Relação entre força de preensão manual, funcionalidade e fragilidade física em pessoas idosas: revisão integrativa / Relación entre fuerza de agarre manual, funcionalidad y fragilidad física en ancianos: una revisión integradora / Relationship between handgrip strength, functionality, and physical frailty in elderly people: an integrative review

RESUMO Objetivo: analisar as publicações científicas sobre a relação entre força de preensão manual, funcionalidade e fragilidade física em pessoas idosas. Método: revisão integrativa realizada nas bases de dados PubMed, CINAHL, Web of Science e Portal BVS, no período amostral de janeiro de 2010 a novembro de 2021. Empregou-se o fluxograma do Preferred Reporting Items for Systematic Reviews and Meta-analyses para apresentar a seleção dos estudos, e o nível de evidência foi avaliado a partir do Oxford Centre for Evidence-Based Medicine e as referências gerenciadas no EndNote Web. Resultados: a busca inicial resultou em 211 estudos após a aplicação dos critérios de elegibilidade, sendo que 7 estudos constituíram a revisão integrativa. A força de preensão manual se revelou um importante indicador de força muscular e crucial para a funcionalidade das pessoas idosas. Quando associada a determinadas ocorrências clínicas, a força de preensão manual colabora para a redução da funcionalidade e dependência na realização das atividades de vida diária em idosos, com maior prejuízo entre aqueles com 75 anos ou mais, de forma mais significativa entre as mulheres. Conclusão: a relação entre a força de preensão reduzida e a diminuição da funcionalidade determina a condição de fragilidade física em pessoas idosas. Isso reforça a importância do investimento dos profissionais de Enfermagem em intervenções que viabilizem a manutenção da força muscular e da funcionalidade e a reversão da fragilidade física nesse segmento populacional.

RESUMEN Objetivo: analizar las publicaciones científicas sobre la relación entre la fuerza de agarre manual, la funcionalidad y la fragilidad física en ancianos. Método: revisión integradora realizada en las bases de datos PubMed, CINAHL, Web of Science y Portal BVS, desde enero de 2010 hasta noviembre de 2021. Se utilizó el diagrama de flujo de los Preferred Reporting Items for Systematic Reviews and Meta-analyses para presentar la selección de estudios, se evaluó el nivel de evidencia del Oxford Centre for Evidence-Based Medicine y se gestionaron las referencias en EndNote Web. Resultados: la búsqueda inicial dio lugar a 211 estudios, tras aplicar los criterios de elegibilidad, siete estudios constituyeron la revisión integradora. La fuerza de agarre de la mano resultó ser un indicador importante de la fuerza muscular y crucial para la funcionalidad de los ancianos. Cuando se asocia a determinadas circunstancias clínicas, la fuerza de la presión manual contribuye a la reducción de la funcionalidad y la dependencia en la realización de las actividades de la vida diaria en los individuos, con mayor prejuicio entre los que tienen 75 años o más y de forma más significativa entre las mujeres. Conclusión: la relación entre la fuerza de agarre reducida y la disminución de la funcionalidad determina la condición de fragilidad física en los ancianos. Esto refuerza la importancia de que los profesionales de Enfermería inviertan en intervenciones que permitan mantener la fuerza y la funcionalidad muscular y revertir la fragilidad física en este segmento de la población.

ABSTRACT Objective: to analyze scientific publications on the relationship between handgrip strength, functionality, and physical frailty in the elderly. Method: integrative review carried out in PubMed, CINAHL, Web of Science and VHL Portal databases, in the sample period from January 2010 to November 2021. The Preferred Reporting Items for Systematic Reviews and Meta-analyses flowchart was used to present the selection of studies, and the level of evidence was assessed from the Oxford Center for Evidence-Based Medicine and references managed in EndNote Web. Results: the initial search resulted in 211 studies after applying the eligibility criteria, with 7 studies constituting the integrative review. Handgrip strength proved to be an important indicator of muscle strength and crucial for the functionality of elderly people. When associated with certain clinical occurrences, handgrip strength contributes to the reduction of functionality and dependence in carrying out activities of daily living in the elderly, with greater impairment among those aged 75 years or older, more significantly among women. Conclusion: the relationship between reduced grip strength and decreased functionality determines the condition of physical frailty in elderly people. This reinforces the importance of investment by Nursing professionals in interventions that enable the maintenance of muscle strength and functionality and the reversal of physical frailty in this population segment.

