Surgery (RMH) - Research Publications
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ItemGlutamate weighted imaging contrast in gliomas with 7 Tesla magnetic resonance imaging(ELSEVIER SCI LTD, 2019)INTRODUCTION: Diffuse gliomas are incurable malignancies, which undergo inevitable progression and are associated with seizure in 50-90% of cases. Glutamate has the potential to be an important glioma biomarker of survival and local epileptogenicity if it can be accurately quantified noninvasively. METHODS: We applied the glutamate-weighted imaging method GluCEST (glutamate chemical exchange saturation transfer) and single voxel MRS (magnetic resonance spectroscopy) at 7 Telsa (7 T) to patients with gliomas. GluCEST contrast and MRS metabolite concentrations were quantified within the tumour region and peritumoural rim. Clinical variables of tumour aggressiveness (prior adjuvant therapy and previous radiological progression) and epilepsy (any prior seizures, seizure in last month and drug refractory epilepsy) were correlated with respective glutamate concentrations. Images were separated into post-hoc determined patterns and clinical variables were compared across patterns. RESULTS: Ten adult patients with a histo-molecular (n = 9) or radiological (n = 1) diagnosis of grade II-III diffuse glioma were recruited, 40.3 +/- 12.3 years. Increased tumour GluCEST contrast was associated with prior adjuvant therapy (p = .001), and increased peritumoural GluCEST contrast was associated with both recent seizures (p = .038) and drug refractory epilepsy (p = .029). We distinguished two unique GluCEST contrast patterns with distinct clinical and radiological features. MRS glutamate correlated with GluCEST contrast within the peritumoural voxel (R = 0.89, p = .003) and a positive trend existed in the tumour voxel (R = 0.65, p = .113). CONCLUSION: This study supports the role of glutamate in diffuse glioma biology. It further implicates elevated peritumoural glutamate in epileptogenesis and altered tumour glutamate homeostasis in glioma aggressiveness. Given the ability to non-invasively visualise and quantify glutamate, our findings raise the prospect of 7 T GluCEST selecting patients for individualised therapies directed at the glutamate pathway. Larger studies with prospective follow-up are required.
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ItemBedside quantification of fat-free mass in acute spinal cord injury using bioelectrical impedance analysis: a psychometric study(NATURE PUBLISHING GROUP, 2018-04)STUDY DESIGN: Psychometric. OBJECTIVES: Assess the validity of bioimpedance-based measures of fat-free mass (FFM) in acute SCI and of current definitions of obesity based on body mass index (BMI). SETTING: Australia. METHODS: All admissions within eight weeks of a new traumatic SCI were screened. 29% were eligible. 71% of those consented. Twenty participants (18 male) completed deuterium dilution (DD) and bioimpedance-based measurements of FFM. Thirteen also underwent dual-energy x-ray absorptiometry. Strength of relationships and agreement were examined using Lin's concordance coefficient and limits of agreement analysis, respectively. Sensitivity and specificity were calculated for three BMI cutoffs for obesity, using percentage fat mass (%FM) obtained from DD as reference. RESULTS: Median time since injury was 41 days (IQR 28-48). FFM from DD and DXA were highly correlated but not identical. Concordance and agreement between DD and seven bioimpedance-based predictive equations are presented. The best-fitting equation demonstrated a low bias (+0.6 kg) and moderate dispersion (±5.2 kg). The cutoff for overweight in able-bodied people (BMI ≥25 kg/m2) provided sensitivity of 43.8%, compared to 25% for the cut-off for obesity (BMI ≥30 kg/m2). FM from bioimpedance gave the highest sensitivity (88.9%). CONCLUSIONS: BMI demonstrates poor specificity to classify obesity in acute SCI. Present findings support the utility of bioimpedance-based measurements for estimating FFM in acute SCI for group comparisons. These results are generalizable to traumatic SCI 4-8 weeks post injury; however, the present data reflect a high proportion of high cervical injuries. Further research is indicated to establish validity for assessment of individuals and for longitudinal monitoring. SPONSORSHIP: The present study was funded by a grant from the Institute for Safety, Compensation and Recovery Research (ISCRR Project #NGE-E-13-078). M Panisset was supported by an Australian Postgraduate Award. K Desneves was supported by the Austin Medical Research Foundation.
