Antifungal prophylactic effectiveness and intrapulmonary concentrations of voriconazole versus posaconazole in lung transplant recipients.

Invasive fungal diseases (IFDs) are one of the leading causes of death in lung transplant recipients. This study aimed to compare the antifungal prophylactic effectiveness, intrapulmonary and plasma levels of voriconazole with posaconazole in lung transplant recipients. This retrospective cohort study analyzed adult recipients who underwent lung transplantation between June 2017 and December 2020. Voriconazole oral tablets or posaconazole oral suspension was used for prophylaxis against posttransplant IFD. Drug concentrations in bronchoalveolar lavage fluid (BALF) and plasma were measured by using liquid chromatography-mass spectrometry. The 182 recipients included 142 in the voriconazole group and 40 in the posaconazole group. The trough plasma levels were comparable between voriconazole and posaconazole (1.65 ± 0.09 vs. 1.69 ± 0.03 µg/ml, P = 0.55). However, the BALF levels were significantly higher for posaconazole than voriconazole (17.47 ± 11.51 vs. 0.56 ± 0.49 µg/ml, P < 0.001). There was no significant difference in the total incidence of breakthrough IFDs between the voriconazole and posaconazole groups (10.6% vs. 7.5%, P = 0.77). The intrapulmonary concentrations of posaconazole were significantly higher than voriconazole. The two agents had comparable antifungal prophylactic effectiveness.

The Effects of Gene Variations of GABRA2, GABRB1, GABRG2, GAD1 and SLC1A3 on Patients with Propofol During Anesthesia Induction.

PURPOSE: Propofol is one of the most commonly used intravenous sedatives in general anesthesia, while the individual variations of propofol are apparent. The objective of this study was to investigate the influence of genetic variations in GABAergic neurons and glutamatergic neurons on time to loss of consciousness (LOC) and the incidence of hypotension during anesthesia induction. PATIENTS AND METHODS: A total of 140 Chinese patients undergoing thyroid surgery or breast surgery were recruited. Genotyping of candidate genes was carried out using the Agena Bioscience MassARRAY system. Anesthesia induction was initiated with a propofol target plasma concentration (Cp) of 4.0 µg mL-1. The LOC latency, systolic blood pressure, diastolic blood pressure, mean arterial pressure were documented. RESULTS: We found that GABRA2 rs35496835, GABRB1 rs1372496, GABRG2 rs11135176, GABRG2 rs209358, GAD1 rs3791878, SLC1A3 rs1049522 and gender were significant determinants of the patient's LOC latency following propofol administration. GABRA2 rs11503014 was highly correlated with blood pressure reduction during anesthesia induction. Multiple linear regression analysis revealed that GABRB1 rs1372496, GABRG2 rs11135176, and SLC1A3 rs1049522 accounted for 35.3% variations in LOC latency following propofol administration. CONCLUSION: Our findings indicate that genetic variants of GABRA2, GABRB1, GABRG2, GAD1 and SLC1A3 may have influence on propofol susceptibility, which would be an important guidance towards building clinical models that can precisely predict the efficacy of propofol with various populations before surgery.

[Construction and function identification of luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR].

This study aims to investigate the function of two SNPs (rs8904C > T and rs696G >A) in 3' untranslated region (3'UTR) of NFKBIA gene by constructing luciferase reporter gene. A patient's genomic DNA with rs8904 CC and rs696 GA genotype was used as the PCR template. Full-length 3'UTR of NFKBIA gene was amplified by different primers. After sequencing validation, these fragments were inserted to the luciferase reporter vector, pGL3-promoter to construct recombinant plasmids containing four kinds of haplotypes, pGL3-rs8904C/rs696G, pGL3-rs8904C/rs696A, pGL3-rs8904T/rs696G and pGL3-rs8904T/rs696A. Then these plasmids were transfected into LS174T cells and the luciferase activity was detected. Compared with pGL3-vector transfected cells (negative control), the luciferase activity of the four kinds of recombinant plasmids was significantly decreased (P < 0.001). For rs696G > A, the luciferase activity of the recombinant plasmids containing A allele (pGL3-rs8904C/rs696A and pGL3-rs8904T/rs696A) was about 45.1% (P < 0.05) and 56.1% (P < 0.001) lower than those containing G allele (pGL3-rs8904C/rs696G and pGL3-rs8904T/rs696G), respectively. For rs8904C > T, there were no significant differences in the luciferase activity between the recombinant plasmids containing T allele and those with C allele. Together, the luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR were constructed successfully and rs696G > A could decrease the luciferase activity while rs8904C >T didn't have much effect on the luciferase activity.