Targeting aging with urolithin A in humans: A systematic review.

Urolithin A (UA) is a gut metabolite derived from ellagic acid. This systematic review assesses the potential geroprotective effect of UA in humans. In five studies including 250 healthy individuals, UA (10 - 1000mg/day) for a duration ranging from 28 days to 4 months, showed a dose-dependent anti-inflammatory effect and upregulated some mitochondrial genes, markers of autophagy, and fatty acid oxidation. It did not affect mitochondrial maximal adenosine triphosphate production, biogenesis, dynamics, or gut microbiota composition. UA increased muscle strength and endurance, however, had no effect on anthropometrics, cardiovascular outcomes, and physical function. Unrelated adverse events were mild or moderate. Further research across more physiological systems and longer intervention periods is required.

Geriatric Syndromes Frequently (Co)-Occur in Geriatric Rehabilitation Inpatients: Restoring Health of Acutely Unwell Adults (RESORT) and Enhancing Muscle Power in Geriatric Rehabilitation (EMPOWER-GR).

OBJECTIVE: To determine the prevalence and co-occurrence of common geriatric syndromes in geriatric rehabilitation inpatients. DESIGN: Restoring Health of Acutely Unwell Adults (RESORT) and Enhancing Muscle Power in Geriatric Rehabilitation (EMPOWER-GR) are observational, longitudinal cohorts. SETTING: Geriatric rehabilitation. PARTICIPANTS: Geriatric rehabilitation inpatients (N=1890 and N=200). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Geriatric syndromes included polypharmacy, multimorbidity (Cumulative Illness Rating Scale), cognitive impairment, depression (Hospital Anxiety and Depression Scale/Geriatric Depression Scale), malnutrition (Global Leadership Initiative on Malnutrition), functional limitation (Katz index), falls, physical frailty (Fried), and sarcopenia (European Working Group on Sarcopenia in Older People 2). RESULTS: Inpatients in RESORT (R) (N=1890, 56% females) had a median age of 83.4 years (interquartile range [IQR], 77.6-88.4) and in EMPOWER-GR (E) (N=200, 57% females) of 79.8 years (IQR, 75.0-85.9). Polypharmacy (R, 82.2%; E, 84.0%), multimorbidity (R, 90.4%; E, 85.5%), functional limitation (R, 96.0%; E, 76.5%), and frailty (R, 91.8%; E, 92.2%) were most prevalent. Most inpatients had ≥5 geriatric syndromes at admission in both cohorts (R, 70.0%; E, 72.4%); few inpatients had only 1 (R, 0.4%; E, 1.5%) or no geriatric syndrome (R, 0.2%; E, 0.0%). Geriatric syndromes did not occur in isolation (without other syndromes), except for multimorbidity (R, 1%; E, 5%), functional limitation (R, 3%; E, 2%), falls (R, 0%; E, 4%), and frailty (R, 2%; E, 5%), which occurred in isolation in some inpatients; sarcopenia did not. CONCLUSIONS: Geriatric syndromes are highly prevalent at admission to geriatric rehabilitation, with a median of 5 co-occurring syndromes. Implications for diagnosis and intervention potential should be further addressed.

Sarcopenia knowledge of geriatric rehabilitation patients is low while they are willing to start sarcopenia treatment: EMPOWER-GR.

