Low- versus High-Chloride Content Intravenous Solutions for Perioperative Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Studies have shown complications of normal saline infusion because of its high-chloride content. Therefore, in the present study, we aimed to explore whether the use of low- versus high-chloride solutions benefited the unselected and specifically perioperative patients and was associated with different outcomes. METHODS: Studies on the use of low- versus high-chloride content intravenous solutions for perioperative patients, published up to July 15, 2019, were systematically reviewed, and primary and secondary outcomes were quantitatively summarized. RESULTS: A total of 14 eligible randomized controlled trials with 943 perioperative patients were included. Five studies reported all-cause mortality, and eight studies provided detailed data on renal replacement therapy (RRT). The pooled result suggested no statistically significant difference in the effect of low- versus high-chloride solutions on all-cause mortality (risk ratio (RR) = 1.39; 95%confidence interval (CI) = 0.23-8.26) and RRT (RR = 1.05; 95%CI = 0.63-1.76). The pooled results on acute kidney injury (AKI) and the use of allogenic blood transfusion (P > 0.05) were similar. CONCLUSION: Among specific perioperative patients, the use of low- versus high-chloride content intravenous solutions did not reduce the all-cause mortality, risk of severe AKI, or rate of RRT use. Further large randomized clinical trials are needed to confirm or refute this finding.

Ultrasound triggered phase-change nanodroplets for doxorubicin prodrug delivery and ultrasound diagnosis: An in vitro study.

Ultrasound-triggered delivery system is among the various multifunctional and stimuli-responsive strategies that hold great potential as a robust solution to the challenges of localized drug delivery and gene therapy. In this work, we developed an ultrasound-triggered delivery system PFP/C9F17-PAsp(DET)/CAD/PGA-g-mPEG nanodroplet, which combined ultrasound responsive phase-change contrast agent, acid-cleavable doxorubicin prodrug and cationic amphiphilic fluorinated polymer carrier, aiming to achieve both high imaging contrast and preferable ultrasound-triggered anti-cancer therapeutic effect. The optimized nanodroplets were characterized as monodispersed particles with a diameter of about 400 nm, slightly positive surface charge and high drug-loading efficiency. The functional augmenter PGA-g-mPEG provided the nanodroplets good sustainability, low cytotoxicity and good serum compatibility, as confirmed by stability and biocompatibility tests. In ultrasound imaging study, the nanodroplets produced significant contrast with ultrasound irradiation (3.5 MHz, MI = 0.08) at 37 ℃. Cell uptake and cytotoxicity studies in HepG2 and CT-26 cells showed the enhanced drug uptake and therapeutic effect with the combination of nanodroplets and ultrasound irradiation. These results suggest that the PFP/CAD-loaded phase change nano-emulsion can be utilized as an efficient theranostic agent for both ultrasound contrast imaging and drug delivery.

Photothermal-Enhanced Phase-Transition Nanodroplets for Ultrasound-Mediated Diagnosis and Gene Transfection.

Gene therapy is one of the promising solutions in cancer therapeutics. Ultrasound-mediated gene delivery showed great potential as a noninvasive strategy for gene therapy. However, the efficiency of gene transfection and incorporation of multiple functions remain key challenges in the development of gene delivery systems. In this study, we developed perfluoropentane (PFP) and gold nanorods (AuNRs) loading nanodroplets for photothermal-enhanced ultrasound-mediated imaging and gene transfection. The nanodroplet theranostic system was formulated with fluorinated cationic poly(aspartamide) based polymer that encapsulated PFP, AuNRs, and plasmid DNA and was stabilized with a negatively charged poly(glutamic acid)-g-MeO-poly(ethylene glycol) (PGA-g-mPEG) coating. The nanodroplets presented good stability, biocompatibility, and DNA binding stability. Upon treatment with both near-infrared and ultrasound energy, the photothermal and ultrasound-responsive system exerted a synergistic effect, in which strong adsorption of light induced hyperthermia that promoted the phase transition of PFP and the following ultrasound irradiation, generating strong acoustic cavitation and sonoporation, thus leading to enhanced ultrasound contrast imaging and gene transfection efficiency both in vitro and in vivo.