High‐energy trauma patients represent the ultimate challenge to trauma care and are at risk of injury‐related mortality and morbidity—a common cause of loss of productivity. The aim of this study was to implement computed tomography (CT)‐derived, artificial intelligence (AI)‐based body composition analysis (BCA) to identify predictors of morbidity.
Abstract Background Sarcopenia in cancer impacts overall survival, surgical complications, and side effects of oncological treatments. Cancer patients frequently receive cross‐sectional imaging, allowing incidental capture of radiological sarcopenia biomarkers. These biomarkers vary by imaging modality, tumour group, patient demographics, and anatomy but lack a consensus with regard to clinical application. In this article, we provide an overview of radiology‐based sarcopenia biomarkers by anatomy and their prevalence in the literature. Methods In accordance with previously published scoping review protocol, we searched PubMed/MEDLINE, Embase, Scopus, and Cochrane between 2007 and June 2021. Studies were independently reviewed by two authors with Cohen's kappa 0.81 and reported using descriptive statistics. Results There were 5649 titles and abstracts reviewed, including 459 full‐text articles. There were 23 additions found through references, resulting in 482 total studies. There is a consistent year‐on‐year increase of new radiological sarcopenia landmarks since 2015, with 49.8% studies reporting novel definitions of sarcopenia. The majority of studies ranged between 50 and 300 participants and featured an abdominal sarcopenia marker (94.4%), of which 75.2% used the skeletal muscle index at L3 (L3SMI). Sarcopenia prevalence ranged from 8.33% to 89.66%. Biomarkers are often applied across genders and ethnicities, regardless of the original population the definition originated from, despite the emergence and availability of ethnic‐specific alternatives. Conclusion There remains a need to incorporate demographics and age into predictive models derived from sarcopenia biomarkers obtained through routine clinical imaging. Use of individual biomarkers needs to be made with careful consideration of the population in which the biomarkers were generated.
Abstract Background Sarcopenia is characterized by the progressive and generalized loss of muscle mass and function. There is an increasing body of evidence to suggest that cancer patients with pre‐existing sarcopenia are at a greater risk of both short‐ and long‐term clinical complications. The aim of this review is to examine the impact of low muscle mass on prognostic outcomes in patients with locally advanced rectal cancer (LARC) who undergo neoadjuvant chemoradiotherapy (nCRT) prior to surgery. Methods MEDLINE, PubMed, and Embase databases were searched from inception to October 2021. Any comparative studies relating to the prognostic outcomes of sarcopenic versus non‐sarcopenic patients with LARC who received nCRT prior to surgery were included. Risk of bias was assessed using the Risk Of Bias In Non‐randomized Studies of Interventions (ROBINS‐I). Meta‐analysis was performed on reported hazard ratios (HR) and 95% confidence intervals (CI) using DerSimonian–Laird random‐effects models. Results A total of 598 patients from five studies were included in the analysis of hazard ratios for overall survival, whereas 505 patients from four studies were available for analysis of HR for disease‐free survival. Meta‐regression analysis showed a significant association between pre‐existing sarcopenia and worse overall survival (HR: 1.69, 95% CI: 1.15–2.48). The association between pre‐existing sarcopenia and shorter disease‐free survival was not statistically significant (HR: 1.07, 95% CI: 0.63–1.82). Conclusions The review highlights the role that body composition can play on prognostic outcomes in patients undergoing multimodal cancer treatment. Given the complex underpinnings of sarcopenia progression, more research is needed to develop strategies to mitigate this impact in a physiologically vulnerable population.
