Medicine (Western Health) - Research Publications

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    Validation of a Semiautomatic Image Analysis Software for the Quantification of Musculoskeletal Tissues
    Imani, M ; Bani Hassan, E ; Vogrin, S ; Ch'Ng, ASTN ; Lane, NE ; Cauley, JA ; Duque, G (SPRINGER, 2021-09-13)
    Accurate quantification of bone, muscle, and their components is still an unmet need in the musculoskeletal field. Current methods to quantify tissue volumes in 3D images are expensive, labor-intensive, and time-consuming; thus, a reliable, valid, and quick application is highly needed. Tissue Compass is a standalone software for semiautomatic segmentation and automatic quantification of musculoskeletal organs. To validate the software, cross-sectional micro-CT scans images of rat femur (n = 19), and CT images of hip and abdomen (n = 100) from the Osteoporotic Fractures in Men (MrOS) Study were used to quantify bone, hematopoietic marrow (HBM), and marrow adipose tissue (MAT) using commercial manual software as a comparator. Also, abdominal CT scans (n = 100) were used to quantify psoas muscle volumes and intermuscular adipose tissue (IMAT) using the same software. We calculated Pearson's correlation coefficients, individual intra-class correlation coefficients (ICC), and Bland-Altman limits of agreement together with Bland-Altman plots to show the inter- and intra-observer agreement between Tissue Compass and commercially available software. In the animal study, the agreement between Tissue Compass and commercial software was r > 0.93 and ICC > 0.93 for rat femur measurements. Bland-Altman limits of agreement was - 720.89 (- 1.5e+04, 13,074.00) for MAT, 4421.11 (- 1.8e+04, 27,149.73) for HBM and - 6073.32 (- 2.9e+04, 16,388.37) for bone. The inter-observer agreement for QCT human study between two observers was r > 0.99 and ICC > 0.99. Bland-Altman limits of agreement was 0.01 (- 0.07, 0.10) for MAT in hip, 0.02 (- 0.08, 0.12) for HBM in hip, 0.05 (- 0.15, 0.25) for bone in hip, 0.02 (- 0.18, 0.22) for MAT in L1, 0.00 (- 0.16, 0.16) for HBM in L1, and 0.02 (- 0.23, 0.27) for bone in L1. The intra-observer agreement for QCT human study between the two applications was r > 0.997 and ICC > 0.99. Bland-Altman limits of agreement was 0.03 (- 0.13, 0.20) for MAT in hip, 0.05 (- 0.08, 0.18) for HBM in hip, 0.05 (- 0.24, 0.34) for bone in hip, - 0.02 (- 0.34, 0.31) for MAT in L1, - 0.14 (- 0.44, 0.17) for HBM in L1, - 0.29 (- 0.62, 0.05) for bone in L1, 0.03 (- 0.08, 0.15) for IMAT in psoas, and 0.02 (- 0.35, 0.38) for muscle in psoas. Compared to a conventional application, Tissue Compass demonstrated high accuracy and non-inferiority while also facilitating easier analyses. Tissue Compass could become the tool of choice to diagnose tissue loss/gain syndromes in the future by requiring a small number of CT sections to detect tissue volumes and fat infiltration.
