SOD mineralized zeolitic imidazole framework-8 for the treatment of chemotherapy-related acute kidney injury.

Acute kidney injury (AKI), a prevalent and fatal adverse event, seriously affects cancer patients undergoing chemotherapy. The most important pathological mechanism of AKI is oxidative stress from reactive oxygen species (ROS). Currently, ROS scavenging is a promising strategy to manage the risk of chemotherapy-induced AKI. Herein, we successfully synthesized SOD@ZIF-8 nanoparticles by biomimetic mineralization, which were taken up by cells and could improve cell viability by limiting oxidative stress damage, as found in in vitro studies. Moreover, SOD@ZIF-8 nanoparticles exhibit broad-spectrum antioxidant properties in addition to significant renal accumulation in AKI mice, preventing clinically related cisplatin-induced AKI in murine models. AKI alleviation in the model was validated by measuring blood serum, staining kidney tissue, and related biomarkers. SOD@ZIF-8 nanoparticle therapeutic efficiency exceeds NAC, a small molecular antioxidant functioning through free radical scavenging. The results suggest SOD@ZIF-8 nanoparticles as a potential therapeutic option for AKI and other ROS-related disorders.

Acute glycemic variability and risk of mortality in patients with sepsis: a meta-analysis.

BACKGROUND: Acute glycemic variability (GV) has been correlated with the severity of sepsis. The aim of the study was to evaluate the potential association between acute GV and mortality risk in patients with sepsis. METHODS: Cohort studies comparing the risk of death within 3 months between septic patients with higher versus lower acute GV were retrieved by systematic search of Medline, Embase, Web of Science, Wanfang and CNKI databases. We used a random-effect model to pool the data by incorporating the between-study heterogeneity. Sensitivity analyses were performed to evaluate the stability of the findings. RESULTS: Ten studies including 4296 patients were available for the meta-analysis. Pooled results showed that septic patients with higher acute GV had significantly increased mortality risk compared to those with lower acute GV, as evidenced by results using different parameters including standard deviation of blood glucose (SDBG, risk ratio [RR]: 1.74, 95% confidence interval [CI] 1.36-2.24, p < 0.001; I2 = 0%), coefficient of variation of blood glucose (RR: 1.91, 95% CI 1.57-2.31, p < 0.001; I2 = 0%), mean amplitude of glycemic excursion (RR: 1.81. 95% CI 1.36-2.40, p < 0.001; I2 = 0%), and glycemic lability index (RR: 2.52, 95% CI 1.72-3.68, p < 0.001; I2 = 0%). Sensitivity analyses by excluding one study at a time did not significantly affect the results (p all < 0.05). CONCLUSIONS: Higher acute GV may be a predictor of mortality risk in patients with sepsis.

Carotid intraplaque neovascularisation as a predictive factor for future vascular events in patients with mild and moderate carotid stenosis: an observational prospective study.

BACKGROUND: Intraplaque neovascularisation (IPN) increases the vulnerability of plaques, which makes them more likely to rupture and increases the risk of vascular events. However, it is unclear whether IPN can predict future vascular events (stroke recurrence and cardiovascular events). Previous studies on IPN have focused on patients with severe stenosis but overlooked patients with mild and moderate stenosis. This study aimed to investigate whether IPN assessed by contrast-enhanced ultrasonography (CEUS) in patients with mild and moderate degrees of stenosis is associated with future vascular events. METHODS: One hundred and twenty-one patients participated in this study. 76 patients who met the inclusion and exclusion criteria were included in the final dataset of the study. IPN was graded from 0 to 2 according to the extent of the microbubbles assessed using CEUS. The degree of carotid stenosis was graded as mild, moderate, or severe. We recorded future vascular events during the follow-up. Univariate and multivariate logistic regression analyses were used to evaluate risk factors for future vascular events. RESULTS: After a follow-up period of 30 ± 6 months, 30 patients (39.5%) experienced subsequent vascular events. Compared with the 'non-recurrent' group, the 'recurrent' group showed a higher proportion of grade 2 neovascularisation (p < 0.05), and it was an independent predictor of subsequent vascular events (odds ratio 6.066, 95% confidence interval 1.565-23.512, p < 0.05). Furthermore, in patients with mild and moderate stenosis, future vascular events occurred in an unexpectedly high proportion (up to 42.9%). In the 'recurrent' group, 55% of patients with mild and moderate stenosis had grade 2 neovascularisation. CONCLUSION: IPN by CEUS was an independent predictor of future vascular events in patients with recent ischemic stroke, and the high proportion of neovascularisation in patients with mild and moderate stenosis requires more attention.

Proton pump inhibitor use and mortality in patients with cirrhosis: a meta-analysis of cohort studies.

