Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are reaching epidemic levels worldwide, but data in Asia remain scarce. This cross-sectional study examined the metabolic and adipokine profiles of Chinese patients with biopsy-proven NAFLD and factors associated with severe disease. METHODS: Eighty ethnic Chinese with NAFLD and 41 healthy controls were recruited. Metabolic parameters and fasting adiponectin, tumor necrosis factor-alpha (TNF-alpha), leptin, and resistin levels were measured on the day of liver biopsy. Histology was scored according to Brunt's criteria. Metabolic syndrome was assessed by using both the International Diabetes Federation and Adult Treatment Panel III criteria. RESULTS: Twenty-eight patients had simple steatosis, and 52 patients had nonalcoholic steatohepatitis (NASH), defined as necroinflammatory grade >/=2 and/or fibrosis by Brunt's criteria. The ethnic-specific International Diabetes Federation criteria identified more cases of metabolic syndrome among NAFLD patients than the Adult Treatment Panel III criteria (70% vs 56%, P < .0001). On multivariate analysis, low adiponectin level, increased leptin level, and diabetes mellitus were associated with NAFLD. High TNF-alpha level and high body mass index were independent factors associated with NASH. TNF-alpha level had positive correlation with necroinflammatory grade (R = .35, P = .002) and fibrosis stage (R = .31, P = .005). CONCLUSIONS: Hypoadiponectinemia and elevated TNF-alpha levels are associated with the development of NAFLD and NASH, respectively, independent of other metabolic factors. Ethnic-specific definition of metabolic syndrome is more useful in the assessment of NAFLD patients.     

MiR-200b/200c/429 subfamily negatively regulates Rho/ROCK signaling pathway to suppress hepatocellular carcinoma metastasis

MiR-200 family is an important regulator of epithelial-mesenchymal transition and has been implicated in human carcinogenesis. However, their expression and functions in human cancers remain controversial. In the work presented here, we showed that miR-200 family members were frequently down-regulated in hepatocellular carcinoma (HCC). Although all five members of miR-200 family inhibited ZEB1/2 expression in HCC cell lines, we showed that overexpression only of the miR-200b/200c/429 subfamily, but not the miR-200a/141 subfamily, resulted in impeded HCC cell migration. Further investigations led to the identification of RhoA and ROCK2 as specific down-stream targets of the miR-200b/200c/429 subfamily. We demonstrated that the miR-200b/200c/429 subfamily inhibited HCC cell migration through modulating Rho/ROCK mediated cell cytoskeletal reorganization and cell-substratum adhesion. Re-expression of miR-200b significantly suppressed lung metastasis of HCC cells in an orthotopic liver implantation model in vivo. In conclusion, our findings identified the miR-200b/200c/429 subfamily as metastasis suppressor microRNAs in human HCC and highlighted the functional discrepancy among miR-200 family members.     

Modulatory effects of adiponectin on the polarization of tumor‐associated macrophages

The plasticity of macrophages with selective functional phenotypes partially arises in respective to their microenvironment. Tumor‐associated macrophages (TAMs) may promote disease progression with tumor specific manner. Here we report that in pediatric malignant soft‐tissue tumors, the presence of TAMs and expression of adiponectin (APN) are heterogeneous. Both APN and TAMs had high expression in rhabdomyosarcoma, especially in the malignant subtype, alveolar rhabdomyosarcoma. To investigate the mode of action of APN on TAM activation, a murine MN/MCA1 sarcoma model was used. The Results revealed that exogenous APN had no effect on MN/MCA1 proliferation but tumor size was markedly reduced in apn^?/? mice versus WT controls. The accumulation of TAMs in apn^?/? mice was also reduced which correlated to downregulated serum levels of MCP‐1. Likewise, TAMs in apn^?/? mice exhibited a M1‐like phenotype, characterized by increase in MHC II^high population and M1 phenotypic markers, such as iNOS gene and serum TNF‐α accompanied by a decrease in M2 markers, namely YM1 gene and serum IL‐10. In addition, APN deficiency increased the number of CD4⁺ T cells, CD8⁺ T cells and NK cells in tumors and reduced tumor metastasis. The altered phenotype of TAMs in apn^?/? mice was associated with a marked decrease in phospho‐p38 and treatment with a p38 MAPK inhibitor significantly reduced tumor size and increased MHC II expression on TAMs in WT mice, implying p38 MAPK signaling pathway may contribute to APN‐mediated TAM polarization. Collectively, our findings suggest that APN may have a potential role in regulating soft tissue sarcoma growth.     