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    Progressive Resistance Training for Concomitant Increases in Muscle Strength and Bone Mineral Density in Older Adults: A Systematic Review and Meta-Analysis
    O'Bryan, SJ ; Giuliano, C ; Woessner, MN ; Vogrin, S ; Smith, C ; Duque, G ; Levinger, I (ADIS INT LTD, 2022-05-24)
    BACKGROUND: Older adults experience considerable muscle and bone loss that are closely interconnected. The efficacy of progressive resistance training programs to concurrently reverse/slow the age-related decline in muscle strength and bone mineral density (BMD) in older adults remains unclear. OBJECTIVES: We aimed to quantify concomitant changes in lower-body muscle strength and BMD in older adults following a progressive resistance training program and to determine how these changes are influenced by mode (resistance only vs. combined resistance and weight-bearing exercises), frequency, volume, load, and program length. METHODS: MEDLINE/PubMed and Embase databases were searched for articles published in English before 1 June, 2021. Randomized controlled trials reporting changes in leg press or knee extension one repetition maximum and femur/hip or lumbar spine BMD following progressive resistance training in men and/or women ≥ 65 years of age were included. A random-effects meta-analysis and meta-regression determined the effects of resistance training and the individual training characteristics on the percent change (∆%) in muscle strength (standardized mean difference) and BMD (mean difference). The quality of the evidence was assessed using the Cochrane risk-of-bias tool (version 2.0) and Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: Seven hundred and eighty studies were identified and 14 were included. Progressive resistance training increased muscle strength (∆ standardized mean difference = 1.1%; 95% confidence interval 0.73, 1.47; p ≤ 0.001) and femur/hip BMD (∆ mean difference = 2.77%; 95% confidence interval 0.44, 5.10; p = 0.02), but not BMD of the lumbar spine (∆ mean difference = 1.60%; 95% confidence interval - 1.44, 4.63; p = 0.30). The certainty for improvement was greater for muscle strength compared with BMD, evidenced by less heterogeneity (I2 = 78.1% vs 98.6%) and a higher overall quality of evidence. No training characteristic significantly affected both outcomes (p > 0.05), although concomitant increases in strength and BMD were favored by higher training frequencies, increases in strength were favored by resistance only and higher volumes, and increases in BMD were favored by combined resistance plus weight-bearing exercises, lower volumes, and higher loads. CONCLUSIONS: Progressive resistance training programs concomitantly increase lower-limb muscle strength and femur/hip bone mineral density in older adults, with greater certainty for strength improvement. Thus, to maximize the efficacy of progressive resistance training programs to concurrently prevent muscle and bone loss in older adults, it is recommended to incorporate training characteristics more likely to improve BMD.
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    Effects of 3 months of multi-nutrient supplementation on the immune system and muscle and respiratory function of older adults in aged care (The Pomerium Study): protocol for a randomised controlled trial
    Al Saedi, A ; Kirk, B ; Iuliano, S ; Zanker, J ; Vogrin, S ; Jayaram, L ; Thomas, S ; Golding, C ; Navarro-Perez, D ; Marusic, P ; Leng, S ; Nanan, R ; Duque, G (BMJ PUBLISHING GROUP, 2022-05-01)
    INTRODUCTION: Immunosenescence leads to increased morbidity and mortality associated with viral infections and weaker vaccine responses. This has been well documented for seasonal influenza and the current pandemic with SARS-CoV-2 (COVID-19), which disproportionately impact older adults, particularly those in residential aged care facilities. Inadequate nutrient intakes associated with impaired immunity, respiratory and muscle function are likely to augment the effects of immunosenescence. In this study, we test whether the impact of inadequate nutrition can be reversed using multi-nutrient supplementation, consequently enhancing vaccine responses, reducing the risk of viral infections and improving respiratory and muscle function. METHODS AND ANALYSIS: The Pomerium Study is a 3-month, single-blind, randomised, controlled trial testing the effects of two daily servings of an oral multi-nutrient supplement (330 kcal, 20 g protein, 1.5 g calcium 3-hydroxy-3-methylbutyrate monohydrate (CaHMB), 449 mg calcium, 500 IU vitamin D3 and 25 vitamins and minerals) on the immune system and muscle and respiratory function of older adults in aged care in Melbourne, Australia. 160 older adults (≥75 years old) will be recruited from aged care facilities and randomised to treatment (multi-nutrient supplement) or control (usual care). The primary outcome is a change in T-cell subsets CD8 + and CD28null counts at months 1 and 3. Secondary outcomes measured at baseline and month 3 are multiple markers of immunosenescence (also at 1 month), body composition (bioimpedance), handgrip strength (dynamometer), physical function (short physical performance battery), respiratory function (spirometry) and quality of life (EQ-5D-5L). Incidence and complications of COVID-19 and/or viral infections (ie, hospitalisation, complications or death) will be recorded throughout the trial, including 3 months after supplementation is ceased. ETHICS AND DISSEMINATION: This study was approved by Melbourne Health Human Research Ethics Committee (Ref No. HREC/73985/MH-2021, ERM Ref No. RMH73985, Melbourne Health Site Ref No. 2021.115). Written informed consent will be obtained from participants. Results will be published in peer-reviewed journals and made available to key aged care stakeholders, including providers, residents, and government bodies. TRIAL REGISTRATION NUMBER: ACTRN12621000420842.
