[Impact of extended-spectrum ß-lactamase on clinical outcome and medical cost in patients with bloodstream infection due to Klebsiella pneumoniae].

OBJECTIVE: To evaluate the impact of extended-spectrum ß-lactamase (ESBL) on clinical outcome and medical cost in patients with bloodstream infection (BSI) due to Klebsiella pneumoniae. METHODS: A retrospective study was conducted in patients admitted into Changhai Hospital between January 2013 and December 2014, who suffered from BSI due to Klebsiella pneumoniae during hospitalization. Patients were divided into two groups according to whether Klebsiella pneumoniae produced ESBL (ESBL positive group and ESBL negative group). They were matched with propensity score matching method in a 1∶1 ratio and then multiple regression model was used to analyze the impact of ESBL on clinical outcome and medical cost. Clinical outcome was evaluated by 30-day mortality post BSI; medical cost was evaluated by total length of stay (LOS), post-BSI LOS, total hospital cost and antimicrobial cost. RESULTS: Before matching, the two groups were significantly different in age, nosocomial infection rate, LOS before BSI and surgical rate during hospitalization (all P<0.05). The ESBL-positive group had higher 30-day mortality post BSI (21.3% vs 8.7%, P=0.054), and higher total LOS [25.0(12.0, 33.0) vs 16.0(10.0, 23.0) d, P=0.015], post-BSI LOS [16.0(9.0, 26.0) vs 10.0(5.0, 16.0) d, P=0.006], total hospital cost [69 409(40 605, 198 021) vs 45 683(28 448, 67 000) ï¿¥, P<0.001] and antimicrobial cost [10 279(4 815, 25 500) vs 3 783(1 596, 11 879) ï¿¥, P<0.001]. After matching, the two groups had no significant differences in clinical characteristics such as sex, age, nosocomial infection rate, LOS before BSI, APACHEⅡ score, Charlson Comorbidity Index, underlying diseases and surgical rate during hospitalization (all P>0.05). Multiple regression analysis indicated that ESBL could significantly increase the total LOS, post-BSI LOS, total hospital cost and antimicrobial cost (all P<0.001), but did not increase the 30-day mortality post BSI (P=0.910). CONCLUSIONS: ESBL can significantly increase the medical cost in patients with BSI due to Klebsiella pneumoniae but does not increase the 30-day mortality post BSI.

[Empirical therapy of bloodstream infections caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae].

OBJECTIVE: To compare the clinical outcomes and costs associated with carbapenems and ß-lactam/ß-lactamase inhibitor combinations (BLBLIs) for the empirical treatment of patients with extended-spectrum ß-lactamase (ESBL)-positive Enterobacteriaceae bloodstream infections (BSIs). METHODS: The medical records of individuals diagnosed with ESBL-producing Escherichia coli and Klebsiella pneumoniae BSIs between January 2014 and June 2015 at Changhai Hospital were reviewed. Patients were divided into two groups based on the empirical therapy (carbapenems group and BLBLIs group). Propensity score matching in a 1∶1 ratio was used to match the patients from two groups. Clinical outcomes and costs were compared before and after matching. RESULTS: One hundred and fifty-eight patients were analyzed, 93 in the carbapenems group and 65 in the BLBLIs group. Before matching, the two groups were significantly different in department distribution, tumor rate, deep vein catheter rate, urinary catheter rate, nasogastric tube rate, and mechanical ventilation rate (all P<0.05), and the carbapenems group had longer total length of stay (LOS) and post-BSI LOS (26.0 vs 18.0 d, P=0.029 and 12.0 vs 10.0 d, P=0.044) , higher hospital cost and daily hospital cost (84 120 vs 39 000 ï¿¥, P<0.001 and 3 451 vs 2 574 ï¿¥, P=0.002). After matching, the two groups had no significant differences in covariates such as sex, age, department distribution, pathogens, comorbidities, invasive interventions, LOS before BSI, multiple admissions, surgical rate during hospitalization and delayed antimicrobial therapy (all P>0.05). Finally, there were no differences between two groups in mortality, post-BSI LOS, total LOS, hospital cost and antimicrobial cost (all P>0.05). CONCLUSION: BLBLIs may provide a reasonable carbapenem-sparing option for the empirical treatment of ESBL producers.

miR-499A>G rs3746444 and miR-146aG>C expression and hepatocellular carcinoma risk in the Chinese population.

