BACKGROUND: Skeletal muscle alterations are associated with higher mortality and morbidity in patients with liver cirrhosis. Assessing these changes seems to be a promising method for identifying patients at a high risk of poor outcomes following liver transplantation (LT). This is particularly important given the current global shortage of organ donors. However, evidence of the impact of these alterations on the prognosis of patients undergoing LT is inconclusive. The aim of our prospective study was to evaluate the impact of skeletal muscle changes, reflected in sarcopenia, myosteatosis and metabolic changes in the calf muscles, on perioperative outcomes and long-term survival after LT. We also sought to determine the posttransplant evolution of the resting muscle metabolism. METHODS: We examined 134 adult LT candidates. Of these, 105 underwent LT. Sarcopenia and myosteatosis were diagnosed by measuring the skeletal muscle index and mean psoas muscle radiation attenuation, respectively, which were obtained from computed tomography (CT) scans taken during pretransplant assessment. Additionally, patients underwent 31P MR spectroscopy (MRS) of the calf muscles at rest before LT and 6, 12 and 24 months thereafter. The median follow-up was 6 years. RESULTS: Patients with abnormal 31P MRS results and CT-diagnosed myosteatosis prior to LT had significantly worse long-term survival after LT (hazard ratio (HR), 3.36; 95% confidence interval (CI), 1.48-7.60; p = 0.0021 and HR, 2.58; 95% CI, 1.06-6.29; p = 0.03, respectively). Multivariable analysis showed that abnormal 31P MR spectra (HR, 3.40; 95% CI, 1.50-7.71; p = 0.003) were a better predictor of worse long-term survival after LT than myosteatosis (HR, 2.78; 95% CI, 1.14-6.78; p = 0.025). Patients with abnormal 31P MR spectra had higher blood loss during LT (p = 0.038), required a higher number of red blood cell transfusions (p = 0.006) and stayed longer in ICU (p = 0.041) and hospital (p = 0.007). Myosteatosis was associated with more revision surgeries following LT (p = 0.038) and a higher number of received red blood cell transfusion units (p = 0.002). Sarcopenia had no significant effect on posttransplant patient survival. An improvement in the resting metabolism of the calf muscles was observed at 12 and 24 months after LT. CONCLUSIONS: Abnormal 31P MRS results of calf muscles were superior to CT-based diagnosis of myosteatosis and sarcopenia in predicting perioperative complications and long-term survival after LT. Resting muscle metabolism normalized 1 year after LT in most recipients.
- MeSH
- dospělí MeSH
- kosterní svaly * diagnostické zobrazování metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie * metody MeSH
- počítačová rentgenová tomografie * metody MeSH
- prognóza MeSH
- prospektivní studie MeSH
- sarkopenie etiologie metabolismus MeSH
- senioři MeSH
- transplantace jater * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Weak muscle strength has been associated with a wide range of adverse health outcomes. Yet, whether individuals with weaker muscle strength are more at risk for hospitalization due to severe COVID-19 is still unclear. The objective of this study was to investigate the independent association between muscle strength and COVID-19 hospitalization. METHODS: Data from adults 50 years of age or older were analysed using logistic models adjusted for several chronic conditions, body-mass index, age, and sex. Hand-grip strength was repeatedly measured between 2004 and 2017 using a handheld dynamometer. COVID-19 hospitalization during the lockdown was self-reported in summer 2020 and was used as an indicator of COVID-19 severity. RESULTS: The study was based on the Survey of Health, Ageing and Retirement in Europe (SHARE) and included 3600 older adults (68.8 ± 8.8 years, 2044 female), among whom 316 were tested positive for the severe acute respiratory syndrome coronavirus 2 (8.8%), and 83 (2.3%) were hospitalized due to COVID-19. Results showed that higher grip strength was associated with a lower risk of COVID-19 hospitalization [adjusted odds ratio (OR) per increase of 1 standard deviation in grip strength = 0.64, 95% confidence interval (95% CI) = 0.45-0.87, P = 0.015]. Results also showed that age (OR for a 10 -year period = 1.70, 95% CI = 1.32-2.20, P < 0.001) and obesity (OR = 2.01, 95% CI = 1.00-3.69, P = 0.025) were associated with higher risk of COVID-19 hospitalization. Sensitivity analyses using different measurements of grip strength as well as robustness analyses based on rare-events logistic regression and a different sample of participants (i.e. COVID-19 patients) were consistent with the main results. CONCLUSIONS: Muscle strength is an independent risk factor for COVID-19 severity in adults 50 years of age or older.