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    Association Between Tryptophan Metabolites, Physical Performance, and Frailty in Older Persons
    Al Saedi, A ; Chow, S ; Vogrin, S ; Guillemin, GJ ; Duque, G (SAGE PUBLICATIONS LTD, 2022-01-01)
    Frailty is defined as a syndrome of physiological decline in late life, characterized by marked vulnerability to adverse health outcomes. A robust biomarker for frailty is still lacking. Tryptophan (TRP) metabolism through the kynurenine pathway (KP) plays essential roles in aging, the musculoskeletal system, and physical performance. In this study, we quantified 7 KP metabolites, including kynurenine (KYN), kynurenine acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), and anthranilic acid (AA) using ultra-high-performance liquid chromatography and gas chromatography-mass spectrometry in the serum of 85 participants (median age 75; 65% female; 28 non-frail, 29 pre-frail, and 28 frail) at the Nepean Osteoporosis and Frailty (NOF) Study. We looked at the association between TRP metabolites and physical performance, sarcopenia, and frailty. After adjusting for age and sex, our results showed that KYN and KYN/TRP were associated with higher interleukin (IL)-6 levels (r = .324 and r = .390, respectively). KYNA and its ratios to other products (mainly KYNA/KYN, KYNA/QUIN, and KYNA/PIC) were associated with a lower likelihood of frailty by Fried's criteria (OR 0.93 [0.88, 0.98], P = .009) and Rockwood index (r = -.241, P = .028) as well as a lower likelihood of sarcopenia (OR 0.88 [0.78, 1.00], P = .049). QUIN and QUIN/KYN showed an association with increased IL-6 (r = .293 and .204 respectively), higher likelihood of frailty (OR 1.02 [1.00, 1.04], P = .029 and OR 6.43 [2.23, 18.51], P = .001 respectively) and lower physical function (r = -.205 and r = -.292). In conclusion, different TRP metabolites have various associations with physical performance, frailty, and sarcopenia. Defining the underlying mechanisms may permit the development and validation of new biomarkers and therapeutics for frailty and musculoskeletal conditions targeting specific metabolites of the TRP catabolic pathway.
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    Higher Levels of Circulating Osteoprogenitor Cells Are Associated With Higher Bone Mineral Density and Lean Mass in Older Adults: A Cross-Sectional Study
    Feehan, J ; Smith, C ; Tripodi, N ; Degabrielle, E ; Al Saedi, A ; Vogrin, S ; Duque, G ; Levinger, I (WILEY, 2021-10-17)
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    Leucine-enriched whey protein supplementation, resistance-based exercise, and cardiometabolic health in older adults: a randomized controlled trial
    Kirk, B ; Mooney, K ; Vogrin, S ; Jackson, M ; Duque, G ; Khaiyat, O ; Amirabdollahian, F (WILEY, 2021-09-14)
    BACKGROUND: Increasing protein intake (above the Recommended Dietary Amount) alone or with resistance-based exercise is suggested to improve cardiometabolic health; however, randomized controlled trials (RCTs) are needed to confirm this. METHODS: The Liverpool Hope University-Sarcopenia Aging Trial (LHU-SAT) was a 16 week RCT (ClinicalTrials.gov Identifier: NCT02912130) of 100 community-dwelling older adults [mean age: 68.73 ± 5.80 years, body mass index: 27.06 ± 5.18 kg/m2 (52% women)] who were randomized to four independent groups [Control (C), Exercise (E), Exercise + Protein (EP), Protein (P)]. E and EP completed supervised and progressive resistance-based exercise (resistance exercise: two times per week, functional circuit exercise: once per week), while EP and P were supplemented with a leucine-enriched whey protein drink (three times