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Author Clark, P.A.; Gaal, J.T.; Strebe, J.K.; Pasch, C.A.; Deming, D.A.; Kuo, J.S.; Robins, H.I.
Title The effects of tumor treating fields and temozolomide in MGMT expressing and non-expressing patient-derived glioblastoma cells Type Journal Article
Year 2017 Publication Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia Abbreviated Journal J Clin Neurosci
Volume 36 Issue Pages 120-124
Keywords Antineoplastic Agents, Alkylating/*pharmacology; Cell Line, Tumor; Cell Proliferation/drug effects/radiation effects; Cell Survival/drug effects/radiation effects; Cells, Cultured; DNA Modification Methylases/genetics/*metabolism; DNA Repair Enzymes/genetics/*metabolism; Dacarbazine/*analogs & derivatives/pharmacology; *Electromagnetic Fields; Glioblastoma/genetics/*metabolism; Humans; Neoplastic Stem Cells/drug effects/radiation effects; Neurons/drug effects/radiation effects; Tumor Suppressor Proteins/genetics/*metabolism; Cancer stem cells; Glioblastoma; MGMT methylation; Temozolomide; Tumor treating fields
Abstract A recent Phase 3 study of newly diagnosed glioblastoma (GBM) demonstrated the addition of tumor treating fields (TTFields) to temozolomide (TMZ) after combined radiation/TMZ significantly increased survival and progression free survival. Preliminary data suggested benefit with both methylated and unmethylated O-6-methylguanine-DNA methyl-transferase (MGMT) promoter status. To date, however, there have been no studies to address the potential interactions of TTFields and TMZ. Thus, the effects of TTFields and TMZ were studied in vitro using patient-derived GBM stem-like cells (GSCs) including MGMT expressing (TMZ resistant: 12.1 and 22GSC) and non-MGMT expressing (TMZ sensitive: 33 and 114GSC) lines. Dose-response curves were constructed using cell proliferation and sphere-forming assays. Results demonstrated a 10-fold increase in TMZ resistance of MGMT-expressing (12.1GSCs: IC50=160muM; 22GSCs: IC50=44muM) compared to MGMT non-expressing (33GSCs: IC50=1.5muM; 114GSCs: IC50=5.2muM) lines. TTFields inhibited 12.1 GSC proliferation at all tested doses (50-500kHz) with an optimal frequency of 200kHz. At 200kHz, TTFields inhibited proliferation and tumor sphere formation of both MGMT GSC subtypes at comparable levels (12.1GSC: 74+/-2.9% and 38+/-3.2%, respectively; 22GSC: 61+/-11% and 38+/-2.6%, respectively; 33GSC: 56+/-9.5% and 60+/-7.1%, respectively; 114 GSC: 79+/-3.5% and 41+/-4.3%, respectively). In combination, TTFields (200kHz) and TMZ showed an additive anti-neoplastic effect with equal efficacy for TTFields in both cell types (i.e., +/- MGMT expression) with no effect on TMZ resistance. This is the first demonstration of the effects of TTFields on cancer stem cells. The expansion of such studies may have clinical implications.
Address (down) University of Wisconsin Carbone Cancer Center, UWSMPH, United States; Division of Hematology and Oncology, Department of Medicine, UWSMPH, United States; William S Middleton Memorial Veterans Hospital, Madison, WI, United States; Department of Neurology, UWSMPH, United States; Department of Human Oncology, UWSMPH, United States. Electronic address: hirobins@wisc.edu
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 0967-5868 ISBN Medium
Area Expedition Conference
Notes PMID:27865821 Approved no
Call Number ref @ user @ Serial 96622
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Author LaGrone, L.N.; Isquith-Dicker, L.N.; Huaman Egoavil, E.; Rodriguez Castro, M.J.A.; Allagual, A.; Revoredo, F.; Mock, C.N.