BACKGROUND: Sarcopenia is prevalent in 20-50% of geriatric rehabilitation inpatients and is associated with functional dependence and mortality. The aim is to assess knowledge of geriatric rehabilitation inpatients on sarcopenia and their willingness and perceived barriers to start treatment. METHODS: Enhancing Muscle POWER in Geriatric Rehabilitation (EMPOWER-GR) is an observational cohort of geriatric rehabilitation inpatients in Amsterdam, the Netherlands. Knowledge of sarcopenia, willingness and perceived barriers to treatment were assessed with a survey among inpatients. Importance of and self-perceived muscle health were rated using a visual analogue scale from 0 to 10. Descriptive statistics were used. RESULTS: Inpatients' (n = 157, 59.9% female) mean age was 80.5 years (SD 7.3). Sarcopenia (European Working Group on Sarcopenia in Older People 2) prevalence was 21.7%. Five inpatients (3.2%) had heard of sarcopenia and had knowledge of its definition. Median muscle health was rated as 6 (interquartile range: 4-7). After explanation of treatment options, 67.1% were willing to start resistance exercise training (RET), 61.1% a high-protein diet and 55.7% oral nutritional supplements (ONS). Inpatients with sarcopenia were less willing (51.6%) to start a high-protein diet compared with inpatients without sarcopenia (77.8%) (P = 0.002); there was no difference for RET and ONS. Most reported barriers to treatment were ONS dislike (17.0%), too many other health issues (13.6%), doubts about treatment effectiveness/importance (12.9%) and RET intensity/difficulty (10.2%). CONCLUSIONS: Knowledge of sarcopenia was low, while the majority of inpatients showed willingness to start treatment. A dislike of ONS, RET difficulty and too many other health issues may reduce willingness to start treatment. Education is important to increase sarcopenia-related health issues in geriatric rehabilitation inpatients.

Consensus guidelines for sarcopenia prevention, diagnosis and management in Australia and New Zealand.

BACKGROUND: Sarcopenia is an age-associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand. METHODS: A four-phase modified Delphi process involving topic experts and informed by consumers, was undertaken between July 2020 and August 2021. Phase 1 involved a structured meeting of 29 Task Force members and a systematic literature search from which the Phase 2 online survey was developed (Qualtrics). Topic experts responded to 18 statements, using 11-point Likert scales with agreement threshold set a priori at >80%, and five multiple-choice questions. Statements with moderate agreement (70%-80%) were revised and re-introduced in Phase 3, and statements with low agreement (<70%) were rejected. In Phase 3, topic experts responded to six revised statements and three additional questions, incorporating results from a parallel Consumer Expert Delphi study. Phase 4 involved finalization of consensus statements. RESULTS: Topic experts from Australia (n = 62, 92.5%) and New Zealand (n = 5, 7.5%) with a mean ± SD age of 45.7 ± 11.8 years participated in Phase 2; 38 (56.7%) were women, 38 (56.7%) were health professionals and 27 (40.3%) were researchers/academics. In Phase 2, 15 of 18 (83.3%) statements on sarcopenia prevention, screening, assessment, management and future research were accepted with strong agreement. The strongest agreement related to encouraging a healthy lifestyle (100%) and offering tailored resistance training to people with sarcopenia (92.5%). Forty-seven experts participated in Phase 3; 5/6 (83.3%) revised statements on prevention, assessment and management were accepted with strong agreement. A majority of experts (87.9%) preferred the revised European Working Group for Sarcopenia in Older Persons (EWGSOP2) definition. Seventeen statements with strong agreement (>80%) were confirmed by the Task Force in Phase 4. CONCLUSIONS: The ANZSSFR Task Force present 17 sarcopenia management and research recommendations for use by health professionals and researchers which includes the recommendation to adopt the EWGSOP2 sarcopenia definition in Australia and New Zealand. This rigorous Delphi process that combined evidence, consumer expert opinion and topic expert consensus can inform similar initiatives in countries/regions lacking consensus on sarcopenia.

Knowledge of Nutrition and Physical Activity Guidelines is Not Associated with Physical Function in Dutch Older Adults Attending a Healthy Ageing Public Engagement Event.