per day) based on individual body weight (0.50 g/kg/meal, 1.50 g/kg/day). Outcome measures including arterial stiffness (pulse wave velocity), fasting plasma/serum biomarkers [glucose/glycated haemoglobin, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, insulin, resistin, leptin, adiponectin, C-reactive protein, tumour necrosis factor-alpha, interleukin-6, cystatin-C, & ferritin], insulin resistance (HOMA-IR), and kidney function (eGFR) were measured before and after intervention. RESULTS: Total protein intake (habitual diet plus supplementation) increased to 1.55 ± 0.69 g/kg/day in EP and to 1.93 ± 0.72 g/kg/day in P, and remained significantly lower (P < 0.001) in unsupplemented groups (E: 1.08 ± 0.33 g/kg/day, C: 1.00 ± 0.26 g/kg/day). At 16 weeks, there was a group-by-time interaction whereby absolute changes in LDL-cholesterol were lower in EP [mean difference: -0.79 mmol/L, 95% confidence interval (CI): -1.29, -0.28, P = 0.002] and P (mean difference: -0.76 mmol/L, 95% CI: -1.26, -0.26, P = 0.003) vs. C. Serum insulin also showed group-by-time interactions at 16 weeks whereby fold changes were lower in EP (mean difference: -0.40, 95% CI: -0.65, -0.16, P = 0.001) and P (mean difference: -0.32, 95% CI: -0.56, -0.08, P = 0.009) vs. C, and fold changes in HOMA-IR improved in EP (mean difference: -0.37, 95% CI: -0.64, -0.10, P = 0.007) and P (mean difference: -0.27, 95% CI: -0.53, -0.00, P = 0.048) vs. C. Serum resistin declined in P only (group-by-time interaction at 16 weeks: P = 0.009). No other interactions were observed in outcome measures (P > 0.05), and kidney function (eGFR) remained unaltered. CONCLUSIONS: Sixteen weeks of leucine-enriched whey protein supplementation alone and combined with resistance-based exercise improved cardiometabolic health markers in older adults.
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    EFFECT OF DENOSUMAB ON FALLS, MUSCLE STRENGTH, AND FUNCTION IN COMMUNITY-DWELLING OLDER ADULTS
    Phu, S ; Hassan, EB ; Vogrin, S ; Kirk, B ; Duque, G (WILEY, 2019-12-01)
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    Association between structural changes in brain with muscle function in sarcopenic older women: the women's healthy ageing project (WHAP)
    Hassan, EB ; Szoeke, C ; Vogrin, S ; Phu, S ; Venkatraman, V ; Desmond, P ; Steward, C ; Duque, G (JMNI, 2019-06-01)
    OBJECTIVES: The involvement of changes in brain structure in the pathophysiology of muscle loss (sarcopenia) with aging remains unclear. In this study, we investigated the associations between brain structure and muscle strength in a group of older women. We hypothesized that structural changes in brain could correlate with functional changes observed in sarcopenic older women. METHODS: In 150 women (median age of 70 years) of the Women's Healthy Ageing Project (WHAP) Study, brain grey (total and cortex) volumes were calculated using magnetic resonance imaging (MRI) analyses. Grip strength and timed up and go (TUG) were measured. The brain volumes were compared between sarcopenic vs. non-sarcopenic subjects and women with previous falls vs. those without. RESULTS: Based on handgrip strength and TUG results respectively, 27% and 15% of women were classified as sarcopenic; and only 5% were sarcopenic based on both criteria. At least one fall was experienced by 15% of participants. There was no difference in brain volumetric data between those with vs. without sarcopenia (p>0.24) or between women with falls (as a symptom of weakness or imbalance) vs. those without history of falls (p>0.25). CONCLUSIONS: Brain structure was not associated with functional changes or falls in this population of older women.
