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Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people1. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing2. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples3,4. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) associated with these changes. On the basis of cross-comparison with genetic data, we also identify key elements of chromatin architecture that mark susceptibility to sarcopenia. Our study provides a basis for identifying targets in the skeletal muscle that are amenable to medical, pharmacological and lifestyle interventions in late life.
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Envejecimiento , Músculo Esquelético , Análisis de la Célula Individual , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Envejecimiento/genética , Envejecimiento/patología , Envejecimiento/fisiología , Núcleo Celular/metabolismo , Cromatina/metabolismo , Cromatina/genética , Susceptibilidad a Enfermedades , Epigénesis Genética , Fragilidad/genética , Fragilidad/patología , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Atrofia Muscular/genética , Atrofia Muscular/patología , Sarcopenia/genética , Sarcopenia/patología , TranscriptomaRESUMEN
INTRODUCTION: Locally advanced non-melanoma skin cancer (NMSC) involving the periosteum or calvarium poses a clinical challenge for patients who are unfit for immunotherapy due to medical comorbidities and/or frailty. This case series aims to investigate outcomes for patients undergoing craniectomy and soft tissue reconstruction. METHOD: Patients who underwent craniectomy and soft tissue reconstruction for invasive NMSC with calvarium or periosteal invasion between 2016 and 2022 were included. Data, including demographics, operative details, and clinical outcomes, were gathered from Nottingham University Hospitals' digital health record and the histopathology electronic database. RESULT: Eight patients (average age: 78.4 years, 3 females 5 males) with significant comorbidities and varying degrees of periosteal or bone invasion fulfilled the inclusion criteria. Diagnoses included four squamous cell carcinomas, two basal cell carcinomas, and two pleomorphic dermal sarcomas. Five patients had a history of prior incomplete deep margin excision. The median sizes for soft tissue defect, tumor and bone defect size were 51.83 cm2, 34.63 cm2 and 42.25 cm2, respectively. Intraoperative complications included one dural tear. Four patients underwent local flap reconstruction and with split-thickness skin grafting, four patients underwent free flap reconstruction. Adjuvant radiotherapy was administered to three patients. Complications comprised partial graft loss in two and complete graft loss in one. There was partial flap loss in one case. One patient required subsequent parotidectomy due to regional progression before achieving disease control. All patients achieved lasting locoregional disease control (average follow-up 29.7 months). CONCLUSION: Craniectomy with soft tissue reconstruction proves to be a safe and effective treatment option in advanced NMSC of the scalp in patients unsuitable for immunotherapy due to frailty or medical co-morbidity.
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Fragilidad , Procedimientos de Cirugía Plástica , Neoplasias Cutáneas , Masculino , Femenino , Humanos , Anciano , Cuero Cabelludo/cirugía , Cuero Cabelludo/patología , Fragilidad/patología , Fragilidad/cirugía , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología , Trasplante de Piel , Craneotomía , Estudios RetrospectivosRESUMEN
Sarcopenia is an age-related disease characterized by a reduction in muscle mass, strength, and function and, therefore, a deterioration in skeletal muscle health and frailty. Although the cause of sarcopenia is still unknown and, thus, there is no treatment, increasing evidence suggests that chronodisruption, particularly alterations in Bmal1 clock gene, can lead to those deficits culminating in sarcopenia. To gain insight into the cause and mechanism of sarcopenia and the protective effect of a therapeutic intervention with exercise and/or melatonin, the gastrocnemius muscles of male and female skeletal muscle-specific and inducible Bmal1 knockout mice (iMS-Bmal1-/- ) were examined by phenotypic tests and light and electron microscopy. Our results revealed a disruption of the normal activity/rest rhythm, a drop in skeletal muscle function and mass, and increased frailty in male and female iMS-Bmal1-/- animals compared to controls. A reduction in muscle fiber size and increased collagenous tissue were also detected, accompanied by reduced mitochondrial oxidative capacity and a compensatory shift towards a more oxidative fiber type. Electron microscopy further supports mitochondrial impairment in mutant mice. Melatonin and exercise ameliorated the damage caused by loss of Bmal1 in mutant mice, except for mitochondrial damage, which was worsened by the latter. Thus, iMS-Bmal1-/- mice let us to identify Bmal1 deficiency as the responsible for the appearance of sarcopenia in the gastrocnemius muscle. Moreover, the results support the exercise and melatonin as therapeutic tools to counteract sarcopenia, by a mechanism that does not require the presence of Bmal1.