Implementation of an integrated home internet of things system for vulnerable older adults using a frailty-centered approach.

Although integrated home internet of things (IoT) services can be beneficial, especially for vulnerable older adults, the hurdle of usability hinders implementation of the technology. This study aimed to evaluate the practical usability of home IoT services in older adults, by frailty status, and to determine the potential obstacles. From August 2019 to July 2020, we randomly selected 20 vulnerable older adults (prefrailty group [n = 11], and frailty group [n = 9]) who had already been identified as needing home IoT services in a community-based prospective cohort study, the Aging Study of the Pyeongchang Rural Area. Integrated home IoT services were provided for 1 year, and a face-to-face survey evaluating usability and satisfaction of each service was conducted. The usability of the integrated home IoT services declined gradually throughout the study. However, prefrail participants showed higher usability than frail older adults (difference-in-difference = - 19.431, p = 0.012). According to the frailty status, the change in usability for each service type also showed a different pattern. During the 12-month study period, the service with the highest satisfaction converged from various service needs to light control by remote control (77.8%) in the prefrailty group and automatic gas circuit breaker (72.7%) in the frailty group. For wider implementation of home IoT services, organizing services expected to have high usability and satisfaction based on user's frailty status is crucial. Also, providing education before service implementation might help older adults coping with digital literacy.

Kinematic characteristics during gait in frail older women identified by principal component analysis.

Frailty is associated with gait variability in several quantitative parameters, including high stride time variability. However, the associations between joint kinematics during walking and increased gait variability with frailty remain unclear. In the current study, principal component analysis was used to identify the key joint kinematics characteristics of gait related to frailty. We analyzed whole kinematic waveforms during the entire gait cycle obtained from the pelvis and lower limb joint angle in 30 older women (frail/prefrail: 15 participants; non-frail: 15 participants). Principal component analysis was conducted using a 60 × 1224 input matrix constructed from participants' time-normalized pelvic and lower-limb-joint angles along three axes (each leg of 30 participants, 51 time points, four angles, three axes, and two variables). Statistical analyses revealed that only principal component vectors 6 and 9 were related to frailty. Recombining the joint kinematics corresponding to these principal component vectors revealed that frail older women tended to exhibit greater variability of knee- and ankle-joint angles in the sagittal plane while walking compared with non-frail older women. We concluded that greater variability of knee- and ankle-joint angles in the sagittal plane are joint kinematic characteristics of gait related to frailty.

The association between heart rate behavior and gait performance: The moderating effect of frailty.

INTRODUCTION: Research suggests that frailty not only influence individual systems, but also it affects the interconnection between them. However, no study exists to show how the interplay between cardiovascular and motor performance is compromised with frailty. AIM: To investigate the effect of frailty on the association between heart rate (HR) dynamics and gait performance. METHODS: Eighty-five older adults (≥65 years and able to walk 9.14 meters) were recruited (October 2016-March 2018) and categorized into 26 non-frail (age = 78.65±7.46 years) and 59 pre-frail/frail individuals (age = 81.01±8.17) based on the Fried frailty phenotype. Participants performed gait tasks while equipped with a wearable electrocardiogram (ECG) sensor attached to the chest, as well as wearable gyroscopes for gait assessment. HR dynamic parameters were extracted, including time to peak HR and percentage increase in HR in response to walking. Using the gyroscope sensors gait parameters were recorded including stride length, stride velocity, mean swing velocity, and double support. RESULTS: Among the pre-frail/frail group, time to peak HR was significantly correlated with all gait parameters (p<0.0001, r = 0.51-0.59); however, for the non-frail group, none of the correlations between HR dynamics and gait performance parameters were significant (p>0.45, r = 0.03-0.15). The moderation analysis of time to peak HR, demonstrated a significant interaction effect of HR dynamics and frailty status on walking velocity (p<0.01), and the interaction effect was marginally non-significant for other gait parameters (p>0.10). CONCLUSIONS: Current findings, for the first time, suggest that a compromised motor and cardiac autonomic interaction exist among pre-frail/frail older adults; an impaired HR performance (i.e., slower increase of HR in response to stressors) may lead to a slower walking performance. Assessing physical performance and its corresponding HR behavior should be studied as a tool for frailty screening and providing insights about the underlying cardiovascular-related mechanism leading to physical frailty.

Exercise Capacity and Frailty Are Associated with Cerebral White Matter Hyperintensity in Older Adults with Cardiovascular Disease.