Abstract Background Thought to capture the nutritional and functional reserve of the cancer patient, whether the computed tomography (CT)‐derived sarcopenia score (CT‐SS) has complimentary prognostic value to commonly utilized pre‐treatment host assessments in patients with oesophago‐gastric (OG) cancer is unknown. The aim of the present study was to examine if the CT‐SS can stratify survival in OG cancer patients with good performance status [Eastern Cooperative Oncology Group Performance Status (ECOG‐PS) 0/1]. Furthermore, if the CT‐SS had complimentary prognostic value to cardiopulmonary exercise testing (CPET) performance and systemic inflammation. Methods Consecutive patients with confirmed OG cancer and good performance status, who received neoadjuvant chemotherapy (NAC) with a view to surgical resection with curative intent, between 1 January 2010 and 31 December 2015, within NHS Greater Glasgow and Clyde (NHSGGC) and NHS Forth Valley (NHSFV), were identified from a prospectively maintained database. CT‐SSs were grouped as 0/1/2. CPET variables recorded included VO2 anaerobic threshold (AT) and peak. Systemic inflammatory response was determined by modified Glasgow prognostic score (mGPS) and neutrophil/lymphocyte ratio (NLR). Associations between categorical variables were examined using χ2 test and binary logistics regression analysis. Results A total of 232 patients met the inclusion criteria. 75% (n = 174) of patients were male, 54% (n = 126) were 65 years or older, and 60% (n = 139) were overweight [body mass index (BMI) ≥25 kg/m2]; 33% (n = 77) of patients had CT‐SS ≥ 1, 36% (n = 83) had a low VO2 AT (≤11 ml/kg/min), and 57% (n = 132) had a low VO2 peak (≤19 ml/kg/min). Of the 200 patients who had pre‐NAC bloods facilitating calculation of the mGPS, 28% (n = 55) had mGPS ≥ 1. Of the 211 patients who had pre‐NAC bloods facilitating calculation of NLR, 38% (n = 80) had an NLR ≥ 3; 82% (n = 190) and 53% (n = 122) were alive at 1 and 3 years post‐NAC, respectively. On univariate analysis, CT‐SS was significantly associated with sex (P < 0.05), histological cell type (P < 0.05), low VO2 AT (P < 0.05), low VO2 peak (P < 0.05), BMI (P < 0.05), mGPS (P < 0.05), and 3‐year survival (P < 0.05). On multivariate analysis, tumour, node, and metastasis (TNM) stage (P < 0.05) and CT‐SS (P < 0.05) remained significantly associated with 3‐year survival. CT‐SS was significantly associated with 3‐year survival in patients who had mGPS 0 (P < 0.05), but not low VO2 AT (P = 0.066) or peak (P = 0.065). Conclusion The CT‐SS would appear to capture the nutritional and functional reserve of the patient and is a useful objective measure for stratifying long‐term survival in patients with good performance status undergoing potentially curative treatment for OG cancer.
Abstract Background This study investigated relative contributions of ankle flexor torque, muscle size, and density on balance and falls. Methods Men and women ≥50 years of age completed a peripheral quantitative computed tomography scan of the mid‐leg to quantify muscle density (MD) and cross‐sectional area; Biodex dynamometry to evaluate maximal isometric ankle flexor torque; and a single‐leg balance test on a force platform with/without eyes closed and cognitive task. Ankle flexor torque, muscle size, and density individually, together, or as interactions were examined for associations with balance (mean step duration, steps/trial) in general linear models, or with falls in Poisson regression, adjusting for age, sex, BMI, glucocorticoid use, osteoarthritis, and physical activity. Visuo‐cognitive conditions were compared. Results Among 105 participants (age: 63.3 ± 9.9 years, BMI: 25.8 ± 5.4 kg/m2, 77.1% female), 41.8% experienced ≥1 fall in the last year. Balance on one leg was dependent on ankle flexor torque when eyes were open (r = −0.220 to −0.284) and on having leaner mid‐leg muscles when eyes were closed (r = −0.123 to −0.142); cognitive challenge blunted these correlations. Individuals with leaner muscles tended to rely more on plantarflexors than dorsiflexors. A 2% lower step‐free fraction in the eyes‐closed paradigm associated with having 1 additional fall [−0.701(−1.235, −0.167)], but neither torque, muscle density, nor size related to number of falls. Conclusions Among ambulatory adults, ankle flexor torque and muscle density showed an interactive influence on balance that depended on visuo‐cognitive input. The complementary roles of torque and muscle density on balance suggest redundancy is important under dual‐tasking conditions.
