SERDI

Aim: the the International Position Statement provides the opportunity to summarise all existing clinical trial and best practice evidence for older people with frailty and diabetes. It is the first document of its kind and is intended to support clinical decisions that will enhance safety in management and promote high quality care. Methods: the Review Group sought evidence from a wide range of studies that provide sufficient confidence (in the absence of grading) for the basis of each recommendation. This was supported by a given rationale and key references for our recommendations in each section, all of which have been reviewed by leading international experts. Searches for any relevant clinical evidence were generally limited to English language citations over the previous 15 years. The following databases were examined: Embase, Medline/PubMed, Cochrane Trials Register, Cinahl, and Science Citation. Hand searching of 16 key major peer-reviewed journals was undertaken by two reviewers (AJS and AA) and these included Lancet, Diabetes, Diabetologia, Diabetes Care, British Medical Journal, New England Journal of Medicine, Journal of the American Medical Association, Journal of Frailty & Aging, Journal of the American Medical Directors Association, and Journals of Gerontology – Series A Biological Sciences and Medical Sciences. Results: two scientific supporting statements have been provided that relate to the area of frailty and diabetes; this is accompanied by evidence-based decisions in 9 clinical domains. The Summary has been supported by diagrammatic figures and a table relating to the inter-relations between frailty and diabetes, a frailty assessment pathway, an exercise-based programme of intervention, a glucose-lowering algorithm with a description of available therapies. Conclusions: we have provided an up to date evidence-based approach to practical decision-making for older adults with frailty and diabetes. This Summary document includes a user-friendly set of recommendations that should be considered for implementation in primary, community-based and secondary care settings.

Sarcopenia is the progressive loss of skeletal mass and strength, particularly in older adults, with consequent reduction in function and independence. Changing population demographics, have resulted in increased prevalence of sarcopenia and this is associated with a considerable economic burden. Whilst simple, effective, non-intrusive management of this condition exists, no routine diagnosis takes place either in the UK or in many other countries, partly due to an absence of pragmatic clinical diagnostic tools to support the early identification of the syndrome. This position paper aims to provide a short overview proposing the potential case for developing ultrasound as a new and alternative diagnostic tool for identifying sarcopenia.

Frailty is a geriatric syndrome associated with progressive physical decline and significantly increases risk for falls, disability, hospitalizations, and death. However, much remains unknown regarding the biological mechanisms that contribute to aging and frailty, and to date, there are no clinically used prognostic or diagnostic molecular biomarkers. The present study profiled exosome-derived microRNAs isolated from the plasma of young, robust older, and frail older individuals and identified eight miRNAs that are uniquely enriched in frailty: miR-10a-3p, miR-92a-3p, miR-185-3p, miR-194-5p, miR-326, miR-532-5p, miR-576-5p, and miR-760. Furthermore, since exosomes can deliver miRNAs to alter cellular activity and behavior, these miRNAs may also provide insights into the biological mechanisms underlying frailty; KEGG analysis of their target genes revealed multiple pathways implicated in aging and age-related processes. Although further validation and research studies are warranted, our study identified eight novel candidate biomarkers of frailty that may help to elucidate the multifactorial pathogenesis of frailty.

Background: Muscle mass is often mentioned not to reflect muscle strength. For muscle mass assessment skeletal muscle index (SMI) is often used. We have reported that dual-energy X-ray absorptiometry (DXA)-derived SMI does not change with age in women, whereas the cross-sectional muscle area (CSMA) derived from computed tomography (CT) does. Objectives: The present study aimed to compare CT and DXA for the assessment of muscle tissue. Design & Setting: Cross-sectional study in the local residents. Participants: A total of 1818 subjects (age 40-89 years) randomly selected from community dwellers underwent CT examination of the right mid-thigh to measure the cross-sectional muscle area (CSMA). Skeletal muscle mass (SMM) was measured by DXA. The subjects performed physical function tests such as grip strength, knee extension strength, leg extension strength, and gait speed. The correlation between CT-derived CSMA and DXA-derived SMM along with their association with physical function was examined. Results: After controlling for related factors, the partial correlation coefficient of muscle cross-sectional area (CSA) with physical function was larger than that of DXA-derived SMM for gait speed in men (p=0.002) and knee extension strength in women (p=0.03). The partial correlation coefficient of quadriceps (Qc) CSA with physical function was larger than that of DXA-derived SMM for leg extension power in both sexes (p=0.01), gait speed in men (p<0.001), and knee extension strength in women (p<0.001). Conclusion: Mid-thigh CT-derived CSMA, especially Qc CSA, showed significant associations with grip strength, knee extension strength, and leg extension power, which were equal to or stronger than those of DXA-derived SMM in community-dwelling middle-aged and older Japanese people. The mid-thigh CSMA may be a predictor of mobility disability, and is considered to be useful in the diagnosis of sarcopenia.