We conducted a case-control study of a possible association of miR-499A>G rs3746444 and miR-146aG>C rs2910164 with risk of hepatocellular carcinoma. Samples from 172 hepatocellular carcinoma patients and 185 cancer-free controls were collected from October 2008 to December 2011. PCR-RFLP analysis was performed to determine the polymorphisms in each individual. The MAFs of miR-146aG>C and miR-499A>G in controls were similar to that known from the SNP database, and frequencies of genotypes in controls were in line with Hardy-Weinberg equilibrium. We found that miR-499 AG was significantly associated with decreased risk for hepatocellular carcinoma when compared with miR-499 AA genotype (adjusted odds ration = 0.74, 95% confidence interval = 0.24-0.96). However, subjects carrying miR-146a GG had a non-significant 0.62-fold decreased risk of hepatocellular carcinoma. We did not find a significant association of miR-146aG>C rs2910164 and miR-499A>G rs3746444 polymorphisms with hepatocellular carcinoma risk in the Chinese population. Further investigations are warranted to clarify the relationship between miRNA polymorphisms and susceptibility to hepatocellular carcinoma risk in various ethnic populations.

Quantitative proteomic study identified cathepsin B associated with doxorubicin-induced damage in H9c2 cardiomyocytes.

The study was performed to analyze the proteomic profiling of doxorubicin-treated H9c2 cardiomyocytes in order to identify novel protein biomarkers associated with doxorubicin-induced cardiomyopathy. The protein profiling of H9c2 cells in response to doxorubicin at an apoptosis-induced concentration of 0.5 µM were compared using iTRAQ analysis. Western-blot analysis was used to confirm differentially expressed proteins identified in the proteomic study. A total of 22 differently expressed proteins were identified in doxorubicin-treated H9c2 cells including 15 up-regulated and 7 down-regulated proteins. Gene Ontology (GO) analysis revealed that 10 altered proteins were enriched in the process of apoptosis. We further validated the expression of cathepsin B and its possible regulator nuclear factor kappa B (NF-κB) in H9c2 cells were increased during doxorubicin treatment using Western-blots. Differentially expressed proteins might provide clues to clarify novel mechanisms underlying doxorubicin-induced cardiomyopathy. Our results also suggest that increased cathepsin B expression might be associated with NF-κB up-regulation, and the exact mechanisms need to be clarified.

Expression of CD147 in advanced non-small cell lung cancer correlated with cisplatin-based chemotherapy resistance.

CD147, a widely expressed cell surface glycoprotein in cancer, is associated with tumor invasiveness and chemotherapy resistance. Recently, CD147 is also regarded as a potential therapeutic target for cancer therapy. The aim of the study was to investigate CD147 expression in non-small cell lung cancer (NSCLC), and evaluate its correlation with cisplatin-based chemotherapy resistance. In this study, we examined immunohistochemically the expression of CD147 in 118 advanced NSCLC cases treated with cisplatin-based chemotherapy, and then the association of CD147 expression with clinicopathological characteristics was analyzed. Furthermore, RNA interference approach was used to silence CD147 expression in a cisplatin-resistant human lung cancer cell line A549/DDP, and the inhibition effect of cisplatin on tumor cells was assayed by MTT. In the overall series, positive CD147 expression was observed in 101/118 (85.6%) cases. A membranous CD147 pattern was identified in 76/101 (75.2%) of CD147 positive tumors. CD147 membranous expression,but not the overall CD147 expression, was associated with poor response to cisplatin-based chemotherapies and a poor prognosis in advanced NSCLC patients. In vitro results showed that silencing CD147 increased the proliferation inhibitory effect of cisplatin to A549/DDP cells. In conclusion, our study indicated that membranous CD147 expression is a predictive factor of the response to cisplatin-based chemotherapies, and the use of CD147-targeted therapeutic adjuvants might be considered in the treatment of advanced NSCLC patients.