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1.
Medicine (Baltimore) ; 98(48): e18113, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770235

RESUMO

The impact of vitamin D deficiency on the recovery of patients with malnutrition remains undefined. Our aim was to study the prevalence of vitamin D deficiency in a well-characterized cohort of patients with malnutrition and its association with outcomes.Within this secondary analysis of a randomized controlled trial, we examined the association of vitamin D deficiency and adverse clinical outcomes over a follow-up of 180 days in hospitalized patients at risk for malnutrition. We measured 25-hydroxyvitamin D levels upon admission and defined Vitamin D deficiency when levels were <50nmol/l. The primary endpoint was 180-day mortality.The prevalence of vitamin D deficiency in our cohort of 828 patients was 58.2% (n = 482). Patients with vitamin D deficiency had increased 180-day mortality rates from 23.1% to 29.9% (odds ratio 1.42, 95% confidence interval [CI] 1.03-1.94, P = .03). When adjusting the analysis for demographics, comorbidities, and randomization, this association remained significant for the subgroup of patients not receiving vitamin D treatment (adjusted odds ratio 1.63, 95% CI 1.01-2.62, P = .04). There was no significantly lower risk for mortality in the subgroup of vitamin D deficient patients receiving vitamin D treatment compared to not receiving treatment (adjusted odds ratio 0.74, 95% CI 0.48-1.13, P = .15).Vitamin D deficiency is highly prevalent in the population of malnourished inpatients and is negatively associated with long-term mortality particularly when patients are not receiving vitamin D treatment. Our findings suggest that malnourished patients might benefit from vitamin D screening and treatment in case of deficiency.


Assuntos
Idoso Fragilizado/estatística & dados numéricos , Fragilidade/mortalidade , Desnutrição/mortalidade , Deficiência de Vitamina D/mortalidade , Deficiência de Vitamina D/terapia , Idoso , Idoso de 80 Anos ou mais , Suplementos Nutricionais , Feminino , Fragilidade/sangue , Fragilidade/complicações , Humanos , Pacientes Internados/estatística & dados numéricos , Masculino , Desnutrição/sangue , Desnutrição/complicações , Prevalência , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações , Vitaminas/uso terapêutico
2.
Exp Hematol ; 77: 12-25.e2, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31476327

RESUMO

Frailty is highly associated with cardiovascular diseases (CVD) and diabetes mellitus (DM). Aging, CVD, and DM are all associated with an increase in platelet function. Therefore, the aim of this study was to evaluate platelet function during frailty. We selected a total of 37 older adults who were divided into two groups, frail (n = 16) and robust (n = 21), with a mean age of 72.4 ± 4.4 years (range: 65-84 years) in robust adults and 72.6 ± 6.6 years (range: 65-88 years) in frail adults; 20 young healthy volunteers, with a mean age of 22.9 ± 2.7 years (range: 20-30 years), were included as a control platelet function was determined using the lumi-aggregometer (aggregation) and flow cytometry (platelet activation). We also performed Western blot to evaluate the intraplatelet activation pathways involved in activation. Platelet count decreased and mean platelet volume, aggregation, and P-selectin expression increased during aging compared with young adults was found. We observed an increase in P-selectin expression in frail adults compared with robust adults. We also evaluated the characteristics of the study population to explain this difference and found a higher prevalence of DM and a tendency toward hyperglycemia in frail adults compared with robust adults. In agreement with this, high doses of glucose were able to increase platelet aggregation and P-selectin expression through thrombin receptors and p38 phosphorylation.


Assuntos
Envelhecimento/sangue , Plaquetas/metabolismo , Doenças Cardiovasculares/sangue , Diabetes Mellitus/sangue , Fragilidade/sangue , Selectina-P/sangue , Agregação Plaquetária , Adulto , Idoso , Idoso de 80 Anos ou mais , Plaquetas/patologia , Doenças Cardiovasculares/patologia , Diabetes Mellitus/patologia , Feminino , Fragilidade/patologia , Regulação da Expressão Gênica , Humanos , Masculino , Volume Plaquetário Médio , Testes de Função Plaquetária
3.
Transplant Proc ; 51(6): 2009-2013, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399181

RESUMO

BACKGROUND: The aim of the study was to investigate the serum concentration of cytokines and biochemical markers of malnutrition in correlation with frailty syndrome in patients qualified for lung transplantation (LTx). METHODS: The study population comprised 31 potential lung recipients, including 18 patients with idiopathic lung disease, 12 patients with chronic obstructive pulmonary disease, and 1 patient with bronchiectasis who qualified for a LTx. Cytokine serum levels were assessed using commercially available enzyme-linked immunosorbent assay kits and the Luminex 200 platform (ProcartaPlex Hu Cytokine/Chemokine Panel 1A 34plex, Invitrogen, Carlsbad, Calif., United States). The patients were also asked to complete a questionnaire, the Clinical Frailty Scale. RESULTS: All patients were found to have higher cytokine concentrations (IL6, IL 2,IL18, IL23, IL 12p70, IL 10, IL 7). No statistically significant differences in the analyzed cytokines were noted when the men's results were compared to those of the women. There were no significant differences between patients who scored 6 vs 7 points on the Canadian Study of Health and Aging Function Scale. In comparing chronic obstructive pulmonary disease to idiopathic lung disease patients, no significant differences were observed in the analyzed cytokine values. Significant correlations were observed between the analyzed cytokines and age of the patients, C-reactive protein, triglycerides, transferrin, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. CONCLUSIONS: Our findings indicate that cytokines may not have a statistically significant effect on the parameters of the frailty syndrome. The results require further investigations on larger study groups. The findings suggest that the analyzed cytokines may play a proinflammatory role in the end stages of lung diseases, but further studies are needed to evaluate whether these cytokines could be used as biomarkers in this group of patients.