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ItemA novel neuromodulation technique for the rehabilitation of balance and gait: A case study(ELSEVIER SCI LTD, 2018-08)Cranial-nerve non-invasive neuromodulation (CN-NINM) through the tongue has been proposed as an adjuvant intervention to improve efficacy of rehabilitation. However, CN-NINM effects have only been explored in multiple sclerosis and stroke populations. In this report we used CN-NINM during a 2-week (2 × 1.5 h sessions daily) physiotherapy program for the rehabilitation of a 57 y/o woman presenting with balance and gait impairments after a surgical resection of a fourth ventricular ependymoma. Clinical and instrumented balance and gait assessments showed improved performance in all tests and without adverse effects This study shows the beneficial effects and feasibility of combined physiotherapy and CN-NINM in this patient.
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ItemMajor trauma in older persons.(Oxford University Press (OUP), 2018-09)BACKGROUND: Globally, populations are ageing, creating challenges for trauma system design. Despite this, little is known about causes of injury and long-term outcomes in older injured patients. This study aims to describe temporal trends in the incidence, causes and functional outcomes of major trauma in older adults. METHODS: The population-based Victorian State Trauma Registry was used to identify patients with major trauma aged 65 years and older with a date of injury between 1 January 2007 and 31 December 2016. Temporal trends in population-based incidence rates were evaluated. Functional outcome was measured using the Glasgow Outcome Scale - Extended. RESULTS: There were 9250 older adults with major trauma during the study period. Low falls were the most common mechanism of injury (62·5 per cent), followed by transport-related events (22·2 per cent) and high falls (9·5 per cent). The number of patients with major trauma aged 65 years and older more than doubled from 2007 to 2016, and the incidence increased by 4·3 per cent per year (incidence rate ratio 1·043, 95 per cent c.i. 1·035 to 1·050; P < 0·001). At 12 months after injury, 41·8 per cent of older adults with major trauma had died, and 52·2 per cent of those who survived to hospital discharge were not living independently. CONCLUSIONS: The number and proportion of older adults with major trauma are increasing rapidly and this will impact on trauma system design. Given the poor long-term outcomes, there needs to be greater emphasis on ensuring that appropriate interventions are targeted to the right patients and enhanced efforts in primary prevention.
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ItemRadiomic features of glucose metabolism enable prediction of outcome in mantle cell lymphoma.(Springer Science and Business Media LLC, 2019-12)PURPOSE: To determine whether [18F]FDG PET/CT-derived radiomic features alone or in combination with clinical, laboratory and biological parameters are predictive of 2-year progression-free survival (PFS) in patients with mantle cell lymphoma (MCL), and whether they enable outcome prognostication. METHODS: Included in this retrospective study were 107 treatment-naive MCL patients scheduled to receive CD20 antibody-based immuno(chemo)therapy. Standardized uptake values (SUV), total lesion glycolysis, and 16 co-occurrence matrix radiomic features were extracted from metabolic tumour volumes on pretherapy [18F]FDG PET/CT scans. A multilayer perceptron neural network in combination with logistic regression analyses for feature selection was used for prediction of 2-year PFS. International prognostic indices for MCL (MIPI and MIPI-b) were calculated and combined with the radiomic data. Kaplan-Meier estimates with log-rank tests were used for PFS prognostication. RESULTS: SUVmean (OR 1.272, P = 0.013) and Entropy (heterogeneity of glucose metabolism; OR 1.131, P = 0.027) were significantly predictive of 2-year PFS: median areas under the curve were 0.72 based on the two radiomic features alone, and 0.82 with the addition of clinical/laboratory/biological data. Higher SUVmean in combination with higher Entropy (SUVmean >3.55 and entropy >3.5), reflecting high "metabolic risk", was associated with a poorer prognosis (median PFS 20.3 vs. 39.4 months, HR 2.285, P = 0.005). The best PFS prognostication was achieved using the MIPI-bm (MIPI-b and metabolic risk combined): median PFS 43.2, 38.2 and 20.3 months in the low-risk, intermediate-risk and high-risk groups respectively (P = 0.005). CONCLUSION: In MCL, the [18F]FDG PET/CT-derived radiomic features SUVmean and Entropy may improve prediction of 2-year PFS and PFS prognostication. The best results may be achieved using a combination of metabolic, clinical, laboratory and biological parameters.
