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Author Meng, X.; Liu, S.; Duan, J.; Huang, X.; Zhou, P.; Xiong, X.; Gong, R.; Zhang, Y.; Liu, Y.; Fu, C.; Li, C.; Wu, A. url  doi
openurl 
  Title Risk factors and medical costs for healthcare-associated carbapenem-resistant Escherichia coli infection among hospitalized patients in a Chinese teaching hospital Type Journal Article
  Year 2017 Publication BMC Infectious Diseases Abbreviated Journal BMC Infect Dis  
  Volume 17 Issue 1 Pages 82  
  Keywords Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents/economics/therapeutic use; Anti-Infective Agents; *Carbapenems; Case-Control Studies; Catheterization, Central Venous/statistics & numerical data; Child; Child, Preschool; China/epidemiology; Cross Infection/drug therapy/economics/*epidemiology/microbiology; Drug Costs; *Drug Resistance, Bacterial; Escherichia coli Infections/drug therapy/economics/*epidemiology/microbiology; Female; Health Care Costs; Hemoglobins; Hospitals, Teaching; Humans; Hyperglycemia/epidemiology; Incidence; Infant; Infant, Newborn; Length of Stay/*statistics & numerical data; Logistic Models; Male; Middle Aged; Multivariate Analysis; Retrospective Studies; Risk Factors; Tertiary Care Centers; Tracheostomy/statistics & numerical data; Urologic Diseases/epidemiology; Young Adult; Crec; Csec; Healthcare-associated infection; Risk factors  
  Abstract BACKGROUND: The emergence and spread of Carbapenem-resistant Escherichia coli (CREC) is becoming a serious problem in Chinese hospitals, however, the data on this is scarce. Therefore, we investigate the risk factors for healthcare-associated CREC infection and study the incidence, antibiotic resistance and medical costs of CREC infections in our hospital. METHODS: We conducted a retrospective, matched case-control-control, parallel study in a tertiary teaching hospital. Patients admitted between January 2012 and December 2015 were included in this study. For patients with healthcare-associated CREC infection, two matched subject groups were created; one group with healthcare-associated CSEC infection and the other group without infection. RESULTS: Multivariate conditional logistic regression analysis demonstrated that prior hospital stay (<6 months) (OR:3.96; 95%CI:1.26-12.42), tracheostomy (OR:2.24; 95%CI: 1.14-4.38), central venous catheter insertion (OR: 8.15; 95%CI: 2.31-28.72), carbapenem exposure (OR: 12.02; 95%CI: 1.52-95.4), urinary system disease (OR: 16.69; 95%CI: 3.01-89.76), low hemoglobin (OR: 2.83; 95%CI: 1.46-5.50), and high blood glucose are associated (OR: 7.01; 95%CI: 1.89-26.02) with CREC infection. Total costs (p = 0.00), medical examination costs (p = 0.00), medical test costs (p = 0.00), total drug costs (p = 0.00) and ant-infective drug costs (p = 0.00) for the CREC group were significantly higher than those for the no infection group. Medical examination costs (p = 0.03), total drug costs (p = 0.03), and anti-infective drug costs (p = 0.01) for the CREC group were significantly higher than for the CSEC group. Mortality in CREC group was significantly higher than the CSEC group (p = 0.01) and no infection group (p = 0.01). CONCLUSION: Many factors were discovered for acquisition of healthcare-associated CREC infection. CREC isolates were resistant to most antibiotics, and had some association with high financial burden and increased mortality.  
