Protocolized exercise improves frailty parameters and lower extremity impairment: A promising prehabilitation strategy for kidney transplant candidates.

BACKGROUND: Frailty and decreased functional status are risk factors for adverse kidney transplant (KT) outcomes. Our objective was to examine the efficacy of an exercise intervention on frailty and decreased functional status in a cohort of patients with advanced chronic kidney disease (CKD). METHODS: We conducted a prospective study involving 21 adults with ≥stage 4 CKD who were (a) frail or pre-frail by Fried phenotype and/or (b) had lower extremity impairment [short physical performance battery score ≤10]. The intervention consisted of two supervised outpatient exercise sessions per week for 8 weeks. RESULTS: Among our cohort, median participant age was 62 years (interquartile range, 53-67) and 85.7% had been evaluated for KT. Following the study, participants reported satisfaction with the intervention and multiple frailty parameters improved significantly, including fatigue, physical activity, walking time, and grip strength. Lower extremity impairment also improved (90.5%-61.9%, P = .03). No study-related adverse events occurred. CONCLUSIONS: Preliminary data from this study suggest that a supervised, outpatient exercise intervention is safe, acceptable, feasible, and associated with improved frailty parameters, and lower extremity function, in patients with advanced CKD. Further studies are needed to confirm these findings and determine whether this prehabilitation strategy improves KT outcomes.

Attributing illness to 'old age:' consequences of a self-directed stereotype for health and mortality.

Stereotypic beliefs about older adults and the aging process have led to endorsement of the myth that 'to be old is to be ill.' This study examined community-dwelling older adults' (N = 105, age 80+) beliefs about the causes of their chronic illness (ie, heart disease, cancer, diabetes, etc.), and tested the hypothesis that attributing the onset of illness to 'old age' is associated with negative health outcomes. A series of multiple regressions (controlling for chronological age, gender, income, severity of chronic conditions, functional status and health locus of control) demonstrated that 'old age' attributions were associated with more frequent perceived health symptoms, poorer health maintenance behaviours and a greater likelihood of mortality at 2-year follow-up. The probability of death was more than double among participants who strongly endorsed the 'old age' attribution as compared to those who did not (36% vs. 14%). Findings are framed in the context of self-directed stereotypes and implications for potential interventions are considered.

Increased severity of bleomycin-induced skin fibrosis in mice with leukocyte-specific protein 1 deficiency.

Fibrosis is a complex process resulting from persistent inflammation following tissue damage. It involves the interaction of numerous cell types, soluble mediators, and extracellular matrix. Recently, a newly identified cell type, the fibrocyte, has been reported to contribute to wound healing and to fibrotic conditions such as hypertrophic scarring. Previously, we established leukocyte-specific protein 1 (LSP1) as a new marker for fibrocytes. In the present study, we examined the biological role of LSP1 in the development of skin fibrosis using bleomycin in an Lsp1(-/-) mice. These animals showed a significant increase in fibrosis, with increased thickness of the skin and collagen content. The skin in Lsp1(-/-) mice injected with bleomycin had higher densities of neutrophils, macrophages, and fibrocytes. In accordance with the increased leukocyte infiltration, the expression levels of macrophage-derived chemokines, transforming growth factor-beta1, and connective tissue growth factor were all upregulated in Lsp1(-/-) mice. These results demonstrate that the absence of LSP1 promotes fibrosis in the skin. The most likely mechanism for this effect seems to be through an increase in leukocyte infiltration, leading to locally elevated synthesis and the release of chemokines and growth factors.

Accelerated wound healing in leukocyte-specific, protein 1-deficient mouse is associated with increased infiltration of leukocytes and fibrocytes.

Wound healing is a complex process involving the integrated actions of numerous cell types, soluble mediators, and ECM. Recently, a newly identified cell type, the fibrocyte, has been reported to contribute to wound healing and fibrotic conditions such as hypertrophic scarring. We previously established leukocyte-specific protein 1 (LSP1) as a marker for fibrocytes. LSP1 is an F-actin binding protein and substrate of p38 mitogen-activated protein kinase and protein kinase C, and has been reported to be important in leukocyte chemotaxis. We examine the biological roles of LSP1 in skin wound healing using Lsp1(-/-) null mice. These animals showed accelerated healing of full-thickness skin wounds, with increased re-epithelialization rates, collagen synthesis, and angiogenesis. Healing wounds in Lsp1(-/-) mice had higher densities of neutrophiles, macrophages, and fibrocytes. Along with increased leukocyte infiltration, levels of macrophage-derived chemokine expression, TGF-beta1, and VEGF were all up-regulated. These results demonstrate that the absence of LSP1 promotes healing of skin wounds. The primary mechanism seems to be an increase in leukocyte infiltration, leading to locally elevated synthesis and release of chemokines and growth factors. Further analysis of Lsp1(-/-) mice may suggest ways to improve wound healing and/or treat fibrotic conditions of skin and other tissue.