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ItemAuthor Correction: Smac mimetics and oncolytic viruses synergize in driving anticancer T-cell responses through complementary mechanisms.(Springer Science and Business Media LLC, 2018-05-24)The originally published version of this article contained an error in the spelling of the author Pankaj Tailor, which was incorrectly given as Pankaj Taylor. This has now been corrected in both the PDF and HTML versions of the article.
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ItemThe effect of surgical approach on early complications of total hip arthoplasty(BMC, 2019-09-03)BACKGROUND: Total hip arthroplasty (THA) is traditionally associated with a low complication rate, with complications such as infection, fracture and dislocation requiring readmission or reoperation. We seek to identify the complication rate among the anterior, direct lateral and posterior surgical approaches. METHODS: We reviewed all THAs performed at the Epworth Healthcare from 1 July 2014 to 30 June 2016. There were 2437 THAs performed by a variety of approaches. No hips were excluded from this study. We surveyed the hospital database and the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) to identify those patients who had been readmitted and/or reoperated on. Details collected included age, gender, laterality of the surgery (left/right/bilateral), surgical approach utilised, complications which occurred. RESULTS: There were 29 peri-prosthetic fractures detected (13 anterior, 9 lateral, 7 posterior) and 10 underwent revision of implant, 19 were fixed. The increased rate of revision in the anterior group was statistically significant. There were 14 dislocations (5 anterior, 1 lateral, 8 posterior) of which 8 prostheses were revised. Three cases operated via the anterior approach and 1 by the lateral had early subsidence without fracture, necessitating revision of the femoral prostheses. Operative site infection occurred in 12 cases (2 anterior, 4 lateral, 6 posterior) with 6 requiring revision of implants. CONCLUSION: The complication rates between the 3 main approaches are similar, but individual surgeons should be vigilant for complications unique to their surgical approaches, such as femoral fractures in the anterior approach and dislocations in the posterior approach.
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ItemPatient-identified information and communication needs in the context of major trauma(BMC, 2018-03-07)BACKGROUND: Navigating complex health care systems during the multiple phases of recovery following major trauma entails many challenges for injured patients. Patients' experiences communicating with health professionals are of particular importance in this context. The aim of this study was to explore seriously injured patients' perceptions of communication with and information provided by health professionals in their first 3-years following injury. METHODS: A qualitative study designed was used, nested within a population-based longitudinal cohort study. Semi-structured telephone interviews were undertaken with 65 major trauma patients, aged 17 years and older at the time of injury, identified through purposive sampling from the Victorian State Trauma Registry. A detailed thematic analysis was undertaken using a framework approach. RESULTS: Many seriously injured patients faced barriers to communication with health professionals in the hospital, rehabilitation and in the community settings. Key themes related to limited contact with health professionals, insufficient information provision, and challenges with information coordination. Communication difficulties were particularly apparent when many health professionals were involved in patient care, or when patients transitioned from hospital to rehabilitation or to the community. Difficulties in patient-health professional engagement compromised communication and exchange of information particularly at transitions of care, e.g., discharge from hospital. Conversely, positive attributes displayed by health professionals such as active discussion, clear language, listening and an empathetic manner, all facilitated effective communication. Most patients preferred communication consistent with patient-centred approaches, and the use of multiple modes to communicate information. CONCLUSIONS: The communication and information needs of seriously injured patients were inconsistently met over the course of their recovery continuum. To assist patients along their recovery trajectories, patient-centred communication approaches and considerations for environmental and patients' health literacy are recommended. Additionally, assistance with information coordination and comprehensive multimodal information provision should be available for injured patients.
