAUTI rate from increasing from a reduced denominator. Implementation of a CAUTI prevention bundle works synergistically to improve patient safety and hospital performance.