Purpose: Evidence-based guidelines on nutrition and physical activity are used to increase knowledge in order to promote a healthy lifestyle. However, actual knowledge of guidelines is limited and whether it is associated with health outcomes is unclear. Participants and Methods: This inception cohort study aimed to investigate the association of knowledge of nutrition and physical activity guidelines with objective measures of physical function and physical activity in community-dwelling older adults attending a public engagement event in Amsterdam, The Netherlands. Knowledge of nutrition and physical activity according to Dutch guidelines was assessed using customized questionnaires. Gait speed and handgrip strength were proxies of physical function and the Minnesota Leisure Time Physical Activity Questionnaire was used to assess physical activity in minutes/week. Linear regression analysis, stratified by gender and adjusted for age, was used to study the association between continuous and categorical knowledge scores with outcomes. Results: In 106 older adults (mean age=70.1 SD=6.6, years) who were highly educated, well-functioning, and generally healthy, there were distinct knowledge gaps in nutrition and physical activity which did not correlate with one another (R2=0.013, p=0.245). Knowledge of nutrition or physical activity guidelines was not associated with physical function or physical activity. However, before age-adjustment nutrition knowledge was positively associated with HGS in males (B= 0.64 (95% CI: 0.05, 1.22)) and having knowledge above the median was associated with faster gait speed in females (B=0.10 (95% CI: 0.01, 0.19)). Conclusion: Our findings may represent a ceiling effect of the impact knowledge has on physical function and activity in the this high performing and educated population and that there may be other determinants of behavior leading to health status such as attitude and perception to consider in future studies.

The Physical Activity and Nutritional INfluences in Ageing (PANINI) Toolkit: A Standardized Approach towards Physical Activity and Nutritional Assessment of Older Adults.

Assessing multiple domains of health in older adults requires multidimensional and large datasets. Consensus on definitions, measurement protocols and outcome measures is a prerequisite. The Physical Activity and Nutritional INfluences In Ageing (PANINI) Toolkit aims to provide a standardized toolkit of best-practice measures for assessing health domains of older adults with an emphasis on nutrition and physical activity. The toolkit was drafted by consensus of multidisciplinary and pan-European experts on ageing to standardize research initiatives in diverse populations within the PANINI consortium. Domains within the PANINI Toolkit include socio-demographics, general health, nutrition, physical activity and physical performance and psychological and cognitive health. Implementation across various countries, settings and ageing populations has proven the feasibility of its use in research. This multidimensional and standardized approach supports interoperability and re-use of data, which is needed to optimize the coordination of research efforts, increase generalizability of findings and ultimately address the challenges of ageing.

Assessment of cell cycle regulators in human peripheral blood cells as markers of cellular senescence.

Cellular senescence has gained increasing interest during recent years, particularly due to causal involvement in the aging process corroborated by multiple experimental findings. Indeed, cellular senescence considered to be one of the hallmarks of aging, is defined as a stable growth arrest predominantly mediated by cell cycle regulators p53, p21 and p16. Senescent cells have frequently been studied in the peripheral blood of humans due to its accessibility. This review summarizes ex vivo studies describing cell cycle regulators as markers of senescence in human peripheral blood cells, along with detection methodologies and associative studies examining demographic and clinical characteristics. The utility of techniques such as the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), microarray, RNA sequencing and nCounter technologies for detection at the transcriptional level, along with Western blotting, enzyme-linked immunosorbent assay and flow cytometry at the translational level, will be brought up at salient points throughout this review. Notably, housekeeping genes or proteins serving as controls such as GAPDH and ß-Actin, were found not to be stably expressed in some contexts. As such, optimization and validation of such genes during experimental design were recommended. In addition, the expression of cell cycle regulators was found to vary not only between different types of blood cells such as T cells and B cells but also between stages of cellular differentiation such as naïve T cells and highly differentiated T cells. On the other hand, the associations of the presence of cell cycle regulators with demographics (age, gender, ethnicity, and socioeconomic status), clinical characteristics (body mass index, specific diseases, disease-related parameters) and lifestyle vary in groups of participants. One envisions that increased understanding and insights into the assessment of cell cycle regulators as markers of senescence in human peripheral blood cells will help inform prognostication and clinical intervention in elderly individuals.

SARC-F Is Inaccurate to Identify Geriatric Rehabilitation Inpatients at Risk for Sarcopenia: RESORT.

