Frailty is a geriatric syndrome that diminishes the potential for functional recovery after a transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) procedure; ...however, its integration in clinical practice has been limited by a lack of consensus on how to measure it.
This study sought to compare the incremental predictive value of 7 different frailty scales to predict poor outcomes following TAVR or SAVR.
A prospective cohort of older adults undergoing TAVR or SAVR was assembled at 14 centers in 3 countries from 2012 to 2016. The following frailty scales were compared: Fried, Fried+, Rockwood, Short Physical Performance Battery, Bern, Columbia, and the Essential Frailty Toolset (EFT). Outcomes of interest were all-cause mortality and disability 1 year after the procedure.
The cohort was composed of 1,020 patients with a median age of 82 years. Depending on the scale used, the prevalence of frailty ranged from 26% to 68%. Frailty as measured by the EFT was the strongest predictor of death at 1 year (adjusted odds ratio OR: 3.72; 95% confidence interval CI: 2.54 to 5.45) with a C-statistic improvement of 0.071 (p < 0.001) and integrated discrimination improvement of 0.067 (p < 0.001). Moreover, the EFT was the strongest predictor of worsening disability at 1 year (adjusted OR: 2.13; 95% CI: 1.57 to 2.87) and death at 30 days (adjusted OR: 3.29; 95% CI: 1.73 to 6.26).
Frailty is a risk factor for death and disability following TAVR and SAVR. A brief 4-item scale encompassing lower-extremity weakness, cognitive impairment, anemia, and hypoalbuminemia outperformed other frailty scales and is recommended for use in this setting. (Frailty Assessment Before Cardiac Surgery & Transcatheter Interventions; NCT01845207).
Frailty assessment can help predict which older adults will experience adverse events after cardiac surgical procedures. Low muscle mass is a core component of frailty that is suboptimally captured ...by self-reported weight loss; refined measures using computed tomographic (CT) images have emerged and are predictive of outcomes in noncardiac surgical procedures. The objective of this study was to evaluate the association between CT muscle area and length of stay (LOS) after cardiac surgical procedures.
Frail patients who had a perioperative abdominal or thoracic CT scan were identified. The CT scans were analyzed to measure cross-sectional lean muscle area at the L4 vertebra (psoas muscle area PMA, lumbar muscle area LMA) and the T4 vertebra (thoracic muscle area TMA). The associations of PMA, LMA, and TMA with frailty markers and postoperative LOS were investigated.
Eighty-two patients were included; the mean age was 69.2 ± 9.97 years. Low muscle area was correlated with lower handgrip strength and short physical performance battery (SPPB) scores indicative of physical frailty. Postoperative LOS was correlated with PMA (R = -0.47, p = 0.004), LMA (R = -0.41, p = 0.01), and TMA (R = -0.29, p = 0.03). After adjustment for the predicted risk of prolonged LOS, age, sex, and body surface area, PMA remained significantly associated with LOS (β = -2.35, 95% CI -4.48 to -0.22). The combination of low PMA and handgrip strength, indicative of sarcopenia, yielded the greatest incremental value in predicting LOS.
Low PMA is a marker of physical frailty associated with increased LOS in older adults undergoing cardiac surgical procedures. Further research is necessary to validate PMA as a prognostic marker and therapeutic target in this vulnerable population.
We previously demonstrated that 1) obesity impairs and 2) sex influences insulin sensitivity of protein metabolism, while 3) poor glycemic control in type 2 diabetes accelerates protein turnover in ...daily fed-fasted states. We hypothesized that type 2 diabetes alters the insulin sensitivity of protein metabolism and that sex modulates it.
Hyperinsulinemic ( approximately 570 pmol/l), euglycemic (5.5 mmol/l), and isoaminoacidemic (kept at postabsorptive concentrations) clamps were performed in 17 hyperglycemic type 2 diabetic subjects and 23 subjects without diabetes matched for age and body composition, after 7 days on a inpatient, protein-controlled, isoenergetic diet. Glucose and leucine kinetics were determined using tracers.
