Carbapenem-Resistant Enterobacteriaceae in Children,United States, 1999–2012

The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) infections is increasing in the United States. However, few studies have addressed their epidemiology in children. To phenotypically identify CRE isolates cultured from patients 1–17 years of age, we used antimicrobial susceptibilities of Enterobacteriaceae reported to 300 laboratories participating in The Surveillance Network–USA database during January 1999–July 2012. Of 316,253 isolates analyzed, 266 (0.08%) were identified as CRE. CRE infection rate increases were highest for Enterobacter species, blood culture isolates, and isolates from intensive care units, increasing from 0.0% in 1999–2000 to 5.2%, 4.5%, and 3.2%, respectively, in 2011–2012. CRE occurrence in children is increasing but remains low and is less common than that for extended-spectrum β-lactamase–producing Enterobacteriaceae. The molecular characterization of CRE isolates from children and clinical epidemiology of infection are essential for development of effective prevention strategies.     

Clinicopathological features and prognostic analysis of metastatic pulmonary sarcomatoid carcinoma: a SEER analysis

BackgroundPulmonary sarcomatoid carcinoma (PSC) is a rare type of non-small cell lung cancer (NSCLC). Metastases are often detected at the first diagnosis. Despite high rates of distant metastasis, there is insufficient data describing the characteristics of PSC metastasis.MethodsWe performed a Surveillance, Epidemiology, and End Results (SEER) database-based analysis of clinicopathological features and prognosis of distant metastasis in PSC patients. Data queried for this analysis included PSC patients in the database between 2010 and 2016.ResultsA total of 934 patients met the criteria for inclusion in the analysis and included, at the time of diagnosis, 512 (54.8%) patients with metastasis, including bone (n=152; 16.3%), brain (n=108; 11.6%), liver (n=70; 7.5%), lung (n=142; 15.2%) metastases. Binary logistic regression showed that patients with giant cell carcinoma [odds ratio (OR) 4.023, 95% confidence interval (CI): 2.113–7.661, P<0.001] and spindle cell carcinoma (OR 3.151, 95% CI: 1.699–5.843, P<0.001) were associated with metastasis. Log-rank test and Kaplan-Meier plots indicated poor prognosis in metastatic patients [the 1-, 3-, and 5-year overall survival (OS) rates were 14.1%, 5.5%, and 4.8%, respectively]. Multivariable analysis showed younger and chemotherapy as improved prognostic factors of PSC patients with single metastasis site.ConclusionsThe SEER database-based analysis revealed the clinical features of distant metastasis of PSC and showed that different histological types posed distinct metastasis potential. Besides, age and chemotherapy were the independent prognostic factors of PSC patients with single metastasis site.     

医院门诊智能寻呼排队系统的构建

为营造公平、合理、有效的门诊就诊环境，建立精确候诊就医通道，通过中国移动集团寻呼功能，结合医院信息系统（HIS），建立了医院门诊智能寻呼排队系统。该系统利用就诊业务流程实现了医院门诊管理的实时、快捷和通畅，提高了服务效率，提升了医院良好的窗口服务形象。     

Hepatotoxicity reports in the FDA adverse event reporting system database: A comparison of drugs that cause injury via mitochondrial or other mechanisms

Drug-induced liver injury (DILI) is a leading reason for preclinical safety attrition and post-market drug withdrawals. Drug-induced mitochondrial toxicity has been shown to play an essential role in various forms of DILI, especially in idiosyncratic liver injury. This study examined liver injury reports submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) for drugs associated with hepatotoxicity via mitochondrial mechanisms compared with non-mitochondrial mechanisms of toxicity. The frequency of hepatotoxicity was determined at a group level and individual drug level. A reporting odds ratio (ROR) was calculated as the measure of effect. Between the two DILI groups, reports for DILI involving mitochondrial mechanisms of toxicity had a 1.43 (95% CI 1.42–1.45; P < 0.0001) times higher odds compared to drugs associated with non-mitochondrial mechanisms of toxicity. Antineoplastic, antiviral, analgesic, antibiotic, and antimycobacterial drugs were the top five drug classes with the highest ROR values. Although the top 20 drugs with the highest ROR values included drugs with both mitochondrial and non-mitochondrial injury mechanisms, the top four drugs (ROR values > 18: benzbromarone, troglitazone, isoniazid, rifampin) were associated with mitochondrial mechanisms of toxicity. The major demographic influence for DILI risk was also examined. There was a higher mean patient age among reports for drugs that were associated with mitochondrial mechanisms of toxicity [56.1 ± 18.33 (SD)] compared to non-mitochondrial mechanisms [48 ± 19.53 (SD)] (P < 0.0001), suggesting that age may play a role in susceptibility to DILI via mitochondrial mechanisms of toxicity. Univariate logistic regression analysis showed that reports of liver injury were 2.2 (odds ratio: 2.2, 95% CI 2.12–2.26) times more likely to be associated with older patient age, as compared with reports involving patients less than 65 years of age. Compared to males, female patients were 37% less likely (odds ratio: 0.63, 95% CI 0.61–0.64) to be subjects of liver injury reports for drugs associated with mitochondrial toxicity mechanisms. Given the higher proportion of severe liver injury reports among drugs associated with mitochondrial mechanisms of toxicity, it is essential to understand if a drug causes mitochondrial toxicity during preclinical drug development when drug design alternatives, more clinically relevant animal models, and better clinical biomarkers may provide a better translation of drug-induced mitochondrial toxicity risk assessment from animals to humans. Our findings from this study align with mitochondrial mechanisms of toxicity being an important cause of DILI, and this should be further investigated in real-world studies with robust designs.     