INTRODUCTION: Sarcopenia is highly prevalent in geriatric rehabilitation inpatients; screening using the Strength, Assistance in walking, Rise from a chair, Climb stairs, Falls history questionnaire (SARC-F) has been recommended. This study assessed the diagnostic accuracy of the SARC-F in identifying sarcopenia according to the European Working Group on Sarcopenia in Older People (EWGSOP), EWGSOP2, and Asian Working Group for Sarcopenia (AWGS) definitions in geriatric rehabilitation inpatients. METHODS: REStOring health of acutely unwell adulTs (RESORT) is an observational, longitudinal cohort of geriatric rehabilitation inpatients. The SARC-F was completed for 2 time-points, status at preadmission (1 month before admission) and at admission; a score ≥4 was considered at risk for sarcopenia. Muscle mass (bioelectrical impedance analysis), handgrip strength (handheld dynamometry), and gait speed (4-m walk test) were measured at admission. Diagnostic accuracy was determined by sensitivity, specificity, and area under the curve (AUC). RESULTS: The sarcopenia prevalence (n = 290, median age 84.0 years [IQR 79.0-89.0], 56.9% female) was 40.3% (EWGSOP1), 25.4% (EWGSOP2), and 38.8% (AWGS). For preadmission and admission status, respectively, the SARC-F identified 67.9 and 82.1% (EWGSOP), 66.0 and 81.0% (EWGSOP2), and 67.5 and 81.6% (AWGS) inpatients at risk for sarcopenia. The SARC-F showed fair sensitivity (67-74%), poor specificity (32-37%), and poor AUC (0.411-0.474) to identify inpatients at risk for sarcopenia at preadmission status, and fair-good sensitivity (79-84%), poor specificity (17-20%), and poor AUC (0.401-0.432) to identify inpatients at risk for sarcopenia at admission, according to EWGSOP, EWGSOP2, and AWGS definitions. CONCLUSION: The SARC-F showed poor diagnostic accuracy in identifying sarcopenia in geriatric rehabilitation inpatients. Assessment of sarcopenia is recommended without screening.

Alpha-Ketoglutarate dietary supplementation to improve health in humans.

Alpha-ketoglutarate (AKG) is an intermediate in the Krebs cycle involved in various metabolic and cellular pathways. As an antioxidant, AKG interferes in nitrogen and ammonia balance, and affects epigenetic and immune regulation. These pleiotropic functions of AKG suggest it may also extend human healthspan. Recent studies in worms and mice support this concept. A few studies published in the 1980s and 1990s in humans suggested the potential benefits of AKG in muscle growth, wound healing, and in promoting faster recovery after surgery. So far there are no recently published studies demonstrating the role of AKG in treating aging and age-related diseases; hence, further clinical studies are required to better understand the role of AKG in humans. This review will discuss the regulatory role of AKG in aging, as well as its potential therapeutic use in humans to treat age-related diseases.

Reliability and Concurrent Validity of the SARC-F and Its Modified Versions: A Systematic Review and Meta-Analysis.

OBJECTIVES: Sarcopenia, being prevalent in up to 40% of older adults, is associated with adverse health outcomes. The international sarcopenia guidelines recommend screening for sarcopenia using the SARC-F. A previous meta-analysis (2017) reported poor validity of the SARC-F among community-dwelling older adults. Since then, modified SARC-F versions were developed and new sarcopenia definitions were published, including the SARC-F for case-finding. This systematic review and meta-analysis aimed to assess the reliability of the SARC-F and its concurrent validity to identify sarcopenia. DESIGN: Systematic review and meta-analyses. SETTING AND PARTICIPANTS: Adults (all ages) from any study population. METHODS: A systematic search was conducted in MEDLINE, EMBASE, Cochrane, and CINAHL (January 1, 2013, to April 6, 2020). Articles were included if they reported on the reliability and/or concurrent validity of the (modified) SARC-F. No restrictions were applied for sex, age, study population, or sarcopenia definition. Reliability measures included inter-rater reliability, test-retest reliability, and internal consistency. Meta-analyses were performed for concurrent validity. RESULTS: The 29 included articles included 21,855 individuals (mean age of 63.3±14.6 years, 61.3% females) among community-dwelling (n = 16), geriatric inpatient (n = 5), geriatric outpatient (n = 2), nursing home (n = 2), and long-term care (n = 1) populations. The SARC-F had good (2/4 articles) to excellent (2/4 articles) inter-rater reliability, moderate (1/6 articles) to good (5/6 articles) test-retest reliability, and low (4/8 articles) to high (4/8 articles) internal consistency. The SARC-F had low to moderate sensitivity (28.9%-55.3%) and moderate to high specificity (68.9%-88.9%) according to the European Working Group on Sarcopenia in Older People (EWGSOP; n = 13), revised EWGSOP definition (EWGSOP2; n = 6), Asian Working Group for Sarcopenia (AWGS; n = 13), Foundation for the National Institutes of Health (FNIH; n = 8), International Working Group on Sarcopenia (IWGS; n = 9), and Society on Sarcopenia, Cachexia and Wasting Disorders (n = 2). The SARC-CalF had low to moderate sensitivity (45.9%-57.2%) and high specificity (87.7%-91.3%) according to the EWGSOP (n = 5), AWGS (n = 4), FNIH (n = 3), and IWGS (n = 3). CONCLUSIONS AND IMPLICATIONS: Despite the good reliability of the SARC-F, its low to moderate sensitivity and moderate to high specificity make it nonoptimal to use for sarcopenia screening. It is recommended to apply the diagnostic criteria for sarcopenia without screening.

