DNA Damage in Circulating Hematopoietic Progenitor Stem Cells as Promising Biological Sensor of Frailty.

Frailty is an age-related syndrome that exposes individuals to increased vulnerability. Although it is potentially reversible, in most cases it leads to negative outcomes, including mortality. The different methods proposed identify frailty after the onset of clinical manifestations. An early diagnosis might make it possible to manage the frailty progression better. The frailty pathophysiology is still unclear although mechanisms, in particular, those linked to inflammation and immunosenescence, have been investigated. A common feature of several clinical aspects involved in senescent organisms is the increase of oxidative stress, described as one of the major causes of deoxyribonucleic acid (DNA) damage accumulation in aged cells including the adult stem cell compartment. Likely, this accumulation is implicated in frailty status. The oxidative status of our frail, pre-frail, and non-frail population was characterized. In addition, the DNA damage in hematopoietic cells was evidenced by analyzing the peripheral blood mononuclear cell and their T lymphocyte, monocyte, circulating hematopoietic progenitor stem cell (cHPSC) subpopulations. The phosphorylation of C-terminal of histone H2AX at amino acid Ser 139 (γ-H2AX), which occurs at the DNA double-strand break focus, was evaluated. In our frail population, increased oxidative stress and a high level of DNA damage in cHPSC were found. This study may have potential implications because the increment of DNA damage in cHPSC could be suggestive of an organism impairment preceding the evident frailty. In addition, it may open the possibility for attenuation of frailty progression throughout specific drugs acting on preventing DNA damage or removing damaged cells.

Frailty predicts failure to discharge patients home from a subacute-care unit: a 3-year Italian experience.

BACKGROUND: The primary purpose of Subacute Care Units (SCU) is to decongest acute hospital wards and facilitate the return of older patients to home. AIMS: We analyzed the clinical characteristics and outcomes of patients admitted to an Italian SCU, and we explored factors associated with discharge to locations other than home (outcome). METHODS: This retrospective observational cohort study was conducted at a medium-sized suburban hospital, enrolling all patients consecutively admitted to one SCU from October 2017 to February 2020. We collected demographics, cause of admission, comorbidities, cognition, Barthel Index (BI), nutritional status, Clinical Frailty Scale (CFS), length of stay, and discharge destination. Delirium was screened with the 4AT score. We adopted a multivariable conditional logistic regression model to identify the factors associated with the outcome. RESULTS: Frail subjects accounted for 58.6% of 406 patients (mean age 78.2 years, SD 11.6), while 61% were classified as functionally dependent. More than half of patients had relevant comorbidity, approximately 80% had a poor nutritional status, and 25% had pre-existing dementia. The overall prevalence of delirium was 14.5%. Most patients came from a hospital setting; recurrent reasons for admission were infections (70.5%) and heart failure (12.7%). Having a urinary bladder catheter at discharge, being overtly frail (CFS > 8), and low BI score were factors independently associated with not being discharged home. DISCUSSION AND CONCLUSION: The routine assessment of frailty, as expressed by the CFS, may help redirecting the patients eligible for SCU admission.