Cerebral white matter hyperintensity (WMH) is highly prevalent among older adults. There is little information about the relationship among WMH extent, frailty status, and exercise capacity in older adults with cardiovascular disease (CVD). We assessed the association of WMH with frailty and exercise capacity in CVD patients.Seventy-eight stable older adults with CVD were evaluated for WMH, the Kihon Checklist (KCL), short physical performance battery score (SPPB), and cardiopulmonary exercise testing. WMH volume was quantified on brain magnetic resonance imaging. Patients were classified into 3 groups (using tertiles of 0.52% and 1.05%) according to WMH as a percentage of intracranial volume (ICV), and their KCL scores and exercise capacities were compared. The 3 WMH/ICV groups were mild (n = 26, 0.26% ± 0.14% of intracranial volume), moderate (n = 26, 0.70% ± 0.15%), and severe (n = 26, 1.75% ± 0.67%). Peak VO2 was 15.2 ± 3.7 mL kg-1 minute-1 (mild group), 12.9 ± 3.5 mL kg-1 min-1 (moderate), and 11.4 ± 2.3 mL kg-1 minute-1 (severe) (mild versus moderate, P = 0.049; mild versus severe, P = 0.001). Multivariate regression analysis showed significant associations of severe WMH/ICV with peak VO2 and SPPB. Cerebral WMH was strongly negatively associated with SPPB and peak VO2. WMH volume may be related to exercise capacity and frailty in stable older adult patients with CVD.

Prehabilitation, enhanced recovery after surgery, or both? A narrative review.

This narrative review presents a biological rationale and evidence to describe how the preoperative condition of the patient contributes to postoperative morbidity. Any preoperative condition that prevents a patient from tolerating the physiological stress of surgery (e.g. poor cardiopulmonary reserve, sarcopaenia), impairs the stress response (e.g. malnutrition, frailty), and/or augments the catabolic response to stress (e.g. insulin resistance) is a risk factor for poor surgical outcomes. Prehabilitation interventions that include exercise, nutrition, and psychosocial components can be applied before surgery to strengthen physiological reserve and enhance functional capacity, which, in turn, supports recovery through attaining surgical resilience. Prehabilitation complements Enhanced Recovery After Surgery (ERAS) care to achieve optimal patient outcomes because recovery is not a passive process and it begins preoperatively.

Neurophysiological and Brain Structural Markers of Cognitive Frailty Differ from Alzheimer's Disease.

With increasing life span and prevalence of dementia, it is important to understand the mechanisms of cognitive aging. Here, we focus on a subgroup of the population we term "cognitively frail," defined by reduced cognitive function in the absence of subjective memory complaints, or a clinical diagnosis of dementia. Cognitive frailty is distinct from cognitive impairment caused by physical frailty. It has been proposed to be a precursor to Alzheimer's disease, but may alternatively represent one end of a nonpathologic spectrum of cognitive aging. We test these hypotheses in humans of both sexes, by comparing the structural and neurophysiological properties of a community-based cohort of cognitive frail adults, to people presenting clinically with diagnoses of Alzheimer's disease or mild cognitive impairment, and community-based cognitively typical older adults. Cognitive performance of the cognitively frail was similar to those with mild cognitive impairment. We used a novel cross-modal paired-associates task that presented images followed by sounds, to induce physiological responses of novelty and associative mismatch, recorded by EEG/MEG. Both controls and cognitively frail showed stronger mismatch responses and larger temporal gray matter volume, compared with people with mild cognitive impairment and Alzheimer's disease. Our results suggest that community-based cognitively frail represents a spectrum of normal aging rather than incipient Alzheimer's disease, despite similar cognitive function. Lower lifelong cognitive reserve, hearing impairment, and cardiovascular comorbidities might contribute to the etiology of the cognitive frailty. Critically, community-based cohorts of older adults with low cognitive performance should not be interpreted as representing undiagnosed Alzheimer's disease.SIGNIFICANCE STATEMENT The current study investigates the neural signatures of cognitive frailty in relation to healthy aging and Alzheimer's disease. We focus on the cognitive aspect of frailty and show that, despite performing similarly to the patients with mild cognitive impairment, a cohort of community-based adults with poor cognitive performance do not show structural atrophy or neurophysiological signatures of Alzheimer's disease. Our results call for caution before assuming that cognitive frailty represents latent Alzheimer's disease. Instead, the cognitive underperformance of cognitively frail adults could result in cumulative effects of multiple psychosocial risk factors over the lifespan, and medical comorbidities.