Assuntos
Citocinas/sangue , Fragilidade/sangue , Pneumopatias/sangue , Transplante de Pulmão/efeitos adversos , Desnutrição/sangue , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Canadá , HDL-Colesterol , Contraindicações de Procedimentos , Ensaio de Imunoadsorção Enzimática , Feminino , Fragilidade/complicações , Fragilidade/cirurgia , Humanos , Interleucina-10/sangue , Pulmão/fisiopatologia , Pneumopatias/complicações , Pneumopatias/cirurgia , Masculino , Desnutrição/complicações , Desnutrição/cirurgia , Pessoa de Meia-Idade , Seleção de Pacientes , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/cirurgia , Triglicerídeos/sangue , Adulto Jovem
4.
J Surg Res ; 243: 539-552, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31377495

RESUMO

BACKGROUND: Frailty predicts poor outcome after vascular surgery. We determined the predictive utility of the modified frailty index (mFI) after first-time revascularization and identified biomarkers of frailty predictive of outcome in veterans with peripheral arterial disease. METHODS: A retrospective study was performed of first-time revascularizations (open surgery [OS] and endovascular surgery [ES]) in male veterans (2003-2016). Preoperative mFI scores were calculated, and serum and nonserum biomarkers of frailty were recorded. The primary endpoint was 2-y incidence of reintervention, amputation, and mortality. Secondary endpoints included 30-day morbidity and readmissions. RESULTS: Four hundred and thirty one patients (OS, n = 188; ES, n = 243), mean age of 66 ± 9 y, and 16 mo of median follow-up were studied. Mean mFI was 0.39 ± 0.16 for OS and 0.38 ± 0.15 for ES (P = 0.43). 30-day complications (adjusted odds ratio, 4.89; 95% confidence interval [CI]: 1.67-14.33) and readmissions (adjusted hazard ratio [aHR] 3.32; 95% CI: 1.16-9.55) were increased in the OS versus ES group when stratified by mFI. Survival analysis showed a correlation between risk of amputation, death, and composite outcome with increasing mFI (P < 0.005) in both groups. Frailty independently predicted major amputation (aHR 2.16; 1.06-4.39), mortality (aHR 2.62; 95% CI: 1.17-5.88), and composite outcome (aHR 1.97; 95% CI: 1.06-3.68) when the groups are combined. Except for absolute neutrophil count, all preoperative lab values correlated with mFI (P < 0.5). Higher albumin was independently associated with lower risk of amputation (aHR: 0.58 [0.36-0.94]) and mortality (aHR: 0.45 [0.25-0.83]); higher hemoglobin predicted limb salvage (aHR 0.7 [0.62-0.84]). CONCLUSIONS: Frailty predicts short- and long-term outcomes after first-time revascularization in veterans. Hypoalbuminemia and anemia are associated with higher mFI and independently predict poor outcome, suggesting albumin and hemoglobin are viable biomarkers of frailty in veterans.


Assuntos
Procedimentos Endovasculares/mortalidade , Fragilidade/complicações , Doença Arterial Periférica/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Biomarcadores/sangue , Fragilidade/sangue , Humanos , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Doença Arterial Periférica/complicações , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Veteranos/estatística & dados numéricos
5.
Clin Interv Aging ; 14: 389-398, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863033

RESUMO

The term "frailty" is used to describe a subset of older adults who appear weaker and more vulnerable than their age-matched counterparts, despite having similar comorbidities, demography, sex, and age. The diagnosis of frailty is usually clinical and based on specific criteria, which are sometimes inconsistent. Therefore, there is an increasing need to identify and validate robust biomarkers for this condition. In this review, we summarize current evidence on the validity and practicality of the most commonly used biomarkers for frailty, while also comparing them with new upcoming strategies to identify this condition.