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Fragilidad , Melatonina , Sarcopenia , Femenino , Masculino , Animales , Ratones , Sarcopenia/tratamiento farmacológico , Sarcopenia/patología , Melatonina/farmacología , Melatonina/uso terapéutico , Fragilidad/tratamiento farmacológico , Fragilidad/patología , Músculo Esquelético/patología , Microscopía ElectrónicaRESUMEN
Aging is characterized by chronic low-level inflammation and is associated with geriatric syndromes such as sarcopenia and frailty. Our aim was to evaluate the longitudinal variation of muscle area, muscle quality, and muscle strength, relative to the variation of leukocyte-derived markers, and to assess the presence of a pathway of associations among derived leukocyte ratios, and the components of muscle health. The InCHIANTI is a longitudinal cohort study of aging that began in 1998 with follow-up visits every 3 years. Out of the 1 453 participants enrolled at baseline, this study includes 1 179 participants with complete data. Muscle strength was assessed by hand grip strength test, whereas muscle density and fat area were considered as indirect markers of muscle quality, derived from peripheral quantitative computed tomography of the calf. Muscle area was associated with neutrophil-to-lymphocyte ratio (NL-ratio), age, gender, comorbidities, and body mass index (BMI). Muscle density variation over time was inversely associated with age, comorbidities, and BMI, while being positively associated with monocyte-to-lymphocyte ratio (ML-ratio) and male gender. Fat area was inversely associated with age, interleukine-6 (IL-6), male gender, and NL-ratio, while being positively associated with ML-ratio, comorbidities, and BMI. Handgrip strength decreased with age, IL-6 levels, comorbidities, and NL-ratio, but increased with ML-ratio, being male, and having a higher BMI. In a path-analysis model, ML-ratio positively correlates with muscle mass, density, and strength, while NL-ratio only correlates inversely with muscle mass and density. NL-ratio and ML-ratio are associated with aging and may be implicated in age-related mechanisms that affect body composition and muscle strength. These ratios may represent a link between aging of the immune system and decline of muscle health with aging. However, further studies are needed to identify their usefulness for early detection of sarcopenia, myosteatosis, and frailty in the older adult.
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Fragilidad , Sarcopenia , Humanos , Masculino , Anciano , Femenino , Sarcopenia/epidemiología , Sarcopenia/patología , Fuerza de la Mano , Estudios Longitudinales , Fragilidad/patología , Interleucina-6 , Envejecimiento/fisiología , Fuerza Muscular , Músculo Esquelético/fisiología , Sistema InmunológicoRESUMEN
The study aims to investigate second primary malignancy (SPM) development and frailty in Turkish geriatric patients with multiple myeloma (MM) and to assess the relationship between overall survival (OS) and various characteristics including SPM and frailty. Seventy-two patients diagnosed with and treated for MM were enrolled in the study. Frailty was determined by the IMWG Frailty Score. Fifty-three participants (73.6%) were found to have clinically-relevant frailty. Seven patients (9.7%) had SPM. Median follow-up was 36.5 (22-48.5) months, and 17 patients died during the follow-up period. Overall (OS) was 49.40 (45.01-53.80) months. Shorter OS was found in patients with SPM (35.29 (19.66-50.91) months) compared to those without (51.05 (46.7-55.4) months) (Kaplan-Meier; p = 0.018). The multivariate cox proportional hazards model revealed that patients with SPM had 4.420-fold higher risk of death than those without (HR: 4.420, 95% CI: 1.371-14.246, p = 0.013). Higher ALT levels were also independently associated with mortality (p = 0.038). The prevalence of SPM and frailty was high in elderly patients with MM in our study. The development of SPM independently reduces survival in MM; however, frailty was not found to be independently associated with survival. Our results suggest the importance of individualized approaches in the management of patients with MM, particularly with regard to SPM development.
