Expert Consensus on the Application of Stem Cells in Psoriasis Research and Clinical Trials.

Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.

Expert Consensus on Prevention and Treatment of Aging-Related Gonadal Dysfunction.

Aging-related hypogonadism involves complex mechanisms in humans, predominantly relating to the decline of multiple hormones and senile gonads. Late-onset hypogonadism (LOH) and erectile dysfunction (ED) are the main manifestations in men, while premature ovarian insufficiency (POI) and menopause are the main forms in women. Anti-aging measures include lifestyle modification and resistance training, hormonal supplementation, stem cell therapy, metformin, and rapamycin. In this expert consensus, the mechanisms, efficacy, and side effects of stem cell therapy on aging gonadal function are reviewed. Furthermore, various methods of stem cell therapy, administered intravenously, intracavernously, and intra-ovarially, are exemplified in detail. More clinical trials on aging-related gonadal dysfunction are required to solidify the foundation of this topic.

Expert consensus on Prospective Precision Diagnosis and Treatment Strategies for Osteoporotic Fractures.

Osteoporotic fractures are the most severe complications of osteoporosis, characterized by poor bone quality, difficult realignment and fixation, slow fracture healing, and a high risk of recurrence. Clinically managing these fractures is relatively challenging, and in the context of rapid aging, they pose significant social hazards. The rapid advancement of disciplines such as biophysics and biochemistry brings new opportunities for future medical diagnosis and treatment. However, there has been limited attention to precision diagnosis and treatment strategies for osteoporotic fractures both domestically and internationally. In response to this, the Chinese Medical Association Orthopaedic Branch Youth Osteoporosis Group, Chinese Geriatrics Society Geriatric Orthopaedics Committee, Chinese Medical Doctor Association Orthopaedic Physicians Branch Youth Committee Osteoporosis Group, and Shanghai Association of Integrated Traditional Chinese and Western Medicine Osteoporosis Professional Committee have collaborated to develop this consensus. It aims to elucidate emerging technologies that may play a pivotal role in both diagnosis and treatment, advocating for clinicians to embrace interdisciplinary approaches and incorporate these new technologies into their practice. Ultimately, the goal is to improve the prognosis and quality of life for elderly patients with osteoporotic fractures.

Do Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio Need to Be Stratified for Age and Comorbidities in COVID-19 Disease? A Subgroup Analysis of Two Distinct Cohorts over Disease Course.

Several studies described neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) as markers of COVID-19 severity. In a recently published study, age and frailty affected NLR and PLR more than disease severity. The study compared two distinct cohorts. The first comprised older frailer patients positive for SARS-CoV-2, with mild or asymptomatic disease, admitted to designated COVID-19 departments in a large geriatric medical center (GMC). The second cohort comprised COVID-19 patients admitted to a large general hospital (GH) for symptomatic disease. This was a follow-up study comparing a subgroup of patients who had NLR and PLR values measured a week after admission. Only 100 of 177 patients in the original GMC cohort had a second NLR test compared to almost all (287 of 289) patients in the general hospital (GH) cohort. The subgroup baseline characteristics did not change significantly from that of the original cohort. Disease symptoms were more prevalent in the GH cohort. In the GMC group, the median second NLR rose from 3.9 to 4.6, while in the GH cohort, the NLR value dropped from 3.5 to 2.8, enhancing the NLR differences between the groups. Smaller changes were observed in the second PLR. These results strengthen the prior results that age and frailty seem to have a stronger impact on NLR and PLR than disease severity.

Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio, are they markers of COVID-19 severity or old age and frailty? A comparison of two distinct cohorts.

The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are simple markers of systemic inflammatory responses. It has been previously suggested that they can predict COVID-19 severity. Age and frailty may also influence their values. This study aimed to evaluate the impact of COVID-19 severity versus age and frailty on NLR and PLR values. This was a retrospective, observational two cohorts' comparative study. The first cohort is comprised of patents positive for SARS-CoV-2, with mild or asymptomatic disease, admitted to designated COVID-19 departments in a large geriatric medical center (GMC). The second included patients with COVID-19 admitted to designated COVID-19 departments in a large general hospital for symptomatic disease from March 2020 to March 2021. We compared baseline characteristics including comorbidities and chronic medications, disease symptoms, laboratory tests and compared the NLR and PLR between the two groups. The 177 patients admitted to the COVID-designated department in the GMC were over three decades older than the 289 COVID-19 patients admitted to the general hospital care (HC). They had substantially more comorbidities and chronic medications. All common disease symptoms were significantly more common in the HC group. Almost two thirds of the GMC patients remained asymptomatic compared to 2.1% in the HC group. Inflammatory markers, such as CRP and LDH, were significantly higher in the HC group. The NLR and PLR were both significantly higher in the GMC cohort comprised of older frailer patients with milder disease. NLR and PLR seem to be affected more by age and frailty than COVID-19 severity.

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.

Interdisciplinary Research in Alzheimer's Disease and the Roles International Societies Can Play.

An ever-increasing ageing population has elevated Alzheimer's disease to be one of the biggest challenges in modern medicine. Alzheimer's disease is highly complex, and we are still no closer to understanding the causes, let alone an effective treatment. The lack of good experimental models and lack of critical understanding has led to high failure rates of clinical trials with high associated costs, as well as difficulties in implementing treatments. The multifaceted nature of this disease highlights the need for an interdisciplinary approach to address these concerns. In this essay, we suggest how collaborative work can be useful in addressing some of the above issues. We then propose that international organisations and publishers need to support interdisciplinary research by creating platforms, lobbying funders, and pushing for interdisciplinary publications. We further highlight some of the issues involved in implementing these suggestions and argue that willpower of the research community, together with a re-evaluation of evaluation metrics and incentive systems, are needed in order to foster interdisciplinary research. Overall, we emphasise the need for interdisciplinary research in Alzheimer's disease and suggest that international societies should play a huge role in this endeavour.

