Fisetin, a flavonoid naturally occurring in plants, fruits, and vegetables, has recently gained attention for its potential role as a senotherapeutic agent for the treatment of age-related chronic diseases. Senotherapeutics target senescent cells, which accumulate with age and disease, in both circulating immune cell populations and solid organs and tissues. Senescent cells contribute to development of many chronic diseases, primarily by eliciting systemic chronic inflammation through their senescence-associated secretory phenotype. Here, we explore whether fisetin as a senotherapeutic can eliminate senescent cells, and thereby alleviate chronic diseases, by examining current evidence from in vitro studies and animal models that investigate fisetin's impact on age-related diseases, as well as from phase I/II trials in various patient populations. We discuss the application of fisetin in humans, including challenges and future directions. Our review of available data suggests that targeting senescent cells with fisetin offers a promising strategy for managing multiple chronic diseases, potentially transforming future healthcare for older and multimorbid patients. However, further studies are needed to establish the safety, pharmacokinetics, and efficacy of fisetin as a senotherapeutic, identify relevant and reliable outcome measures in human trials, optimize dosing, and better understand the possible limitations of fisetin as a senotherapeutic agent.

Medication review for older patients with polypharmacy in the emergency department (ED) is crucial to prevent inappropriate prescribing. Our objective was to assess the feasibility of a collaborative medication review in older medical patients (≥65 years) using polypharmacy (≥5 long-term medications). A pharmacist performed the medication review using the tools: Screening Tool of Older Persons’ potentially inappropriate Prescriptions (STOPP) criteria, a drug–drug interaction database (SFINX), and Renbase^® (renal dosing database). A geriatrician received the medication review and decided which recommendations should be implemented. The outcomes were: differences in Medication Appropriateness Index (MAI) and Assessment of Underutilization Index (AOU) scores between admission and 30 days after discharge and the percentage of patients for which the intervention was completed before discharge. Sixty patients were included from the ED, the intervention was completed before discharge for 50 patients (83%), and 39 (61.5% male; median age 80 years) completed the follow-up 30 days after discharge. The median MAI score decreased from 14 (IQR 8-20) at admission to 8 (IQR 2-13) 30 days after discharge (p < 0.001). The number of patients with an AOU score ≥1 was reduced from 36% to 10% (p < 0.001). Thirty days after discharge, 83% of the changes were sustained and for 28 patients (72%), 1≥ medication had been deprescribed. In conclusion, a collaborative medication review and deprescribing intervention is feasible to perform in the ED.

There is a lack of knowledge about malnutrition and risk of malnutrition upon admission and after discharge in older medical patients. This study aimed to describe prevalence, risk factors, and screening tools for malnutrition in older medical patients. In a prospective observational study, malnutrition was evaluated in 128 older medical patients (≥65 years) using the Nutritional Risk Screening 2002 (NRS-2002), the Mini Nutritional Assessment-Short Form (MNA-SF) and the Eating Validation Scheme (EVS). The European Society of Clinical Nutrition (ESPEN) diagnostic criteria from 2015 were applied for diagnosis. Agreement between the screening tools was evaluated by kappa statistics. Risk factors for malnutrition included polypharmacy, dysphagia, depression, low functional capacity, eating-related problems and lowered cognitive function. Malnutrition or risk of malnutrition were prevalent at baseline (59–98%) and follow-up (30–88%). The baseline, follow-up and transitional agreements ranged from slight to moderate. NRS-2002 and MNA-SF yielded the highest agreement (kappa: 0.31 (95% Confidence Interval (CI) 0.18–0.44) to 0.57 (95%CI 0.42–0.72)). Prevalence of risk factors ranged from 17–68%. Applying ESPEN 2015 diagnostic criteria, 15% had malnutrition at baseline and 13% at follow-up. In conclusion, malnutrition, risk of malnutrition and risk factors hereof are prevalent in older medical patients. MNA-SF and NRS-2002 showed the highest agreement at baseline, follow-up, and transitionally.