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Fragilidad , Mieloma Múltiple , Neoplasias Primarias Secundarias , Humanos , Anciano , Mieloma Múltiple/patología , Fragilidad/diagnóstico , Fragilidad/patología , Modelos de Riesgos ProporcionalesRESUMEN
Age-related differences in colon and rectal cancer survival have been observed, even after accounting for differences in background mortality. To determine how stage, tumour site, and histology contribute to these differences, we extracted age-specific one-year relative survival ratio (RS) stratified by these factors. We used colon and rectal cancer cases diagnosed between 2012 and 2016 from 18 United States Surveillance Epidemiology and End Results cancer registries. For colon cancer, 1-year RS ranged from 87.8 % [95 % Confidence Interval: 87.5-88.2] in the 50-64-year-olds to 62.3 % [61.3-63.3] in 85-99-year-olds and for rectal cancer ranged from 92.3 % [91.8-92.7] to 65.0 % [62.3-67.5]. With respect to stage, absolute differences in RS between 50-64-year-olds and 75-84-year-olds increased with increasing stage (from 6 [5-7] %-points in localised disease to 27 [25-29] %-points in distant disease) and were the highest for cancers of unknown stage (> 28 %-points). Age-related differences in survival were smallest for persons with tumours in the right-sided colon (8 [7-9] %-points) and largest for tumours of the colon without tumour site further specified (25 [21-29] %-points). With respect to histology, differences ranged from 7.4 % to 10.6 %-points for cancers with one of the three primary histologies (adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma) and were several-fold higher (42 %-points) for those with unknown/other histology (< 6 % of cases). Because age-related differences in survival were observed for all histologies and tumour sites, RS differences are unlikely to be driven by differences in the distribution of these factors by age. Differences in stage distribution by age are likely to contribute toward age-related differences in survival. Within stage groups, age differences in survival could be explained by frailty and/or therapy. Future studies incorporating data on treatment and geriatric conditions including frailty and comorbidity would support further understanding of the age gap in colon and rectal cancer survival.
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Adenocarcinoma , Neoplasias del Colon , Fragilidad , Neoplasias del Recto , Humanos , Estados Unidos/epidemiología , Anciano , Fragilidad/patología , Neoplasias del Recto/epidemiología , Neoplasias del Recto/patología , Neoplasias del Colon/patología , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Sarcopenia has a significant medical and economic impact. Serum fibroblast growth factor 19 (FGF19) has recently been described as promoting muscle mass and strength, and could be an interesting marker for early diagnosis of sarcopenia and prevention of its consequences. Ultrasound is a robust non-invasive technique used to measure muscle parameters, which cannot be evaluated by usual body composition measures, but are known to be associated with muscle function. In this cross-sectional cohort study, we aimed to determine whether FGF19 levels were correlated with functional muscle tests and muscle ultrasound parameters. METHODS: Patients over 70 years old with a mobility disability risk were recruited from the cohort of the "well on your feet" mobility loss prevention program. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older Patients 2 (EWGSOP2) criteria. We have performed functional battery tests, muscle ultrasound measures and bioimpedance spectroscopy. FGF19 levels were measured by the ELISA method. RESULTS: Out of 52 patients involved (34 women, mean age 81.3 years), 30 patients were sarcopenic (15 patients with probable sarcopenia and 15 with certain sarcopenia). Sarcopenic patients were older (mean 82.8 versus 79.6 years, P = 0.033), with higher frailty Fried score (P = 0.006), lower IADL score (P = 0.008), had lower daily protein intakes (P = 0.023) and were less performant to muscle functional tests than non-sarcopenic patients. Serum FGF19 levels were negatively correlated with the SPPB score (rs = 0.28; P = 0.045). FGF19 levels were correlated positively with the pennation angle (rs = 0.31; P = 0.024), but negatively with muscle fiber length (rs = -0.44; P = 0.001). We found no association between FGF19 and muscle thickness (P = 0.243). CONCLUSION: We highlighted in older patients significant correlations between FGF19 levels, pennation angle and muscle fiber length, suggesting that FGF19 could provide an enabling environment for the development of large muscle fibers, as previously suggested in histological studies in mice. However, high FGF-19 levels were unexpectedly associated with a low SPPB score. Further studies are needed to validate and further elucidate these exploratory findings.