Assuntos
Fragilidade/sangue , Hormônios/sangue , Inflamação/sangue , Células-Tronco Mesenquimais , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Fragilidade/complicações , Hemoglobina A Glicada/metabolismo , Humanos , Inflamação/complicações , Interleucina-6/sangue , Lamina Tipo A/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fator de Necrose Tumoral alfa/sangue
6.
Clin Interv Aging ; 14: 473-484, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880928

RESUMO

Background: We aimed to evaluate the abilities of a 21-item frailty index based on laboratory blood and urine tests (FI-Lab21) assessed at different points in time, ie, at admission to hospital (FI-Lab21admission) and before discharge from hospital (FI-Lab21discharge), and the change of the FI-Lab21 during the hospital stay to predict 6-month and 1-year mortality in hospitalized geriatric patients. Methods: Five hundred hospitalized geriatric patients aged ≥65 years were included in this analysis. Follow-up data were acquired after a period of 6 months and 1 year. Results: The FI-Lab21admission and FI-Lab21discharge scores were 0.33±0.15 and 0.31±0.14, respectively (P<0.001). The FI-Lab21admission and FI-Lab21discharge both predicted 6-month and 1-year mortality (areas under the receiver operating characteristic curves: 0.72, 0.72, 0.77, and 0.75, respectively, all P<0.001). The predictive abilities for 6-month and 1-year mortality of the FI-Lab21admission were inferior compared with those of the FI-Lab21discharge (all P<0.05). Patients with a reduction in or stable FI-Lab21 score during the hospital stay revealed lower 6-month and 1-year mortality rates compared with the persons whose FI-Lab21 score increased during the hospital stay (all P<0.05). After adjustment for age, sex, and FI-Lab21admission, each 1% decrease in the FI-Lab21 during the hospital stay was associated with a decrease in 6-month and 1-year mortality of 5.9% and 5.3% (both P<0.001), respectively. Conclusion: The FI-Lab21 assessed at admission or discharge and the changes of the FI-Lab21 during the hospital stay emerged as interesting and feasible approaches to stratify mortality risk in hospitalized geriatric patients.


Assuntos
Fragilidade/sangue , Fragilidade/urina , Idoso , Idoso de 80 Anos ou mais , Feminino , Fragilidade/mortalidade , Avaliação Geriátrica , Humanos , Masculino , Admissão do Paciente , Alta do Paciente , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Índice de Gravidade de Doença , Taxa de Sobrevida , Fatores de Tempo
7.
J Trauma Acute Care Surg ; 87(1): 54-60, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30768559

RESUMO

BACKGROUND: Frailty is a geriatric syndrome characterized by decreased physiological reserves, increased inflammation, and decreased anabolic-endocrine response. The biomarkers associated with frailty are poorly understood in trauma. The aim of this study was to analyze the association between frailty and immune: IL-1ß, IL-6, IL-2Rα, tumor necrosis factor (TNF)-α, and endocrine biomarkers: insulin-like growth factor-1 and growth hormone in trauma patients. METHODS: We conducted a 1-year (2017-2018) prospective analysis of geriatric (≥65 years) trauma patients admitted to our Level I trauma center. Frailty was measured using the trauma-specific frailty index (TSFI) and blood samples were collected within 24 hours of admission. Patients were stratified into two groups: frail (TSFI > 0.25) and nonfrail (TSFI ≤ 0.25). We then measured the levels of immune and endocrine biomarkers by a colorimetric output that was read by a spectrophotometer (Quantikine ELISA). The outcome measures were the levels of the immune and endocrine markers in the two groups. Multivariable linear regression was performed. RESULTS: A total of 100 geriatric trauma patients were consented and enrolled. The mean age was 77.1 ± 9.8 years and 34% were female. Thirty-nine (39%) patients were frail. Frail patients were more likely to present after falls (p = 0.01). There was no difference in age (p = 0.78), sex (p = 0.77), systolic blood pressure (p = 0.16), and heart rate (p = 0.24) between the two groups. Frail patients had higher levels of TNF-α (p = 0.01), IL-1ß (p = 0.01), and IL-6(p = 0.01) but lower levels of growth hormone (p = 0.03) and insulin-like growth factor-1 (p < 0.04) compared with nonfrail patients. There was no difference in the level of IL-2Rα (p = 0.25). On regression analysis, frailty was positively correlated with the levels of proinflammatory biomarkers, that is, TNF- α, IL-1 ß, and IL-6 and negatively correlated with endocrine biomarkers. CONCLUSION: This study supports the association between frailty and immune and endocrine markers. Frailty acts synergistically with trauma in increasing the acute inflammatory response. Moreover, frail patients have lower levels of anabolic hormones. Understanding the inflammatory and endocrine response in frail trauma patients may result in better therapeutic strategies.


Assuntos
Fragilidade/complicações , Inflamação/etiologia , Ferimentos e Lesões/complicações , Idoso , Biomarcadores/sangue , Feminino , Idoso Fragilizado , Fragilidade/sangue , Hormônio do Crescimento Humano/sangue , Humanos , Inflamação/sangue , Fator de Crescimento Insulin-Like I/análise , Interleucina-1beta/sangue , Subunidade alfa de Receptor de Interleucina-2/sangue , Interleucina-6/sangue , Masculino , Estudos Prospectivos , Fator de Necrose Tumoral alfa/sangue , Ferimentos e Lesões/sangue
8.
J Frailty Aging ; 8(1): 17-20, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30734826

RESUMO

In this cross-sectional study of 141 Aboriginal Australians aged ≥45 years living in the remote Kimberley region of Western Australia, we explored whether glycated haemoglobin (HbA1c) levels were associated with frailty. Sixty-four participants (45.4%) had a HbA1c level ≥6.5% and 84 participants (59.6%) were frail. A significant trend was observed with regard to HbA1c levels and frailty, with those having HbA1c levels ≥6.5% having the greatest prevalence of frailty (70.3%). In binary logistic regression analyses, having a HbA1c level ≥6.5% was associated with being frail after adjustment for age, sex, and education. This association was attenuated after further adjustment for body mass index (BMI). Poorer glycaemic control is very common and a potential risk factor for frailty in remote-living Aboriginal Australians, and appears to be partly mediated by BMI, a known risk factor for diabetes mellitus. Obesity and diabetes mellitus are potentially important modifiable risk factors for frailty.


