IL-6-GP130 signaling protects human hepatocytes against lipid droplet accumulation in humanized liver models.

Liver steatosis is an increasing health issue with few therapeutic options, partly because of a paucity of experimental models. In humanized liver rodent models, abnormal lipid accumulation in transplanted human hepatocytes occurs spontaneously. Here, we demonstrate that this abnormality is associated with compromised interleukin-6 (IL-6)-glycoprotein 130 (GP130) signaling in human hepatocytes because of incompatibility between host rodent IL-6 and human IL-6 receptor (IL-6R) on donor hepatocytes. Restoration of hepatic IL-6-GP130 signaling, through ectopic expression of rodent IL-6R, constitutive activation of GP130 in human hepatocytes, or humanization of an Il6 allele in recipient mice, substantially reduced hepatosteatosis. Notably, providing human Kupffer cells via hematopoietic stem cell engraftment in humanized liver mice also corrected the abnormality. Our observations suggest an important role of IL-6-GP130 pathway in regulating lipid accumulation in hepatocytes and not only provide a method to improve humanized liver models but also suggest therapeutic potential for manipulating GP130 signaling in human liver steatosis.

Resident-performed compression ultrasonography for the detection of proximal deep vein thrombosis: fast and accurate.

OBJECTIVES: To assess whether emergency medicine residents (EMRs) could quickly perform accurate compression ultrasonography (CUS) for the detection of proximal lower extremity deep vein thromboses (PLEDVTs) with minimal training. METHODS: A prospective, observational study using a convenience sample of patients presenting with signs and/or symptoms for PLEDVT. Vascular laboratory and department of radiology studies were considered the criterion standard. CUS of the femoral vessels was performed. Incompressibility or visualized thrombus was considered "positive." RESULTS: Eight residents with limited ultrasound (US) experience and no prior experience with deep vein thrombosis (DVT) US volunteered to participate in this study, enrolling 72 patients. Their average scan time was 11.7 minutes (95% CI = 9.4 to 14). There were 23 true positives, 4 false positives, 45 true negatives, and 0 false negatives. The test characteristics for PLEDVT gave a sensitivity of 100% (95% CI = 82.2 to 100) and a specificity of 91.8% (95% CI = 79.5 to 97.4). CONCLUSION: Emergency medicine residents with limited US experience were able to quickly perform CUS after minimal training for the detection of PLEDVT in a select group of patients.