P53 and VEGF are promising biomarkers for sorafenib efficacy in an experimental model of NASH-related HCC.

The efficacy of systemic therapy for hepatocellular carcinoma (HCC) related to non-alcoholic steatohepatitis (NASH) is poorly understood. In this study we evaluated the effects of sorafenib based on the expression of molecular markers related to major hepatocarcinogenesis pathways and angiogenesis in a NASH-related HCC model. Forty male rats were submitted to NASH-HCC induction through the combination of a high-fat and choline deficient diet and diethylnitrosamine (100 mg/L) administration in the drinking water for 13 and 16 weeks. After the induction period, the rats received daily gavage administration of saline solution (control) or Sorafenib (5 mg/kg/day) for 3 weeks. Thereafter, the animals were euthanized and samples from liver nodules were collected for histopathological analysis and immunohistochemical assessment of HEP-PAR-1, glutamine-synthetase, VEGF, survivin, ß-catenin and p53. A semi-quantitative score was used for VEGF, survivin and ß-catenin analysis. For p53, the percentage of positive cells was determined. Results were processed by Wilcoxon's test or Student's t-test. Both protocols efficiently induced HCC, most of them being moderately to poorly differentiated. Sorafenib-treated animals showed a decreased expression of VEGF and p53 in HCCs generated at 13 weeks when compared to control animals (p = 0.03; p = 0.04, respectively). No significant difference in ß-catenin and survivin were observed. There was a significant decrease in VEGF and p53 expression when comparing the two control groups (13 vs. 16 weeks, p < 0.01). p53 and VEGF are promising biomarkers for assessment of efficacy of Sorafenib, whereas survivin and ß-catenin were not found useful. Decreased immunohistochemical expression of p53 and VEGF in the 16 week control group may indicate a different metabolic status of HCC.

Trochanteric fractures: Tip-Apex distance, Calcar Tip-Apex distance, and Chang criteria-a multiple variable analysis.

Failure of osteosynthesis is a common complication of the nailing of trochanteric fractures which typically occurs through form of cut-out. Tip-Apex distance (TAD), Calcar Tip-Apex distance (CalTAD), and Chang criteria are validated variables to predict failure of cephalomedullary nailing. This is a retrospective study which analyzes treatment of trochanteric fractures from 2018 to 2020 (n = 296) evaluating postoperative radiographs and factors of mechanical failure. Our objective was to assess correlation among these variables and their influence on mechanical failure, either individually or creating a new score. Our results support the CalTAD and Chang's criteria as valid predictors of mechanical failure. Furthermore, they empathize the importance of fracture reduction and proper placement of cervical screw. To our knowledge, this is the first study performing multivariate analysis including these 3 variables.