Is There an Association between Norton Scale and Cognitive Impairment in Hip Fractured Elderly Patients?

INTRODUCTION: Geriatric assessment as an integrative part of assessment is a composite of a large number of scales. Sometimes it is difficult to transfer all of them. The Norton Scale Score (NSS) assesses the degree of risk to develop bedsores. In previous studies, a correlation between Norton Scale and function was found. A correlation between Norton Scale and cognitive assessments was not evaluated yet. The aim of this study was to determine if there is an association between Norton Scale Score and cognitive impairment. This association can further facilitate geriatric assessment in frail older patients, especially in older patients with communicative difficulties. METHODS: We have performed an observational cohort study which included hip fractured older patients consecutively admitted to the rehabilitation ward of the Shmuel Harofe Geriatric Medical Center. The collected data included demographic data and data on chronic illnesses. Results of cognitive status assessment (Mini-Mental State Examination - MMSE) and Norton Scale assessment were received from the computerized patients' charts. We evaluated the association between these 2 scales. RESULTS: The study included 224 consecutive hip fracture patients with a mean age of 81.78 ± 7.19 years. Norton scores at admission, age, education, and previous stroke emerged as the only statistically significant parameters differing between those with cognitive decline and those without it. After adjusting for confounding variables, lower Norton scores at admission (OR 1.303, CI: 1.097-1.548, p = 0.003) were associated with an increased risk finding for cognitive impairment. CONCLUSION: Our findings suggest that there is an association between Norton Scale Scores and cognitive impairment. Norton score parameters, under certain circumstances, such as speech and other communication difficulties, can be used as a proxy measure for MMSE to indicate cognitive impairment. These findings can be even more helpful in the present time of "COVID-19," when we have to evaluate older patients with facial masks and other defensive suits.

Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms.

The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors - CX3CR1 and L-selectin - were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.

Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia.

A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11bmid regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2- and TMPRSS2- which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.

Innate and Adaptive Immunity in Aging and Longevity: The Foundation of Resilience.

The interrelation of the processes of immunity and senescence now receives an unprecedented emphasis during the COVID-19 pandemic, which brings to the fore the critical need to combat immunosenescence and improve the immune function and resilience of older persons. Here we review the historical origins and the current state of the science of innate and adaptive immunity in aging and longevity. From the modern point of view, innate and adaptive immunity are not only affected by aging but also are important parts of its underlying mechanisms. Excessive levels or activity of antimicrobial peptides, C-reactive protein, complement system, TLR/NF-κB, cGAS/STING/IFN 1,3 and AGEs/RAGE pathways, myeloid cells and NLRP3 inflammasome, declined levels of NK cells in innate immunity, thymus involution and decreased amount of naive T-cells in adaptive immunity, are biomarkers of aging and predisposition factors for cellular senescence and aging-related pathologies. Long-living species, human centenarians, and women are characterized by less inflamm-aging and decelerated immunosenescence. Despite recent progress in understanding, the harmonious theory of immunosenescence is still developing. Geroprotectors targeting these mechanisms are just emerging and are comprehensively discussed in this article.

Geroscience in the Age of COVID-19.

The data on COVID-19 is clear on at least one point: Older adults are most vulnerable to hospitalization, disability and death following infection with the novel coronavirus. Therefore, therapeutically addressing degenerative aging processes as the main risk factors appears promising for tackling the present crisis and is expected to be relevant when tackling future infections, epidemics and pandemics. Therefore, utilizing a geroscience approach, targeting aging processes to prevent multimorbidity, via initiating broad clinical trials of potential geroprotective therapies, is recommended.