Background: Altered monocyte NF-κB signaling is a possible cause of inflammaging and driver of aging, however, evidence from human aging studies is sparse. We assessed monocyte NF-κB signaling across different aging trajectories by comparing healthy older adults to older adults with a recent emergency department (ED) admission and to young adults.Methods: We used data from: 52 older (≥65 years) Patients collected upon ED admission and at follow-up 30-days after discharge; 52 age- and sex-matched Older Controls without recent hospitalization; and 60 healthy Young Controls (20–35 years). Using flow cytometry, we assessed basal NF-κB phosphorylation (pNF-κB p65/RelA; Ser529) and induction of pNF-κB following stimulation with LPS or TNF-α in monocytes. We assessed frailty (FI-OutRef), physical and cognitive function, and plasma levels of IL-6, IL-18, TNF-α, and soluble urokinase plasminogen activator receptor.Results: Patients at follow-up were frailer, had higher levels of inflammatory markers and decreased physical and cognitive function than Older Controls. Patients at follow-up had higher basal pNF-κB levels than Older Controls (median fluorescence intensity (MFI): 125, IQR: 105–153 vs. MFI: 80, IQR: 71–90,p < 0.0001), and reduced pNF-κB induction in response to LPS (mean pNF-κB MFI fold change calculated as the log10 ratio of LPS-stimulation to the PBS-control: 0.10, 95% CI: 0.08 to 0.12 vs. 0.13, 95% CI: 0.10 to 0.15,p = 0.05) and TNF-α stimulation (0.02, 95% CI: − 0.00 to 0.05 vs. 0.10, 95% CI: 0.08 to 0.12,p < 0.0001). Older Controls had higher levels of inflammatory markers than Young Controls, but basal pNF-κB MFI did not differ between Older and Young Controls (MFI: 81, IQR: 70–86;p = 0.72). Older Controls had reduced pNF-κB induction in response to LPS and TNF-α compared to Young Controls (LPS: 0.40, 95% CI: 0.35 to 0.44,p < 0.0001; and TNF-α: 0.33, 95% CI: 0.27 to 0.40,p < 0.0001). In Older Controls, basal pNF-κB MFI was associated with FI-OutRef (p = 0.02).Conclusions: Increased basal pNF-κB activity in monocytes could be involved in the processes of frailty and accelerated aging. Furthermore, we show that monocyte NF-κB activation upon stimulation was impaired in frail older adults, which could result in reduced immune responses and vaccine effectiveness.

Medication reconciliation is crucial to prevent medication errors. In Denmark, primary and secondary care physicians can prescribe medication in the same electronic prescribing system known as the Shared Medication Record (SMR). However, the SMR is not always updated by physicians, which can lead to discrepancies between the SMR and patients’ actual use of medication. These discrepancies may compromise patient safety upon admission to the emergency department (ED). Here, we investigated (a) the occurrence of discrepancies, (b) factors associated with discrepancies, and (c) the percentage of patients accessible to a clinical pharmacist during pharmacy working hours. The study included all patients age ≥ 18 years who were admitted to the Hvidovre Hospital ED on three consecutive days in June 2020. The clinical pharmacists performed medicines reconciliation to identify prescribing discrepancies. In total, 100 patients (52% male; median age 66.5 years) were included. The patients had a median of 10 [IQR 7–13] medications listed in the SMR and a median of two [IQR 1–3.25] discrepancies. Factors associated with increased rate of prescribing discrepancies were age < 65 years, time since last update of the SMR ≥ 115 days, and patients’ self-dispensing their medications. Eighty-four percent of patients were available for medicines reconciliations during the normal working hours of the clinical pharmacist. In conclusion, we found that discrepancies between the SMR and patients’ actual medication use upon admission to the ED are frequent, and we identified several risk factors associated with the increased rate of discrepancies.