  Address (up) Infection Control Centre, Xiangya Hospital of Central South University, Changsha, China. xywuanhua@csu.edu.cn  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1471-2334 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28095785 Approved no  
  Call Number ref @ user @ Serial 99123  
Permanent link to this record
 

 
Author Meng, X.; Liu, S.; Duan, J.; Huang, X.; Zhou, P.; Xiong, X.; Gong, R.; Zhang, Y.; Liu, Y.; Fu, C.; Li, C.; Wu, A. url  doi
openurl 
  Title Risk factors and medical costs for healthcare-associated carbapenem-resistant Escherichia coli infection among hospitalized patients in a Chinese teaching hospital Type Journal Article
  Year 2017 Publication BMC Infectious Diseases Abbreviated Journal BMC Infect Dis  
  Volume 17 Issue 1 Pages 82  
  Keywords Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents/economics/therapeutic use; Anti-Infective Agents; *Carbapenems; Case-Control Studies; Catheterization, Central Venous/statistics & numerical data; Child; Child, Preschool; China/epidemiology; Cross Infection/drug therapy/economics/*epidemiology/microbiology; Drug Costs; *Drug Resistance, Bacterial; Escherichia coli Infections/drug therapy/economics/*epidemiology/microbiology; Female; Health Care Costs; Hemoglobins; Hospitals, Teaching; Humans; Hyperglycemia/epidemiology; Incidence; Infant; Infant, Newborn; Length of Stay/*statistics & numerical data; Logistic Models; Male; Middle Aged; Multivariate Analysis; Retrospective Studies; Risk Factors; Tertiary Care Centers; Tracheostomy/statistics & numerical data; Urologic Diseases/epidemiology; Young Adult; Crec; Csec; Healthcare-associated infection; Risk factors  
  Abstract BACKGROUND: The emergence and spread of Carbapenem-resistant Escherichia coli (CREC) is becoming a serious problem in Chinese hospitals, however, the data on this is scarce. Therefore, we investigate the risk factors for healthcare-associated CREC infection and study the incidence, antibiotic resistance and medical costs of CREC infections in our hospital. METHODS: We conducted a retrospective, matched case-control-control, parallel study in a tertiary teaching hospital. Patients admitted between January 2012 and December 2015 were included in this study. For patients with healthcare-associated CREC infection, two matched subject groups were created; one group with healthcare-associated CSEC infection and the other group without infection. RESULTS: Multivariate conditional logistic regression analysis demonstrated that prior hospital stay (<6 months) (OR:3.96; 95%CI:1.26-12.42), tracheostomy (OR:2.24; 95%CI: 1.14-4.38), central venous catheter insertion (OR: 8.15; 95%CI: 2.31-28.72), carbapenem exposure (OR: 12.02; 95%CI: 1.52-95.4), urinary system disease (OR: 16.69; 95%CI: 3.01-89.76), low hemoglobin (OR: 2.83; 95%CI: 1.46-5.50), and high blood glucose are associated (OR: 7.01; 95%CI: 1.89-26.02) with CREC infection. Total costs (p = 0.00), medical examination costs (p = 0.00), medical test costs (p = 0.00), total drug costs (p = 0.00) and ant-infective drug costs (p = 0.00) for the CREC group were significantly higher than those for the no infection group. Medical examination costs (p = 0.03), total drug costs (p = 0.03), and anti-infective drug costs (p = 0.01) for the CREC group were significantly higher than for the CSEC group. Mortality in CREC group was significantly higher than the CSEC group (p = 0.01) and no infection group (p = 0.01). CONCLUSION: Many factors were discovered for acquisition of healthcare-associated CREC infection. CREC isolates were resistant to most antibiotics, and had some association with high financial burden and increased mortality.  
