Retrospective analysis on incidence and risk factors of early onset acute kidney injury after lung transplantation and its association with mortality.

OBJECTIVES: Acute kidney injury (AKI) is a common complication after lung transplantation (LTx) which is closely related to the poor prognosis of patients. We aimed to explore potential risk factors and outcomes associated with early post-operative AKI after LTx. METHODS: A retrospective study was conducted in 136 patients who underwent LTx at our institution from 2017 to 2019. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline. Univariate and multivariate analyses were conducted to identify risk factors related to AKI. The primary outcome was the incidence of AKI after LTx. Secondary outcomes were associations between AKI and short-term clinical outcomes and mortality. RESULTS: Of the 136 patients analyzed, 110 developed AKI (80.9%). AKI was associated with higher baseline eGFR (odds ratio (OR) 1.01 (95% confidence interval (CI): 1.00-1.03)) and median tacrolimus (TAC) concentration (OR 1.15 (95% CI: 1.02-1.30)). Patients with AKI suffered longer mechanical ventilation days (p = .015) and ICU stay days (p = .011). AKI stage 2-3 patients had higher risk of 1-year mortality (HR 16.98 (95% CI: 2.25-128.45)) compared with no-AKI and stage 1 patients. CONCLUSIONS: Our results suggested early post-operative AKI may be associated with higher baseline eGFR and TAC concentrations. AKI stage 1 may have no influence on survival rate, whereas AKI stage 2-3 may be associated with increased mortality at 1-year.

Interlaboratory analysis of teicoplanin plasma concentration assays among Chinese laboratories.

WHAT IS KNOWN AND OBJECTIVE: Teicoplanin is widely used for the treatment of infections caused by drug-resistant Gram-positive bacteria. Since there is a good correlation between trough levels and clinical outcome, therapeutic drug monitoring (TDM) is recommended to achieve better clinical curative effects. However, TDM of teicoplanin is not routine in China. So, a programme was initiated in 2017, including both HPLC method establishment and interlaboratory quality assessment, for the measurement of teicoplanin. METHODS: A main centre and a quality control centre were set up in the study. An HPLC-based method of teicoplanin determination in plasma was developed by the main centre. Analysis was performed using a Waters Symmetry C18 column (250 mm × 4.6 mm, 5 µm). The mobile phase was NaH2 PO4 (0.01 mol/L) and acetonitrile (75:25 v/v; pH 3.3), with a flow rate of 1.0 mL/min and a detection wavelength of 215 nm. Piperacillin sodium was selected as an internal standard (IS). Twenty-six additional TDM centres were then recruited to adopt this method. Then, all the centres were asked to take part in a quality control assessment evaluated by the quality control centre. RESULTS: For all TDM centres, linearity of teicoplanin concentration ranges was between 3.125 and 100 µg/mL. Intraday and interday accuracies ranged from 87.1% to 118.4%. Intraday and interday precision ranged from 0.3% to 13.8%. Therapeutic drug monitoring centres all passed inter-room quality assessment. All samples tested met the acceptance criteria. Then, 542 samples were collected. Patients with sub-optimal (≤10 mg/L) plasma teicoplanin concentrations constituted 42% of the total study population. WHAT IS NEW AND CONCLUSIONS: For the first time, a simple, rapid and accurate HPLC method for determining teicoplanin levels was successfully applied to therapeutic drug monitoring in clinical practice for twenty-seven TDM centres in China. The results demonstrated excellent interlaboratory agreement for teicoplanin testing and provide support for clinical laboratory quality management and results inter-accreditation.

Context- and time-dependent neurobiological and behavioral sensitization induced by a single morphine exposure in mice.

RATIONALE: Drug-induced sensitization in the mesocorticolimbic systems is thought to play an important role in certain aspects of drug addiction, including the involvement of drug-associated cues and environments in mediating drug-seeking behaviors. Our previous studies have identified the significance of heat shock protein 70 (Hsp70) in the development of a single morphine exposure-induced behavioral sensitization. OBJECTIVES: The present study expands upon these findings by investigating the effect of environment on the expression of behavioral sensitization induced by a single morphine exposure, and the potential involvement of Hsp70 protein levels in these effects. METHODS: Mice were pretreated with a single morphine injection in test chambers (morphine-paired) or home cages (morphine-unpaired) on day 1 and challenged on day 2 or 8, in test chambers. Hsp70 expression in the nucleus accumbens (NAc) was analyzed after the challenge. RESULTS: The expression of single morphine exposure-induced behavioral sensitization was accompanied by a significant increase in Hsp70 expression in NAc. In contrast, the unpaired morphine-treated group failed to exhibit behavioral sensitization or higher Hsp70 expression. Additionally, by adding a habituation process prior to the challenge, we demonstrated that conditioned hyperactivity, which was not accompanied by an increased expression of Hsp70, is not essential for behavioral sensitization. CONCLUSIONS: Behavioral sensitization induced by a single morphine exposure in mice exhibits context and time dependency, with environmental context likely functioning via an inhibitory conditioning mechanism. Furthermore, alterations in Hsp70 expression in the NAc may represent a neurobiological sensitization mechanism mediating context- and time-dependent behavioral sensitization.