Abstract Background In rheumatoid cachexia (RC), high resting energy expenditure (REE) is associated with loss of muscle mass driven by proinflammatory cytokines. The objectives of this study were to investigate parameters associated with RC and the interaction between systemic inflammation and modifiable risk factors for RC on REE. Methods Thirty‐five rheumatoid arthritis (RA) and 19 non‐RA controls comparable in age/sex/race/body mass index (BMI) underwent measures of REE by indirect calorimetry. Homeostasis model assessment for insulin resistance (HOMA‐IR) and serum interleukin‐6 (IL‐6) were used as parameters of IR and systemic inflammation, respectively. Regression models tested association between REE and dependent variables, including pre‐specified interaction tests involving HOMA‐IR and IL‐6 and dietary intake of protein per weight (PPW) and IL‐6. Results Rheumatoid arthritis subjects were mostly women (94%) and had a median age of 54 years (50.5, 70) and BMI of 30.5 kg/m2 (26.1, 36.9). Approximately two‐thirds of RA participants were seropositive, with median disease duration [interquartile range (IQR)] and a DAS‐28 C‐reactive protein [IQR] of 7.83 years [4.89, 18.14] and 1.7 mg/day [1.21, 2.78], respectively. RA participants demonstrated significantly higher levels of HOMA‐IR compared with non‐RA controls (P = 0.006). Fat‐free mass index (FFMI, P = 0.33), REE (P = 0.68), IL‐6 (P = 0.13), and estimates of dietary intake including PPW tertiles (P = 0.83) were not significantly different between RA and non‐RA. In univariate analyses, REE was positively associated with BMI (P = <0.001), FFMI and FMI (P = <0.001), and HOMA‐IR (P = 0.001), but not with PPW (P = 0.10). After adjustment for age and FFMI, we did not observe significant associations of HOMA‐IR [β = 4.66, 95% confidence interval (CI) [−33.16, 42.48], P = 0.80], IL‐6 (β = −9.45, 95% CI [−25.61, 6.72], P = 0.24), or the interaction between HOMA‐IR and IL‐6 (β = 6.00, 95% CI [−5.47, 17.46], P = 0.29) with REE. In multiple regression models with IL‐6, PPW, and their interaction term, we observed a significant crossover interaction effect between PPW and IL‐6 on REE. The upper tertile of PPW demonstrated a significant negative correlation between REE and IL‐6 (β = −19.97, 95% CI [−35.41, −4.54], P = 0.01). The lower tertile of PPW demonstrated a significant positive correlation between REE and IL‐6 (β = 42.24, 95% CI [4.25, 80.23], P = 0.03). This supports an interplay between PPW and IL‐6 on REE. Animal protein intake, which has more of an anabolic effect compared with vegetable protein, was significantly higher among RA subjects in the higher tertile of PPW compared with RA subjects in the lower tertile of PPW (P = <0.001). Conclusions While IR can lead to muscle catabolism, IR was not significantly associated with REE in RA individuals. Higher dietary protein intake could attenuate the effect of systemic inflammation on REE in RA patients.
AbstractBackgroundNicotinamide adenine dinucleotide (NAD) is a key molecule in muscle metabolism and energy production; skeletal muscle concentrations are low in older people with sarcopenia. Although preclinical data suggest beneficial effects of NAD precursor supplementation, the effects on skeletal muscle function and physical frailty in humans are unclear. This systematic review evaluated the effects of NAD precursor supplementation on measures of physical performance and physical frailty in humans.MethodsWe included randomized controlled trials assessing outcomes relevant to either physical performance or any of Fried's frailty phenotype domains: slowness, weakness, exhaustion, low physical activity and weight loss. All review stages were conducted independently by two separate authors. A systematic search strategy was used searching multiple databases (MEDLINE, EMBASE, CINAHL, CENTRAL, ISRCTN, ClinicalTrials.gov, NHS e‐Library, and Google Scholar) to find appropriate trials. Risk of bias was assessed using the Cochrane Risk‐of‐Bias 2 tool. Results were grouped by intervention and phenotypic domain and were described through narrative synthesis. Sensitivity analyses were conducted for trials with a mean age >60 years and trials with low risk of bias.ResultsTwenty‐six trial populations across 23 studies met inclusion criteria; size ranged from 2 to 77 participants. No trials assessed frailty as a composite outcome, though at least one Fried frailty domain was assessed in almost all included trials. A range of interventions were investigated; niacin (n = 8) and nicotinamide riboside (n = 7) were the most commonly assessed. Most trials examined short‐term interventions of up to 6 months duration, with 13 out of 26 trials lasting 1 week or less. A total of 96 primary outcomes were assessed across trials, 10 of which were in favour of an NAD precursor whereas 1 was in favour of placebo; the remainder were not statistically significant in any clear direction. Methodological heterogeneity across trials precluded meta‐analysis for any outcome. Trial populations were heterogeneous and only four trials enrolled participants with a mean age ≥60 years. Risk of bias analysis found unclear or high risk of bias in all but one trial. There was no clear pattern as to whether NAD precursors improved any measure of physical performance or any domain of the frailty phenotype; the majority of trials reported neutral findings for most outcomes.ConclusionsThere is insufficient evidence to ascertain whether NAD precursor supplementation can improve physical performance or physical frailty measures in humans. Future trials need to be longer, larger, and target older people with skeletal muscle dysfunction.