Assuntos
Fragilidade/etnologia , Hemoglobina A Glicada/análise , Grupo com Ancestrais Oceânicos/estatística & dados numéricos , Austrália , Estudos Transversais , Fragilidade/sangue , Humanos , Pessoa de Meia-Idade , Fatores de Risco
9.
J Gerontol A Biol Sci Med Sci ; 74(3): 343-349, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29534173

RESUMO

BACKGROUND: Evidence suggests that systemic inflammation may have a mechanistic role in age-related frailty, yet prospective data is limited. We examined whether systemic inflammation during midlife was associated with late-life frailty within the community-based Atherosclerosis Risk in Communities Study. METHODS: Plasma levels of four inflammatory markers (fibrinogen, von Willebrand factor, and Factor VIII, and white blood cell count) were measured during Visit 1 (1987-1989; mean age: 52 [5]), standardized into z-scores, and combined to create an inflammation composite score. High-sensitivity C-reactive protein (CRP) was measured 3 (Visit 2, 1990-1992) and 9 (Visit 4, 1996-1999) years later. Frailty was evaluated in 5,760 participants during late life (Visit 5, 2011-2013; mean age: 75 [5]). Analyses were adjusted for demographic and physiological variables, and midlife medical comorbidity using logistic regression. RESULTS: A 1 SD increase in midlife inflammation composite score was associated with higher odds of frailty 24 years later (odds ratio [OR] = 1.39, 95% confidence interval [CI]: 1.18-1.65). Similarly, each standard deviation increase in Visit 2 CRP (OR = 1.24, 95% CI: 1.09-1.40) and Visit 4 CRP (OR = 1.35, 95% CI: 1.19-1.53) was associated with a higher odds of frailty 21 and 15 years later. Participants who maintained elevated CRP (≥3 mg/L) at Visits 2 and 4 or transitioned to a state of elevated CRP during this period were more likely to subsequently meet frailty criteria compared to those who maintained low CRP. These associations were stronger among white, compared to African American, participants (p-interactions < .038). CONCLUSIONS: Systemic inflammation during midlife may independently promote pathophysiological changes underlying frailty in a subset of the population.


Assuntos
Fragilidade/sangue , Fragilidade/etiologia , Inflamação/sangue , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Fator VIII/metabolismo , Feminino , Fibrinogênio/metabolismo , Humanos , Inflamação/complicações , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fator de von Willebrand/metabolismo
10.
Eur J Nutr ; 58(1): 379-389, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29380043

RESUMO

PURPOSE: To investigate the cross-sectional and prospective associations between patterns of serum fat-soluble micronutrients and frailty in four European cohorts of older adults 65 years of age and older. METHODS: Participants from the Three-City (Bordeaux, France), AMI (Gironde, France), TSHA (Toledo, Spain) and InCHIANTI (Tuscany, Italy) cohorts with available data on serum α-carotene, ß-carotene, lycopene, cryptoxanthin, lutein + zeaxanthin, retinol, α-tocopherol, γ-tocopherol and 25-hydroxyvitamin D3 (25(OH)D) were included. A principal component (PC) analysis was used to derive micronutrient patterns. Frailty was defined using Fried's criteria. Multivariate logistic regression models adjusted for socio-demographic and health-related covariates were performed to assess the association between micronutrient patterns and prevalent frailty in 1324 participants, and the risk of frailty in 915 initially non-frail participants. RESULTS: Three different patterns were identified: the first pattern was characterized by higher serum carotenoids and α-tocopherol levels; the second was characterized by high loadings for serum vitamins A and E levels and low loadings for carotenes level; the third one had the highest loading for serum 25(OH)D and cryptoxanthin level and the lowest loading for vitamin A and E. A significant cross-sectional association was only observed between the seconnd PC and prevalent frailty (p = 0.02). Compared to the highest quartile, participants in the lowest quartile-i.e., high carotenes and low vitamins E and A levels-had higher odds of frailty (Odds ratio = 2.2; 95% confidence interval 1.3-3.8). No association with the risk of frailty was observed. CONCLUSIONS: These findings suggest that some specific micronutrient patterns are markers but not predictors of frailty in these European cohorts of older adults.