Correlation of physical and cognitive impairment in diabetic and hypertensive frail older adults.

BACKGROUND: Diabetes and hypertension are common in older adults and represent established risk factors for frailty. Frailty is a multidimensional condition due to reserve loss and susceptibility to stressors with a high risk of death, hospitalizations, functional and cognitive impairment. Comorbidities such as diabetes and hypertension play a key role in increasing the risk of mortality, hospitalization, and disability. Moreover, frail patients with diabetes and hypertension are known to have an increased risk of cognitive and physical impairment. Nevertheless, no study assessed the correlation between physical and cognitive impairment in frail older adults with diabetes and hypertension. METHODS: We evaluated consecutive frail older patients with diabetes and hypertension who presented at ASL (local health unit of the Italian Ministry of Health) Avellino, Italy, from March 2021 to October 2021. The inclusion criteria were: a previous diagnosis of diabetes and hypertension with no evidence of secondary causes; age > 65 years; a frailty status; Montreal Cognitive Assessment (MoCA) score < 26. RESULTS: 179 patients successfully completed the study. We found a strong and significant correlation between MoCA score and 5-m gait speed test (r: 0.877; p < 0.001). To further verify our results, we performed a linear multivariate analysis adjusting for potential confounding factors, with MoCA score as dependent variable, which confirmed the significant association with glycemia (p < 0.001). CONCLUSIONS: This is the first study showing a significant correlation between 5-m gait speed test and MoCA score in frail diabetic and hypertensive older adults.

Systolic Blood Pressure and Mortality in Community-Dwelling Older Adults: Frailty as an Effect Modifier.

Current evidence is insufficient to support different hypertension treatment targets in older adults. We evaluated whether frailty modifies the association between systolic blood pressure (SBP) and 8-year all-cause mortality in community-dwelling older adults. Longitudinal data from the ActiFE Ulm study (Activity and Function in the Elderly in Ulm; Germany) was collected. The association between SBP and mortality was analyzed using Cox proportional hazards models adjusted for age, sex, education, smoking, alcohol consumption, sleep disturbance, diastolic blood pressure, and antihypertensive medications, evaluating the presence of effect modification by frailty according to a frailty index based on the accumulation of deficits. Among 1170 participants (median age 73.9 years, 41.6% women), the prevalence of history of hypertension was 53.8% (median SBP, 144.0 mm Hg [interquartile range, 135.0-149.5], median diastolic blood pressure 78.0 mm Hg [interquartile range, 71.0-86.5]). The median follow-up time was 8.1 years, detecting 268 deaths. We identified 251 (21.5%, 114 deaths) frail participants (frailty index ≥0.2). Effect modification by frailty was detected. Among non-frail a J-shaped association was found with hazard ratio, 4.01 (95% CI, 1.13-14.28) for SBP<110 mm Hg, hazard ratio, 0.92 (95% CI, 0.53-1.59) for SBP 140-150 mm Hg, and hazard ratio, 1.98 (95% CI, 0.75-5.27) for SBP≥160 mm Hg. For frail older adults, a tendency toward lower risk among those with SBP≥130 mm Hg was observed. Our results suggest the presence of effect modification by frailty indicating a possible protective effect for elevated SBP in frail older adults with respect to all-cause mortality even after adjusting for diastolic blood pressure and antihypertensive treatment.

Preoperative Point-of-Care Ultrasound to Identify Frailty and Predict Postoperative Outcomes: A Diagnostic Accuracy Study.

