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Brisbane, Australia

Dwan T.M.,Griffith University | Ownsworth T.,Griffith University | Chambers S.,Griffith University | Walker D.G.,NEWRO Foundation | Shum D.H.K.,Griffith University
Frontiers in Oncology | Year: 2015

Approaches to classifying neuropsychological impairment after brain tumor vary according to testing level (individual tests, domains or global index) and source of reference (i.e., norms, controls and premorbid functioning). This study aimed to compare rates of impairment according to different classification approaches. Participants were 44 individuals (57% female) with a primary brain tumor diagnosis (mean age = 45.6 years) and 44 matched control participants (59% female, mean age = 44.5 years). All participants completed a test battery that assesses premorbid IQ (Wechsler Adult Reading Test), attention/processing speed (Digit Span, Trail Making Test A), memory (Hopkins Verbal Learning Test - Revised, Rey-Osterrieth Complex Figure-recall) and executive function (Trail Making Test B, Rey- Osterrieth Complex Figure copy, Controlled Oral Word Association Test). Results indicated that across the different sources of reference, 86-93% of participants were classified as impaired at a test-specific level, 61-73% were classified as impaired at a domain-specific level, and 32-50% were classified as impaired at a global level. Rates of impairment did not significantly differ according to source of reference (p>.05); however, at the individual participant level, classification based on estimated premorbid IQ was often inconsistent with classification based on the norms or controls. Participants with brain tumor performed significantly poorer than matched controls on tests of neuropsychological functioning, including executive function (p=001) and memory (p<.001), but not attention/processing speed (p>.05). These results highlight the need to examine individuals' performance across a multi-faceted neuropsychological test battery to avoid over- or under-estimation of impairment. © 2015 Dwan, Ownsworth, Chambers, Walker and Shum. Source

Crough T.,Queensland Institute of Medical Research | Beagley L.,Queensland Institute of Medical Research | Smith C.,Queensland Institute of Medical Research | Jones L.,Queensland Institute of Medical Research | And 2 more authors.
Immunology and Cell Biology | Year: 2012

The frequent detection of human cytomegalovirus (CMV) antigens in glioblastoma multiforme (GBM) has raised the possibility of exploiting CMV-specific T-cell immunotherapy to control this disease in CMV - seropositive patients. Here, we have conducted a comprehensive ex vivo profiling of CMV-specific CD8+ T-cell responses in a cohort of GBM patients. Of the patients analyzed, approximately half exhibited serological evidence of past infection with CMV. Although no CMV-specific CD8+ T-cell responses could be detected in the serologically negative GBM patients, virus-specific CD8+ T-cell responses were detected in all seropositive GBM patients. Using major histocompatibility complex-peptide multimers, the frequency of CMV-specific T-cells in the patients detected ranged from 0.1 to 22% of CD8 + T-cells and a high proportion of these cells were positive for the human natural killer-1 glycoprotein CD57. Furthermore, ex vivo polychromatic functional analysis of the CMV-specific T-cells from GBM patients revealed that large proportions of these cells were unable to produce multiple cytokines (macrophage inflammatory protein (MIP)-1β, tumor necrosis factor (TNF)α and interferon (IFN)γ) and displayed limited cytolytic function (CD107a mobilization) following stimulation with CMV peptide epitopes. However, in vitro stimulation with CMV peptide epitopes in the presence of γC cytokine dramatically reversed the polyfunctional profile of these antigen-specific T-cells with high levels of MIP-1β, TNFα, IFNγ and CD107a mobilization. Most importantly, adoptive transfer of these in vitro-expanded T-cells in combination with temozolomide (TMZ) therapy into a patient with recurrent GBM was coincident with a long-term disease-free survival. These studies provide an important platform for a formal assessment of combination therapies based on CMV-specific T-cells and TMZ for recurrent GBM. © 2012 Australasian Society for Immunology Inc. All rights reserved. Source