Assuntos
Calcifediol/sangue , Carotenoides/sangue , Fragilidade/sangue , Fragilidade/epidemiologia , alfa-Tocoferol/sangue , gama-Tocoferol/sangue , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos Transversais , Feminino , França/epidemiologia , Avaliação Geriátrica/métodos , Avaliação Geriátrica/estatística & dados numéricos , Humanos , Itália/epidemiologia , Masculino , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Vitaminas/sangue
11.
Eur J Nutr ; 58(3): 1173-1181, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29691654

RESUMO

PURPOSE: Sufficient 25-hydroxyvitamin D (25(OH)D) concentrations might prevent a decline in physical performance, and are considered important for the prevention of frailty. This study investigates the association of serum 25(OH)D concentration with physical performance and frailty status in Dutch older adults. METHODS: This cross-sectional study included 756 men and women, aged ≥ 65 years. Serum 25(OH)D concentration and frailty status (Fried criteria) were assessed in the total population. Screening for frailty status included functional tests of gait speed and hand grip strength. In a subgroup (n = 494), the Timed Up and Go test (TUG) and knee-extension strength were measured. Associations of serum 25(OH)D status with physical performance were examined by multiple linear regression. Prevalence ratios (PR) were used to quantify associations between serum 25(OH)D deficiency (< 50 nmol/L) and frailty. RESULTS: In total, 45% of the participants were vitamin D deficient. Participants with vitamin D status < 50 and 50-75 nmol/L had significantly lower scores on the TUG and gait speed test, compared to participants with vitamin D status > 75 nmol/L. No significant associations with serum 25(OH)D concentrations were observed for handgrip strength or knee-extension strength. Participants with serum 25(OH)D status < 50 nmol/L were about two times more likely to be frail compared to participants with serum 25(OH)D status ≥ 50 nmol/L. No significant associations were observed between the pre-frail state and serum 25(OH)D status. CONCLUSION: In this study, serum 25(OH)D concentrations were significantly associated with frailty status and measures of physical performance, including gait speed and TUG, but not with strength-related outcomes.


Assuntos
Idoso Fragilizado/estatística & dados numéricos , Fragilidade/sangue , Avaliação Geriátrica/métodos , Avaliação Geriátrica/estatística & dados numéricos , Desempenho Físico Funcional , Vitamina D/análogos & derivados , Idoso , Estudos Transversais , Feminino , Força da Mão , Humanos , Masculino , Países Baixos , Vitamina D/sangue
12.
J Gerontol A Biol Sci Med Sci ; 74(3): 275-282, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29788087

RESUMO

A frailty index (FI) based on clinical deficit accumulation (FI-Clinical) quantifies frailty in aging mice. We aimed to develop a laboratory test-based murine FI tool (FI-Lab) and to investigate the effects of age and sex on FI-Lab scores, FI-Clinical scores, and the combination (FI-Combined), as well as to explore links between frailty and inflammation. Studies used older (17 and 23 months) C57BL/6 mice of both sexes. We developed an FI-Lab (blood pressure, blood chemistry, echocardiography) based on deviation from reference values in younger adults (12 months), which showed similar characteristics to a human FI-Lab tool. Interestingly, while FI-Clinical scores were higher in females, the opposite was true for FI-Lab scores and there was no sex difference in FI-Combined scores. All three FI tools revealed a positive correlation between pro-inflammatory cytokine levels and frailty in aging mice that differed between the sexes. Elevated levels of the pro-inflammatory cytokines interleukin (IL)-6, IL-9, and interferon-γ were associated with higher FI scores in aging females, while levels of IL-12p40 rose as FI scores increased in older males. Thus, an FI tool based on common laboratory tests can quantify frailty in mice; the positive correlation between inflammation and frailty scores in naturally aging mice differs between the sexes.


Assuntos
Envelhecimento/sangue , Citocinas/sangue , Fragilidade/sangue , Fragilidade/diagnóstico , Inflamação/sangue , Interleucinas/sangue , Fatores Etários , Animais , Pressão Sanguínea , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores Sexuais
13.
J Acquir Immune Defic Syndr ; 80(1): 118-125, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30299347

RESUMO

BACKGROUND: In the Multicenter AIDS Cohort Study, we examined whether fibroblast growth factor-23 (FGF-23), a bone-derived phosphaturic hormone involved in bone metabolism, is associated with incident frailty. Furthermore, we examined whether this association differs by HIV serostatus and race. METHODS: Of 715 men assessed for frailty and selected for FGF-23 measurements using stored blood samples (2007-2011), 512 men were nonfrail at/before the baseline visit. Frailty was defined by the presence of ≥3 of the following on 2 consecutive 6-month visits within 1 year: unintentional weight loss ≥10 pounds, weakness, slowness, low energy, and low physical activity. We determined the association of FGF-23 levels with incident frailty using proportional hazards models adjusting for sociodemographics, comorbidities, and kidney function. RESULTS: Sixty-five percent were HIV-infected; 29% were black. Median baseline FGF-23 levels were lower in HIV-infected vs. HIV-uninfected men (33.7 vs. 39.9 rU/mL, P = 0.006) but similar by race. During a median follow-up of 6.6 years, 32 men developed frailty; they had higher baseline FGF-23 levels vs. men who remained nonfrail (45 vs. 36 rU/mL, P = 0.02). FGF-23 (per doubling) was associated with a 1.63-fold risk of frailty [95% confidence interval (CI): 1.19 to 2.23]; results did not differ by HIV serostatus. Conversely, FGF-23 was associated with a 2.72-fold risk of frailty among blacks (95% CI: 1.51 to 4.91) but had minimal association among nonblacks (hazard ratio = 1.26, 95% CI: 0.77 to 2.05; p-interaction = 0.024). CONCLUSIONS: Among men with or at-risk of HIV infection, higher FGF-23 was associated with greater risk of frailty, particularly in blacks. The mechanisms by which FGF-23 may contribute to frailty warrant further study.


Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Fragilidade/fisiopatologia , Infecções por HIV/fisiopatologia , Adulto , Idoso , Biomarcadores/sangue , Angiografia Coronária , Grupos Étnicos , Fragilidade/sangue , Fragilidade/virologia , Infecções por HIV/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Modelos de Riscos Proporcionais , Estudos Prospectivos
14.
Gerontology ; 65(3): 229-239, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30463070

RESUMO

BACKGROUND: Myostatin has been proposed as a candidate biomarker for frailty and sarcopenia. However, the relationship of myostatin with these conditions remains inconclusive. OBJECTIVE: To determine the association of serum myostatin concentration with body composition, physical fitness, physical activity level, and frailty in long-term nursing home residents. We also aimed to ascertain the effect of an exercise program on myostatin levels. METHODS: We obtained study data on 112 participants from long-term nursing homes. Participants were randomly assigned to a control or an intervention group and performed a 6-month multicomponent exercise program. Serum myostatin levels were analyzed by ELISA. Assessments also included body composition (anthropometry and bioelectrical impedance), physical fitness (Senior Fitness Test), physical activity level (accelerometry), and frailty (Fried frailty criteria, Clinical Frailty Scale, and Tilburg frailty indicator). RESULTS: The concentration of myostatin at baseline was positively correlated with: a leaner body composition (p < 0.05), and a higher number of steps per day and light and moderate-vigorous physical activity in women (p < 0.005); greater upper and lower limb strength, endurance, and poorer flexibility (p < 0.05) in men; and better performance (less time) in the 8-ft timed up-and-go test in both women (p < 0.01) and men (p < 0.005). We observed higher concentrations of serum myostatin in non-frail than in frail participants (p < 0.05). Additionally, we found that the implemented physical exercise intervention, which was effective to improve physical fitness, increased myostatin concentration in men (p < 0.05) but not in women. The improvements in physical condition were related with increases in serum myostatin only in men (p < 0.05-0.01). CONCLUSIONS: Higher serum levels of myostatin were found to be associated with better physical fitness. The improvements in physical fitness after the intervention were positively related to increases in myostatin concentrations in men. These results seem to rule out the idea that high serum myostatin levels are indicative of frailty in long-term nursing home residents. However, although the direction of association was opposite to that expected for the function of myostatin, the use of this protein as a biomarker for physical fitness, rather than frailty, merits further study.


Assuntos
Terapia por Exercício , Exercício/fisiologia , Fragilidade/sangue , Miostatina/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Composição Corporal , Feminino , Idoso Fragilizado , Geriatria , Instituição de Longa Permanência para Idosos , Humanos , Masculino , Casas de Saúde , Aptidão Física , Método Simples-Cego
15.
Clin Interv Aging ; 13: 2013-2020, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30410318

RESUMO

Purpose: Frailty is associated with adverse health outcomes. Its biological markers are essential to enhance diagnostic ease and would contribute to surveillance of the condition. Considering the involvement of pro-inflammatory and nutritional states in frailty, we aimed to investigate whether inflammatory mediators and adipokines are associated with frailty and their relationship with physical function. Patients and methods: We recruited 130 older adults (90 nonfrail participants and 40 frail participants, mean age: 72.80±8.61 years) who underwent a comprehensive medical history and frailty assessment. The biochemical indicators (eg, blood urea nitrogen [BUN], high-density lipoprotein [HDL], and hemoglobin [HGB]), insulin pathway (glucose, insulin, and insulin-like growth factor 1 [IGF-1]), circulating inflammatory biomarkers (IL-6, tumor necrosis factor receptor 1, and C-reactive protein), and adipokines (adiponectin, vaspin, and leptin) were compared between the two groups. We further analyzed their correlation with physical function. Results: Frail older adults showed higher levels of BUN, IL-6, adiponectin, vaspin, and glucose and lower levels of IGF-1, HDL, and HGB compared with nonfrail participants. Serum IL-6 levels were negatively correlated with both grip strength (P=0.03) and gait speed (P=0.04). Levels of circulating adiponectin and leptin were adversely correlated with grip strength (P=0.01) and gait speed (P=0.03), respectively. After adjustment for age and sex, the only markers correlated with physical function were IL-6 (r=-0.180, P=0.044) and adiponectin (r=-0.195, P=0.029). Conclusion: High levels of IL-6, adiponectin, vaspin, and glucose as well as low levels of IGF-1 were found in frail older adults. Furthermore, IL-6, adiponectin, and leptin levels were negatively correlated with physical function, suggesting that inflammatory mediators and adipokines are biomarkers for frailty and decreased function in older adults.