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    Body composition reference ranges in community-dwelling adults using dual-energy X-ray absorptiometry: the Australian Body Composition (ABC) Study
    Kirk, B ; Bani Hassan, E ; Brennan-Olsen, S ; Vogrin, S ; Bird, S ; Zanker, J ; Phu, S ; Meerkin, JD ; Heymsfield, SB ; Duque, G (WILEY, 2021-05-14)
    BACKGROUND: Reference ranges for lean mass (LM) and fat mass (FM) are essential in identifying soft tissue disorders; however, no such reference ranges exist for the most commonly used Hologic dual-energy X-ray absorptiometry (DXA) machine in Australia. METHODS: Cross-sectional study of community-dwelling adults (aged 18-88 years) who underwent a Hologic DXA scan at one of three commercialized densitometry centres in Australia. Age-specific and sex-specific percentile curves were generated for LM [LM, appendicular lean mass (ALM), ALM adjusted for height squared (ALM/h2 ), and ALM adjusted for body mass index (ALM/BMI)] and FM [FM, FM adjusted for height squared (FM/h2 ), appendicular fat mass, and android and gynoid fat] parameters using the LMS statistical method. Cutpoints equivalent to T-scores of -1, -2, and -2.5 standard deviations below the young mean reference group (20-29 years) were also generated for LM parameters. RESULTS: A total of 15 479 community-dwelling adults (54% men) with a median age of 33 years (interquartile range: 28, 42) were included. LM, ALM, and ALM/h2 remained stable until age 50, after which these parameters started to decline in both sexes. Compared with age 50, median percentiles of LM, ALM, and ALM/h2 declined by -5.9 kg, -3.7 kg, and -0.86 kg/m2 in men and by -2.5 kg, -1.8 kg, and -0.10 kg/m2 in women at age 70, respectively. Adjusting ALM for BMI (rather than height squared) resulted in different trends, with ALM/BMI decreasing from as early as age 20. Compared with age 20, median percentiles of ALM/BMI at age 40 declined by -0.10 kg/kg/m2 in men and by -0.06 kg/kg/m2 in women; and at age 70, ALM/BMI declined by -0.25 kg/kg/m2 in men and by -0.20 kg/kg/m2 in women. Cutpoints equivalent to T-scores of -1, -2, and -2.5 standard deviations for ALM/BMI were 1.01, 0.86, and 0.77 kg/kg/m2 in men and 0.70, 0.59, and 0.53 kg/kg/m2 in women, respectively. All FM parameters progressively increased from age 20 and continued up until age 70. CONCLUSIONS: We developed reference ranges for LM and FM parameters from Hologic DXA machines in a large cohort of Australian adults, which will assist researchers and clinicians in identifying soft tissue disorders such as obesity, sarcopenia, and cachexia.
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    Does Exercise Influence Kynurenine/Tryptophan Metabolism and Psychological Outcomes in Persons With Age-Related Diseases? A Systematic Review
    Lim, A ; Harijanto, C ; Vogrin, S ; Guillemin, G ; Duque, G (SAGE PUBLICATIONS LTD, 2021-02-01)
    BACKGROUND: The kynurenine (KYN) pathway has been implicated in many diseases associated with inflammation and aging ("inflammaging"). Targeting the kynurenine pathway to modify disease outcomes has been trialled pharmacologically, but the evidence of non-pharmacological means (ie, exercise) remains unclear. OBJECTIVE: We aim to assess the evidence of the effects of exercise on the kynurenine pathway and psychological outcomes. METHODS: Under Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, a systematic literature search was performed in MEDLINE, EMBASE, EMCARE, and the Cochrane Central Registry of Controlled Trials. The main outcomes were changes in kynurenine pathway metabolite levels and psychological outcomes. RESULTS: Six studies were analyzed (total n = 379) with exercise demonstrating significant concomitant effects on kynurenine pathway metabolite levels and associated psychological outcomes in domains of somatization, anxiety, and depression. CONCLUSION: Exercise has significant concomitant effect on kynurenine pathway metabolite levels and psychological outcomes. However, clear limitations exist in determining if the changes in the kynurenine pathway can fully explain the changes in psychological outcomes, or whether different diseases and exercise interventions act as confounding factors.