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ItemUtility of Self-Destructing CRISPR/Cas Constructs for Targeted Gene Editing in the Retina(MARY ANN LIEBERT, INC, 2019-11-01)Safe delivery of CRISPR/Cas endonucleases remains one of the major barriers to the widespread application of in vivo genome editing. We previously reported the utility of adeno-associated virus (AAV)-mediated CRISPR/Cas genome editing in the retina; however, with this type of viral delivery system, active endonucleases will remain in the retina for an extended period, making genotoxicity a significant consideration in clinical applications. To address this issue, we have designed a self-destructing "kamikaze" CRISPR/Cas system that disrupts the Cas enzyme itself following expression. Four guide RNAs (sgRNAs) were initially designed to target Streptococcus pyogenes Cas9 (SpCas9) and after in situ validation, the selected sgRNAs were cloned into a dual AAV vector. One construct was used to deliver SpCas9 and the other delivered sgRNAs directed against SpCas9 and the target locus (yellow fluorescent protein [YFP]), in the presence of mCherry. Both constructs were packaged into AAV2 vectors and intravitreally administered in C57BL/6 and Thy1-YFP transgenic mice. After 8 weeks, the expression of SpCas9 and the efficacy of YFP gene disruption were quantified. A reduction of SpCas9 mRNA was found in retinas treated with AAV2-mediated YFP/SpCas9 targeting CRISPR/Cas compared with those treated with YFP targeting CRISPR/Cas alone. We also show that AAV2-mediated delivery of YFP/SpCas9 targeting CRISPR/Cas significantly reduced the number of YFP fluorescent cells among mCherry-expressing cells (∼85.5% reduction compared with LacZ/SpCas9 targeting CRISPR/Cas) in the transfected retina of Thy1-YFP transgenic mice. In conclusion, our data suggest that a self-destructive "kamikaze" CRISPR/Cas system can be used as a robust tool for genome editing in the retina, without compromising on-target efficiency.
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ItemEnd-of-life care in rural general practice: how best to support commitment and meet challenges?(BMC, 2019-06-25)BACKGROUND: Few studies have specifically assessed the scope, nature and challenges of palliative and end-of-life care in rural general practice. These knowledge gaps limit the development of evidence-based policies and services for patients in the last months of life. This study aimed to explore the perspectives of general practitioners (GPs) and other stakeholders on rural GPs' involvement and challenges in providing palliative and end-of-life care in regional Australia. METHODS: A qualitative study involving five focus groups with 26 GPs based in rural/regional Western Australia together with 15 individual telephone interviews with four GPs and 11 other stakeholders involved in end-of-life care across Australia. RESULTS: The rural GPs' central role in end-of-life care was recognized by the majority of participants but multiple challenges were also identified. Some challenges were comparable to those found in urban settings but others were more pronounced, including resource limitations and lack of training. Inappropriate payment models discouraged GPs' involvement in some aspects of end-of-life care, such as case conferences and home visits. Compared to GPs in urban settings, those in rural/regional communities often reported closer doctor-patient relationships and better care integration and collaboration. These positive aspects of care could be further developed to enhance service provision. Our study highlighted the importance of regular interactions with other professionals and patients in providing end-of-life care, but many GPs and other stakeholders found such interactions more challenging than the more "technical" aspects of care. CONCLUSIONS: Rural/regional GPs appear to be disproportionately affected by inappropriate payment models and limited resources, but may benefit from closer doctor-patient relationships and better care integration and collaboration relative to urban GPs. Systematic collection of empirical data on GP management at end-of-life is required to build on these strengths and address the challenges.