Assuntos
Adipocinas/sangue , Fragilidade , Fator de Crescimento Insulin-Like I/análise , Interleucina-6/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biomarcadores/sangue , Glicemia/análise , China/epidemiologia , Feminino , Idoso Fragilizado , Fragilidade/sangue , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/fisiopatologia , Avaliação Geriátrica/métodos , Humanos , Masculino , Pessoa de Meia-Idade
16.
BMC Geriatr ; 18(1): 268, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30400833

RESUMO

BACKGROUND: The complex physiology underpinning the frailty syndrome is responsible for the absence of robust biomarkers that can be used for screening, diagnostic and/or prognostic purposes and has made clinical implementation difficult. Considering socially vulnerable populations, who have poor health status and increased morbidity and mortality, this scenario is even more complex. However, to the best of our knowledge, there are no studies available to investigate frailty biomarkers in socially vulnerable populations. Thus, the aim of this cross-sectional study was to identify potential blood-based biomarkers of frailty in a socially vulnerable population. METHODS: A sample consisting of 347 community-dwelling older people living in a context of high social vulnerability was divided into non-frail (robust), pre-frail and frail groups, according to modified Fried frailty phenotype criteria. Blood samples were collected and analyzed for basic metabolic parameters and for inflammatory cytokines. RESULTS: Levels of Interleukin-1α (IL-1α) and Tumor Necrosis Factor α (TNF-α) were significantly higher in pre-frail subjects, compared to non-frail ones. Tumor Necrosis Factor ß (TNF-ß) levels presented higher values in the frail compared to non-frail individuals. Interleukin-6 (IL-6) levels in pre-frail and frail subjects were significantly higher compared to the levels of non-frail subjects. Using an ordinal regression analysis, we observed that socially vulnerable older people at higher risk of developing frailty were subjects above 80 years old (OR: 2.5; 95% CI: 1.1-5.6) and who presented higher levels of TNF-ß (≥0.81 pg/mL, OR: 2.53; 95% CI: 1.3-4.9). CONCLUSION: As vulnerable populations continue to age, it is imperative to have a greater understanding of the frailty condition, identifying novel potential blood-based biomarkers. The results presented here could help to implement preventive healthcare strategies by evaluating frailty and at the same time measuring a set of inflammatory biomarkers, paying special attention to TNF-ß plasmatic levels.


Assuntos
Idoso Fragilizado/estatística & dados numéricos , Fragilidade/sangue , Avaliação Geriátrica/métodos , Vida Independente , Linfotoxina-alfa/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Brasil/epidemiologia , Estudos Transversais , Feminino , Fragilidade/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade
17.
Nutrients ; 10(11)2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30404172

RESUMO

Physical frailty and sarcopenia (PF&S) are hallmarks of aging that share a common pathogenic background. Perturbations in protein/amino acid metabolism may play a role in the development of PF&S. In this initial report, 68 community-dwellers aged 70 years and older, 38 with PF&S and 30 non-sarcopenic, non-frail controls (nonPF&S), were enrolled as part as the "BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons" (BIOSPHERE) study. A panel of 37 serum amino acids and derivatives was assayed by UPLC-MS. Partial Least Squares⁻Discriminant Analysis (PLS-DA) was used to characterize the amino acid profile of PF&S. The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classification was 76.6 ± 3.9% (75.1 ± 4.6% for enrollees with PF&S; 78.5 ± 6.0% for nonPF&S). Older adults with PF&S were characterized by higher levels of asparagine, aspartic acid, citrulline, ethanolamine, glutamic acid, sarcosine, and taurine. The profile of nonPF&S participants was defined by higher concentrations of α-aminobutyric acid and methionine. Distinct profiles of circulating amino acids and derivatives characterize older people with PF&S. The dissection of these patterns may provide novel insights into the role played by protein/amino acid perturbations in the disabling cascade and possible new targets for interventions.


Assuntos
Aminoácidos/sangue , Idoso Fragilizado , Fragilidade/sangue , Sarcopenia/sangue , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Biomarcadores/sangue , Feminino , Humanos , Masculino , Força Muscular
18.
Ageing Res Rev ; 48: 145-152, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30391341

RESUMO

Frailty is an emerging geriatric syndrome characterized by decreased physiologic reserve and increased vulnerability to environmental factors. Several studies have examined the association between persistent cytomegalovirus (CMV) infection and poor clinical outcomes in the elderly, but the results are often contradictory. Here, we performed a systematic review and meta-analysis to analyze the association between human herpesvirus seropositivity [CMV, Epstein-Barr virus (EBV), Varicella zoster virus (VZV), and Herpes simplex virus (HSV)] and frailty in elderly people. Searches were performed in PubMed, SCOPUS, Lilacs, IBECS, and Web of Science databases. We used the odds ratio (OR) as a measure of the association between herpesvirus infections and frailty. Summary estimates were calculated using random-effects models. Six studies were included in the present systematic review. The data from 2559 elderly subjects were analyzed; 1571 of the subjects had ages between 60 and 79 years, and 988 of the subjects were older than 80. We found an association between CMV seropositivity and frailty in the elderly aged 60-79 years (OR 2.33, CI 95% 1.48-3.67) but not in the oldest-old subjects (OR 0.67, CI 95% 0.42-1.05). Moreover, no association was found between EBV, VZV, and HSV infections and frailty. Current evidence suggests an association between CMV seropositivity and frailty in individuals aged 60-79 years old.