The association between Norton scale gain and functional outcome among older hip fracture patients.

AIM: This study examines interrelations between gains of Norton Scale Score (NSS) and functional outcome measured by Functional Independence Measurement (FIM) among older hip fracture patients. DESIGN: Retrospective study. METHODS: We examined 227 patients consecutively hospitalized in a geriatric postacute rehabilitation ward. The data were collected during 2012-2017. Data were analysed using Student's t test, chi-square test, Pearson's correlation coefficient and linear regression. RESULTS: Patients with positive NSS gains demonstrated statistically significant higher total FIM, motor FIM and total FIM gain scores at hospital discharge, compared with patients showing no NSS gains or negative NSS. Multiple regression analysis indicated that positive NSS gains were independently predictive for higher total FIM and motor FIM scores at hospital discharge and higher motor FIM gains at discharge. CONCLUSION: Our results suggest that positive NSS gains are associated with higher FIM scores at hospital discharge and may assist in predicting the functional outcome of hospitalized older hip fracture patients.

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.

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.

An information-theoretical analysis of gene nucleotide sequence structuredness for a selection of aging and cancer-related genes.

We provide an algorithm for the construction and analysis of autocorrelation (information) functions of gene nucleotide sequences. As a measure of correlation between discrete random variables, we use normalized mutual information. The information functions are indicative of the degree of structuredness of gene sequences. We construct the information functions for selected gene sequences. We find a significant difference between information functions of genes of different types. We hypothesize that the features of information functions of gene nucleotide sequences are related to phenotypes of these genes.

An Information Theory Approach for the Analysis of Individual and Combined Evaluation Parameters of Multiple Age-Related Diseases.

In view of the frequent presence of several aging-related diseases in geriatric patients, there is a need to develop analytical methodologies that would be able to perform diagnostic evaluation of several diseases at once by individual or combined evaluation parameters and select the most informative parameters or parameter combinations. So far there have been no established formal methods to enable such capabilities. We develop a new formal method for the evaluation of multiple age-related diseases by calculating the informative values (normalized mutual information) of particular parameters or parameter combinations on particular diseases, and then combine the ranks of informative values to provide an overall estimation (or correlation) on several diseases at once. Using this methodology, we evaluate a geriatric cohort, with several common age-related diseases, including cognitive and physical impairments (dementia, chronic obstructive pulmonary disease-COPD and ischemic heart disease), utilizing a set of evaluation parameters (such as demographic data and blood biomarkers) routinely available in geriatric clinical practice. This method permitted us to establish the most informative parameters and parameter combinations for several diseases at once. Combinations of evaluation parameters were shown to be more informative than individual parameters. This method, with additional clinical data, may help establish the most informative parameters and parameter combinations for the diagnostic evaluation of multiple age-related diseases and enhance specific assessment for older multi-morbid patients and treatments against old-age multimorbidity.

Recognizing Degenerative Aging as a Treatable Medical Condition: Methodology and Policy.

It is becoming increasingly clear that in order to accomplish healthy longevity for the population, there is an urgent need for the research and development of effective therapies against degenerative aging processes underlying major aging-related diseases, including heart disease, neurodegenerative diseases, type 2 diabetes, cancer, pulmonary obstructive diseases, as well as aging-related complications and susceptibilities of infectious communicable diseases. Yet, an important incentive for the research and development of such therapies appears to be the development of clinically applicable and scientifically grounded definitions and criteria for the multifactorial degenerative aging process (or "senility" using the existing ICD category), underlying those diseases, as well as for the safety and effectiveness of interventions against it. Such generally agreed definitions and criteria are currently absent. The devising of such criteria is important not only for the sake of their scientific value and their utility for the development of therapeutic solutions for the aging population, but also to comply with and implement major existing national and international programmatic and regulatory requirements. Some methodological suggestions and potential pitfalls for the development of such criteria are examined.

The application of information theory for the estimation of old-age multimorbidity.

Elderly patients are commonly characterized by the presence of several chronic aging-related diseases at once, or old-age "multimorbidity," with critical implications for diagnosis and therapy. However, at the present there is no agreed or formal method to diagnose or even define "multimorbidity." There is also no formal quantitative method to evaluate the effects of individual or combined diagnostic parameters and therapeutic interventions on multimorbidity. The present work outlines a methodology to provide such a measurement and definition, using information theoretical measure of normalized mutual information. A cohort of geriatric patients, suffering from several age-related diseases (multimorbidity), including ischemic heart disease, COPD, and dementia, were evaluated by a variety of diagnostic parameters, including static as well as dynamic biochemical, functional-behavioral, immunological, and hematological parameters. Multimorbidity was formally coded and measured as a composite of several chronic age-related diseases. The normalized mutual information allowed establishing the exact informative value of particular parameters and their combinations about the multimorbidity value. With the currently intensifying attempts to reduce aging-related multimorbidity by therapeutic interventions into its underlying aging processes, the proposed method may outline a valuable direction toward the formal indication and evidence-based evaluation of effectiveness of such interventions.