  Address (up) Infection Control Centre, Xiangya Hospital of Central South University, Changsha, China. xywuanhua@csu.edu.cn  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1471-2334 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28095785 Approved no  
  Call Number ref @ user @ Serial 100153  
Permanent link to this record
 

 
Author Khalifa, J.; Tensaouti, F.; Lusque, A.; Plas, B.; Lotterie, J.-A.; Benouaich-Amiel, A.; Uro-Coste, E.; Lubrano, V.; Cohen-Jonathan Moyal, E. url  doi
openurl 
  Title Subventricular zones: new key targets for glioblastoma treatment Type Journal Article
  Year 2017 Publication Radiation Oncology (London, England) Abbreviated Journal Radiat Oncol  
  Volume 12 Issue 1 Pages 67  
  Keywords Glioblastoma; Prognostic factors; Radiotherapy; Stem-cell niche; Subventricular Zone  
  Abstract BACKGROUND: We aimed to identify subventricular zone (SVZ)-related prognostic factors of survival and patterns of recurrence among patients with glioblastoma. METHODS: Forty-three patients with primary diagnosed glioblastoma treated in our Cancer Center between 2006 and 2010 were identified. All patients received surgical resection, followed by temozolomide-based chemoradiation. Ipsilateral (iSVZ), contralateral (cSVZ) and bilateral (bSVZ) SVZs were retrospectively segmented and radiation dose-volume histograms were generated. Multivariate analysis using the Cox proportional hazards model was assessed to examine the relationship between prognostic factors and time to progression (TTP) or overall survival (OS). RESULTS: Median age was 59 years (range: 25-85). Median follow-up, OS and TTP were 22.7 months (range 7.5-69.7 months), 22.7 months (95% CI 14.5-26.2 months) and 6.4 months (95% CI 4.4-9.3 months), respectively. On univariate analysis, initial contact to SVZ was a poor prognostic factor for OS (18.7 vs 41.7 months, p = 0.014) and TTP (4.6 vs 12.9 months, p = 0.002). Patients whose bSVZ volume receiving at least 20 Gy (V20Gy) was greater than 84% had a significantly improved TTP (17.7 months vs 5.2 months, p = 0.017). This radiation dose coverage was compatible with an hippocampal sparing. On multivariate analysis, initial contact to SVZ and V20 Gy to bSVZ lesser than 84% remained poor prognostic factors for TTP (HR = 3.07, p = 0.012 and HR = 2.67, p = 0.047, respectively). CONCLUSION: Our results suggest that contact to SVZ, as well as insufficient bSVZ radiation dose coverage (V20Gy <84%), might be independent poor prognostic factors for TTP. Therefore, targeting SVZ could be of crucial interest for optimizing glioblastoma treatment.  
  Address (up) INSERM U1037, Centre de Recherche contre le Cancer de Toulouse, 1 avenue Irene Joliot-Curie, Toulouse Cedex, 31059, France  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1748-717X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28424082 Approved no  
  Call Number ref @ user @ Serial 96593  
Permanent link to this record
 

 
Author Munthe, S.; Halle, B.; Boldt, H.B.; Christiansen, H.; Schmidt, S.; Kaimal, V.; Xu, J.; Zabludoff, S.; Mollenhauer, J.; Poulsen, F.R.; Kristensen, B.W. url  doi
openurl 
  Title Shift of microRNA profile upon glioma cell migration using patient-derived spheroids and serum-free conditions Type Journal Article
  Year 2017 Publication Journal of Neuro-Oncology Abbreviated Journal J Neurooncol  
  Volume 132 Issue 1 Pages 45-54  
  Keywords Glioblastoma; MicroRNA; Migration; Serum-free; Target  
  Abstract Glioblastoma multiforme (GBM) is the most frequent malignant primary brain tumor. A major reason for the overall median survival being only 14.6 months is migrating tumor cells left behind after surgery. Another major reason is tumor cells having a so-called cancer stem cell phenotype being therefore resistant towards traditional chemo- and radiotherapy. A group of novel molecular targets are microRNAs (miRNAs). MiRNAs are small non-coding RNAs exerting post-transcriptional regulation of gene expression. The aim of this study was to identify differentially expressed miRNAs in migrating GBM cells using serum-free stem cell conditions. We used patient-derived GBM spheroid cultures for a novel serum-free migration assay. MiRNA expression of migrating tumor cells isolated at maximum migration speed was compared with corresponding spheroids using an OpenArray Real-Time PCR System. The miRNA profiling revealed 30 miRNAs to be differentially expressed. In total 13 miRNAs were upregulated and 17 downregulated in migrating cells compared to corresponding spheroids. The three most deregulated miRNAs, miR-1227 (up-regulated), miR-32 (down-regulated) and miR-222 (down-regulated), were experimentally overexpressed. A non-significantly increased migration rate was observed after miR-1227 overexpression. A significantly reduced migration rate was observed after miR-32 and miR-222 overexpression. In conclusion a shift in microRNA profile upon glioma cell migration was identified using an assay avoiding serum-induced migration. Both the miRNA profiling and the functional validation suggested that miR-1227 may be associated with increased migration and miR-32 and miR-222 with decreased migration. These miRNAs may represent potential novel targets in migrating glioma cells.  