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Fragilidad , Sarcopenia , Femenino , Estudios Transversales , Fragilidad/patología , Fuerza de la Mano , Fibras Musculares Esqueléticas/patología , Músculo Esquelético/patología , Sarcopenia/diagnóstico , Humanos , Masculino , Anciano de 80 o más Años , AncianoRESUMEN
Sarcopenia and frailty are urgent socio-economic problems worldwide. Here we demonstrate a functional connection between the lateral hypothalamus (LH) and skeletal muscle through Slc12a8, a recently identified nicotinamide mononucleotide transporter, and its relationship to sarcopenia and frailty. Slc12a8-expressing cells are mainly localized in the LH. LH-specific knockdown of Slc12a8 in young mice decreases activity-dependent energy and carbohydrate expenditure and skeletal muscle functions, including muscle mass, muscle force, intramuscular glycolysis, and protein synthesis. LH-specific Slc12a8 knockdown also decreases sympathetic nerve signals at neuromuscular junctions and ß2-adrenergic receptors in skeletal muscle, indicating the importance of the LH-sympathetic nerve-ß2-adrenergic receptor axis. LH-specific overexpression of Slc12a8 in aged mice significantly ameliorates age-associated decreases in energy expenditure and skeletal muscle functions. Our results highlight an important role of Slc12a8 in the LH for regulation of whole-body metabolism and skeletal muscle functions and provide insights into the pathogenesis of sarcopenia and frailty during aging.
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Fragilidad , Sarcopenia , Envejecimiento/fisiología , Animales , Metabolismo Energético , Fragilidad/metabolismo , Fragilidad/patología , Área Hipotalámica Lateral , Ratones , Músculo Esquelético/metabolismo , Sarcopenia/metabolismoRESUMEN
Cognitive frailty (CF) is a clinical condition defined by the presence of both mild cognitive impairment (MCI) and physical frailty (PF). Elderly with CF are at greater risk of dementia than those with MCI or PF alone, but there are few known clinical or neuroimaging features to reliably distinguish CF from PF or MCI. We therefore conducted a population-based cross-sectional study of community elderly combining physical, cognitive, neuropsychiatric, and multisequence magnetic resonance imaging (MRI) evaluations. The MRI evaluation parameters included white matter (WM) lesion volumes, perivascular and deep subcortical WM lesion grades, lacunar infarct prevalence, microbleed number, and regional medial temporal lobe (MTL) volumes. Participants were divided into 4 groups according to the presence or absence of MCI and PF-(1) no MCI, PF (n = 27); (2) no PF, MCI (n = 119); (3) CF (MCI + PF) (n = 21), (4) normal controls (n = 716). Unique features of CF included shorter one-leg standing time; severe depressive symptoms; and MRI signs of significantly more WM lesions, lacunar infarcts, small-vessel disease lesions, microbleeds, and reduced MTL volumes. These unique deficits suggest that interventions for CF prevention and treatment should focus on motor skills, depressive symptoms, and vascular disease risk factor control.
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Disfunción Cognitiva , Fragilidad , Accidente Vascular Cerebral Lacunar , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Cognición , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/patología , Estudios Transversales , Fragilidad/epidemiología , Fragilidad/patología , Humanos , Vida Independiente , Japón/epidemiología , Imagen por Resonancia Magnética/métodos , Pruebas Neuropsicológicas , Accidente Vascular Cerebral Lacunar/patologíaRESUMEN
BACKGROUND: Alzheimer's disease (AD) is a biologically heterogenous disease. Previous studies have reported the existence of various AD subtypes, and the various clinical features of the subtypes. However, inconsistent results have been obtained. OBJECTIVE: To clarify the clinical characteristics of the various AD subtypes, by classifying probable AD into subtypes based on magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) findings. METHODS: A total of 245 patients with probable AD were classified into the typical AD (TAD) subtype, limbic-predominant (LP) subtype, hippocampal-sparing (HS) subtype, and minimal-change (MC) subtype, based on the presence of medial temporal lobe atrophy on MRI and posterior cerebral hypoperfusion on SPECT. Demographics, including age, sex, body mass index, disease duration, education years, comorbidities, frailty, leisure activity, and neuropsychological findings were compared between the AD subtypes. RESULTS: he frequency of TAD, LP, HS, and MC subtypes was 49%, 20%, 18%, and 13%, respectively. Patients with the LP subtype were older and characterized by fewer major comorbidities, higher frailty, and slower progression of disease. Patients with the HS subtype were younger and characterized by shorter disease duration, lower frailty, and preserved memory, but had prominent constructional dysfunction. Patients of the MC subtype were characterized by shorter disease duration, lower education level, less leisure activity, less impaired memory and orientation, and slower progression. CONCLUSION: Patients with different AD subtypes differed in their demographic and clinical features. The characterization of patients' AD subtypes may provide effective support for the diagnosis, treatment, and care of AD patients.