Identification of potential drugs for diffuse large b-cell lymphoma based on bioinformatics and Connectivity Map database

Diffuse large B-cell lymphoma (DLBCL) is the most main subtype in non-Hodgkin lymphoma. After chemotherapy, about 30% of patients with DLBCL develop resistance and relapse. This study was to identify potential therapeutic drugs for DLBCL using the bioinformatics method. The differentially expressed genes (DEGs) between DLBCL and non-cancer samples were downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were analyzed using the Database for Annotation, Visualization, and Integrated Discovery. The R software package (SubpathwayMiner) was used to perform pathway analysis on DEGs affected by drugs found in the Connectivity Map (CMap) database. Protein–protein interaction (PPI) networks of DEGs were constructed using the Search Tool for the Retrieval of Interacting Genes online database and Cytoscape software. In order to identify potential novel drugs for DLBCL, the DLBCL-related pathways and drug-affected pathways were integrated. The results showed that 1927 DEGs were identified from TCGA and GEO. We found 54 significant pathways of DLBCL using KEGG pathway analysis. By integrating pathways, we identified five overlapping pathways and 47 drugs that affected these pathways. The PPI network analysis results showed that the CDK2 is closely associated with three overlapping pathways (cell cycle, p53 signaling pathway, and small cell lung cancer). The further literature verification results showed that etoposide, rinotecan, methotrexate, resveratrol, and irinotecan have been used as classic clinical drugs for DLBCL. Anisomycin, naproxen, gossypol, vorinostat, emetine, mycophenolic acid and daunorubicin also act on DLBCL. It was found through bioinformatics analysis that paclitaxel in the drug-pathway network can be used as a potential novel drug for DLBCL.     

Australia

In the context of Australia's land, people, and turbulent social history, this article explores the Australian health care system, the health issues of Aboriginals, and the role of the social worker in health care.     

Lipidomics investigation of reversal effect of glycyrrhizin (GL) towards lithocholic acid (LCA)-induced alteration of phospholipid profiles

Context: Glycyrrhizin (GL), the major ingredient isolated from licorice, exerts multiple pharmacological activities.

Objective: To elucidate the protective mechanism of GL towards lithocholic acid (LCA)-induced liver toxicity using lipidomics.

Materials and methods: GL (200?mg/kg) dissolved in corn oil was treated intraperitoneally for 7?d. On the 4th day, 200?mg/kg LCA was used to treat mice (i.p., twice daily) for another 4?d. The protective role of GL towards LCA-induced liver toxicity was investigated through evaluating the liver histology and the activity of alanine transaminase (ALT). The complete lipid profile was employed using UFLC-Triple TOF MS-based lipidomics.

Results: Intraperitoneal (i.p.) administration of 200?mg/kg GL can significantly protect LCA-induced liver damage, indicated by alleviated histology alteration and prevention of the ALT elevation. Lipidomics analysis can well separate the control group from LCA-treated group, and three lipid components were major contributors, including LPC 16:0, LPC 18:0, and LPC 18:2. GL treatment can significantly prevent LCA-induced reduction of these three lipid compounds, providing a new explanation for GL's protection mechanism towards LCA-induced liver toxicity.

Discussion and conclusion: The recent study highlights the importance of lipidomics in elucidating the therapeutic mechanism of herbs.