Title Surgeons' and Trauma Care Physicians' Perception of the Impact of the Globalization of Medical Education on Quality of Care in Lima, Peru Type Observational Study
Year 2017 Publication JAMA Surgery Abbreviated Journal JAMA Surg
Volume 152 Issue 3 Pages 251-256
Keywords *Attitude of Health Personnel; *Developing Countries; Education, Distance; *Education, Medical; Faculty, Medical/psychology; General Surgery/*education/standards; Humans; International Educational Exchange; Internationality; Internship and Residency; Interviews as Topic; Perception; Peru; Qualitative Research; *Quality of Health Care; Surgeons/*psychology; *Traumatology
Abstract Importance: The globalization of medical education-the process by which trainees in any region gain access to international training (electronic or in-person)-is a growing trend. More data are needed to inform next steps in the responsible stewardship of this process, from the perspective of trainees and institutions at all income levels, and for use by national and international policymakers. Objective: To describe the impact of the globalization of medical education on surgical care in Peru from the perspective of Peruvian surgeons who received international training. Design, Setting, and Participants: Observational study of qualitative interviews conducted from September 2015 to January 2016 using grounded theory qualitative research methods. The study was conducted at 10 large public institutions that provide most of the trauma care in Lima, Peru, and included urban resident and faculty surgery and trauma care physicians. Exposures: Access to international surgical rotations and medical information. Main Outcomes and Measures: Outcome measures defining the impact of globalization on surgical care were developed as part of simultaneous data collection and analysis during qualitative research as part of a larger project on trauma quality improvement practices in Peru. Results: Fifty qualitative interviews of surgeons and emergency medicine physicians were conducted at 10 hospitals, including multiple from the public and social security systems. A median of 4 interviews were conducted at each hospital, and fewer than 3 interviews were conducted at only 1 hospital. From the broader theme of globalization emerged subthemes of an eroded sense of agency and a perception of inadequate training on the adaptation of international standards as negative effects of globalization on surgical care in Peru. Access to research funds, provision of incentives for acquisition of advanced clinical training, increased expectations for patient outcomes, and education in quality improvement skills are ways in which globalization positively affected surgeons and their patients in Peru. Conclusions and Relevance: Short-term overseas training of surgeons from low- and middle-income countries may improve care in the surgeons' country of origin through the acquisition of skills and altered expectations for excellence. Prioritization of evidence-based medical education is necessary given widespread internet access and thus clinician exposure to variable quality medical information. Finally, the establishment of centers of excellence in low- and middle-income countries may address the eroded sense of agency attributable to globalization and offer a local example of world-class surgical outcomes, diminishing surgeons' most frequently cited reason for emigration: access to better surgical training.
Address (down) University of Washington, Seattle
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 2168-6254 ISBN Medium
Area Expedition Conference
Notes PMID:27893012 Approved no
Call Number ref @ user @ Serial 97649
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Author Ramirez-Blanco, C.E.; Ramirez-Rivero, C.E.; Diaz-Martinez, L.A.; Sosa-Avila, L.M.
Title Infection in burn patients in a referral center in Colombia Type Journal Article
Year 2017 Publication Burns : Journal of the International Society for Burn Injuries Abbreviated Journal Burns
Volume 43 Issue 3 Pages 642-653
Keywords Acinetobacter Infections/drug therapy/epidemiology/microbiology; Acinetobacter baumannii; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents/therapeutic use; Bacteremia/drug therapy/*epidemiology/microbiology; Burns/*epidemiology; Catheter-Related Infections/drug therapy/*epidemiology/microbiology; Central Venous Catheters; Cephalosporins/therapeutic use; Child; Child, Preschool; Colombia/epidemiology; Drug Resistance, Microbial; Escherichia coli; Escherichia coli Infections/drug therapy/epidemiology/microbiology; Female; Folliculitis/drug therapy/*epidemiology/microbiology; Humans; Infant; Infant, Newborn; Klebsiella Infections/drug therapy/epidemiology/microbiology; Klebsiella pneumoniae; Male; Middle Aged; Oxacillin/therapeutic use; Pneumonia/drug therapy/*epidemiology/microbiology; Pseudomonas Infections/drug therapy/epidemiology/microbiology; Pseudomonas aeruginosa; Staphylococcal Infections/drug therapy/epidemiology/microbiology; Staphylococcus aureus; Urinary Tract Infections/drug therapy/*epidemiology/microbiology; Wound Infection/drug therapy/*epidemiology/microbiology; Young Adult; Burn wound infection; Burns; Health care related infection; Nosocomial infection; Pneumonia; Urinary tract infection
