Nature medicine
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Liver disease is one of the leading causes of death worldwide. Patients with cirrhosis display an increased predisposition to and mortality from infection due to multimodal defects in the innate immune system; however, the causative mechanism has remained elusive. We present evidence that the cyclooxygenase (COX)-derived eicosanoid prostaglandin E2 (PGE2) drives cirrhosis-associated immunosuppression. ⋯ Two mouse models of liver injury (bile duct ligation and carbon tetrachloride) also exhibited elevated PGE2, reduced circulating albumin concentrations and EP2-mediated immunosuppression. Treatment with COX inhibitors or albumin restored immune competence and survival following infection with group B Streptococcus. Taken together, human albumin solution infusions may be used to reduce circulating PGE2 levels, attenuating immune suppression and reducing the risk of infection in patients with acutely decompensated cirrhosis or ESLD.
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For more than four decades, the US Institute of Medicine (IOM) has operated as an independent nonprofit organization with a mission of providing guiding documents on matters of health and biomedical research, many of which are commissioned by the government. The IOM--part of the 151-year-old National Academy of Sciences--issues reports on a wide range of topics, from salt consumption to clinical trial data sharing, and convenes workshops at its headquarters in Washington, DC. The institute counts almost 2,000 experts among its members, including Victor Dzau. ⋯ During his time at Duke, he has broadened the reach of the institution by helping to launch the Duke-National University of Singapore Graduate Medical School, the Duke Global Health Institute and the International Partnership for Innovative Healthcare Delivery. Roxanne Khamsi spoke with Dzau about his vision for the IOM. The conversation has been edited for clarity.