Lung transplantation for cystic fibrosis: a single center experience of 100 consecutive cases†

OBJECTIVE Lung transplantation is the ultimate treatment option for patients with end-stage cystic fibrosis (CF) lung disease. Despite poorer reports on survival benefit for CF patients undergoing lung transplantation, several centers, including ours were able to show a survival benefit. This study compares our center's experience with 100 consecutive recipients in two different eras. METHODS All CF patients who underwent lung transplantation at our center were included (1992-2009). Survival rates were calculated and compared between the earlier era (before 2000) and later era (since 2000). RESULTS CF patients constituted 35% of all transplantations performed at our institution. Mean age at transplantation was 27 years (range 12-52). Fifty-one percent of the patients were female. Waiting list time was lower in the earlier era compared to the later era (p=0.04). Lobar transplantation was performed in 10 cases. Thirty-four percent of the cases required downsizing of the graft. In 33% of the cases, transplantations were done on cardiopulmonary bypass. There were no anastomotic complications. Total intensive care unit stay was significantly lower in the later era compared to earlier era (p=0.001). The other parameters such as C-reactive protein at the time of transplantation, total cold ischemic time, and total operation time were comparable between the two eras. Overall 30-day mortality was 5%. The 30-day mortality was significantly lower in the second period (p=0.006). In the earlier era, 3-month, 1-year, and 5-year survival were 85±6%, 77±8%, and 60±9%, respectively, and in the later era improved to 96±2%, 92±3%, and 78±5% (p=0.03). CONCLUSION Improved results obtained in the early postoperative period since 2000 is most likely due to change in surgical management approach. Improved surgical outcome for CF patients can be obtained, especially in experienced transplant center

Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance

The systemic expression of the bile acid (BA) sensor farnesoid X receptor (FXR) has led to promising new therapies targeting cholesterol metabolism, triglyceride production, hepatic steatosis and biliary cholestasis. In contrast to systemic therapy, bile acid release during a meal selectively activates intestinal FXR. By mimicking this tissue-selective effect, the gut-restricted FXR agonist fexaramine (Fex) robustly induces enteric fibroblast growth factor 15 (FGF15), leading to alterations in BA composition, but does so without activating FXR target genes in the liver. However, unlike systemic agonism, we find that Fex reduces diet-induced weight gain, body-wide inflammation and hepatic glucose production, while enhancing thermogenesis and browning of white adipose tissue (WAT). These pronounced metabolic improvements suggest tissue-restricted FXR activation as a new approach in the treatment of obesity and metabolic syndrome