Abstract INTRODUCTION: Worldwide, burns are responsible for more than 300,000 deaths annually; infection is a major cause of morbidity and mortality in these patients. Early identification and treatment of infection improves outcome. Toward this end it's necessary to identify the institutions flora and organisms that most frequently produces infection. OBJECTIVES: To characterize infections developed by burn patients hospitalized at the University Hospital of Santander (HUS). METHODOLOGY: Burn patients hospitalized in the HUS from January 1 to December 2014 were followed. Medical information regarding infections, laboratory and pathology reports were obtained. Statistical analysis with measures of central tendency, proportions, global and specific incidence density plus overall and specific incidence was obtained. For the microbiological profile proportions were established. RESULTS: 402 burn patients were included, 234 (58.2%) men and 168 (41.8%) women, aged between 6 days and 83 years, median 12.5 years. The burn agents include scald (52.5%), fire (10.0%), gasoline (9.2%), electricity (7.5%), among others. Burn area ranged from 1% to 80% TBS. Cumulative mortality was 1.5%. 27.8% of burned patients had one or more infections. Identified infections include folliculitis (27.0%), urinary tract infection (19.0%), infection of the burn wound (10.4%), pneumonia (8.6%), Central venous catheter (7.4%), bloodstream infection (7.4%) and skin grafts infection (4.3%) among others. Bacteria were responsible for 88.5% of the cases and fungi 11.5%. The most frequently isolated germs were P. aeruginosa, A. baumannii, E. coli, S. aureus and K. pneumoniae. Most gram-negative bacteria were sensitive to Amikacin, gram positive bacteria were sensitive to multiple antibiotics. CONCLUSION: Burns is a severe trauma that occurs in adult and pediatric patients, has several causative agents and can compromise the patient's life. The burned patient is at risk for a variety of infections. According to the type of infection it is possible to infer the most common causative organisms and their antibiotic sensitivity/resistance which allow a directed early empiric treatment.
Address (down) University Hospital of Santander, Universidad Industrial de Santander, Colombia. Electronic address: lumisosa@gmail.com
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 0305-4179 ISBN Medium
Area Expedition Conference
Notes PMID:28185802 Approved no
Call Number ref @ user @ Serial 99267
Permanent link to this record
 

 
Author Ramirez-Blanco, C.E.; Ramirez-Rivero, C.E.; Diaz-Martinez, L.A.; Sosa-Avila, L.M.
Title Infection in burn patients in a referral center in Colombia Type Journal Article
Year 2017 Publication Burns : Journal of the International Society for Burn Injuries Abbreviated Journal Burns
Volume 43 Issue 3 Pages 642-653
Keywords Acinetobacter Infections/drug therapy/epidemiology/microbiology; Acinetobacter baumannii; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents/therapeutic use; Bacteremia/drug therapy/*epidemiology/microbiology; Burns/*epidemiology; Catheter-Related Infections/drug therapy/*epidemiology/microbiology; Central Venous Catheters; Cephalosporins/therapeutic use; Child; Child, Preschool; Colombia/epidemiology; Drug Resistance, Microbial; Escherichia coli; Escherichia coli Infections/drug therapy/epidemiology/microbiology; Female; Folliculitis/drug therapy/*epidemiology/microbiology; Humans; Infant; Infant, Newborn; Klebsiella Infections/drug therapy/epidemiology/microbiology; Klebsiella pneumoniae; Male; Middle Aged; Oxacillin/therapeutic use; Pneumonia/drug therapy/*epidemiology/microbiology; Pseudomonas Infections/drug therapy/epidemiology/microbiology; Pseudomonas aeruginosa; Staphylococcal Infections/drug therapy/epidemiology/microbiology; Staphylococcus aureus; Urinary Tract Infections/drug therapy/*epidemiology/microbiology; Wound Infection/drug therapy/*epidemiology/microbiology; Young Adult; Burn wound infection; Burns; Health care related infection; Nosocomial infection; Pneumonia; Urinary tract infection
