Exosome is a subgroup of extracellular vesicles, which has been serving as an efficient therapeutic tool for various diseases. Engineered exosomes are the sort of exosomes modified with surface decoration and internal therapeutic molecules. After appropriate modification, engineered exosomes are able to deliver antitumor drugs to tumor sites efficiently and precisely with fewer treatment-related adverse effects. However, there still exist many challenges for the clinical translation of engineered exosomes. For instance, what sources and modification strategies could endow exosomes with the most efficient antitumor activity is still poorly understood. Additionally, how to choose appropriately engineered exosomes in different antitumor therapies is another unresolved problem. In this review, we summarized the characteristics of engineered exosomes, especially the spatial and temporal properties. Additionally, we concluded the recent advances in engineered exosomes in the cancer fields, including the sources, isolation technologies, modification strategies, and labeling and imaging methods of engineered exosomes. Furthermore, the applications of engineered exosomes in different antitumor therapies were summarized, such as photodynamic therapy, gene therapy, and immunotherapy. Consequently, the above provides the cancer researchers in this community with the latest ideas on engineered exosome modification and new direction of new drug development, which is prospective to accelerate the clinical translation of engineered exosomes for cancer-targeted therapy.
Organ shortage has led to an increased use of kidneys from cardiac death donors (DCDs), but controversies about the methods of organ preservation still exist. This study aims to compare the effect of machine perfusion (MP) and cold storage (CS) in protecting kidneys harvested from DCDs. 141 kidney pairs from DCDs between July 2010 and July 2015 were included in this randomized controlled study. One kidney from each donor was randomly assigned to MP and the contralateral kidney was assigned to CS. Delayed graft function (DGF) rate, resistance index of renal arteries, early renal function, and survival rates were used to estimate the effect of preservation. The results showed that MP decreased the rate of DGF from 33.3 to 22.0% (P = 0.033). Ultrasound of the kidneys within 48 h after transplantation showed that the resistance index of renal main artery (0.673 ± 0.063 vs. 0.793 ± 0.124, P < 0.001), sub segmental artery (0.66 ± 0.062 vs. 0.764 ± 0.077, P < 0.001) and interlobular artery (0.648 ± 0.056 vs. 0.745 ± 0.111, P = 0.023) were all significantly lower in the MP group than those in the CS group. Furthermore, compared to the CS group, in the first 7 days following transplantation, the median urine volume was significantly higher (4080 mL vs. 3000 mL, P = 0.047) in kidneys sustained using MP and the median serum creatinine was remarkably lower (180 µmol/L vs. 390 µmol/L, P = 0.024). More importantly, MP group had higher 1- and 3-year graft survival rates (98% vs. 93%, P = 0.026; 93% vs. 82%, P = 0.036, respectively). Hypothermic MP improved the outcomes of DCD kidney transplantation.
To improve the outcomes of transplantation, more effective therapeutic treatments are of paramount importance when older SOT recipients with bacteremia due to ESKAPE/rESKAPE organisms present with septic shock.
BackgroundAlthough multidrug-resistant (MDR) gram-negative bacteremia (GNB) has been recognized as an important cause of morbidity and mortality among abdominal solid organ transplant (ASOT) recipients, there are no data on its prognostic factors after an interim standard definition of MDR was proposed in 2012. The objective of this study was to describe the epidemiology, microbiology, and predictors of infection-related 30-day mortality in ASOT recipients with MDR GNB.MethodsWe performed a retrospective, double-center analysis of ASOT patients with MDR GNB over a 13-year study period. Univariate and multivariate analyses were performed to identify the risk factors for mortality.ResultsDuring the observational period, 2169 subjects underwent ASOT. Ninety-nine episodes of MDR GNB were diagnosed in 91 (4.6%) ASOT recipients, with a predominance of E.coli (29 isolates, 29.3%) and A.baumanii (24 isolates, 24.2%). The median age of these 91 recipients was 45 years (interquartile range 35–54). Mortality after the first episode of MDR GNB was 39.6% (36 deaths). The univariate analysis identified the following variables as predictors of MDR GNB-related mortality: lung focus (P = 0.001),nosocomial origin (P = 0.002), graft from donation after cardiac death or deceased donors (P = 0.023), presence of other concomitant bloodstream infection (P < 0.001), temperature of 40 °C or greater at the onset of MDR GNB (P = 0.039), creatinine > 1.5 mg/dl (P = 0.006), albumin < 30 g/L (P = 0.009), platelet count < 50,000/mm3 (P < 0.001), and septic shock (P < 0.001). In the multivariate logistic regression analysis, septic shock (odds ratio (OR) = 160.463, 95% confidence interval (CI) = 19.377–1328.832, P < .001), as well as creatinine > 1.5 mg/dl (OR = 24.498, 95% CI = 3.449–173.998, P = 0.001), nosocomial origin (OR = 23.963, 95% CI = 1.285–46.991, P = 0.033), and presence of other concomitant bloodstream infections (OR = 27.074, 95% CI = 3.937–186.210, P = 0.001) were the variables associated with MDR GNB-related 30-day mortality.ConclusionsMDR GNB was associated with high morbidity and mortality in ASOT recipients, with a predominant causative organisms being E.coli and A.baumanii. Nosocomial origin, as well as presence of other concomitant bloodstream infections, increased creatinine level and septic shock were the main predictors of MDR GNB-related 30-day mortality.
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