Abstract Background Linear measurement analysis using computed tomography (CT) scans to quantify abdominal muscle mass has been validated as a clinically practical approach for screening individuals with low muscle mass. However, there is still a need to validate such analysis using magnetic resonance imaging (MRI) imaging. The aim of this study is to assess the reproducibility and concordance of CT and MRI imaging for linear measurement analyses of skeletal muscle at mid‐L3. Methods We retrospectively analysed 66 patients with available CT and MRI images within 30 days of one other to evaluate linear measurement CT and MRI concordance. Linear measurement analysis for abdominal/pelvic CT and MRI scans for eight patients was conducted independently three times by the same person separated by at least 1 week to assess intra‐rater variability. The intra‐observer variability for both CT and MRI was assessed using the intraclass correlation coefficient (ICC). The concordance and correlation of CT and MRI mid‐L3 for linear measurements were assessed using Pearson correlation coefficients and Bland–Altman plots. Results The intra‐rater reliability of linear measurements for both CT and MRI was high, as measured by the ICC (CT range: 0.788–0.992; MRI range: 0.766–0.984). CT and MRI linear measurements were found to be significantly positively correlated for all psoas (total psoas r = 0.98; P < 0.0001) and paraspinal muscle measurements (total paraspinal r = 0.99; P < 0.0001). Bland–Altman analysis revealed a mean bias of 0.83 (range: 0.03–5.56) for MRI over CT linear measurements. Conclusions CT and MRI images were shown to be concordant for linear measurement analysis of abdominal muscle mass. T2‐weighted MRI sequences can be used interchangeably with CT in the assessment of sarcopenia using linear measurement analysis.
Abstract Background The Barthel Index (BI) is among the most widely used instruments for evaluating physical function, yet its applicability has not been well studied in the oldest‐old population. Objective To test the psychometric properties of the BI for evaluating physical activities of daily living (ADL) in a large representative sample of oldest‐old population in China. Methods Participants were 1750 oldest‐old adults (aged 80–116 years, 72.11% female) including 956 centenarians. ADL were assessed during face‐to‐face interviews. Multiple methodologies were applied to evaluate the reliability, validity and measurement invariance of the BI. An item response theory (IRT) framework was conducted to estimate the parameters of each item. Results 48.91% participants had function dependence. Cronbach's α coefficient of the BI was 0.902, but ‘Stair climbing’ impaired the overall internal consistency. The known‐group validity of the BI was confirmed by significant differences in the BI score across age (P < 0.001), gender (P < 0.001), education (P < 0.001) and ethnicity (P = 0.038). The criterion‐related validity was supported by significant correlations between the BI score with depression symptoms (r = −0.36, P < 0.001), subjective well‐being (r = 0.23, P < 0.001) and self‐report health status (r = 0.22, P < 0.001). Factor analysis yielded a two‐factor structure (somatic function and physiological self‐care) with appropriate invariance. Ten items showed acceptable discrimination parameters (1.80–5.87) and difficulty parameters (−2.65–1.11) but had variant test information (1.73–10.22). ‘Bower control’ and ‘Bladder control’ were not conducive to the local independence. Conclusions The BI has appropriate reliability, validity and measurement precision for community‐based Chinese oldest‐old and centenarians, but individual items have low quality. Somatic disability and incontinence are two latent categories of functional dependence in this population. Living environment needs to be taken into consideration for ADL instrument development and modification.
Abstract Background Hip fractures (HF) are a high‐impact geriatric syndrome. Vitamin B12 deficiency is an HF risk factor. There are few studies on prevalence of B12 deficiency in older adults with HF. The objectives are as follows: in older adults with HF, to describe/characterize plasma levels of vitamin B12 (PL‐B12); to verify presence/absence of a subgroup with borderline, near‐deficient PLB12; to describe HF incidence; and to analyse relationships between PL‐B12 and studied variables. Methods Cross‐sectional, observational study, analytical component. Complete Collection sample (01.08.2016–31.08.2018). Variables: PL‐B12, age, sex, HF location, time of year, in‐hospital stay length. Medians/percentiles, non‐parametric tests. PL‐B12 cut‐off points according to the WHO, proposing new cut‐off points to capture borderline values. Results A total of 580 subjects. HF incidence = 264/100 000 ≥ 65 years, 79% female, 72% extracapsular HF. Medians: age = 83 years; PL‐B12 = 349 pg/cc; hospitalization = 13 days. Significantly lower PL‐B12 in males (P = 0.023) and extracapsular fractures (P = 0.013). No significant differences between age groups, length of hospitalization, and season of the year. Thirty‐five per cent B12 deficiency (16% deficiency and 19% mild deficiency). By increasing cut‐off point for deficiency to 400 pg/cc, prevalence increased to 58%. Conclusions High prevalence of vitamin B12 deficiency among older adults with HF, significantly higher in men and extracapsular HF. Twenty‐four per cent normal PL‐B12 according to WHO criteria, but with borderline, near‐deficient levels, at the time of HF. In older adults with HF, we recommend measuring PL‐B12 and raising the cut‐off level required to diagnose deficiency. We consider that older adults with HF are a specific risk group for vitamin B12 deficiency.
