A real-world experience of venetoclax combined with hypomethylating agents vs. monotherapy hypomethylating agents in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia patients.

Introduction: Current clinical research has reported the effectiveness and safety of venetoclax in combination with hypomethylating agents (VEN-HMA) in patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Thus, this study aimed to examine the effectiveness and safety of VEN-HMA therapy in patients with MDS and CMML and compared its short-term and long-term therapeutic effects with HMA monotherapy. Method: We analyzed data from our center, comprising 19 patients with MDS and CMML who received VEN-HMA therapy, compared to 32 patients treated with HMA monotherapy. Results: The overall response rate (ORR) in the VEN-HMA group was 73.7%, compared to 59.4% in the HMA group. The survival analysis revealed that the median overall survival (mOS) time in the VEN-HMA group was 16 months, with a median progression-free survival (mPFS) time of 9 months, both of which were longer than those observed in the HMA group (p < 0.05). Key adverse events (AEs) included grade 3-4 neutropenia (89.5% in VEN-HMA group vs. 87.5% in HMA group), grade 3-4 thrombocytopenia (73.7% vs. 71.9%), and anemia (73.7% vs. 90.6%). Infection of grade 3 or higher occurred in 63.2% of patients in the VEN-HMA group and 65.6% of patients in the HMA group. Discussion: Our study has confirmed the effectiveness and safety of the combined treatment of HMAs and venetoclax, which offers significant advantages to patients due to the relatively high and rapid response rates.

Single injection by LC-ESI-MS/MS for simultaneous determination of organophosphate tri- and di-esters in plant tissue based on ultrasonic-assisted sequential extraction and single-step purification.

A novel methodology based on ultrasonic-assisted sequential extraction, dispersive-SPE purification, and single-injection on liquid chromatography-tandem mass spectrometry (LC-MS/MS) is proposed, for the first time, to simultaneously measure 14 tri-OPEs and 9 di-OPEs in plant tissues. The samples were successively ultrasonicated with a mixture of hexane:dichloromethane (1:1, v/v) and 8% acetic acid in acetonitrile for extracting tri- and di-OPEs purified with graphitized carbon black and quantitated on LC-MS/MS at the same time. The recoveries of targeted tri- and di-OPEs in the matrix spike ranged from 66% to 120% and 71% to 110% respectively. The proposed method was validated by processing eight types of common vegetables including spinach (Spinacia oleracea L.), lettuce (Lactuca sativa), carrot (Daucus carota var. sativa Hoffm.), sweet potato (Solanum tuberosum L.), cucumber (Cucumis sativus L.), tomato (Solanum lycopersicum L.), green beans (Phaseolus vulgaris), and cowpeas (Vigna unguiculata), with the recoveries of surrogates ranging from 84% to 98%.

Determination of polyoxymethylene-water partition coefficients for diverse organophosphate esters (OPEs) and prediction of the free-dissolved OPEs in OPE-contaminated soil.

Increasing attention on the estimation of bioavailability of organophosphate esters (OPEs) in soil or sediment has urged the development of techniques to measure soil-/sediment-associated porewater concentrations of OPEs. In this study, we investigated the sorption dynamics of 8 OPEs to polyoxymethylene (POM) spanning one order of magnitude of aqueous OPE concentrations and proposed POM-water partitioning coefficients (Kpom/w) for OPEs. The results showed that the Kpom/w values were mainly affected by the hydrophobicity of OPEs. OPEs with high solubility preferentially partitioned into the aqueous phase indicated by the low log Kpom/w values; while lipophilic OPEs were observed to be taken up by POM. The concentration of lipophilic OPEs in the aqueous phase had a strong impact on their sorption dynamics on POM, with higher aqueous concentrations accelerating the sorption dynamics and shortening the time for equilibration. We proposed that the required time to reach equilibration for targeted OPEs should be 42 d. The proposed equilibration time and Kpom/w values were further validated by applying POM to soil artificially contaminated with OPEs to measure OPEs soil-water partitioning coefficients (Ks). The variations of Ks among soil types implied the need to elucidate the effects of soil properties and chemical properties of OPEs on their distribution between soil and water in the future.

Fetal brain development at 25-39 weeks gestational age: A preliminary study using intravoxel incoherent motion diffusion-weighted imaging.

BACKGROUND: The fetal brain developmental changes of water diffusivity and perfusion has not been extensively explored. PURPOSE/HYPOTHESIS: To evaluate the fetal brain developmental changes of water diffusivity and perfusion using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). STUDY TYPE: Prospective. POPULATION: Seventy-nine normal singleton fetuses were scanned without sedation of healthy pregnant women. FIELD STRENGTH/SEQUENCE: 5 T MRI/T1 /2 -weighted image and IVIM-DWI. ASSESSMENT: Pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) values were calculated in the frontal (FWM), temporal (TWM), parietal (PWM), and occipital white matter (OWM) as well as cerebellar hemisphere (CH), basal ganglia region (BGR), thalamus (TH), and pons using an IVIM model. STATISTICAL TESTS: One-way analysis of variable (ANOVA) followed by Bonferroni post-hoc multiple comparison was employed to reveal the difference of IVIM parameters among the investigated brain regions. The linear and the nonlinear polynomial regression analyses were utilized to reveal the correlation between gestational age (GA) and IVIM parameters. RESULTS: There were significant differences in both D (F(7,623) = 96.64, P = 0.000) and f values (F(7,623) = 2.361, P = 0.0219), but not D* values among the varied brain regions. D values from TWM (r2 = 0.1402, P = 0.0002), PWM (r2 = 0.2245, P = 0.0002), OWM (r2 = 0.2519, P = 0.0002), CH (r2 = 0.2245, P = 0.0002), BGR (r2 = 0.3393, P = 0.0001), TH (r2 = 0.1259, P = 0.0001), and D* value from pons (r2 = 0.2206, P = 0.0002) were significantly correlated with GA using linear regression analysis. Quadratic regression analysis led to results similar to those using the linear regression model. DATA CONCLUSION: IVIM-DWI parameters may indicate fetal brain developmental alterations but the conclusion is far from reached due to the not as high-powered correlation between IVIM parameters and GA. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:899-909.