Computed tomography arterial portography for assessment of portal vein injury after blunt hepatic trauma

PURPOSE

Intrahepatic portal vein injuries secondary to blunt abdominal trauma are difficult to diagnose and can result in insidious bleeding. We aimed to compare computed tomography arterial portography (CTAP), reperfusion CTAP (rCTAP), and conventional computed tomography (CT) for diagnosing portal vein injuries after blunt hepatic trauma.

METHODS

Patients with blunt hepatic trauma, who were eligible for nonoperative management, underwent CTAP, rCTAP, and CT. The number and size of perfusion defects observed using the three methods were compared.

RESULTS

A total of 13 patients (seven males/six females) with a mean age of 34.5±14.1 years were included in the study. A total of 36 hepatic segments had perfusion defects on rCTAP and CT, while there were 47 hepatic segments with perfusion defects on CTAP. The size of perfusion defects on CT (239 cm³; interquartile range [IQR]: 129.5, 309.5) and rCTAP (238 cm³; IQR: 129.5, 310.5) were significantly smaller compared with CTAP (291 cm³; IQR: 136, 371) (both, P = 0.002).

CONCLUSION

Perfusion defects measured by CTAP were significantly greater than those determined by either rCTAP or CT in cases of blunt hepatic trauma. This finding suggests that CTAP is superior to rCTAP and CT in evaluating portal vein injuries after blunt liver trauma.The liver is one of the most frequently injured solid abdominal organs in the setting of blunt abdominal trauma (1). Fortunately, most patients with blunt hepatic trauma have relatively stable vital signs and need only supportive treatment or transarterial embolization (TAE) (1–9). Only 15% of patients, who present with hemodynamic instability or fail with nonoperative management, require operative intervention to manage their liver injury.Embolic therapy has been shown to have a high success rate in hemodynamically stable patients with blunt hepatic injury. TAE is associated with decreased abdominal infections, decreased transfusions, and decreased length of hospital stay compared with operative management (2, 3, 7). However, angiography can only detect bleeding from the hepatic artery; it cannot locate bleeding from the hepatic or portal vein. In the literature, portal vein injuries are not commonly described and most are the result of penetrating injuries to the extrahepatic portal veins. Mortality after a portal vein injury due to trauma is primarily due to hypovolemic shock and can be as high as 50% or greater (10, 11).Since the intrahepatic portions of the hepatic and portal veins are low pressure systems, they can bleed insidiously. Nevertheless, this subtle bleeding may require multiple transfusions and result in a prolonged hospital stay. Relative to an extrahepatic portal vein injury, patients with an intrahepatic portal vein injury may have relatively stable vital signs and slowly decreasing hemoglobin levels (10, 11). In addition, traumatic occlusion and/or thrombosis of the portal vein may cause large hepatic parenchymal infarction.Computed tomography arterial portography (CTAP) is a useful method based on portal enhancement of the liver by infusion of contrast material through the superior mesenteric artery for evaluating the portal venous system (12–15) and is widely used in patients with hepatic tumors with portal venous invasion (13, 16, 17). CTAP has a high sensitivity and specificity in the evaluation of portal vein thrombosis due to tumor (90% sensitivity, 99% specificity, 95% positive predictive value, 97% negative predictive value) (14). However, few studies have focused specifically on the utility of CTAP in the evaluation of portal vein injury as a result of trauma.The liver has a dual blood supply and receives between 66% and 75% of its blood supply from the hepatic portal vein with the remainder supplied by the hepatic artery (18). CTAP reflects only portal venous perfusion while reperfusion CTAP (rCTAP) reflects hepatic arterial reperfusion. Both rCTAP and conventional computed tomography (CT) are useful for determining certain liver injuries. However, they do not specifically evaluate the portal vein.The purpose of this study was to compare CTAP, rCTAP, and CT for diagnosing portal vein injuries after blunt hepatic trauma. We hypothesized that CTAP would be superior to rCTAP and CT in assessing portal vein injury after blunt hepatic trauma.     

Focused Cardiac Ultrasonography: Current Applications and Future Directions

Focused cardiac ultrasonography is performed by clinicians at the bedside and is used in time‐sensitive scenarios to evaluate a patient's cardiovascular status when comprehensive echocardiography is not immediately available. This simplified cardiac ultrasonography is often performed by noncardiologists using small, portable devices to augment the physical examination, triage patients, and direct management in both critical care and outpatient settings. However, as the use of focused cardiac ultrasonography continues to expand, careful consideration is required regarding training, scope of practice, impact on patient outcomes, and medicolegal implications. In this review, we examine some of the challenges with rapid uptake of this technique and explore the benefits and potential risk of focused cardiac ultrasonography. We propose possible mechanisms for cross‐specialty collaboration, quality improvement, and oversight.