Renal replacement therapy and concurrent fluconazole therapy increase linezolid-related thrombocytopenia among adult patients.

Linezolid has been reported to be associated with thrombocytopenia. However, limited information is available on susceptibility to thrombocytopenia after linezolid usage. We aimed to investigate the risk factors for linezolid-associated thrombocytopenia (LAT). We conducted a retrospective cohort study of patients aged ≥ 18 years who received linezolid for ≥ 5 d during hospitalization in 2019. Information was extracted from electronic medical records. Thrombocytopenia was defined as a platelet count of < 100 × 109/L or a reduction from baseline ≥ 25%. Binary logistic regression and survival analyses were used to evaluate the risk factors for LAT. A total of 98 patients were enrolled. Thrombocytopenia occurred in 53.1% patients, with a median of 9 d after initiation of linezolid. There was no significant difference in the mortality or proportion of platelet transfusions between patients with and without thrombocytopenia. A higher risk of LAT was found in patients who received renal replacement therapy (RRT) (OR 4.8 [1.4-16.4]), or concurrent fluconazole (OR 3.5 [1.2-9.8]). Patients who received RRT (8 vs. 15 d) or concurrent fluconazole (11 vs. 15 d) had a shorter median time to develop thrombocytopenia. Those who simultaneously received RRT and fluconazole had the shortest median of time (6.5 d) and the highest risk of developing thrombocytopenia (87.5%).

Chrysin-induced ERK1/2 Phosphorylation Enhances the Sensitivity of Human Hepatocellular Carcinoma Cells to Sorafenib.

BACKGROUND/AIM: Sorafenib is now standard treatment for advanced hepatocellular carcinoma (HCC). However, therapeutic efficacy is not as good as was predicted. Many efforts are being made to improve HCC sensitivity to sorafenib. Our previous study demonstrated that co-treatment with chrysin enhanced sorafenib sensitivity through inhibition of ATP-binding cassette super-family G member 2 (ABCG2). Whether there is another mechanism other than inhibition of ABCG2 underlying chrysin-mediated synergistic effect is still not completely elucidated. MATERIALS AND METHODS: Phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) was examined by western blot. Cell viability was examined by crystal violet staining. The importance of ERK1/2 phosphorylation was assessed by overexpression and blockage of mitogen-activated protein kinase kinase 1 (MEK1). RESULTS: Chrysin induced sustained ERK1/2 phosphorylation of HCC cells in both time- and dose-dependent manners. Overexpression of MEK1 enhanced, whereas blockage of MEK1 led to loss of chrysin-synergized sorafenib effect, through modulating ERK1/2 phosphorylation level. CONCLUSION: These results identify another novel mechanism underlying chrysin-mediated synergistic effect on sorafenib activity in HCC cells.