Surgery (RMH) - Research Publications
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ItemDoes early exercise attenuate muscle atrophy or bone loss after spinal cord injury?(NATURE PUBLISHING GROUP, 2016-02-01)OBJECTIVES: To systematically identify and assess the evidence on the efficacy of exercise initiated early after traumatic spinal cord injury (SCI). METHODS: A comprehensive search (Any-2014) of eleven databases identified studies evaluating exercise interventions initiated within 12 weeks after SCI on muscle and bone loss in paralyzed limbs and comparing with standard care or immobilization. Two reviewers assessed methodological quality. One reviewer extracted data and critiqued results according to the Spinal Cord Injury Rehabilitation Evidence body of evidence framework. RESULTS: A total of 2811 titles were screened. Eleven studies were included: five randomized controlled trials, four cohort studies and two within-subject control studies. All provided level II evidence with a moderate risk of bias. Two studies found significant positive effects of high-load FES-resisted stance on physiological measures of muscle. Three reported positive effects of 3 months of Functional Electrical Stimulation (FES) on muscle size. Two studies found positive effects of 6-month body-weight supported treadmill training or FES on trabecular bone using pQCT. CONCLUSION: We found consistent evidence of positive effects of early exercise on muscle, possibly related to load intensity of the protocol. However, the heterogeneity of interventions and outcomes makes this determination speculative. Evidence for the effectiveness of early exercise on bone is scant and confined to measures of trabecular bone mineral density via pQCT. Transparent reporting of methods and variability of data, combined with standardization of valid and sensitive measures of muscle atrophy and bone loss, could facilitate future meta-analysis on this topic.
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ItemFactors Associated with Long-Term Functional and Psychological Outcomes in Persons with Moderate to Severe Traumatic Brain Injury(Medical Journals Sweden, 2016-05-01)Objective: To examine factors impacting long-term functional and psychological outcomes in persons with moderate-severe traumatic brain injury. Methods: A prospective cross-sectional study (n = 103) assessed the long-term (up to 5 years) impact of traumatic brain injury on participants’ current activity and restriction in participation using validated questionnaires. Results: Participants’ median age was 49. 5 years (interquartile range (IQR) 20. 4–23. 8), the majority were male (77%), and 49% had some form of previous rehabilitation. The common causes of traumatic brain injury were falls (42%) and motor vehicle accidents (27%). Traumatic brain injury-related symptoms were: pain/headache (47%), dizziness (36%), bladder/bowel impairment (34%), and sensory-perceptual deficits (34%). Participants reported minimal change in their physical function and cognition (Functional Assessment Measure: motor (median 102, IQR 93–111) and cognition (median 89, IQR 78–95)). Participants were well-adjusted to community-living; however, they reported high levels of depression. Factors significantly associated with poorer current level of functioning/well-being included: older age (≥ 60 years), presence of traumatic brain injury-related symptoms, a lack of previous rehabilitation and those classified in “severe disability categories” at admission. Caregivers reported high levels of strain and burden (55%). Conclusion: Cognitive and psychosocial problems are more commonly reported than physical disability in the longer-term. A greater focus on participation and ageing with disability in these persons is needed.
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ItemSCIPA Switch-On: A Randomized Controlled Trial Investigating the Efficacy and Safety of Functional Electrical Stimulation-Assisted Cycling and Passive Cycling Initiated Early After Traumatic Spinal Cord Injury(SAGE PUBLICATIONS INC, 2017-06-01)Background. Substantial skeletal muscle atrophy after spinal cord injury (SCI) carries significant repercussions for functional recovery and longer-term health. Objective. To compare the efficacy, safety, and feasibility of functional electrical stimulation-assisted cycling (FESC) and passive cycling (PC) to attenuate muscle atrophy after acute SCI. Methods. This multicenter, assessor-blinded phase I/II trial randomized participants at 4 weeks post-SCI to FESC or PC (4 sessions per week, 1 hour maximum per session, over 12 weeks). The primary outcome measure was mean maximum cross-sectional area (CSA) of thigh and calf muscles (magnetic resonance imaging), and secondary outcome measures comprised body composition (dual energy