Senescence in tissue samples of humans with age-related diseases: A systematic review.

BACKGROUND: Higher numbers of senescent cells have been implicated in age-related disease pathologies. However, whether different diseases have different senescent phenotypes is unknown. Here we provide a systematic overview of the current available evidence of senescent cells in age-related diseases pathologies in humans and the markers currently used to detect senescence levels in humans. METHODS: PubMed, Web of Science and EMBASE were systematically searched from inception to the 29th of September 2019, using keywords related to 'senescence', 'age-related diseases' and 'biopsies'. RESULTS: In total 12,590 articles were retrieved of which 103 articles were included in this review. The role of senescence in age-related disease has been assessed in 9 different human organ system and 27 different age-related diseases of which heart (27/103) and the respiratory systems (18/103) are the most investigated. Overall, 27 different markers of senescence have been used to determine cellular senescence and the cell cycle regulator p16ink4a is most often used (23/27 age-related pathologies). CONCLUSION: This review demonstrates that a higher expression of senescence markers are observed within disease pathologies. However, not all markers to detect senescence have been assessed in all tissue types.

The association of comorbidity measures and mortality in geriatric rehabilitation inpatients by cancer status: RESORT.

BACKGROUND: Multimorbidity is highly prevalent in older adults, both those with and without cancer, and is associated with an increased risk of mortality. The aim of this study was to investigate if multimorbidity measures in geriatric rehabilitation inpatients differ in their association with mortality, dependent on a diagnosis of cancer. METHODS: REStORing health of acutely unwell adulTs (RESORT) is an ongoing longitudinal inception cohort of geriatric rehabilitation inpatients. Comorbidity was measured at admission using the Charlson Comorbidity Index (CCI), age-adjusted CCI (CCI-A), Cumulative Illness Rating Scale-Geriatrics (CIRS-G) and the CIRS-G severity index. Patients were allocated to a cancer status group (no cancer, history of cancer, or active cancer). The association of comorbidity indices with mortality was analyzed using Cox regression analyses. RESULTS: Of the 693 patients (mean age 82.2 ± 7.5 years), 523 (75.4%) had no history of cancer, 96 (13.9%) past cancer, and 74 (10.7%) active cancer. Three months post-discharge, patients with active cancer had a higher mortality risk compared to patients with no cancer (HR = 3.57, 95% CI 2.03-6.23). CCI and CCI-A scores were significantly associated with higher mortality risk in all cancer status groups. CONCLUSION: In geriatric rehabilitation patients, incremental CCI and CCI-A scores were associated with higher mortality in all three cancer status groups. However, patients with active cancer had a significantly higher 3-month mortality compared to those with no or past cancer, and this is likely determined by the advanced nature of the malignancies in this group.

Pathophysiological mechanisms explaining poor clinical outcome of older cancer patients with low skeletal muscle mass.