BACKGROUND: Frailty is increasingly being recognized as a public health issue, straining healthcare resources and increasing costs to care for these patients. Frailty is the decline in physical and cognitive reserves leading to increased vulnerability to stressors such as surgery or disease states. The goal of this pilot diagnostic accuracy study was to identify whether point-of-care ultrasound measurements of the quadriceps and rectus femoris muscles can be used to discriminate between frail and not-frail patients and predict postoperative outcomes. This study hypothesized that ultrasound could discriminate between frail and not-frail patients before surgery. METHODS: Preoperative ultrasound measurements of the quadriceps and rectus femoris were obtained in patients with previous computed tomography scans. Using the computed tomography scans, psoas muscle area was measured in all patients for comparative purposes. Frailty was identified using the Fried phenotype assessment. Postoperative outcomes included unplanned intensive care unit admission, delirium, intensive care unit length of stay, hospital length of stay, unplanned skilled nursing facility admission, rehospitalization, falls within 30 days, and all-cause 30-day and 1-yr mortality. RESULTS: A total of 32 patients and 20 healthy volunteers were included. Frailty was identified in 18 of the 32 patients. Receiver operating characteristic curve analysis showed that quadriceps depth and psoas muscle area are able to identify frailty (area under the curve-receiver operating characteristic, 0.80 [95% CI, 0.64 to 0.97] and 0.88 [95% CI, 0.76 to 1.00], respectively), whereas the cross-sectional area of the rectus femoris is less promising (area under the curve-receiver operating characteristic, 0.70 [95% CI, 0.49 to 0.91]). Quadriceps depth was also associated with unplanned postoperative skilled nursing facility discharge disposition (area under the curve 0.81 [95% CI, 0.61 to 1.00]) and delirium (area under the curve 0.89 [95% CI, 0.77 to 1.00]). CONCLUSIONS: Similar to computed tomography measurements of psoas muscle area, preoperative ultrasound measurements of quadriceps depth shows promise in discriminating between frail and not-frail patients before surgery. It was also associated with skilled nursing facility admission and postoperative delirium.

Gait speed is a preoperative indicator of postoperative events after elective proximal aortic surgery.

OBJECTIVE: The study objective was to evaluate whether 5-m gait speed, an established marker of frailty, is associated with postoperative events after elective proximal aortic surgery. METHODS: We performed a retrospective review of 435 patients aged more than 60 years who underwent elective proximal aortic surgery, defined as surgery on the aortic root, ascending aorta, or aortic arch through median sternotomy. Patients completed a 5-m gait speed test within 30 days before surgery. We evaluated the association between categoric (slow, ≤0.83 m/s and normal, >0.83 m/s) and continuous gait speed and the likelihood of experiencing the composite outcome before and after adjustment for European System for Cardiac Operative Risk Evaluation II. The composite outcome included in-hospital mortality, renal failure, prolonged ventilation, and discharge location. Secondary outcomes were 1-year mortality and 5-year survival. RESULTS: Of the study population, 30.3% (132/435) were categorized as slow. Slow walkers were significantly more likely to have in-hospital mortality, prolonged ventilation, and renal failure, and were less likely to be discharged home (all P < .05). The composite outcome was 2 times more likely to occur for slow walkers (gait speed categoric adjusted odds ratio, 2.08; 95% confidence interval, 1.27-3.40; P = .004). Moreover, a unit (1 m/s) increase in gait speed (continuous) was associated with 73% lower risk of experiencing the composite outcome (odds ratio, 0.27; 95% confidence interval, 0.11-0.68; P = .006). CONCLUSIONS: Slow gait speed is a preoperative indicator of risk for postoperative events after elective proximal aortic surgery. Gait speed may be an important tool to complement existing operative risk models, and its application may identify patients who may benefit from presurgical and postsurgical rehabilitation.

Inflammatory Bowel Disease Patients Who Respond to Treatment with Anti-tumor Necrosis Factor Agents Demonstrate Improvement in Pre-treatment Frailty.

BACKGROUND: Frailty may be a risk factor for complications in inflammatory bowel diseases (IBD) patients. We examined the impact of treatment on IBD patients who were frail prior to treatment and identified predictors of post-treatment change in frailty. METHODS: In an electronic health record-based cohort of IBD patients initiating anti-tumor necrosis factor (TNF)-α agents, we applied a validated claims-based frailty index to determine frailty in the 1 year prior to and after treatment initiation. We characterized treatment non-response using a composite outcome of IBD-related hospitalization, surgery, change in therapy, or initiation of systemic steroids. We constructed multivariable logistic regression models to identify determinants of post-treatment frailty. RESULTS: The 1210 patients initiating anti-TNF therapy had a median age of 30 years; 20% were ≥ 50 years. In the first year after anti-TNF initiation, 40% were non-responders. Many more treatment non-responders were frail in the year following treatment compared with treatment responders (27% vs 7%, p < 0.001). Pre-treatment frailty (OR 2.01, 95% CI 1.35-3.00) and prior IBD-related hospitalization (OR 1.63, 95% CI 1.15-2.30) were independently predictive of higher likelihood of post-treatment frailty. Therapy response was associated with a lower likelihood (OR 0.24, 95% CI 0.16-0.34) of post-treatment frailty. Nearly 85% of patients who were frail prior to treatment demonstrated improvement in frailty following treatment CONCLUSIONS: Response to anti-TNF therapy is an important determinant of post-treatment frailty in patients with IBD. Our findings suggest that effectively treating inflammatory states in older patients with IBD may improve frailty.