In type 2 diabetes, postabsorptive (baseline) glycemia was 8-9 mmol/l, glucose production (R(a)) and disposal (R(d)) were elevated, and once clamped, endogenous glucose R(a) remained greater and R(d) was less (P < 0.05) than in control subjects. Baseline leucine kinetics did not differ despite higher insulin levels. The latter was an independent predictor of leucine flux within each sex. With clamp, total flux increased less (P = 0.016) in type 2 diabetic men, although protein breakdown decreased equally ( approximately 20%) in male groups but less in female groups. Whereas protein synthesis increased in male control subjects and in both female groups, it did not in male subjects with type 2 diabetes. In men, homeostasis model assessment of insulin resistance predicted 44%, and, in women, waist-to-hip ratio predicted 40% of the change in synthesis.
During our clamp, men with type 2 diabetes have greater insulin resistance of protein metabolism than that conferred by excess adiposity itself, whereas women do not. These results may have implications for dietary protein requirements.
Studies have shown that an even protein intake distribution across meals increased 24-h muscle protein synthesis in young adults compared with a skewed intake. Whether this short-term result ...translates into long-term preservation of lean mass (LM) in older adults remains unknown.
The aim was to examine the extent to which protein quantity and distribution are associated with LM and appendicular LM (aLM), and their 2-y decline, in community-dwelling older adults.
Baseline and 2-y follow-up data from 351 men and 361 women (aged 67-84 y) in the NuAge study (Quebec Longitudinal Study on Nutrition as a Determinant of Successful Aging) with available body-composition data (by dual-energy X-ray absorptiometry) were used. Food intake was assessed with the use of three 24-h food recalls collected at baseline and 3 collected at the 2-y follow-up. Protein distribution across meals was calculated as the CV of protein ingested per meal, with lower values reflecting evenness of protein intake. Linear mixed-model analysis was performed to examine changes in LM and aLM across time, by sex, as conditioned by the quantity and distribution of protein intake, adjusted for potential covariates.
Over 2 y, LM declined in both men (-2.5% ± 4.0%) and women (-2.0% ± 3.4%) (P < 0.05), whereas aLM loss was not significant (men: -1.5% ± 4.8%; women: -1.2% ± 5.3%; P > 0.05). The decline in LM was not independently affected by the quantity and distribution of protein intake. Yet men and women with evenly distributed protein intakes and men with high protein intakes showed higher LM or aLM throughout the entire follow-up period, even after potential confounders were controlled for (P < 0.05).
Our results suggest that greater protein intakes and a more even distribution across meals are modifiable factors associated with higher muscle mass in older adults but not with losses over 2 y. Interventional studies should determine longer-term effects on preserving LM with aging.
Functional status declines with aging, thus impeding autonomy. Recently, a more even mealtime distribution of dietary protein was positively associated with muscle mass, but the relation of this ...distribution to physical performance remains unknown.
We examined the relation between mealtime protein-intake distribution and physical performance and its 3-y decline in community-dwelling older adults.
Three-year follow-up data from 827 men and 914 women (67–84 y) in the longitudinal study on nutrition and aging Quebec longitudinal study on Nutrition as a Determinant of Successful Aging (NuAge study); Quebec, Canada were analyzed. Physical performance, which was measured yearly, was grouped into the following 2 functional composite scores: muscle strength (handgrip, arm, and leg) and mobility (timed-up-and-go, chair stand, and walking speed). Dietary data were collected in 2 sets of three 24-h food recalls at baseline and year 2. The individual mealtime protein distribution was calculated as the CV (i.e., SD divided by the mean) of grams of protein per meal. A mixed model analysis was used to examine trajectories of muscle strength and mobility across time by sex as conditioned by the protein distribution and adjusted for potential covariates.
Physical performance deteriorated over 3 y with muscle strength declining more than the mobility score in men (−1.51 ± 1.68 compared with −0.66 ± 2.81) and women (−1.35 ± 1.77 compared with −0.78 ± 2.63) (means ± SD, P < 0.001). More-evenly distributed protein intake, independent of the total quantity, was associated with a higher muscle-strength score in both sexes throughout follow-up. It was also associated with a greater mobility score, but only in men and only before adjustment for covariates. Strength and mobility rates of decline were not affected by protein-intake distribution in either sex.