X-ray absorptiometry), anthropometry, quality of life, and adverse events (AEs). Results. Of 24 participants, 19 completed the 12-week trial (10 FESC, 9 PC, 18 male). Those participants completed >80% of training sessions (FESC, 83.5%; PC, 85.9%). No significant between-group difference in postintervention muscle CSA was found. No significant between-group difference was found for any other tissue, anthropometric parameter, or behavioral variable or AEs. Six participants experienced thigh hypertrophy (FESC = 3; PC = 3). Atrophy was attenuated (<30%) in 15 cases (FESC = 7; PC = 8). Conclusions. Both cycle ergometry regimens examined were safe, feasible, and well tolerated early after SCI. No conclusions regarding efficacy can be drawn from our data. Further investigation of both modalities early after SCI is 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, 2018-04-01)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, 2018-08-01)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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ItemFactors influencing thigh muscle volume change with cycling exercises in acute spinal cord injury - a secondary analysis of a randomized controlled trial(TAYLOR & FRANCIS LTD, 2020-09-19)Objective: To conduct a per-protocol analysis on thigh muscle volume outcomes from the Spinal Cord Injury and Physical Activity (SCIPA) Switch-On Trial.Design: Secondary analysis from an assessor-blind randomized, controlled trial.Setting: Four acute/sub-acute hospitals in Australia and New Zealand.Participants: 24 adults (1 female) within four weeks of motor complete or incomplete spinal cord injury (SCI)Intervention: Functional electrical stimulation-assisted cycling (FESC) or passive cycling (PC) 4x/week for 12 weeks.Outcome Measures: Whole thigh and muscle group volumes calculated from manually segmented MR images.Results: 19/24 participants completed ≥ twelve weeks of the intervention. Five participants experienced hypertrophy (4 FESC; 1 PC) and eight attenuation of atrophy (<20% volume loss) (3 FESC; 5 PC) in thigh muscle volume. Six participants were non-responders, exhibiting atrophy >20% (3 FESC; 3 PC). Mean (SD) change for FESC was -2.3% (25.3%) and PC was -14.0% (12.3%). After controlling for baseline muscle volumes, a strong significant correlation was found between mean weekly exercise frequency and quadriceps and hamstring volumes (r=6.25, P=0.006), regardless of mode. Average watts was highly correlated to quadriceps volumes only (r=5.92, P=0.01), while total number of sessions was strongly correlated with hamstring volumes only (r=5.91, P=0.01).Conclusion: This per-protocol analysis of FESC and PC early after SCI reports a partial response in 42% and a beneficial response in 25% of patients who completed 12 weeks intervention, regardless of mode. Strong correlations show a dose-response according to exercise frequency. Characteristics of non-responders are discussed to inform clinical decision-making.
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ItemA Novel Biosignature Identifies Patients With DCIS With High Risk of Local Recurrence After Breast Conserving Surgery and Radiation Therapy.(Elsevier BV, 2023-01-01)PURPOSE: There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT. METHODS AND MATERIALS: Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated. Patients were classified into 3 biosignature risk groups using the decision score (DS) and the RRt category: (1) Low Risk (DS ≤2.8 without RRt), (2) Elevated Risk (DS >2.8 without RRt), and (3) Residual Risk (DS >2.8 with RRt). Total and invasive IBR rates were assessed by risk group and treatment. RESULTS: In patients at low risk, there was no significant difference in IBR rates with or without RT (total, P = .8; invasive IBR, P = .7), and there were low overall 10-year rates (total, 5.1%; invasive, 2.7%). In patients with elevated risk, IBR rates were decreased with RT (total: hazard ratio [HR], 0.25; P < .001; invasive: HR, 0.28; P = .005); 10-year rates were 20.6% versus 4.9% (total) and 10.9% versus 3.1% (invasive). In patients with residual risk, although IBR rates decreased with RT after BCS (total: HR, 0.21; P < .001; invasive: HR, 0.29; P = .028), IBR rates remained significantly higher after RT compared with patients with elevated risk (HR, 2.5; 95% CI, 1.2-5.4; P = .018), with 10-year rates of 42.1% versus 14.7% (total) and 18.3% versus 6.5% (invasive). CONCLUSIONS: The novel biosignature identified patients with 3 distinct risk profiles: Low Risk patients with a low recurrence risk with or without adjuvant RT, Elevated Risk patients with excellent outcomes after BCS plus RT, and Residual Risk patients with an elevated recurrence risk remaining after BCS plus RT, warranting potential intensified or alternative treatment approaches.