BACKGROUND: Proton pump inhibitor (PPI) is commonly used in patients with cirrhosis. However, some studies demonstrated that PPI use was associated with adverse outcome in patients with cirrhosis. We aimed to perform a meta-analysis of cohort studies to evaluate the association between PPI use and mortality in cirrhotic patients. METHODS: Relevant studies were obtained via search of PubMed and Embase databases. A randomized-effect model was used to pool the results. Subgroup analyses were performed to evaluate the source of heterogeneity. RESULTS: Overall, 21 cohort studies with 20,899 patients and 7457 death events were included. The pooled results with a randomized-effect model showed that PPI use was associated with significantly increased risk of mortality in patients with cirrhosis (adjusted relative risk [RR] = RR: 1.39, P<0.001) with considerable heterogeneity (I2=73%). Subgroup analyses showed that characteristics such as patient ethnicity, sample size, definition of PPI use, and complications of patients did not affect the association. However, the association between PPI use and mortality was independent of study characteristics including patient ethnicity, sample size, complications, definition of PPI use, and follow-up duration. However, the association between PPI use and mortality in cirrhotic patients was significant in retrospective studies (RR: 1.40, P<0.001), but not in prospective studies (RR: 1.34, P=0.33). CONCLUSIONS: PPI use may be associated with moderately increased mortality in cirrhotic patients. Although prospective cohort studies are needed to validate our findings, PPI should only prescribed to cirrhotic patients with indications for the treatment.

Efficacy of anti-VEGF agents in the treatment of elderly hepatocellular carcinoma: a systematic review.

PURPOSE: We aimed to investigate the role of anti-vascular endothelial growth factor (VEGF) agents, including tyrosine-kinase inhibitors or monoclonal anti-bodies, in the treatment of elderly hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up to March 31, 2017 were searched to identify relevant studies. The endpoints were overall survival (OS) and progression-free survival (PFS). Data were examined using age cutoffs of 65 years. RESULTS: A total of 1,309 elderly (aged ≥ 65 years) HCC patients from seven trials were included for analysis. Our results demonstrated that the use of anti-VEGF agents MTAs in patients aged ≥ 65 years significantly improved PFS (HR 0.65, 95% CI: 0.55-0.76, p < 0.001) but not for OS (HR 0.87, 95% CI: 0.73-1.05, p = 0.15). Sub-group analysis according to treatment line showed that the use of anti-VEGF agents as second-line treatment significantly improved PFS (HR 0.55, 95% CI: 0.45-0.67, p < 0.001) and marginally improved OS (HR 0.83, 95% CI: 0.68-1.01, p = 0.061). Additionally, no survival benefits were observed in elderly HCC received first-line anti-VEGF treatments in terms of PFS (HR 0.87, 95% CI: 0.67-1.13, p = 0.29) and OS (HR 1.19, 95% CI: 0.74-1.36, p = 0.47). No publication bias was detected by Begg's and Egger's tests for OS. CONCLUSIONS: The findings of this study show that elderly HCC patients who relapsed after a first-line sorafenib treatment obtains a survival benefits from anti-VEGF agents rechallenge. Further studies are recommended to search for predictors of good responders in these patients received anti-VEGF agents.

Microsatellite instability in gastric cancer and pre-cancerous lesions.

AIM: To investigate the microsatellite instability (MSI) in cancer and pre-cancerous lesions of the stomach and its mechanisms underlying the development of gastric cancer. METHODS: Thirty-six gastric cancer samples were obtained from patients undergoing surgery. Forty-one gastric mucosa samples with dysplasia and 51 with intestinal metaplasia (IM) were obtained from patients with chronic gastritis undergoing gastro-endoscopy. Genomic DNA was extracted from the samples. Silver staining single strand conformation polymorphis-polymerize chain reaction (SSCP-PCR) was used to screen MSI markers at 5 loci (Bat-25, Bat-26, D5S346, D17S250, and D2S123) in fresh tissues and formalin-fixed, paraffin-embedded samples and their corresponding normal gastric mucosa. RESULTS: The abnormal shifting of the single-strand DNA (MSI) was identified in 21 out of 36 (58.3%) gastric cancers. Seven cases showed high-level MSI (two or more loci altered) and 14 showed low-level MSI (one locus altered). Gastric cancer with MSI had a tendency to be located in the distal stomach. MSI was also detected in 11 out of 41 (26.8%) dysplasia samples and in 9 of 51 (17.6%) IM samples respectively. Three cases of dysplasia and one case of IM showed high-level MSI. Eight cases of dysplasia and 8 cases of IM displayed low-level MSI. MIS in IM was found only in moderate or severe-grade IM. No association was detected between MSI and dysplasia grade. CONCLUSION: Accumulation of MSI in dysplasia and intestinal metaplasia of gastric mucosa may be an early molecular event during gastric carcinogenesis and may contribute to the acquisition of transformed cell phenotype and the development of gastric cancer.