In addition to the previously observed association with lean mass, an even distribution of daily protein intake across meals is independently associated with greater muscle strength, but not with the mobility score, in older adults. A longer-term investigation of the role of protein intake and its distribution on physical performance is warranted, as are intervention studies, to support future recommendations.
A new paradigm is emerging in which mobility and cognitive impairments, previously studied, diagnosed, and managed separately in older adults, are in fact regulated by shared brain resources. ...Deterioration in these shared brain mechanisms by normal aging and neurodegeneration increases the risk of developing dementia, falls, and fractures. This new paradigm requires an integrated approach to measuring both domains. We aim to identify a complementary battery of existing tests of mobility and cognition in community-dwelling older adults that enable assessment of motor-cognitive interactions.
Experts on mobility and cognition in aging participated in a semistructured consensus based on the Delphi process. After performing a scoping review to select candidate tests, multiple rounds of consultations provided structured feedback on tests that captured shared characteristics of mobility and cognition. These tests needed to be sensitive to changes in both mobility and cognition, applicable across research studies and clinics, sensitive to interventions, feasible to perform in older adults, been previously validated, and have minimal ceiling/floor effects.
From 17 tests appraised, 10 tests fulfilled prespecified criteria and were selected as part of the "Core-battery" of tests. The expert panel also recommended a "Minimum-battery" of tests that included gait speed, dual-task gait speed, the Montreal Cognitive Assessment and Trail Making Test A&B.
A standardized assessment battery that captures shared characteristics of mobility and cognition seen in aging and neurodegeneration may increase comparability across research studies, detection of subtle or common reversible factors, and accelerate research progress in dementia, falls, and aging-related disabilities.
Background: Intravenous lipid emulsions (ILEs) were initially developed to provide parenteral nutrition. In recent years, ILE has emerged as a treatment for poisoning by local anesthetics and various ...other drugs. The dosing regimen for the clinical toxicology indications differs significantly from those used for parenteral nutrition. The evidence on the efficacy of ILE to reverse acute toxicity of diverse substances consists mainly of case reports and animal experiments. Adverse events to ILE are important to consider when clinicians need to make a risk/benefit analysis for this therapy. Methods: Multiple publication databases were searched to identify reports of adverse effects associated with acute ILE administration for either treatment of acute poisoning or parenteral nutrition. Articles were selected based on pre-defined criteria to reflect acute use of ILE. Experimental studies and reports of adverse effects as a complication of long-term therapy exceeding 14 days were excluded. Results: The search identified 789 full-text articles, of which 114 met the study criteria. 27 were animal studies, and 87 were human studies. The adverse effects associated with acute ILE administration included acute kidney injury, cardiac arrest, ventilation perfusion mismatch, acute lung injury, venous thromboembolism, hypersensitivity, fat embolism, fat overload syndrome, pancreatitis, extracorporeal circulation machine circuit obstruction, allergic reaction, and increased susceptibility to infection. Conclusion: The emerging use of ILE administration in clinical toxicology warrants careful attention to its potential adverse effects. The dosing regimen and context of administration leading to the adverse events documented in this review are not generalizable to all clinical toxicology scenarios. Adverse effects seem to be proportional to the rate of infusion as well as total dose received. Further safety studies in humans and reporting of adverse events associated with ILE administration at the doses advocated in current clinical toxicology literature are needed.