- MeSH
- COVID-19 * MeSH
- hospitalizace MeSH
- kontrola infekčních nemocí MeSH
- lidé MeSH
- rizikové faktory MeSH
- SARS-CoV-2 MeSH
- senioři MeSH
- svalová síla MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: Cachexia worsens long-term prognosis of patients with heart failure (HF). Effective treatment of cachexia is missing. We seek to characterize mechanisms of cachexia in adipose tissue, which could serve as novel targets for the treatment. METHODS: The study was conducted in advanced HF patients (n = 52; 83% male patients) undergoing heart transplantation. Patients with ≥7.5% non-intentional body weight (BW) loss during the last 6 months were rated cachectic. Clinical characteristics and circulating markers were compared between cachectic (n = 17) and the remaining, BW-stable patients. In epicardial adipose tissue (EAT), expression of selected genes was evaluated, and a combined metabolomic/lipidomic analysis was performed to assess (i) the role of adipose tissue metabolism in the development of cachexia and (ii) potential impact of cachexia-associated changes on EAT-myocardium environment. RESULTS: Cachectic vs. BW-stable patients had higher plasma levels of natriuretic peptide B (BNP; 2007 ± 1229 vs. 1411 ± 1272 pg/mL; P = 0.010) and lower EAT thickness (2.1 ± 0.8 vs. 2.9 ± 1.4 mm; P = 0.010), and they were treated with ~2.5-fold lower dose of both β-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACE/ARB-inhibitors). The overall pattern of EAT gene expression suggested simultaneous activation of lipolysis and lipogenesis in cachexia. Lower ratio between expression levels of natriuretic peptide receptors C and A was observed in cachectic vs. BW-stable patients (0.47 vs. 1.30), supporting activation of EAT lipolysis by natriuretic peptides. Fundamental differences in metabolome/lipidome between BW-stable and cachectic patients were found. Mitochondrial phospholipid cardiolipin (CL), specifically the least abundant CL 70:6 species (containing C16:1, C18:1, and C18:2 acyls), was the most discriminating analyte (partial least squares discriminant analysis; variable importance in projection score = 4). Its EAT levels were higher in cachectic as compared with BW-stable patients and correlated with the degree of BW loss during the last 6 months (r = -0.94; P = 0.036). CONCLUSIONS: Our results suggest that (i) BNP signalling contributes to changes in EAT metabolism in cardiac cachexia and (ii) maintenance of stable BW and 'healthy' EAT-myocardium microenvironment depends on the ability to tolerate higher doses of both ACE/ARB inhibitors and β-adrenergic blockers. In line with preclinical studies, we show for the first time in humans the association of cachexia with increased adipose tissue levels of CL. Specifically, CL 70:6 could precipitate wasting of adipose tissue, and thus, it could represent a therapeutic target to ameliorate cachexia.