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Enfermedad de Alzheimer , Fragilidad , Enfermedad de Alzheimer/patología , Encéfalo/patología , Fragilidad/patología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Perfusión , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
BACKGROUND: In most eukaryotic cells, the mitochondrial DNA (mtDNA) is transmitted uniparentally and present in multiple copies derived from the clonal expansion of maternally inherited mtDNA. All copies are therefore near-identical, or homoplasmic. The presence of >1 mtDNA variant in the same cytoplasm can arise naturally or result from new medical technologies aimed at preventing mitochondrial genetic diseases and improving fertility. The latter is called divergent nonpathologic mtDNA heteroplasmy (DNPH). We hypothesized that DNPH is maladaptive and usually prevented by the cell. METHODS: We engineered and characterized DNPH mice throughout their lifespan using transcriptomic, metabolomic, biochemical, physiologic, and phenotyping techniques. We focused on in vivo imaging techniques for noninvasive assessment of cardiac and pulmonary energy metabolism. RESULTS: We show that DNPH impairs mitochondrial function, with profound consequences in critical tissues that cannot resolve heteroplasmy, particularly cardiac and skeletal muscle. Progressive metabolic stress in these tissues leads to severe pathology in adulthood, including pulmonary hypertension and heart failure, skeletal muscle wasting, frailty, and premature death. Symptom severity is strongly modulated by the nuclear context. CONCLUSIONS: Medical interventions that may generate DNPH should address potential incompatibilities between donor and recipient mtDNA.
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Fragilidad , Cardiopatías , Hipertensión Pulmonar , Adulto , Animales , ADN Mitocondrial/genética , Fragilidad/patología , Cardiopatías/patología , Heteroplasmia , Humanos , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/patología , Ratones , Mitocondrias/genéticaRESUMEN
OBJECTIVE: To explore the clinical implications of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for diagnosing frailty in patients with maintenance hemodialysis (MHD) and their correlations with patient prognosis. METHODS: A total of 185 patients with MHD admitted to the hemodialysis center of our hospital were selected, 72 of whom were diagnosed with frailty according to the Chinese version of Tilburg Frailty Indicator (TFI). The relevant data were collected, and the influencing factors of frailty in MHD patients were analyzed by one-way analysis of variance (ANOVA) and multivariate logistic regression. The value of NLR and PLR in diagnosing frailty in MHD patients was observed, and patients' all-cause mortality was compared during the 3-year follow-up. The influences of different levels of NLR and PLR on the survival of MHD patients were investigated. RESULTS: Multivariate regression analysis identified that serum albumin, dialysis adequacy, NLR, and PLR are independent risk factors for frailty in MHD patients (P < 0.05). The area under the receiver operating characteristic (ROC) curve of NLR and PLR in diagnosing frailty in MHD patients was 0.859 and 0.799, respectively. Compared with the nonfrailty group, the 3-year mortality was higher, and the 3-year survival rate assessed by survival analysis was lower in the frailty group (P < 0.05). Patients with high NLR and PLR levels showed a lower 3-year survival rate. CONCLUSIONS: Dialysis adequacy, serum albumin, NLR, and PLR are independently associated with frailty in MHD patients. NLR and PLR are of a certain diagnostic value for frailty in MHD patients. MHD patients with frailty have an unfavorable prognosis, as of those with high NLR and PLR levels.