Low skeletal muscle mass is highly prevalent in older cancer patients and affects 5% to 89% depending on the type and stage of cancer. Low skeletal muscle mass is associated with poor clinical outcomes such as post-operative complications, chemotherapy toxicity and mortality in older cancer patients. Little is known about the mediating pathophysiological mechanisms. In this review, we summarize proposed pathophysiological mechanisms underlying the association between low skeletal muscle mass and poor clinical outcomes in older cancer patients including a) systemic inflammation; b) insulin-dependent glucose handling; c) mitochondrial function; d) protein status and; e) pharmacokinetics of anticancer drugs. The mechanisms of altered myokine balance negatively affecting the innate and adaptive immune system, and altered pharmacokinetics of anticancer drugs leading to a relative overdosage of anticancer drugs are best-substantiated. The effects of glucose intolerance and circulating mitochondrial DNA as a consequence of low skeletal muscle mass are topics of interest for future research. Restoring myokine balance through physical exercise, exercise mimetics, neuro-muscular activation and adapting anticancer drug dosing on skeletal muscle mass could be targeted approaches to improve clinical outcomes in older cancer patients with low skeletal muscle mass.

Predicting outcome in older patients with cancer: Comprehensive geriatric assessment and clinical judgment.

OBJECTIVES: Comprehensive Geriatric Assessment (CGA) has been incorporated into geriatric oncology to prevent unfavorable outcome from anticancer treatment. This study determined the value of CGA and medical oncologist's clinical judgment in predicting unfavorable outcome and explored whether treatment decisions can be based on CGA. PATIENTS AND METHODS: In this prospective cohort study, a multidomain CGA was performed by a geriatric nurse and geriatrician in 110 consecutive patients aged ≥70 years, newly referred to a multidisciplinary oncology clinic. CGA domains included comorbidity, polypharmacy, mood, cognition, nutrition, functionality and physical performance. Medical oncologist's clinical judgment on expected tolerance of standard treatment was noted (N = 62). Unfavorable outcome was defined as any ≥grade three chemotherapy toxicity, dose reduction, postponement of treatment, death before start of treatment and early progression before first evaluation of treatment (N = 80). RESULTS: CGA identified multidomain problems in 77 out of 110 patients (70.0%) and the medical oncologist had doubts about standard treatment tolerance in 30 out of 62 patients (48.4%). Unfavorable outcome occurred in 48 out of 80 patients (60%) who received anticancer treatment but could not be predicted by CGA, medical oncologists' clinical judgment or their combination. There was discrepancy between CGA and clinical judgment in 24 out of 62 patients (38.7%). CONCLUSION: Neither CGA, medical oncologist's clinical judgment or a combination could predict unfavorable outcome in our heterogeneous sample. CGA and clinical judgment did not align in more than one-third of patients.

Factors influencing the efficacy of nutritional interventions on muscle mass in older adults: a systematic review and meta-analysis.

CONTEXT: Nutritional interventions stimulate muscle protein synthesis in older adults. To optimize muscle mass preservation and gains, several factors, including type, dose, frequency, timing, duration, and adherence have to be considered. OBJECTIVE: This systematic review and meta-analysis aimed to summarize these factors influencing the efficacy of nutritional interventions on muscle mass in older adults. DATA SOURCES: A systematic search was performed using the electronic databases MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and SPORTDiscus from inception date to November 22, 2017, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria included randomized controlled trials, mean or median age ≥65 years, and reporting muscle mass at baseline and postintervention. Exclusion criteria included genetically inherited diseases, anabolic drugs or hormone therapies, neuromuscular electrical stimulation, chronic kidney disease, kidney failure, neuromuscular disorders, and cancer. DATA EXTRACTION: Extracted data included study characteristics (ie, population, sample size, age, sex), muscle mass measurements (ie, method, measure, unit), effect of the intervention vs the control group, and nutritional intervention factors (ie, type, composition, dose, duration, frequency, timing, and adherence). DATA ANALYSIS: Standardized mean differences and 95%CIs were calculated from baseline to postintervention. A meta-analysis was performed using a random-effects model and grouped by the type of intervention. CONCLUSIONS: Twenty-nine studies were included, encompassing 2255 participants (mean age, 78.1 years; SD, 2.22). Amino acids, creatine, ß-hydroxy-ß-methylbutyrate, and protein with amino acids supplementation significantly improved muscle mass. No effect was found for protein supplementation alone, protein and other components, and polyunsaturated fatty acids. High interstudy variability was observed regarding the dose, duration, and frequency, coupled with inconsistency in reporting timing and adherence. Overall, several nutritional interventions could be effective to improve muscle mass measures in older adults. Because of the substantial variability of the intervention factors among studies, the optimum profile is yet to be established. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42018111306.