- MeSH
- antagonisté receptorů pro angiotenzin MeSH
- inhibitory ACE MeSH
- kachexie * etiologie MeSH
- kardiolipiny MeSH
- lidé MeSH
- natriuretické peptidy MeSH
- srdeční selhání * komplikace MeSH
- tuková tkáň * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Type 2 diabetes, a highly prevalent chronic disease, is associated with increasing frailty and functional decline in older people. We aimed to evaluate the effectiveness of a multimodal intervention on functional performance in frail and pre-frail participants aged ≥70 years with type 2 diabetes mellitus. METHODS: The MID-Frail study was a cluster-randomized multicenter clinical trial conducted in 74 trial sites across seven European countries. The trial recruited 964 participants who were aged >70 years [mean age in intervention group, 78.4 (SD 5.6) years, 49.2% male and 77.6 (SD 5.29) years, 52.4% male in usual care group], with type diabetes mellitus and determined to be frail or pre-frail using Fried's frailty phenotype. Participants were allocated by trial site to follow either usual care (UCG) or intervention procedures (IG). Intervention group participants received a multimodal intervention composed of (i) an individualized and progressive resistance exercise programme for 16 weeks; (ii) a structured diabetes and nutritional educational programme over seven sessions; and (iii) Investigator-linked training to ensure optimal diabetes care. Short Physical Performance Battery (SPPB) scores were used to assess change in functional performance at 12 months between the groups. An analysis of the cost-effectiveness of the intervention was undertaken using the incremental cost-effectiveness ratio (ICER). Secondary outcomes included mortality, hospitalization, institutionalization, quality of life, burden on caregivers, the frequency and severity of hypoglycaemia episodes, and the cost-effectiveness of the intervention. RESULTS: After 12 months, IG participants had mean SPPB scores 0.85 points higher than those in the UCG (95% CI, 0.44 to 1.26, P < 0.0001). Dropouts were higher in frail participants and in the intervention group, but significant differences in SPPB between treatment groups remained consistent after sensitivity analysis. Estimates suggest a mean saving following intervention of 428.02 EUR (2016) per patient per year, with ICER analysis indicating a consistent benefit of the described health care intervention over usual care. No statistically significant differences between groups were detected in any of the other secondary outcomes. CONCLUSIONS: We have demonstrated that a 12 month structured multimodal intervention programme across several clinical settings in different European countries leads to a clinically relevant and cost-effective improvement in the functional status of older frail and pre-frail participants with type 2 diabetes mellitus.
- MeSH
- diabetes mellitus 2. typu terapie MeSH
- kombinovaná terapie MeSH
- kvalita života psychologie MeSH
- lidé MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the essential amino acid leucine that has been reported to have anabolic effects on protein metabolism. The aims of this article were to summarize the results of studies of the effects of HMB on skeletal muscle and to examine the evidence for the rationale to use HMB as a nutritional supplement to exert beneficial effects on muscle mass and function in various conditions of health and disease. The data presented here indicate that the beneficial effects of HMB have been well characterized in strength-power and endurance exercise. HMB attenuates exercise-induced muscle damage and enhances muscle hypertrophy and strength, aerobic performance, resistance to fatigue, and regenerative capacity. HMB is particularly effective in untrained individuals who are exposed to strenuous exercise and in trained individuals who are exposed to periods of high physical stress. The low effectiveness of HMB in strength-trained athletes could be due to the suppression of the proteolysis that is induced by the adaptation to training, which may blunt the effects of HMB. Studies performed with older people have demonstrated that HMB can attenuate the development of sarcopenia in elderly subjects and that the optimal effects of HMB on muscle growth and strength occur when it is combined with exercise. Studies performed under in vitro conditions and in various animal models suggest that HMB may be effective in treatment of muscle wasting in various forms of cachexia. However, there are few clinical reports of the effects of HMB on muscle wasting in cachexia; in addition, most of these studies evaluated the therapeutic potential of combinations of various agents. Therefore, it has not been possible to determine whether HMB was effective or if there was a synergistic effect. Although most of the endogenous HMB is produced in the liver, there are no reports regarding the levels and the effects of HMB supplementation in subjects with liver disease. Several studies have suggested that anabolic effects of HMB supplementation on skeletal muscle do not occur in healthy, non-exercising subjects. It is concluded that (i) HMB may be applied to enhance increases in the mass and strength of skeletal muscles in subjects who exercise and in the elderly and (ii) studies examining the effects of HMB administered alone are needed to obtain conclusions regarding the specific effectiveness in attenuating muscle wasting in various muscle-wasting disorders.
- MeSH
- kachexie dietoterapie patofyziologie MeSH
- kosterní svaly účinky léků fyziologie MeSH
- lidé MeSH
- potravní doplňky MeSH
- sarkopenie dietoterapie patofyziologie MeSH
- svalová atrofie dietoterapie patofyziologie MeSH
- svalová síla účinky léků MeSH
- syndrom chřadnutí dietoterapie patofyziologie MeSH
- valeráty aplikace a dávkování farmakologie MeSH
- zdraví MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