AbstractBackgroundSarcopenia has been defined as a loss of muscle mass and function. CT‐derived muscle measurements, skeletal muscle index (SMI) and density (SMD), taken together may provide an objective measure of sarcopenia. The aim of the present study was to examine the relationship between CT‐derived sarcopenia (low SMI and SMD), clinicopathological characteristics, systemic inflammation and survival in patients undergoing surgery for colorectal cancer.MethodsConsecutive patients who underwent resections for colorectal cancer (TNM I–III) at our institution, between April 2008 and 2018, were identified from a prospectively maintained database. CT‐derived muscle mass (SMI) and density (SMD) measurements were combined to form the CT‐Sarcopenia score (CT‐SS). Thresholds for low SMI and SMD reported by Martin and co‐workers and Caan/Xiao and co‐workers were combined to form two iterations of the CT‐SS. Patients were categorized as normal/high SMI (irrespective of SMD) = 0, low SMI and normal/high SMD = 1 and low SMI and low SMD = 2. The Pearson Chi square test was used to examine the associations between categorical variables and the Chi square test for linear trend was used for ordered variables with multiple categories. Survival data were analysed using univariate and multivariate Cox regression.ResultsOne thousand and two patients met the study inclusion criteria. Fifty‐five per cent (n = 554) of patients were male and 66% (n = 657) were aged 65 years or older. Twenty‐four per cent (n = 240) of patients had TNM stage I disease, 40% (n = 404) stage II and 36% (n = 358) stage III. Eighteen per cent (n = 174) of patients were at risk of malnutrition. Forty‐eight per cent (n = 479) of patients had an NLR ≥ 3 and 27% (n = 271) had an mGPS ≥ 1. Similar numbers of patients defined as CT‐SS 0, 1 and 2 irrespective of thresholds applied (49%/12%/39% vs. 43%/19%/38%, respectively). Eight hundred and thirty four (n = 834) patients who underwent surgical resection for non‐metastatic colorectal cancer with curative intent were alive at 3 years. On univariate analysis, both the CT‐SS (Martin/Martin) and CT‐SS (Caan/Xaio) were significantly associated with age (P < 0.001 and P < 0.001, respectively), ASA (P < 0.01 and P < 0.001, respectively), MUST (P < 0.001 and P < 0.005, respectively), mGPS (P < 0.001 and P < 0.001, respectively), NLR (P < 0.001 and P < 0.001, respectively), and overall survival (P < 0.001 and P < 0.001, respectively). CT‐SS (Caan/Xaio) was significantly associated with TNM stage (P < 0.05), but not CT‐SS (Martin/Martin, P = 0.221).ConclusionsThe objective CT‐SS was significantly associated with older age, co‐morbidity, nutritional risk, systemic inflammation and poorer survival, irrespective of thresholds used. However, the relationship between CT‐SS and TNM stage was inconsistent and threshold dependent.
Abstract Background To externally evaluate the first picture archiving communications system (PACS)‐integrated artificial intelligence (AI)‐based workflow, trained to automatically detect a predefined computed tomography (CT) slice at the third lumbar vertebra (L3) and automatically perform complete image segmentation for analysis of CT body composition and to compare its performance with that of an established semi‐automatic segmentation tool regarding speed and accuracy of tissue area calculation. Methods For fully automatic analysis of body composition with L3 recognition, U‐Nets were trained (Visage) and compared with a conventional image segmentation software (TomoVision). Tissue was differentiated into psoas muscle, skeletal muscle, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Mid‐L3 level images from randomly selected DICOM slice files of 20 CT scans acquired with various imaging protocols were segmented with both methods. Results Success rate of AI‐based L3 recognition was 100%. Compared with semi‐automatic, fully automatic AI‐based image segmentation yielded relative differences of 0.22% and 0.16% for skeletal muscle, 0.47% and 0.49% for psoas muscle, 0.42% and 0.42% for VAT and 0.18% and 0.18% for SAT. AI‐based fully automatic segmentation was significantly faster than semi‐automatic segmentation (3 ± 0 s vs. 170 ± 40 s, P < 0.001, for User 1 and 152 ± 40 s, P < 0.001, for User 2). Conclusion Rapid fully automatic AI‐based, PACS‐integrated assessment of body composition yields identical results without transfer of critical patient data. Additional metabolic information can be inserted into the patient's image report and offered to the referring clinicians.