Schuessler A.,QIMR Berghofer Medical Research Institute | Walker D.G.,NEWRO Foundation | Khanna R.,QIMR Berghofer Medical Research Institute
OncoImmunology | Year: 2014

Glioblastoma multiforme (GBM) has a very poor prognosis, despite multimodal therapy including surgery, radiation and chemotherapy. A novel adoptive immunotherapy that exploits the presence of cytomegalovirus antigens in malignant brain cancer cells has been shown to be safe and elicit potential clinical benefit for the treatment of recurrent GBM. © 2014 Landes Bioscience. Source

Clement R.C.,University of North Carolina at Chapel Hill | Welander A.,Boston Consulting Group | Stowell C.,International Consortium for Health Outcomes Measurement | Cha T.D.,Massachusetts General Hospital | And 22 more authors.
Acta Orthopaedica | Year: 2015

Background and purpose-Outcome measurement has been shown to improve performance in several fields of healthcare. This understanding has driven a growing interest in value-based healthcare, where value is defined as outcomes achieved per money spent. While low back pain (LBP) constitutes an enormous burden of disease, no universal set of metrics has yet been accepted to measure and compare outcomes. Here, we aim to define such a set.Patients and methods-An international group of 22 specialists in several disciplines of spine care was assembled to review literature and select LBP outcome metrics through a 6-round modified Delphi process. The scope of the outcome set was degenerative lumbar conditions.Results-Patient-reported metrics include numerical pain scales, lumbar-related function using the Oswestry disability index, health-related quality of life using the EQ-5D-3L questionnaire, and questions assessing work status and analgesic use. Specific common and serious complications are included. Recommended follow-up intervals include 6, 12, and 24 months after initiating treatment, with optional follow-up at 3 months and 5 years. Metrics for risk stratification are selected based on pre-existing tools.Interpretation-The outcome measures recommended here are structured around specific etiologies of LBP, span a patients entire cycle of care, and allow for risk adjustment. Thus, when implemented, this set can be expected to facilitate meaningful comparisons and ultimately provide a continuous feedback loop, enabling ongoing improvements in quality of care. Much work lies ahead in implementation, revision, and validation of this set, but it is an essential first step toward establishing a community of LBP providers focused on maximizing the value of the care we deliver. © 2015 Nordic Orthopaedic Federation. Source

Schuessler A.,Center for Immunotherapy and Vaccine Development | Smith C.,Center for Immunotherapy and Vaccine Development | Beagley L.,Center for Immunotherapy and Vaccine Development | Boyle G.M.,Cancer Drug Mechanisms Group | And 10 more authors.
Cancer Research | Year: 2014

Glioblastoma multiforme (GBM) is one of the most aggressive human brain malignancies. Even with optimal treatment, median survival is less than 6 months for patients with recurrent GBM. Immune-based therapies have the potential to improve patient outcome by supplementing standard treatment. Expression of human cytomegalovirus (CMV) antigens in GBM tissues provides the unique opportunity to target viral antigens for GBM therapy. Here, we report findings of a formal clinical assessment of safety and potential clinical efficacy of autologous CMV-specific T-cell therapy as a consolidative treatment for recurrent GBM. From a total of 19 patients with recurrent GBM, CMV-specific T cells were successfully expanded from 13 patients (68.4%), 11 of whom received up to four T-cell infusions. Combination therapy based on T-cell infusion and chemotherapy was well tolerated, and we detected only minor adverse events. The overall survival of these patients since first recurrence ranged from 133 to 2,428 days, with a median overall survival of 403 days. Most importantly, 4 of 10 patients that completed the treatment remained progression free during the study period. Furthermore, molecular profiling of CMV-specific T-cell therapy from these patients revealed distinct gene expression signatures, which correlated with their clinical response. Our study suggests that a combination therapy with autologous CMV-specific T cells and chemotherapy is a safe novel treatment option and may offer clinical benefit for patients with recurrent GBM. Cancer Res; 74(13); 3466-76. © 2014 American Association for Cancer Research. Source

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