Links Between Inflammation, Mood, and Physical Function Among Older Adults With HIV.

OBJECTIVES: People living with human immunodeficiency virus (PLWH) treated with antiretrovirals have life spans similar to their HIV-negative peers. Yet, they experience elevated inflammation-related multimorbidity. Drawing on biopsychosocial determinants of health may inform interventions, but these links are understudied in older PLWH. We investigated cross-sectional relationships between psychosocial factors (mood, loneliness, and stigma), inflammatory markers, and age-related health outcomes among 143 PLWH aged 54-78 years. METHOD: Participants provided blood samples for serum cytokine and C-reactive protein (CRP) analyses, completed surveys assessing psychosocial factors and health, and completed frailty assessments. Regression models tested relationships between key psychosocial-, inflammation, and age-related health variables, adjusting for relevant sociodemographic and clinical factors. RESULTS: Participants with more depressive symptoms had higher composite cytokine levels than those with fewer depressive symptoms (ß = 0.22, t(126) = 2.71, p = .008). Those with higher cytokine levels were more likely to be prefrail or frail (adjusted odds ratio = 1.72, 95% confidence interval = 1.01-2.93) and reported worse physical function (ß = -0.23, t(129) = -2.64, p = .009) and more cognitive complaints (ß = -0.20, t(129) = -2.16, p = .03) than those with lower cytokine levels. CRP was not significantly related to these outcomes; 6-month fall history was not significantly related to inflammatory markers. DISCUSSION: Novel approaches are needed to manage comorbidities and maximize quality of life among older PLWH. Illustrating key expected biopsychosocial links, our findings highlight several factors (e.g., depressive symptoms, poorer physical function) that may share bidirectional relationships with chronic inflammation, a key factor driving morbidity. These links may be leveraged to modify factors that drive excessive health risk among older PLWH.

A single center's 15-year experience with palliative limb care for chronic limb threatening ischemia in frail patients.

OBJECTIVE: Our institution's multidisciplinary Prevention of Amputation in Veterans Everywhere (PAVE) program allocates veterans with critical limb threatening ischemia (CLTI) to immediate revascularization, conservative care, primary amputation, or palliative limb care according to previously reported criteria. These four groups align with the approaches outlined by the global guidelines for the management of CLTI. In the present study, we have delineated the natural history of the palliative limb care group of patients and quantified the procedural risks and outcomes. METHODS: Veterans prospectively enrolled into the palliative limb cohort of our PAVE program from January 2005 to January 2020 were analyzed. The primary outcome was mortality. The secondary outcomes included overall and limb-related readmissions, limb loss, and wound healing. The clinical frailty scale (CFS) score was calculated, and the 5-year expected mortality was estimated using the Veterans Affairs Quality Enhancement Research Initiative tool. Regression analysis was performed to establish associations among the following variables: mortality, wound, ischemia, and foot infection (WIfI) score, CFS score, overall admissions, and limb-related admissions. RESULTS: The PAVE program enrolled 1158 limbs during 15 years. Of the 1158 limbs, 157 (13.5%) in 145 patients were allocated to the palliative limb care group. The overall mortality of the group was 88.2% (median interval, 3.5 months; range, 0-91 months). Of the 128 patients who had died, 64 (50%) had died within 3 months of enrollment. The predicted 5-year mortality for the group was 66%. The average CFS score for the group was 6.2, denoting persons moderately to severely frail. Using the CFS score, 106 patients were considered frail and 39 were considered not frail. No differences were found in mortality between the frail and nonfrail patients. However, a statistically significant difference was found in early (<3 months) mortality (56.2% vs 37.5%; P = .032). The 30-day limb-related readmission rate was 4.7%. Eventual major amputation was necessary for 18 limbs (11.5%). Wound healing occurred in 30 patients (20.6%). Regression analysis demonstrated no association between the CFS score and mortality (r = 0.55; P = .159) or between the WIfI score and mortality (r = 0.0165; P = .98). However, a significant association was found between the WIfI score and limb-related admissions (r = 0.97; P < .001). CONCLUSIONS: Frail patients with CLTI had high early mortality and a low risk of limb-related complications. They also had a low incidence of deferred primary amputation or limb-related readmissions. In our cohort, the vast majority of patients had died within a few months of enrollment without requiring an amputation. A comprehensive approach to the treatment of CLTI patients should include a palliative limb care option because a significant proportion of these patients will have limited survival and can potentially avoid unnecessary surgery and major amputation.