AbstractBackgroundBody composition is of clinical importance in colorectal cancer patients, but is rarely assessed because of time‐consuming manual segmentation. We developed and tested BodySegAI, a deep learning‐based software for automated body composition quantification from routinely acquired computed tomography (CT) scans.MethodsA two‐dimensional U‐Net convolutional network was trained on 2989 abdominal CT slices from L2 to S1 to segment skeletal muscle (SM), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and intermuscular and intramuscular adipose tissue (IMAT). Human ground truth was established by combining segmentations from three human readers. BodySegAI was tested using 154 slices against the human ground truth and compared with a software named AutoMATiCA.ResultsMedian Dice scores for BodySegAI against human ground truth were 0.969, 0.814, 0.986, and 0.990 for SM, IMAT, VAT, and SAT, respectively. The mean differences per slice for SM were −0.09 cm3, IMAT: −0.17 cm3, VAT: −0.12 cm3, and SAT: 0.67 cm3. Median absolute errors for SM, IMAT, VAT, and SAT were 1.35, 10.54, 0.91, and 1.07%, respectively. When analysing different anatomical levels separately, L3 and S1 demonstrated the overall highest and lowest Dice scores, respectively. On average, BodySegAI segmented 148 times faster than human readers (4.9 vs. 726.5 seconds, P < 0.001). Also, BodySegAI presented higher Dice scores for SM, IMAT, SAT, and VAT than AutoMATiCA (slices = 154).ConclusionsBodySegAI rapidly generates excellent segmentation of SM, VAT, and SAT and good segmentation of IMAT in L2 to S1 among colorectal cancer patients and may replace semi‐manual segmentation.
AbstractBackgroundThere is a high incidence of preoperative undernutrition in hospitalised patients in low and middle‐income countries (LMICs), leading to increased postoperative complications, length of hospital stay and early mortality. Review aims are to establish the prevalence of undernutrition and assess the use of validated nutritional screening tools in surgical patients across LMICs.MethodsProtocol was PRISMA compliant and Prospero registered (CRD42019126765). Twelve international databases were searched from January 1990 to April 2021. Included studies were on nutritional screening in adults (≥16 years) undergoing surgery in LMICs. Two researchers screened studies and assessed quality. Prevalence of undernutrition was presented as a weighted percentage with confidence intervals (CI).ResultsOf the 4649 records identified, 16 studies (n = 4032) were eligible. Subjective global assessment (SGA) or patient generated (PG)‐SGA were the tools used most widely. SGA and PG‐SGA showed a high prevalence of undernutrition overall (0.61, 95% CI 0.50, 0.73), with a proportion identified with moderate undernutrition (0.44, 95% CI 0.31, 0.57) or severe undernutrition (0.32, 95% CI 0.19, 0.45).ConclusionsData show the prevalence of undernutrition in surgical patients as high as three in five patients within LMICs. Results indicate that the SGA is suitable for assessing this group of patients and that it may be the most appropriate tool to use due to its subjectivity and reliability. PG‐SGA although similar includes more symptom assessment, which is important for nutritionally depleted cancer patients. The limited data on validity and reliability of nutritional screening tools in LMICs indicates further research is required.
Abstract Background Cancer cachexia is manifested by loss in muscle, adipose, weight, and appetite. PET 18F‐FDG uptake identifies tumour metabolic and inflammatory changes, potentially associated with cachexia development. We examined if primary gastroesophageal tumour 18F‐FDG uptake correlates with cachexia development and survival in cancer patients. Methods One hundred twenty‐six oesophageal (n = 87) and gastroesophageal junction (n = 39) cancer patients, with a median age at diagnosis of 63 years (IQR 54–71), evaluated between 2006 and 2014 with pre‐treatment PET imaging and cachexia determination at diagnosis were included in the study cohort (22.1% female; 6.7%, 24.4%, 50.4%, and 18.5% with tumour stage I, II, III, and IV, respectively). Maximum primary tumour standardized uptake values were obtained and dichotomized based off the calculated cut‐point SUVMax of 8.5 (P = 0.0018). Associations between survival, cachexia development, and primary tumour 18F‐FDG uptake were evaluated using univariate and multivariate analyses. Results Cancer‐associated weight loss (cachexia) and primary tumour SUVMax at or above the statistically determined cut‐point of 8.5 were present in 54% and 57% of patients, respectively. Primary tumour SUVMax above the cut‐point was significantly associated with pre‐treatment cancer‐associated weight loss (P = 0.0033) and, in multivariate analysis, correlated with a 2.3‐fold increased risk of death (95% CI 1.4, 3.7; P = 0.0010). When divided into cohorts defined by their combined cachexia and high versus low SUVMax tumour status, positive cachexia status or/and high SUVMax tumours were associated with similar significant decrements in survival. Conclusion A positive association was present between cancer‐associated weight loss and SUVMax of the primary tumour, suggesting greater glycolytic metabolism in gastroesophageal tumours that induce cachexia. This interpretation of routinely administered PET scans could lead to earlier categorization of patients with cachexia‐inducing tumours. Both cachexia and high SUVMax status were independently associated with worsened survival outcomes, further supporting their prognostic relevance in patients with gastroesophageal cancer.