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Fragilidad , Linfocitos , Neutrófilos , Diálisis Renal , Fragilidad/sangre , Fragilidad/diagnóstico , Fragilidad/patología , Humanos , Linfocitos/patología , Neutrófilos/patología , Recuento de Plaquetas , Pronóstico , Curva ROC , Estudios Retrospectivos , Albúmina Sérica/metabolismoRESUMEN
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.
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Envejecimiento/patología , Enfermedad de Alzheimer/fisiopatología , Encéfalo/fisiopatología , Disfunción Cognitiva/fisiopatología , Fragilidad/fisiopatología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Encéfalo/patología , Disfunción Cognitiva/patología , Electroencefalografía , Femenino , Fragilidad/patología , Humanos , Magnetoencefalografía , MasculinoRESUMEN
BACKGROUND: Population-derived cutoffs for low skeletal muscle mass, skeletal muscle strength, and frailty among Indians are lacking. Studies describing sarcopenia and frailty among patients with chronic liver diseases have used cutoffs derived from Caucasian populations giving erroneous results. AIMS: We aimed to derive gender-specific cutoffs for low skeletal muscle mass and skeletal muscle strength from healthy Indians. METHODS: Healthy Indian population consisted of two groups. Group 1 (Gp I) included 242 healthy liver donors and group 2 (Gp II) 272 healthy health care workers. Skeletal muscle index (SMI) was calculated from computed tomography (CT) abdomen performed prior to donor hepatectomy only in Gp I. Liver frailty index (LFI) was computed using the online calculator, after recording hand grip strength (HGS), chair stand-up test (CSUT), and balance test in both groups. HGS was measured using the Smedley handgrip dynamometer. CSUT was noted as time to complete 5 chair stand-ups with subjects' arms folded across the chest. Gender-specific cutoffs of SMI and HGS were derived as <5th percentile of the distribution values and as >95th percentile for CSUT and LFI values. RESULTS: The SMI was measured from Gp I subjects (n=242; 120 males [mean age 31.13] and 122 females [mean age 36.60]). The HGS, CSUT, and LFI were measured in Gp I and Gp II subjects (n=514; 272 males [mean age 34.30] and 242 females [mean age 37.52]). The cutoffs for SMI, HGS, CSUT, and LFI were <27.72 cm2/m2, <25.63 kg, >10 s, and >3.49, respectively for healthy males. The corresponding cutoffs for healthy females were <24.4 cm2/m2, <16.7 kg, > 10 s, and >3.68, respectively. CONCLUSIONS: We derived gender-specific cutoffs for SMI, HGS, CSUT, and LFI from healthy adult Indian population, which can be used to detect sarcopenia and frailty among patients with liver diseases, as well as other conditions.
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Fragilidad , Sarcopenia , Masculino , Adulto , Femenino , Humanos , Sarcopenia/diagnóstico , Sarcopenia/epidemiología , Sarcopenia/patología , Fuerza de la Mano/fisiología , Fragilidad/diagnóstico , Fragilidad/patología , Fuerza Muscular , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Músculo Esquelético/fisiologíaRESUMEN
OBJECTIVE: The aim of our study was to describe spine immobilization in a multicentric cohort of vertebral osteomyelitis (VO), and evaluate its association with neurological complications during follow-up. METHODS: We prospectively included patients from 2016 to 2019 in 11 centers. Immobilization, imaging, and neurological findings were specifically analyzed during a 6-month follow-up period. RESULTS: 250 patients were included, mostly men (67.2%, n=168). Mean age was 66.7±15 years. Diagnosis delay was 25 days. The lumbo-sacral spine was most frequently involved (56.4%). At diagnosis, 25.6% patients (n=64) had minor neurological signs and 9.2% (n=23) had major ones. Rigid bracing was prescribed for 63.5% (n=162) of patients, for a median of 6 weeks, with variability between centers (P<0.001). The presence of epidural inflammation and abscess on imaging was associated with higher rates of rigid bracing prescription (OR 2.33, P=0.01). Frailness and endocarditis were negatively associated with rigid bracing prescription (OR 0.65, P<0.01, and OR 0.42, P<0.05, respectively). During follow up, new minor or major neurological complications occurred in respectively 9.2% (n=23) and 6.8% (n=17) of patients, with similar distribution between immobilized and non-immobilized patients. CONCLUSION: Spine immobilization prescription during VO remains heterogeneous and seems associated inflammatory lesions on imaging but negatively associated with frailness and presence of endocarditis. Neurological complications can occur despite rigid bracing. Our data suggest that in absence of any factor associated with neurological complication spine bracing might not be systematically indicated. We suggest that spine immobilization should be discussed for each patient after carefully evaluating their clinical signs and imaging findings.