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ItemA meta-analysis of clinicopathologic features that predict necrosis or fibrosis at post-chemotherapy retroperitoneal lymph node dissection in individuals receiving treatment for non-seminoma germ cell tumours(FRONTIERS MEDIA SA, 2022-08-17)PURPOSE: Post-chemotherapy retroperitoneal lymph node dissection (pcRPLND) for residual nodal masses is a critical component of care in metastatic testicular germ cell tumour (GCT). However, the procedure is not of therapeutic value in up to 50% of individuals in whom histopathology demonstrates post-treatment necrosis or fibrosis alone. Improved diagnostic tools and clinicopathologic features are needed to separate individuals who benefit from pcRPLND and avoid surgery in those who do not. METHODS: A prospectively registered meta-analysis of studies reporting clinicopathologic features associated with teratoma, GCT and/or necrosis/fibrosis at pcRPLND for metastatic non-seminoma GCT (NSGCT) was undertaken. We examined the effect of various clinicopathologic factors on the finding of necrosis/fibrosis at pcRPLND. The log odds ratios (ORs) of each association were pooled using random-effects models. RESULTS: Using the initial search strategy, 4,178 potentially eligible abstracts were identified. We included studies providing OR relating to clinicopathologic factors predicting pcRPLND histopathology, or where individual patient-level data were available to permit the calculation of OR. A total of 31 studies evaluating pcRPLND histopathology in 3,390 patients were eligible for inclusion, including two identified through hand-searching the reference lists of eligible studies. The following were associated with the presence of necrosis/fibrosis at pcRPLND: absence of teratomatous elements in orchidectomy (OR 3.45, 95% confidence interval [CI] 2.94-4.17); presence of seminomatous elements at orchidectomy (OR 2.71, 95% CI 1.37-5.37); normal pre-chemotherapy serum bHCG (OR 1.96, 95% CI 1.62-2.36); normal AFP (OR 3.22, 95% CI 2.49-4.15); elevated LDH (OR 1.72, 95% CI 1.37-2.17); >50% change in mass during chemotherapy (OR 4.84, 95% CI 3.94-5.94); and smaller residual mass size (<2 cm versus >2 cm: OR 3.93, 95% CI 3.23-4.77; <5 cm versus >5 cm: OR 4.13, 95% CI 3.26-5.23). CONCLUSIONS: In this meta-analysis, clinicopathologic features helped predict the presence of pcRPLND necrosis/fibrosis. Collaboration between centres that provide individual patient-level data is required to develop and validate clinical models and inform routine care to direct pcRPLND to individuals most likely to derive benefits. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42021279699.
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ItemCrosstalk between epithelium, myeloid and innate lymphoid cells during gut homeostasis and disease.(Frontiers Media SA, 2022)The gut epithelium not only provides a physical barrier to separate a noxious outside from a sterile inside but also allows for highly regulated interactions between bacteria and their products, and components of the immune system. Homeostatic maintenance of an intact epithelial barrier is paramount to health, requiring an intricately regulated and highly adaptive response of various cells of the immune system. Prolonged homeostatic imbalance can result in chronic inflammation, tumorigenesis and inefficient antitumor immune control. Here we provide an update on the role of innate lymphoid cells, macrophages and dendritic cells, which collectively play a critical role in epithelial barrier maintenance and provide an important linkage between the classical innate and adaptive arm of the immune system. These interactions modify the capacity of the gut epithelium to undergo continuous renewal, safeguard against tumor formation and provide feedback to the gut microbiome, which acts as a seminal contributor to cellular homeostasis of the gut.
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ItemReliability and validity of sit-to-stand test protocols in patients with coronary artery disease(FRONTIERS MEDIA SA, 2022-08-25)BACKGROUND: Sit-To-Stand (STS) tests are reported as feasible alternatives for the assessment of functional fitness but the reliability of these tests in people with coronary artery disease (CAD) has not been reported. This study explored the test-retest reliability, convergent and known-groups validity of the five times, 30-sec and 1-min sit-to-stand test (FTSTS test, 30-s STS test and 1-min STS test respectively) in patients with CAD. The feasibility of applying these tests to distinguish the level of risk for cardiovascular events in CAD patients was also investigated. METHODS: Patients with stable CAD performed a 6MWT and 3 STS tests in random order on the same day. Receiver operating characteristic (ROC) curve analyses were conducted using STS test data to differentiate patients with low or high risk of cardiovascular events based on the risk level determined by distance covered in the 6MWT as > or ≤ 419 m. Thirty patients repeated the 3 STS tests on the following day. RESULTS: 112 subjects with diagnoses of atherosclerosis or post-percutaneous coronary intervention, or post-acute myocardial infarction (post-AMI) participated in the validity analysis. All 3 STS tests demonstrated moderate and significant correlation with the 6MWT (coefficient values r for the FTSTS, 30-s STS and 1-min STS tests were-0.53, 0.57 and 0.55 respectively). Correlations between left ventricular ejection fraction (LVEF) and all STS tests and between 6MWT and LVEF were only weak (r values ranged from 0.27 to 0.31). Subgroup analysis showed participants in the post-AMI group performed worse in all tests compared to non-myocardial infarction (non-MI) group. The area under the curve (AUC) was 0.80 for FTSTS (sensitivity: 75.0%, specificity: 73.8%, optimal cut-off: >11.7 sec), and the AUC, sensitivity, specificity and optimal cut-off for 30-s STS and 1-min STS test were 0.83, 75.0%, 76.2%, ≤ 12 repetitions and 0.80, 71.4%, 73.8%, ≤ 23 repetitions respectively. The intraclass correlation coefficients (ICC) for repeated measurements of the FTSTS, 30-s STS and 1-min STS tests were 0.96, 0.95 and 0.96 respectively, with the minimal detectable change (MDC95) computed to be 1.1 sec 1.8 repetitions and 3.9 repetitions respectively. CONCLUSIONS: All STS tests demonstrated good test-retest reliability, convergent and known-groups validity. STS tests may discriminate low from high levels of risk for a cardiovascular event in patients with CAD.