Abstract Background Myostatin (MSTN) is a key negative regulator of muscle mass in humans and animals, having direct and indirect influences on molecular regulators of atrophy and hypertrophy, thus potentially impacting fitness and physical function. We have shown that myostatin is elevated in conditions of chronic disability (e.g. paretic limb of stroke). Our hypothesis is that myostatin would be elevated in older adults with sarcopenia. The purpose of this study was to examine the role of skeletal muscle myostatin in sarcopenia. Methods Sixty‐four overweight to obese aged 45–81 years underwent a maximal aerobic capacity (VO2max) test, dual‐energy X‐ray absorptiometry (DXA) scan to determine appendicular lean tissue (ALM), and vastus lateralis muscle biopsy to determine myostatin mRNA expression by quantitative real time PCR (Q‐RT‐PCR). Rates of sarcopenia were determined using (ALM/BMI), and sarcopenia was defined as <0.789 in men and <0.512 in women. Subjects had low fitness (VO2max: 22.7 ± 0.7 mL/kg/min) and on average 40.9 ± 1% body fat. Results The prevalence of sarcopenia in this cohort was 16%. BMI, % body fat, and fat mass were higher in adults with sarcopenia than those without sarcopenia (all P < 0.001). Myostatin mRNA expression was lower in those without sarcopenia than those with sarcopenia (P < 0.05) and higher in men than women (P < 0.001). Myostatin expression was associated with BMI (r = 0.36, P < 0.01) and mid‐thigh intramuscular fat (r = 0.29, P < 0.05). Conclusion Given that myostatin is important in muscle atrophy, fat accumulation, and sarcopenia, further work could address its implication in other aging cohorts of disability and chronic disease.
e21049 Background: Sarcopenia has been receiving attention due to its association with prognoses in patients with cancer. We investigated the association between evolving sarcopenia assessed with computed tomography (CT) and outcome of non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs). Methods: In this retrospective study, 47 NSCLC patients who received ICIs at our Hirosaki University Hospital were enrolled. Skeletal muscle area at the level of the third lumbar vertebra (L3-SMA) was measured from CT images before and 90 days after the ICI treatment. The factor related to the poor efficacy of ICIs was determined by logistic regression analysis. The prognostic cut-off value was estimated by a receiver operating characteristic (ROC) curve. As covariate factors, age, gender, smoking history, histology, performance status (PS), PD-L1 tumor proportion score (TPS), status of driver mutations, body mass index (BMI), serum protein and albumin levels, and lymphocyte count were included. Results: In the univariate analysis, reduction rate of L3-SMA, PS, BMI, serum protein and albumin levels, and lymphocyte count were significantly associated with efficacy. In the multivariate analysis, only reduction rate of L3-SMA was significant. The cut-off value was estimated to be 6%. The study subjects were divided into two groups by the cut-off value. In both of progression free and overall survival analysis, those with more than 6% of reduction had significantly shorter period being free of events than that of the other. Conclusions: Evolving sarcopenia assessed with CT images is promising as a prognostic factor in Japanese NSCLC patients receiving ICIs.
Abstract Background This study investigated the effects of methylmercury intoxication on mice skeletal muscle subjected or not to progressive resistance training (RT). Methods Four experimental groups were formed. Control and Con + RT received water and methylmercury (MeHg) and MeHg + RT groups received methylmercury (5 mg/kg/day), via gavage for 14 days. The Con + RT and MeHg + RT animals performed weighted ladder climbing RT, three times a week for 4 weeks. Animal muscle strength and gastrocnemius and soleus cross‐section area, fibrosis, myosin heavy chains (MyHCs), E3‐ligases MAFbx and MuRF1, 20S proteasome (P20S) and LC3‐II content were analysed. In addition, P20S chymotrypsin‐like activity was evaluated. Results Resistance training protected MeHg + RT mice against strength loss but not against muscle atrophy. The latter appeared to be associated with MyHCs significant content reductions observed in the MeHg and MeHg + RT groups. In soleus muscle, there was an increase in E3‐ligases and P20S levels and P20S activity in both methylmercury groups compared with control ones. This pattern was also observed for gastrocnemius muscle, except for P20S content and activity that decreased. The P‐AKT content decreased in the soleus and gastrocnemius of the MeHg animals while significant elevation of LC3‐II content levels occurred. Conclusions The accumulation of methylmercury caused an increase in skeletal muscle MyHCs degradation, resulting in muscle atrophy that was reinforced by the elevated fibrosis area. Although RT did not reverse this condition, maintenance of muscle strength levels in animals submitted to MeHg + RT was detected. We believe that RT somewhat protected MeHg from damage to neural muscle structures, to be further investigated.