Abstract INTRODUCTION: Worldwide, burns are responsible for more than 300,000 deaths annually; infection is a major cause of morbidity and mortality in these patients. Early identification and treatment of infection improves outcome. Toward this end it's necessary to identify the institutions flora and organisms that most frequently produces infection. OBJECTIVES: To characterize infections developed by burn patients hospitalized at the University Hospital of Santander (HUS). METHODOLOGY: Burn patients hospitalized in the HUS from January 1 to December 2014 were followed. Medical information regarding infections, laboratory and pathology reports were obtained. Statistical analysis with measures of central tendency, proportions, global and specific incidence density plus overall and specific incidence was obtained. For the microbiological profile proportions were established. RESULTS: 402 burn patients were included, 234 (58.2%) men and 168 (41.8%) women, aged between 6 days and 83 years, median 12.5 years. The burn agents include scald (52.5%), fire (10.0%), gasoline (9.2%), electricity (7.5%), among others. Burn area ranged from 1% to 80% TBS. Cumulative mortality was 1.5%. 27.8% of burned patients had one or more infections. Identified infections include folliculitis (27.0%), urinary tract infection (19.0%), infection of the burn wound (10.4%), pneumonia (8.6%), Central venous catheter (7.4%), bloodstream infection (7.4%) and skin grafts infection (4.3%) among others. Bacteria were responsible for 88.5% of the cases and fungi 11.5%. The most frequently isolated germs were P. aeruginosa, A. baumannii, E. coli, S. aureus and K. pneumoniae. Most gram-negative bacteria were sensitive to Amikacin, gram positive bacteria were sensitive to multiple antibiotics. CONCLUSION: Burns is a severe trauma that occurs in adult and pediatric patients, has several causative agents and can compromise the patient's life. The burned patient is at risk for a variety of infections. According to the type of infection it is possible to infer the most common causative organisms and their antibiotic sensitivity/resistance which allow a directed early empiric treatment.
Address (down) University Hospital of Santander, Universidad Industrial de Santander, Colombia. Electronic address: lumisosa@gmail.com
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 0305-4179 ISBN Medium
Area Expedition Conference
Notes PMID:28185802 Approved no
Call Number ref @ user @ Serial 100297
Permanent link to this record
 

 
Author Foro Arnalot, P.; Pera, O.; Rodriguez, N.; Sanz, X.; Reig, A.; Membrive, I.; Ortiz, A.; Granados, R.; Algara, M.
Title Influence of incidental radiation dose in the subventricular zone on survival in patients with glioblastoma multiforme treated with surgery, radiotherapy, and temozolomide Type Journal Article
Year 2017 Publication Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico Abbreviated Journal Clin Transl Oncol
Volume Issue Pages
Keywords Glioblastoma; Radiotherapy; Subventricular zone
Abstract PURPOSE: To determine if there is an association between the incidental radiation dose to the subventricular zone and survival in patients with glioblastoma multiforme treated with surgery, radiotherapy and temozolomide. METHODS AND MATERIALS: Sixty-five patients, treated between 2006 and 2015, were included in this retrospective study. The doses (75th percentile; p75) administered to the ipsilateral, contralateral and bilateral subventricular zone were compared to overall survival and progression-free survival using Cox proportional hazards models. Covariates included: age, sex, surgery, tumor location, and concomitant and adjuvant temozolomide. RESULTS: Median progression-free survival and overall survival were 11.5 +/- 9.96 and 18.8 +/- 18.5 months, respectively. The p75 doses to the ipsilateral, contralateral and bilateral subventrivular zone were, respectively, 57.30, 48.8, and 52.7 Gy. Patients who received a dose >/=48.8 Gy in the contralateral subventricular zone had better progression-free survival than those who received lower doses (HR 0.46; 95% CI 0.23-0.91 P = 0.028). This association was not found for overall survival (HR 0.60; 95% CI 0.30-1.22 P = 0.16). Administration of adjuvant temozolomide was significantly associated with improved progression-free survival (HR 0.19; 95% CI 0.09-0.41 P < 0.0001) and overall survival (HR 0.11; 95% CI 0.05-0.24 P = 0.001). In the subgroup of 46 patients whose O6-methylguanine-DNA methyltransferase gene promoter status was known, the methylation had no effect on either progression-free survival (P = 0.491) or overall survival (P = 0.203). CONCLUSION: High-dose radiation in the contralateral subventricular zone was associated with a significant improvement in progression-free survival but not overall survival in patients treated for glioblastoma multiforme.
Address (down) Universitat Pompeu Fabra, Barcelona, Spain
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 1699-048X ISBN Medium
Area Expedition Conference
Notes PMID:28389881 Approved no
Call Number ref @ user @ Serial 96597
Permanent link to this record