Frailty is associated with increased risk of cirrhosis disease progression and death.

BACKGROUND AND AIMS: The Liver Frailty Index (LFI) is a well-studied tool that evaluates frailty in patients with cirrhosis. Consisting of grip strength, chair stands, and balance testing, the LFI has been associated with increased mortality in patients awaiting liver transplant. We aimed to extend our understanding of frailty in cirrhosis by exploring the relationship between the LFI and the risk of (1) cirrhosis progression, (2) mortality, and (3) unplanned hospitalizations, in both compensated and decompensated disease. APPROACH AND RESULTS: Adult patients with cirrhosis from four centers in North America and one in India were included. Frailty was measured at baseline using the LFI and categorized as robust (LFI < 3.2), prefrail (LFI 3.2-4.5), and frail (LFI > 4.5). Progression of cirrhosis was defined by an increase in clinical stage, ranging from 1 to 5, from baseline using the D'Amico classification. Factors associated with progression, mortality, and hospitalizations were evaluated using multivariate regression models, with transplant as a competing risk. In total, 822 patients with cirrhosis were included. Average Model for End-Stage Liver Disease (MELD) score was 15.5 ± 6.0. In patients with compensated cirrhosis, being frail versus robust was associated with increased risk of progression to the next cirrhosis stage or to death (HR, 2.45; 95% CI, 1.14-5.29) and with an increased risk of unplanned hospitalizations (2.32; 95% CI, 1.13-4.79), after adjusting for age, sex, and MELD score. Similar HRs were observed in patients with decompensated cirrhosis. CONCLUSIONS: Frailty was an independent predictor of cirrhosis progression or death and unplanned hospitalization across patients with compensated and decompensated cirrhosis. Future studies are needed to evaluate the possibility of slowing cirrhosis disease progression by reversing or preventing frailty.

Sex-Specific Differences in the Effect of Free Testosterone on Sarcopenia Components in Older Adults.

Objective: The association of free testosterone (FT) with sarcopenia and its components is well known in men but incompletely understood in women. We examined the association of baseline FT with the prevalence and incidence of sarcopenia and its components in community-dwelling older adults. Design: Cross-sectional and longitudinal analysis from the prospective population-based Korean Frailty and Aging Cohort Study. Methods: A total of 1,879 community-dwelling older adults aged 70-84 years were enrolled for cross-sectional analysis and 1,583 subjects who participated in the 2-year follow-up survey were included for longitudinal analysis. Baseline FT levels was measured by radioimmunoassay. Skeletal muscle mass, handgrip strength, and physical performance tests were measured at baseline and after 2-year follow-up. Sarcopenia was defined by the diagnostic criteria of the Asian Working Group for Sarcopenia (AWGS). Results: Continuous FT levels was positively associated with the prevalence of sarcopenia in men (odds ratio [OR]=0.95; 95% confidence interval [CI]=0.89-1.00)] and women (OR=0.64, 95% CI=0.42-0.99) after adjusting for multiple confounders. In prospective analysis, low FT levels was associated with a decrease in handgrip strength in women (ß=-0.61; p=0.010) and a reduction in Timed "Up and Go" (TUG) test (ß=0.53; p=0.008) in men after 2 years. No significant correlations were found between FT levels and the incidence of sarcopenia. Conclusions: Low levels of FT may be a significant determinant of decreases in muscle strength in women and declines in physical performance in men after 2 years. Low FT do not predict loss of muscle mass in both men and women.

Mesenchymal Stem Cell Transplantation for the Treatment of Age-Related Musculoskeletal Frailty.

