A Population Pharmacokinetics Model for Vancomycin Dosage Optimization Based on Serum Cystatin C.

BACKGROUND AND OBJECTIVES: Renal function has an important influence on the pharmacokinetics of vancomycin, and serum cystatin C (CysC) exhibits accurate predictive performance as a marker for renal function. This study aimed to develop a population pharmacokinetics (PopPK) model of vancomycin based on serum CysC in pediatric patients. In addition, vancomycin dosage was optimized with the area under the serum concentration-time curve over 24 h (AUC0-24)/minimum inhibitory concentration (MIC) ratio in the target range of 400-700 and the steady-state trough concentration (Css,trough). METHODS: Data were retrospectively obtained from pediatric patients aged 2-18 years who received vancomycin treatment for infection from January 2014 to June 2019. PopPK analysis and Monte Carlo simulations were conducted using nonlinear mixed effects model (NONMEM) software. RESULTS: A total of 220 children were included. Serum CysC and age were significant covariates affecting the pharmacokinetics of vancomycin. The final typical value of clearance was 2.25 L/h; the volume of distribution was 8.17 L. The average probability of target attainment values of AUC0-24/MIC ratios within 400-700 in the 2-7, 7-12, and 12-18 years age groups were 66.1%, 68.1% and 66.5%, respectively. The median Css,trough values of vancomycin for the 2-7, 7-12, and 12-18 years age groups were 7.49-11.84, 5.98-11.32, and 5.15-11.39 mg/L, respectively, and were highly correlated with AUC0-24/MIC ratios in the range of 400-700 when the MIC was 1 mg/L. CONCLUSIONS: The pharmacokinetic parameters for vancomycin in pediatric patients were estimated using a serum CysC model. The simulated dosages provide a reference for vancomycin therapy.

The prognostic value of the postoperative serum CEA levels/preoperative serum CEA levels ratio in colorectal cancer patients with high preoperative serum CEA levels.

PURPOSE: This study aimed to assess the prognostic value of the postoperative serum carcinoembryonic antigen (CEA) levels/preoperative serum CEA levels ratio (CEA ratio) in colorectal cancer (CRC) patients with high preoperative serum CEA levels and to identify the optimal prognostic cutoff value. PATIENTS AND METHODS: The medical records of 187 CRC patients in a single center who underwent surgery between September 2012 and September 2014 were retrospectively reviewed. CEA ratio was defined as the ratio between the postoperative serum CEA and preoperative serum CEA. The optimal cutoff values for the CEA ratio were determined by time-dependent receiver operating characteristic (ROC) curve analyses. The Chi-square test or Fisher's exact probability test were used to test the correlation between CEA ratio and clinicopathological characteristics. Univariate, multivariate, and subgroup Cox proportional hazards analysis were used to identify independent prognostic factors. Kaplan-Meier method was used for establishing survival curves. RESULTS: The median follow-up time was 62 months (range 3-88 months). The optimal CEA ratio cutoff value closely related to disease-free survival was 0.295. In the Chi-square test, the CEA ratio was associated with pN stage (p=0.003) and postoperative CEA (p<0.001). In the multivariate analysis, the CEA ratio was an independent prognostic factor for disease-free survival (p=0.003, HR 2.300 [95% CI: 1.326-3.988]) and cancer-special survival (p=0.003, HR 2.525 [95% CI: 1.381-4.614]). The CEA ratio reflected the prognosis of CRC patients more accurately than postoperative CEA levels alone, and the CEA ratio of 0.295 was more likely to reflect the prognosis than other cutoff values. CONCLUSION: The CEA ratio is a simple and useful tool for further forecasting the prognosis of CRC patients with high preoperative CEA levels and may help develop strategies for the postoperative treatment of CRC patients.

[Significance of Forkhead Box m1b (Foxm1b) gene in cell proliferation and carcinogenesis].

Forkhead Box m1b (Foxm1b) is a subtype of the Fox transcription factor family. It is detected in all proliferative cells, but disappears when cells enter into their terminal differentiation phase. Foxm1b is closely related to hepatocellular growth, mainly through inhibiting cyclin-dependent kinase (CDK) inhibitors to influence cell proliferation. It also participates in growth hormone (GH) mediated cell multiplication, but does not induce tumors. The expression of Foxm1b has been observed in many tumor cell lines and malignant tumors, indicating that it might be an essential proto-oncogene in carcinogenesis. Furthermore, Foxm1b may take part in liver regeneration after hepatectomy, hepatic failure and liver transplantation. Foxm1b is a new potential target for the treatment human hepatic cell carcinoma (HCC).