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Endocarditis , Fragilidad , Osteomielitis , Anciano , Anciano de 80 o más Años , Endocarditis/patología , Espacio Epidural , Femenino , Fragilidad/patología , Humanos , Masculino , Persona de Mediana Edad , Osteomielitis/diagnóstico , Osteomielitis/etiología , Osteomielitis/terapia , Estudios Prospectivos , Estudios Retrospectivos , Columna VertebralRESUMEN
While metabolic syndrome (MetS) is associated with frailty, the correlation of serum lactate dehydrogenase (sLDH) and frailty with MetS remain uncertain. To investigate the relationship between sLDH and frail components in the US with MetS. A total of 4,066 participants aged 40-90 years were assessed from the database of the third National Health and Nutrition Examination Survey, 1988-1994. The participants were classified into MetS and non-MetS groups. Multivariate logistic regression analysis with four models were performed to assess the odds ratio (OR) of the divided tertiles of sLDH levels with frailty, and frail components including slow walking (SW), weakness, exhaustion, low physical activity (LPA), and low body weight (LBW). Higher sLDH levels were positively associated with frailty in the MetS group (p = 0.024) but not in non-MetS group (p = 0.102). After covariate adjustments, the OR of frailty in the upper two tertiles compared to the lowest tertile and revealed statistical significance (p < 0.05). Frail components of SW, weakness, exhaustion, and LPA were associated with higher sLDH (p < 0.05) except for LBW in MetS and non-MetS groups. The results demonstrated the strong association of higher sLDH levels and frailty among US individuals with MetS.
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Peso Corporal , Fragilidad/epidemiología , Lactato Deshidrogenasas/sangre , Síndrome Metabólico/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Fragilidad/sangre , Fragilidad/patología , Humanos , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/patología , Persona de Mediana EdadRESUMEN
BACKGROUND: Physical performance decline associated with aging is clinically important in the development of disability in the older population. More recently, procollagen type III N-terminal peptide (P3NP) and synaptosomal-associated protein of 25 kDa (SNAP25) have been suggested as potential biomarkers for physical performance decline. OBJECTIVE: The objective of this pilot study was to examine plasma P3NP and SNAP25 levels in relation to muscle mass, strength, and performance status, and to investigate the association of plasma P3NP and SNAP25 levels with sarcopenia components. METHODS: Seventy-nine community-dwelling elderly men (mean age: 78.1 ± 3.5 years) were randomly selected and matched by age from the Korean Frailty and Aging Cohort Study. The sample was classified into the "normal," "low muscle mass only," "sarcopenia," and "low physical performance only" groups according to the criteria of the Asian Working Group for Sarcopenia 2019. Estimates and 95% confidence intervals (CIs) of log P3NP and log SNAP25 levels by muscle mass, strength, and performance status were obtained using a generalized linear model. Pearson correlations and multiple linear regression analyses were used to assess the association of log P3NP and log SNAP25 levels with appendicular skeletal muscle mass (ASM) index, handgrip strength, and physical performance. RESULTS: Log P3NP levels tended to be associated with low physical performance compared with the normal group (estimate = 0.54; 95% CI = -0.05, 1.14; p = 0.072). Log P3NP levels were inversely associated with physical performance (short physical performance battery and five-times sit-to-stand test) after adjusting for potential confounders (all p < 0.05) and tended to have an inverse association with gait speed (p = 0.078). Log P3NP levels tended to have a positive correlation with the ASM index (r2 = 0.042; p = 0.070), but not with handgrip strength (r2 = 0.0009; p = 0.795). However, no significant association between plasma SNAP25 levels and physical performance was observed. CONCLUSION: Plasma P3NP levels might be a potential biomarker for decreased physical performance in elderly men. Further studies with larger sample sizes are needed to confirm our findings.