Abstract Cancer cachexia (CC) is a syndrome characterized by wasting of lean body mass and fat, often driven by decreased food intake, hypermetabolism, and inflammation resulting in decreased ...lifespan and quality of life. Classification of cancer cachexia has improved, but few clinically relevant diagnostic tools exist for its early identification and characterization. The abridged Patient-Generated Subjective Global Assessment (aPG-SGA) is a modification of the original Patient-Generated Subjective Global Assessment, and consists of a four-part questionnaire that scores patients' weight history, food intake, appetite, and performance status. The purpose of this study was to determine whether the aPG-SGA is associated with both features and clinical sequelae of cancer cachexia. In this prospective cohort study, 207 advanced lung and gastrointestinal cancer patients completed the following tests: aPG-SGA, Edmonton Symptom Assessment System, handgrip strength, a complete blood count, albumin, apolipoprotein A and B, and C-reactive protein. Ninety-four participants with good performance status as assessed by the Eastern Cooperative Oncology Group Performance Status completed additional questionnaires and underwent body composition testing. Of these, 68 patients tested for quadriceps strength and completed a 3-day food recall. Multivariable regression models revealed that higher aPG-SGA scores (≥9 vs 0 to 1) are significantly associated ( P <0.05) with the following: unfavorable biological markers of cancer cachexia, such as higher white blood cell counts (10.0 vs 6.7×109 /L; lower hemoglobin (115.6 vs 127.7 g/L), elevated C-reactive protein (42.7 vs 18.2 mg/L 406.7 vs 173.3 nmol/L); decreased anthropometric and physical measures, such as body mass index (22.5 vs 27.1); fat mass (14.4 vs 26.0 kg), handgrip (24.7 vs 34.9 kg) and leg strength; an average 12% greater length of hospital stay; a dose reduction in chemotherapy; and increased mortality. Given its association with the main features of cancer cachexia and its ease of use, the aPG-SGA appears to be a useful tool for detecting and predicting outcomes of cancer cachexia. Additional research is required to determine what impact the aPG-SGA has on quality of care when used in the clinical setting.
Key points
Susceptibility to age‐related muscle atrophy relates to the degree of muscle denervation and the capacity of successful reinnervation. However, the specific role of denervation as a ...determinant of the severity of muscle aging between populations with low versus high physical function has not been addressed.
We show that prefrail/frail elderly women exhibited marked features of muscle denervation, whereas world class octogenarian female master athletes showed attenuated indices of denervation and greater reinnervation capacity.
These findings suggest that the difference in age‐related muscle impact between low‐ and high‐functioning elderly women is the robustness of the response to denervation of myofibers.
Ageing muscle degeneration is a key contributor to physical frailty; however, the factors responsible for exacerbated vs. muted ageing muscle impact are largely unknown. Based upon evidence that susceptibility to neurogenic impact is an important determinant of the severity of ageing muscle degeneration, we aimed to determine the presence and extent of denervation in pre‐frail/frail elderly (FE, 77.9 ± 6.2 years) women compared to young physically inactive (YI, 24.0 ± 3.5 years) females, and contrast these findings to high‐functioning world class octogenarian female masters athletes (MA, 80.9 ± 6.6 years). Muscle biopsies from vastus lateralis muscle were obtained from all three groups to assess denervation‐related morphological and transcriptional markers. The FE group displayed marked grouping of slow fibres, accumulation of very small myofibres, a severe reduction in type IIa/I size ratio, highly variable inter‐subject accumulation of neural cell adhesion molecule (NCAM)‐positive myofibres, and an accumulation of pyknotic nuclei, indicative of recurring cycles of denervation/reinnervation and persistent denervation. The MA group exhibited a smaller decline in type IIa/I size ratio and fewer pyknotic nuclei, accompanied by a higher degree of type I fibre grouping and larger fibre group size, suggesting a greater reinnervation of denervated fibres. Consistent with this interpretation, MA had higher mRNA levels of the reinnervation‐promoting cytokine fibroblast growth factor binding protein 1 (FGFBP1) than FE. Our results indicate that the muscle of FE women has significant neurogenic atrophy, whereas MA muscle exhibit superior reinnervation capacity, suggesting that the difference in age‐related muscle impact between low‐ and high‐functioning elderly women is the robustness of the response to denervation of myofibres.
Key points
Susceptibility to age‐related muscle atrophy relates to the degree of muscle denervation and the capacity of successful reinnervation. However, the specific role of denervation as a determinant of the severity of muscle aging between populations with low versus high physical function has not been addressed.
We show that prefrail/frail elderly women exhibited marked features of muscle denervation, whereas world class octogenarian female master athletes showed attenuated indices of denervation and greater reinnervation capacity.
These findings suggest that the difference in age‐related muscle impact between low‐ and high‐functioning elderly women is the robustness of the response to denervation of myofibers.
PDF