  Address (up) Institute of Clinical Research, University of Southern Denmark, Winslowparken 19, 5000, Odense C, Denmark. bjarne.winther.kristensen@rsyd.dk  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0167-594X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28091986 Approved no  
  Call Number ref @ user @ Serial 96611  
Permanent link to this record
 

 
Author Jensen, S.S.; Petterson, S.A.; Halle, B.; Aaberg-Jessen, C.; Kristensen, B.W. url  doi
openurl 
  Title Effects of the lysosomal destabilizing drug siramesine on glioblastoma in vitro and in vivo Type Journal Article
  Year 2017 Publication BMC Cancer Abbreviated Journal BMC Cancer  
  Volume 17 Issue 1 Pages 178  
  Keywords Brain slice cultures; Cancer stem cell; Glioblastoma; Lysosomes; Siramesine; Spheroids  
  Abstract BACKGROUND: Glioblastoma is the most frequent and most malignant brain tumor with the patients having a median survival of only 14.6 months. Although glioblastoma patients are treated with surgery, radiation and chemotherapy recurrence is inevitable. A stem-like population of radio- and chemoresistant brain tumor-initiating cells combined with the invasive properties of the tumors is believed to be critical for treatment resistance. In the present study, the aim was to investigate the effect of a novel therapeutic strategy using the lysosomotropic detergent siramesine on glioblastomas. METHODS: Standard glioma cell lines and patient-derived spheroids cultures with tumor-initiating stem-like cells were used to investigate effects of siramesine on proliferation and cell death. Responsible mechanisms were investigated by inhibitors of caspases and cathepsins. Effects of siramesine on migrating tumor cells were investigated by a flat surface migration assay and by implanting spheroids into organotypic rat brain slice cultures followed by confocal time-lapse imaging. Finally the effect of siramesine was investigated in an orthotopic mouse glioblastoma model. Results obtained in vitro and in vivo were confirmed by immunohistochemical staining of histological sections of spheroids, spheroids in brain slice cultures and tumors in mice brains. RESULTS: The results showed that siramesine killed standard glioma cell lines in vitro, and loss of acridine orange staining suggested a compromised lysosomal membrane. Co-treatment of the cell lines with inhibitors of caspases and cathepsins suggested differential involvement in cell death. Siramesine caused tumor cell death and reduced secondary spheroid formation of patient-derived spheroid cultures. In the flat surface migration model siramesine caused tumor cell death and inhibited tumor cell migration. This could not be reproduced in the organotypic three dimensional spheroid-brain slice culture model or in the mice xenograft model. CONCLUSIONS: In conclusion the in vitro results obtained with tumor cells and spheroids suggest a potential of lysosomal destabilizing drugs in killing glioblastoma cells, but siramesine was without effect in the organotypic spheroid-brain slice culture model and the in vivo xenograft model.  
  Address (up) Institute of Clinical Research, University of Southern Denmark, Winslowparken 19.3, 5000, Odense C, Denmark. bjarne.winther.kristensen@rsyd.dk  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1471-2407 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28270132 Approved no  
  Call Number ref @ user @ Serial 96603  
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