Objectives: The primary purpose of this study was to determine the time-varying associations between decreased handgrip strength (HGS) and individual instrumental activities of daily living (IADL) impairments for a nationally-representative sample of aging adults in the United States. Design: Longitudinal-Panel. Setting: Detailed interviews were completed in person and core interviews were typically completed over the telephone. Participants: A total of 15,336 participants aged at least 50 years who participated in the 2006 wave of the Health and Retirement Study were followed biennially for 8-years. Measurements: A hand-held dynamometer assessed HGS and performance in IADLs were self-reported. Results: Every 5-kilogram decrease in HGS was associated with an increased odds ratio for the following IADL impairments: 1.11 (95% confidence interval (CI): 1.09, 1.13) for using a map, 1.10 (CI: 1.07, 1.12) for grocery shopping, 1.09 (CI: 1.05, 1.14) for taking medications, 1.07 (CI: 1.05, 1.09) for preparing hot meals, 1.06 (CI: 1.04, 1.08) for managing money, and 1.05 (CI: 1.02, 1.09) for using a telephone. Conclusions: Decreased HGS was associated with each IADL impairment, and slightly different associations were observed in individual IADL tasks for aging adults in the United States. Our findings suggest that decreased HGS, which is reflective of reduced function of the neuromuscular system, is associated with diminished performance in autonomous living tasks during aging. Losses in HGS may lead to the development of an IADL impairment. Therefore, health-care providers working with aging adults should utilize measures of HGS as a screening tool for identifying future deficits in neuromuscular functioning. Interventions designed to preserve IADLs in aging adults should also include measures of HGS for detecting early changes in IADL capacity, and intervening at the onset of HGS declines may help aging adults retain their ability to live autonomously.

Background: Declines in muscle mass and function are inevitable developments of the advanced aging process. Corresponding dimensions of longitudinal changes in at-risk populations are still scarce although clinically relevant. The present study monitored changes in morphologic and functional sarcopenia criteria related to sarcopenia in older men with low muscle mass over a period of 24 months. Objectives: The main objective of the present study was to determine whether changes in muscle mass and function were comparable across the body. Our hypothesis was that both (1) fat free mass (FFM) and (2) function decline at a significantly higher rate in the lower versus the upper extremities. Design: We conducted an observational study of 24 months. Setting: Community dwelling men living in the area of Northern Bavaria were initially included in the Franconian Sarcopenic Obesity (FranSO) study by the Institute of Medical Physics University of Erlangen-Nürnberg, Germany. Participants: One hundred and seventy-seven (177) men (77.5±4.5 years) within the lowest skeletal muscle mass index (SMI) quartile of the FranSO study were included in the present 24 month analysis. Measurements: Fat free mass (direct-segmental, multi-frequency Bio-Impedance-Analysis (DSM-BIA)), handgrip strength (hand-dynamometer) and 10-m habitual gait velocity (photo sensors) were assessed at baseline and 24-month follow-up. Results: Lower extremity fat free mass (LEFFM: -2.0±2.4%), handgrip strength (-12.8±11.0%) and gait velocity (-3.5±9.0%) declined significantly (p<.001) during the follow-up period, while upper extremity FFM was maintained unchanged (UEFFM: 0.1±3.1%). Changes in LEFFM were significantly higher (p<.001) compared with UEFFM, however contrary to our expectation the decline in handgrip strength representing upper extremity muscle function was 3.7-fold higher (p<.001) than the decline in gait velocity. Conclusion: Medical experts involved in diagnosis, monitoring and management of sarcopenia should consider that parameters constituting morphologic and functional sarcopenia criteria feature different rates of decline during the aging process.

Objectives: However, the information regarding the impact of sarcopenia on mortality in older individuals is rising, there is a lack of knowledge concerning this issue among geriatric hospitalized patients. Therefore, aim of the present study was to investigate the associations between sarcopenia and 1-year mortality in a prospectively recruited sample of geriatric inpatients with different mobility and dependency status. Design and setting: Sarcopenia was diagnosed using the criteria of the European Working Group on Sarcopenia in Older People (EWGSOP). Hand grip strength and skeletal muscle mass were measured using Jamar dynamometer and bioelectrical impedance analysis, respectively. Physical function was assessed with the Short Physical Performance Battery. Dependency status was defined by Barthel-Index (BI). Mobility limitation was defined according to walking ability as described in BI. The survival status was ascertained by telephone interview. Results: The recruited population comprised 198 patients from a geriatric acute ward with a mean age of 82.8 ± 5.9 (70.2% females). 50 (25.3%) patients had sarcopenia, while 148 (74.7%) had no sarcopenia. 14 (28%) patients died among sarcopenic subjects compared with 28 (19%) non-sarcopenic subjects (P=0.229). After adjustment for potential confounders, sarcopenia was associated with increased mortality among patients with limited mobility prior to admission (n=138, hazard ratio, HR: 2.52, 95% CI: 1.17-5.44) and at time of discharge (n=162, HR: 1.93, 95% CI: 0.67-3.22). In a sub-group of patients with pre-admission BI<60 (n=45), <70 (n=73) and <80 (n=108), the risk of death was 3.63, 2.80 and 2.55 times higher in sarcopenic patients, respectively. In contrast, no significant relationships were observed between sarcopenia and mortality across the different scores of BI during admission and at time of discharge. Conclusion: Sarcopenia is significantly associated with higher risk of mortality among sub-groups of older patients with limited mobility and impaired functional status, independently of age and other clinical variables.