Asunto(s)
Fragilidad , Sarcopenia , Anciano , Anciano de 80 o más Años , Envejecimiento , Estudios de Cohortes , Colágeno Tipo III , Estudios Transversales , Fragilidad/patología , Fuerza de la Mano , Humanos , Masculino , Fuerza Muscular , Músculo Esquelético/patología , Rendimiento Físico Funcional , Proyectos Piloto , República de Corea , Sarcopenia/patologíaRESUMEN
BACKGROUND: Frailty is a state of increased vulnerability to stressors, and predicts risk of adverse outcomes, such as mortality. Frailty can be defined by a frailty index (FI) using an accumulation of deficits approach. An FI comprised of 20 items derived from our previously studied test-based frailty index (TBFI) and an additional 33 survey-based elements sourced from the standard CGA was developed to evaluate if predictive validity of survival was improved. METHODS: One hundred eighty-nine cancer patients during acute hospitalization were consented between September 2018 and May 2019. Frailty scores were calculated, and patients were categorized into four groups: non-frail (0-0.2), mildly frail (0.2-0.3), moderately frail (0.3-0.4), and severely frail (>0.4). Patients were followed for 1-year to assess FI and TBFI prediction of survival. Area under the curve (AUC) statistics from ROC analyses were compared for the FI versus TBFI. RESULTS: Increasing frailty was similarly associated with increased risk of mortality (HR, 4.5 [95% CI, 2.519-8.075] and HR, 4.1 [95%CI, 1.692-9.942]) and the likelihood of death at 6 months was about 11-fold (odds ratio, 10.9 [95% CI, 3.97-33.24]) and 9.73-fold (95% CI, 2.85-38.50) higher for severely frail patients compared to non-frail patients for FI and TBFI, respectively. This association was independent of age and type of cancer. The FI and TBFI were predictive of survival for older and younger cancer patients with no significant differences between models in discriminating survival (FI AUC, 0.747 [95% CI, 0.6772-0.8157] and TBFI AUC, 0.724 [95% CI, 0.6513-0.7957]). CONCLUSIONS: The TBFI was predictive of survival, and the addition of an in-person assessment (FI) did not greatly improve predictive validity. Increasing frailty, as measured by a TBFI, resulted in a meaningfully increased risk of mortality and may be well-suited for screening of hospitalized cancer patients.
Asunto(s)
Fragilidad/etiología , Neoplasias/complicaciones , Neoplasias/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Fragilidad/patología , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
BACKGROUND: Emerging evidence suggests that there is significant variability in the progression of frailty in aging. We aimed to identify latent subpopulations of frailty trajectories, and examine their clinical and biological correlates. METHODS: We characterized frailty using a 41-item cumulative deficit score at baseline and annual visits up to 12 years in 681 older adults (55% women, mean age 74·6 years). Clinical risk profile and walking while talking performance as a clinical marker of trajectories were examined. Mortality risk associated with trajectories was evaluated using Cox regression adjusted for established survival predictors, and reported as hazard ratios (HR). Proteome-wide analysis was done. FINDINGS: Latent class modeling identified 4 distinct frailty trajectories: relatively stable (34·4%) as well as mild (36·1%), moderate (24·1%) and severely frail (5·4%). Four distinct classes of frailty trajectories were also shown in an independent sample of 515 older adults (60% women, 68% White, 26% Black). The stable group took a median of 31 months to accumulate one additional deficit compared to 20 months in the severely frail group. The worst trajectories were associated with modifiable risk factors such as low education, living alone, obesity, and physical inactivity as well as slower walking while talking speed. In the pooled sample, mild (HR 2·33, 95% CI 1·30-4·18), moderate (HR 2·49, 95% CI 1·33-4·66), and severely frail trajectories (HR 5·28, 95% CI 2·68-10·41) had higher mortality compared to the stable group. Proteomic analysis showed 11 proteins in lipid metabolism and growth factor pathways associated with frailty trajectories. CONCLUSION: Frailty shows both stable and accelerated patterns in aging, which can be distinguished clinically and biologically.