Markers of inflammation and their association with muscle strength and mass: A systematic review and meta-analysis.

BACKGROUND: Chronic inflammation has been associated with sarcopenia and its components skeletal muscle strength and muscle mass. The aim of this systematic review and meta-analysis was to determine the relationship between systemic inflammation, muscle strength and/or muscle mass in adults. METHODS: An electronic search using keywords such as 'acute phase proteins, cytokines and sarcopenia, muscle mass, muscle strength' was conducted via Pubmed, Web of Science and Embase from inception until the 30th of June 2020. A meta-analysis using correlation data was performed to determine the overall relationship between inflammation and muscle strength and muscle mass in adults. RESULTS: Overall, 168 articles; 149 cross-sectional articles (n = 76,899 participants, 47.0 % male) and 19 longitudinal articles (n = 12,295 participants, 31.9 % male) met inclusion criteria. Independent of disease state, higher levels of C reactive protein (CRP), Interleukin (IL)-6 and Tumor necrosis factor (TNF)α were associated with lower handgrip and knee extension strength (CRP; r = -0.10, p < 0.001, IL-6; r = -0.13, p < 0.001, TNFα; r = -0.08, p < 0.001 and CRP; r = -0.18, p < 0.001, IL-6; r = -0.11, p < 0.001, TNFα; r = -0.13, p < 0.001 respectively) and muscle mass (CRP; r = -0.12, p < 0.001, IL-6; r = -0.09, p < 0.001, TNFα; r = -0.15, p < 0.001). Furthermore, higher levels of systemic inflammatory markers appeared to be associated with lower muscle strength and muscle mass over time. CONCLUSION: Higher levels of circulating inflammatory markers are significantly associated with lower skeletal muscle strength and muscle mass.

Clinical determinants of resting metabolic rate in geriatric outpatients.

PURPOSE: Accurate estimation of the energy requirements including resting metabolic rate (RMR) is important for optimal nutritional care, yet its clinical determinants are unknown. This study examined the associations between clinical determinants of the Comprehensive Geriatric Assessment (CGA) domains with RMR among geriatric outpatients. MATERIALS & METHODS: Data were retrieved from cohorts of community-dwelling older adults (n = 84, 54 female) referring to geriatrics outpatient mobility clinics in both Amsterdam, The Netherlands and Melbourne, Australia. Determinants within domains of the CGA included diseases (number, type and severity of diseases, polypharmacy), nutrition (body weight, body mass index, absolute and relative skeletal muscle mass, fat-free mass and fat mass, risk of malnutrition), physical function (handgrip strength, Short Physical Performance Battery, Timed Up & Go), cognition (Mini-Mental State Examination), psychological wellbeing (Geriatric Depression Scale) and blood pressure. RMR was objectively measured using indirect calorimetry with a canopy hood. Association between the clinical determinants with standardized RMR (country and sex-specific z-score) were analysed with linear regression adjusted for age, sex and body weight. RESULTS: Determinants within the nutritional domain were associated with RMR; body weight showed the strongest association with RMR. Significant associations between determinants within the nutritional domain with RMR disappeared after further adjustment for body weight. None of the other domains were associated with RMR. CONCLUSIONS: Body weight is the strongest clinical determinant of RMR and should be taken into account when estimating RMR in geriatric care.

Prevalence of malnutrition comparing the GLIM criteria, ESPEN definition and MST malnutrition risk in geriatric rehabilitation patients: RESORT.