Abstract Background ‘Mitochondrial Myopathy’ (MM) refers to genetically‐confirmed Primary Mitochondrial Disease (PMD) that predominantly impairs skeletal muscle function. Validated outcome measures encompassing core MM domains of muscle weakness, muscle fatigue, imbalance, impaired dexterity, and exercise intolerance do not exist. The goal of this study was to validate clinically‐meaningful, quantitative outcome measures specific to MM. Methods This was a single centre study. Objective measures evaluated included hand‐held dynamometry, balance assessments, Nine Hole Peg Test (9HPT), Functional Dexterity Test (FDT), 30 second Sit to Stand (30s STS), and 6‐minute walk test (6MWT). Results were assessed as z‐scores, with < −2 standard deviations considered abnormal. Performance relative to the North Star Ambulatory Assessment (NSAA) of functional mobility was assessed by Pearson's correlation. Results In genetically‐confirmed MM participants [n = 59, mean age 21.6 ± 13.9 (range 7 – 64.6 years), 44.1% male], with nuclear gene aetiologies, n = 18/59, or mitochondrial (mtDNA) aetiologies, n = 41/59, dynamometry measurements demonstrated both proximal [dominant elbow flexion (−2.6 ± 2.1, mean z‐score ± standard deviation, SD), hip flexion (−2.5 ± 2.3), and knee flexion (−2.8 ± 1.3)] and distal muscle weakness [wrist extension (−3.4 ± 1.7), palmar pinch (−2.5 ± 2.8), and ankle dorsiflexion (−2.4 ± 2.5)]. Balance [Tandem Stance (TS) Eyes Open (−3.2 ± 8.8, n = 53) and TS Eyes Closed (−2.6 ± 2.7, n = 52)] and dexterity [FDT (−5.9 ± 6.0, n = 44) and 9HPT (−8.3 ± 11.2, n = 53)] assessments also revealed impairment. Exercise intolerance was confirmed by strength‐based 30s STS test (−2.0 ± 0.8, n = 38) and mobility‐based 6MWT mean z‐score (−2.9 ± 1.3, n = 46) with significant decline in minute distances (slope −0.9, p = 0.03, n = 46). Muscle fatigue was quantified by dynamometry repetitions with strength decrement noted between first and sixth repetitions at dominant elbow flexors (−14.7 ± 2.2%, mean ± standard error, SEM, n = 21). All assessments were incorporated in the MM‐Composite Assessment Tool (MM‐COAST). MM‐COAST composite score for MM participants was 1.3 ± 0.1 (n = 53) with a higher score indicating greater MM disease severity, and correlated to NSAA (r = −0.64, p < 0.0001, n = 52) to indicate clinical meaning. Test–retest reliability of MM‐COAST assessments in an MM subset (n = 14) revealed an intraclass correlation coefficient (ICC) of 0.81 (95% confidence interval: 0.59–0.92) indicating good reliability. Conclusions We have developed and successfully validated a MM‐specific Composite Assessment Tool to quantify the key domains of MM, shown to be abnormal in a Definite MM cohort. MM‐COAST may hold particular utility as a meaningful outcome measure in future MM intervention trials.
Abstract Background Concurrent chemoradiotherapy is the recommended treatment for limited stage small cell lung cancer. Severe side‐effects, which might cause loss of muscle mass, are frequent. Low skeletal muscle index (SMI) and radiodensity (SMD) are associated with inferior survival and more toxicity in cancer patients, but few have investigated this in small cell lung cancer, and none have investigated whether these muscle measures change during chemoradiotherapy. Patients from a trial comparing two schedules of thoracic radiotherapy (TRT) were analysed (n = 157). We investigated if SMI and SMD changed during treatment; whether changes are negative prognostic factors; or associated with severe toxicity. Methods Skeletal muscle index and SMD were assessed from computerized tomography scans taken before and after chemoradiotherapy. Patients with analysable computerized tomography scans who completed TRT were eligible. Results Sixty‐eight patients (43.3%) were analysed. Median age was 63 (range 40–85), 16% had performance status 2 and 92% stage III. Mean SMI decreased from 46.25 to 42.13 cm2/m2 and mean SMD from 38.40 to 37.46 Hounsfield units. Loss of SMD was significantly associated with less Grades 3–4 toxicity (P = 0.027) and less Grades 3–4 esophagitis (P = 0.029). Loss of SMI was significantly associated with shorter survival in multivariable (P = 0.037) but not in univariable analysis (P = 0.094). Loss of SMD was significantly associated with better survival in both univariable (P = 0.006) and multivariable analyses (P = 0.013). Conclusions There were large individual variations in changes in muscle measures during chemoradiotherapy, but the majority experienced a loss of both SMI and SMD. There was no consistent prognostic value of changes in muscle measures or consistent associations with severe treatment toxicity.
