Population pharmacokinetics of the anti-PD-1 antibody camrelizumab in patients with multiple tumor types and model-informed dosing strategy.

Camrelizumab, a programmed cell death 1 (PD-1) inhibitor, has been approved for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma, nasopharyngeal cancer and non-small cell lung cancer. The aim of this study was to perform a population pharmacokinetic (PK) analysis of camrelizumab to quantify the impact of patient characteristics and to investigate the appropriateness of a flat dose in the dosing regimen. A total of 3092 camrelizumab concentrations from 133 patients in four clinical trials with advanced melanoma, relapsed or refractory classical Hodgkin lymphoma and other solid tumor types were analyzed using nonlinear mixed effects modeling. The PKs of camrelizumab were properly described using a two-compartment model with parallel linear and nonlinear clearance. Then, covariate model building was conducted using stepwise forward addition and backward elimination. The results showed that baseline albumin had significant effects on linear clearance, while actual body weight affected intercompartmental clearance. However, their impacts were limited, and no dose adjustments were required. The final model was further evaluated by goodness-of-fit plots, bootstrap procedures, and visual predictive checks and showed satisfactory model performance. Moreover, dosing regimens of 200 mg every 2 weeks and 3 mg/kg every 2 weeks provided similar exposure distributions by model-based Monte Carlo simulation. The population analyses demonstrated that patient characteristics have no clinically meaningful impact on the PKs of camrelizumab and present evidence for no advantage of either the flat dose or weight-based dose regimen for most patients with advanced solid tumors.

[Application of panoramic film in predicting orthodontic treatment time for impacted maxillary canine].

PURPOSE: To evaluate the influence of pretreatment radiographic features (angle, distance, and location) on the duration of active orthodontic traction. METHODS: Sixty maxillary unilateral impacted canines were selected to analyze the panoramic features(angle, line spacing, and location) in pre-treatment patients， the results were evaluated using SPSS19.0 software package for multivariate regression analysis. RESULTS: Pretreatment radiographic variables (angle, line spacing, and location) were significantly associated with the duration of orthodontic traction. The sex and site of impaction did not significantly affect the duration of traction. CONCLUSIONS: Impacted canine angle, distance and position can predict the orthodontic traction time.

Digital image analysis of collagen assessment of progression of fibrosis in recurrent HCV after liver transplantation.

BACKGROUND & AIMS: Histological assessment of fibrosis progression is currently performed by staging systems which are not continuous quantitative measurements. We aimed at assessing a quantitative measurement of fibrosis collagen proportionate area (CPA), to evaluate fibrosis progression and compare it to Ishak stage progression. METHODS: We studied a consecutive cohort of 155 patients with recurrent HCV hepatitis after liver transplantation (LT), who had liver biopsies at one year and were subsequently evaluated for progression of fibrosis using CPA and Ishak staging, and correlated with clinical decompensation. The upper quartile of distribution of fibrosis rates (difference in CPA or Ishak stage between paired biopsies) defined fast fibrosers. RESULTS: Patients had 610 biopsies and a median follow-up of 116 (18-252) months. Decompensation occurred in 29 (18%) patients. Median Ishak stage progression rate was 0.42 units/year: (24 (15%) fast fibrosers). Median CPA fibrosis progression rate was 0.71%/year (36 (23%) fast fibrosers). Clinical decompensation was independently associated by Cox regression only with CPA (p=0.007), with AUROCs of 0.81 (95% CI 0.71-0.91) compared to 0.68 (95% CI 0.56-0.81) for Ishak stage. Fast fibrosis defined by CPA progression was independently associated with histological de novo hepatitis (OR: 3.77), older donor age (OR: 1.03) and non-use/discontinuation of azathioprine before 1 year post-LT (OR: 3.85), whereas when defined by Ishak progression, fast fibrosers was only associated with histological de novo hepatitis. CONCLUSIONS: CPA fibrosis progression rate is a better predictor of clinical outcome than progression by Ishak stage. Histological de novo hepatitis, older donor age and non-use/discontinuation of azathioprine are associated with rapid fibrosis progression in recurrent HCV chronic hepatitis after liver transplantation.