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) has developed new criteria for the diagnosis of malnutrition. This study aimed 1) to determine and compare malnutrition prevalence and risk using the GLIM criteria, European Society for Clinical Nutrition and Metabolism (ESPEN) definition of malnutrition and the Malnutrition Screening Tool (MST) in patients admitted to subacute geriatric rehabilitation wards, 2) to explore the agreement of malnutrition prevalence determined by each definition, and 3) to determine the accuracy of the MST against the GLIM criteria and ESPEN definition as references. METHODS: Geriatric rehabilitation patients (n = 444) from the observational, longitudinal REStORing health of acutely unwell adulTs (RESORT) cohort in Melbourne, Australia were included. The GLIM criteria, ESPEN definition and MST were applied. Accuracy was determined by the sensitivity, specificity and Area Under the Curve (AUC). RESULTS: According to the GLIM criteria, the overall prevalence of malnutrition was 52.0%. The ESPEN definition diagnosed 12.6% of patients as malnourished and the MST identified 44.4% of patients at risk for malnutrition. Agreement was low; 7% of patients were malnourished and at risk for malnutrition according to all three definitions. The accuracy of the MST compared to the GLIM criteria was fair (sensitivity 56.7%, specificity 69.0%) and sufficient (AUC 0.63); MST compared to the ESPEN definition was fair (sensitivity 60.7%, specificity 58.0%) and poor (AUC 0.59). CONCLUSIONS: According to the GLIM criteria, half of geriatric rehabilitation patients were malnourished, whereas the prevalence was much lower applying the ESPEN definition. This highlights the need for further studies to determine diagnostic accuracy of the GLIM criteria compared to pre-existing validated tools.

Computed Tomography-Based Body Composition Is Not Consistently Associated with Outcome in Older Patients with Colorectal Cancer.

BACKGROUND: Current literature is inconsistent in the associations between computed tomography (CT)-based body composition measures and adverse outcomes in older patients with colorectal cancer (CRC). Moreover, the associations with consecutive treatment modalities have not been studied. This study compared the associations of CT-based body composition measures with surgery- and chemotherapy-related complications and survival in older patients with CRC. MATERIALS AND METHODS: A retrospective single-center cohort study was conducted in patients with CRC aged ≥65 years who underwent elective surgery between 2010 and 2014. Gender-specific standardized scores of preoperative CT-based skeletal muscle (SM), muscle density, intermuscular adipose tissue (IMAT), visceral adipose tissue (VAT), subcutaneous adipose tissue, IMAT percentage, SM/VAT, and body mass index (BMI) were tested for their associations with severe postoperative complications, prolonged length of stay (LOS), readmission, and dose-limiting toxicity using logistic regression and 1-year and long-term survival (range 3.7-6.6 years) using Cox regression. Bonferroni correction was applied to account for multiple testing. RESULTS: The study population consisted of 378 patients with CRC with a median age of 73.4 (interquartile range 69.5-78.4) years. Severe postoperative complications occurred in 13.0%, and 39.4% of patients died during follow-up. Dose-limiting toxicity occurred in 77.4% of patients receiving chemotherapy (n = 53). SM, muscle density, VAT, SM/VAT, and BMI were associated with surgery-related complications, and muscle density, IMAT, IMAT percentage, and SM/VAT were associated with long-term survival. After Bonferroni correction, no CT-based body composition measure was significantly associated with adverse outcomes. Higher BMI was associated with prolonged LOS. CONCLUSION: The associations between CT-based body composition measures and adverse outcomes of consecutive treatment modalities in older patients with CRC were not consistent or statistically significant. IMPLICATIONS FOR PRACTICE: Computed tomography (CT)-based body composition, including muscle mass, muscle density, and intermuscular, visceral, and subcutaneous adipose tissue, showed inconsistent and nonsignificant associations with surgery-related complications, dose-limiting toxicity, and overall survival in older adults with colorectal cancer. This study underscores the need to verify whether CT-based body composition measures are worth implementing in clinical practice.