Assuntos
Fragilidade/sangue , Fragilidade/virologia , Infecções por Herpesviridae/sangue , Herpesvirus Humano 3/metabolismo , Herpesvirus Humano 4/metabolismo , Simplexvirus/metabolismo , Idoso , Idoso de 80 Anos ou mais , Citomegalovirus/metabolismo , Fragilidade/epidemiologia , Infecções por Herpesviridae/epidemiologia , Humanos , Pessoa de Meia-Idade
19.
J Frailty Aging ; 7(4): 253-257, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30298174

RESUMO

BACKGROUND: Frailty is associated with poor outcomes hence identification of risks factors is pivotal. Since the independent role of parathyroid hormone (PTH) in frailty remains unexplored, we aimed to determine this in a population of older individuals with a history of falling. DESIGN: Cross-sectional study. SETTING: Falls and Fracture Clinic, Nepean Hospital (Penrith, Australia). PARTICIPANTS: 692 subjects (mean age=79, 65% women) assessed between 2009-2015. MEASUREMENTS: Assessment included clinical examination, mood, nutrition, grip strength, gait velocity, bone densitometry and posturography. Chemistry included serum PTH, calcium, vitamin D (25(OH)D3), creatinine and albumin. Normocalcemic subjects were divided into 4 groups: (1) Normal: 25(OH)D3 >50nmol/L and PTH between 1.6-6.8pmol/L; (2) PTH responsive: low 25(OH)D3 (<50nmol/L) and high PTH (>6.8pmol/L); (3) PTH unresponsive: low 25(OH)D3 and normal PTH; (4) Hyper PTH (>6.8pmol/L) with normal 25(OH)D3. Frailty was defined using Fried's criteria. Difference between the groups was assessed using one-way ANOVA and X2 analysis. Multinomial logistic regression evaluated the association between the groups and the number of Fried's criteria adjusted for age, BMI, renal function, 25(OH)D3 levels, and albumin. RESULTS: 22.6% subjects had high PTH levels (>6.8pmol/L). All subjects in the high PTH groups had significantly lower grip strength, gait velocity, limits of stability, and higher BMI. The PTH responsive group had a higher risk of pre-frailty (ß=3.8, 95% CI = 3.42 - 5.22, p≷ 0.01) and frailty (ß=8.26, 95% CI = 2.8-16.1, p<0.01). The risk of frailty was also higher in the Hyper PTH group (ß=2.3, 95% CI = 1.74-4.32, p<0.01). CONCLUSION: We have reported an independent association of high PTH levels with high number of falls and with the clinical components of physical frailty in community dwelling older persons. Our results suggest a possible role of PTH in frailty that deserves further exploration.


Assuntos
Idoso Fragilizado/estatística & dados numéricos , Fragilidade/sangue , Hormônio Paratireóideo/sangue , Idoso , Austrália/epidemiologia , Estudos Transversais , Feminino , Fragilidade/epidemiologia , Humanos , Masculino , Fatores de Risco
20.
Curr Opin Crit Care ; 24(6): 547-553, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30308542

RESUMO

PURPOSE OF REVIEW: Timely identification of high-risk surgical candidates facilitate surgical decision-making and allows appropriate tailoring of perioperative management strategies. This review aims to summarize the recent advances in perioperative risk stratification. RECENT FINDINGS: Use of indices which include various combinations of preoperative and postoperative variables remain the most commonly used risk-stratification strategy. Incorporation of biomarkers (troponin and natriuretic peptides), comprehensive objective assessment of functional capacity, and frailty into the current framework enhance perioperative risk estimation. Intraoperative hemodynamic parameters can provide further signals towards identifying patients at risk of adverse postoperative outcomes. Implementation of machine-learning algorithms is showing promising results in real-time forecasting of perioperative outcomes. SUMMARY: Perioperative risk estimation is multidimensional including validated indices, biomarkers, functional capacity estimation, and intraoperative hemodynamics. Identification and implementation of targeted strategies which mitigate predicted risk remains a greater challenge.


Assuntos
Peptídeos Natriuréticos/sangue , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/prevenção & controle , Medição de Risco/métodos , Procedimentos Cirúrgicos Operatórios/mortalidade , Troponina/sangue , Biomarcadores/sangue , Cuidados Críticos , Sistemas de Apoio a Decisões Clínicas , Fragilidade/sangue , Humanos , Complicações Pós-Operatórias/mortalidade , Procedimentos Cirúrgicos Operatórios/efeitos adversos
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