Risk factors for delayed methotrexate elimination in pediatric patients with hematological malignancies: a retrospective analysis

Delayed elimination of methotrexate(MTX) is a major clinical concern in patients receiving high-dose MTX(HD-MTX) therapy. In the present study, we aimed to retrospectively explore the factors associated with MTX concentrations and elimination delay in pediatric patients with hematological malignancies. Cycles of HD-MTX therapy were categorized into the normal elimination group and delayed elimination group according to the serum MTX concentrations at 24(C) or 42 h(C) after the start of MTX therapy. Clinical characteristics associated with MTX concentrations and elimination delay were assessed by χ^(2) test, Fisher’s exact test, Mann-Whitney test, or Spearman’s correlation coefficient. Generalized Estimating Equations(GEE) were used to adjust for the clustering effects of multiple cycles in one patient and confounders. A total of 43 patients with 138 cycles of HD-MTX chemotherapy were included and evaluated in the current study. Dose, white blood cells(WBC), hemoglobin(HB), and blood urea nitrogen(BUN) were significantly correlated with MTX C(all P < 0.05). No significant correlations were noticed between baseline characteristics and MTX C. Delayed MTX elimination was observed in 34(24.6%) courses. Dose, WBC, HB, BUN, and concurrent infection were the significant risk factors for delayed MTX elimination(all P < 0.05). Our study identified several risk factors associated with MTX levels and elimination, which might be used to recognize patients with a high risk of delayed MTX elimination. However, the findings need to be confirmed in further large-scale studies.

The influence of correlation delay and spectral asymmetry on acoustic Doppler velocimetry bias

The influence of correlation delay and spectral amplitude asymmetry of the received signal on acoustic Doppler velocimetry bias with the complex covariance approach are studied.Neglecting the simplifying error of the velocimetry formula,the velocimetry bias is simplified to the Doppler shift measurement bias.It is deduced that if not considering the beam angle,the narrowband frequency measurement is unbiased while the broadband frequency measurement is biased;and if considering the beam angle,the narrowband and broadband frequency measurement are all biased.Inaccurate correlation delay and asymmetric spectrum are important sources of the biases.Simulation analysis shows that the frequency measurement bias can be reduced to 0 by eliminating the correlation delay inaccuracy or spectral asymmetry.Based on the above findings,the ellipse grid frequency measurement model with dual weighting of signal phase and amplitude for the bottom tracking Doppler velocimetry sonar is proposed;the theoretical analysis for the difference between the broadband and narrowband frequency measurement bias with the same pulse length is given.The proposed broadband frequency measurement model is utilized to simulate the fitting curve of the Doppler shift and the frequency estimation bias,with which the actual data is corrected.In the water tank experiment,the relative velocimetry bias decreases from 1.14%to 0.78%,and the maximum absolute value decreases from 2.83%to 1.83%;and for sea trial,the relative velocimetry bias decreases from 4.79%to 3.82%.