Các tương tác giữa các con đường sinh lý liên quan đến loãng xương và tình trạng suy giảm cơ bắp được cho là góp phần vào sự khởi phát của trạng thái dễ tổn thương. Nhóm công tác Nghiên cứu về trạng thái dễ tổn thương và suy giảm cơ bắp quốc tế đã gặp gỡ vào tháng 3 năm 2020 để khám phá cách mà các can thiệp mới nổi nhằm quản lý gãy xương và loãng xương ở người cao tuổi có thể giảm thiểu tình trạng yếu ớt, tàn tật, bệnh tật và tỷ lệ tử vong trong dân số cao tuổi. Cả can thiệp bằng dược phẩm và can thiệp phi dược phẩm (bao gồm can thiệp dinh dưỡng, tập thể dục và các thay đổi lối sống khác) đã được thảo luận. Các phương pháp điều trị dược phẩm cho loãng xương bao gồm các tác nhân thúc đẩy tạo xương và các tác nhân chống tái hấp thu, có thể được sử dụng tối ưu trong các liệu trình nối tiếp hoặc kết hợp. Vì các cơ chế tương tự liên quan đến tái hấp thu dưới đây những thay đổi sinh lý trong cơ bắp và xương, các can thiệp này có thể mang lại lợi ích ngoài việc điều trị loãng xương. Tuy nhiên, các thử nghiệm lâm sàng để kiểm nghiệm những can thiệp này thường loại trừ những người cao tuổi dễ tổn thương do các bệnh kèm theo (như khuyết tật về di chuyển và suy giảm nhận thức) hoặc đa thuốc. Nhóm công tác khuyến nghị rằng các thử nghiệm lâm sàng trong tương lai nên sử dụng các giao thức hài hòa, bao gồm các tiêu chí lựa chọn hài hòa và các biện pháp kết quả tương tự; và rằng họ nên thử nghiệm một loạt các liệu pháp đa lĩnh vực. Họ cũng kêu gọi nghiên cứu chất lượng cao hơn để phát triển các can thiệp đặc biệt cho những người dễ tổn thương và cao tuổi. Chương trình ICOPE do WHO đề xuất dường như được khuyến nghị mạnh mẽ cho những người cao tuổi dễ tổn thương mắc loãng xương.

Background: Frailty in older adults is a rapidly growing unmet medical need. It is an aging-related syndrome characterized by physical decline leading to higher risk of adverse health outcomes. OBJECTIVES: To evaluate the efficacy of Lomecel-B, an allogeneic medicinal signaling cell (MSC) formulation, in older adults with frailty. DESIGN: This multicenter, randomized, parallel-arm, double-blinded, and placebo-controlled phase 2b trial is designed to evaluate dose-range effects of Lomecel-B for frailty on physical functioning, patient-reported outcomes (PROs), frailty status, and biomarkers. SETTING: Eight enrolling clinical research centers, including the Miami Veterans Affairs Medical Center. PARTICIPANTS: Target enrollment is 150 subjects aged 70-85 years of any race, ethnicity, or gender. Enrollment criteria include a Clinical Frailty Score of 5 (“mild”) or 6 (“moderate”), a 6MWT of 200-400 m, and serum tumor necrosis factor-alpha (TNF-α) ≥2.5 pg/mL. INTERVENTION: A single intravenous infusion of Lomecel-B (25, 50, 100, or 200 million cells) or placebo (N=30/arm). Patients are followed for 365 days for safety, and the efficacy assessments performed at 90, 180, and 270 days. MEASUREMENTS: The primary endpoint is change in 6MWT in the Lomecel-B-treated arms versus placebo at 180 days post-infusion. Secondary and exploratory endpoints include change in: 6MWT and other physical function measures at all time points; PROs; frailty status; cognitive status; and an inflammatory biomarkers panel. A pre-specified sub-study examines vascular/endothelial biomarkers. Safety is evaluated throughout the trial. RESULTS: The trial is conducted under a Food and Drug Administration Investigational New Drug (IND), with Institutional Review Board approval, and monitoring by an NIH-appointed independent Data Safety Monitoring Board. CONCLUSION: This clinical trial investigates the use of a regenerative medicine strategy for frailty in older adults. The results will further the understanding of the potential for Lomecel-B in the geriatric condition of frailty.