Projected life expectancy continues to grow worldwide owing to the advancement of new treatments and technologies leading to rapid growth of geriatric population. Thus, age-associated diseases especially in the musculoskeletal system are becoming more common. Loss of bone (osteoporosis) and muscle (sarcopenia) mass are conditions whose prevalence is increasing because of the change in population distribution in the world towards an older mean age. The deterioration in the bone and muscle functions can cause severe disability and seriously affects the patients' quality of life. Currently, there is no treatment to prevent and reverse age-related musculoskeletal frailty. Existing interventions are mainly to slow down and control the signs and symptoms. Mesenchymal stem cell (MSC) transplantation is a promising approach to attenuate age-related musculoskeletal frailty. This review compiles the present knowledge of the causes and changes of the musculoskeletal frailty and the potential of MSC transplantation as a regenerative therapy for age-related musculoskeletal frailty.

Impact of Frailty on Treatment Outcome in Patients With Locally Advanced Esophageal Cancer Undergoing Concurrent Chemoradiotherapy.

BACKGROUND/AIM: The clinical significance of frailty status on treatment outcome in patients with esophageal cancer (EC) has been seldom explored. This study aimed to evaluate the impact of pretreatment frailty on treatment-related toxicity and survival outcome in patients with EC undergoing concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: Patients aged ≥20 years and with newly diagnosed locally advanced EC receiving neoadjuvant radiotherapy and concurrent chemotherapy with weekly administration of carboplatin and paclitaxel for 5 weeks were prospectively enrolled. A pretreatment frailty assessment was performed within 7 days before CCRT initiation. The primary endpoint was treatment-related toxicity and complications of CCRT while the secondary endpoint was overall survival. RESULTS: A total of 87 patients were enrolled, 41 (47%) and 46 (53%) of whom were allocated in the frail and fit group, respectively. Frail patients had a significantly higher incidence of having at least one severe hematological adverse event (63.4% vs. 19.6%, p<0.001), higher risk of emergent room visiting [relative risk 3.72; 95% confidence interval (CI)=1.39-9.91; p=0.009] and hospitalization (relative risk 3.85; 95% CI=1.03-11.2; p=0.013) during the course of CCRT, when compared to fit patients. Overall survival showed significant worsening in the frail group [adjusted hazard ratio (HR)=2.12; 95% CI=1.01-4.42; p=0.046]. CONCLUSION: Frailty is associated with increase of treatment-related toxicities and poor survival outcome in EC patients undergoing CCRT. Our study suggested that pretreatment frailty assessment is imperative to serve as a predictor and prognostic factor for all adult patients with EC undergoing CCRT.

Nutritional status and physical performance using handgrip and SPPB tests in hospitalized older adults.

BACKGROUND & AIMS: Malnutrition and poor physical performance are highly prevalent within hospitalized older adults, and both have in common the loss of muscle mass. Likewise, there is growing interest in identifying markers of physical performance, other than just measuring muscle mass, that might be useful for managing malnutrition. This study aimed to (i) characterize the physical condition of hospitalized older adults in comparison to previously published reference percentile values of same age adults and (ii) to examine the association between the nutritional status and physical performance of older inpatients. METHODS: A total of 604 inpatients (age 84.3 ± 6.8 years, 50.3% women) participated in this cross-sectional study. Patients were assessed for nutritional status (Mini Nutritional Assessment-Short Form (MNA-SF)) and physical performance (handgrip strength and the Short Physical Performance Battery (SPPB)). RESULTS: During hospitalization, 65.7% of the inpatients were at risk of malnutrition or malnourished. More than a half of the older inpatients were unfit (≤P25) for handgrip strength (52.0%) and SPPB total score (86.3%) as well as for two of its subtests, gait speed (86.7%) and 5 times sit-to-stand (91.1%) tests. Patients' nutritional status was significantly associated with better physical performance within all tests (all p < 0.001), as their nutritional status improved so did their physical performance (all p for trend <0.001). Hence, being at risk of malnutrition or malnourished significantly increased the likelihood for being classified as unfit according to handgrip strength (OR: 1.466, 95% CI: 1.045-2.056), SPPB total score (OR: 2.553, 95% CI: 1.592-4.094) and 4-m walking test (OR: 4.049, 95% CI: 2.469-6.640) (all p < 0.05), and as frail (OR: 4.675, 95% CI: 2.812-7.772) according to the SPPB frailty threshold (p < 0.001). CONCLUSIONS: This study reinforces the use of handgrip strength and SPPB, as well as its subtests (gait speed and 5 times sit-to-stand tests), in hospitalized older adults as alternative measures of muscle mass for malnutrition management. Hence, it seems that risk of malnutrition or malnutrition assessed by MNA-SF might help to predict poor physical performance in older inpatients.