Definition of the Post-COVID syndrome using a symptom-based Post-COVID score in a prospective, multi-center, cross-sectoral cohort of the German National Pandemic Cohort Network (NAPKON).

PURPOSE: The objective examination of the Post-COVID syndrome (PCS) remains difficult due to heterogeneous definitions and clinical phenotypes. The aim of the study was to verify the functionality and correlates of a recently developed PCS score. METHODS: The PCS score was applied to the prospective, multi-center cross-sectoral cohort (in- and outpatients with SARS-CoV-2 infection) of the "National Pandemic Cohort Network (NAPKON, Germany)". Symptom assessment and patient-reported outcome measure questionnaires were analyzed at 3 and 12 months (3/12MFU) after diagnosis. Scores indicative of PCS severity were compared and correlated to demographic and clinical characteristics as well as quality of life (QoL, EQ-5D-5L). RESULTS: Six hundred three patients (mean 54.0 years, 60.6% male, 82.0% hospitalized) were included. Among those, 35.7% (215) had no and 64.3% (388) had mild, moderate, or severe PCS. PCS severity groups differed considering sex and pre-existing respiratory diseases. 3MFU PCS worsened with clinical severity of acute infection (p = .011), and number of comorbidities (p = .004). PCS severity was associated with poor QoL at the 3MFU and 12MFU (p < .001). CONCLUSION: The PCS score correlated with patients' QoL and demonstrated to be instructive for clinical characterization and stratification across health care settings. Further studies should critically address the high prevalence, clinical relevance, and the role of comorbidities. TRAIL REGISTRATION NUMBER: The cohort is registered at www. CLINICALTRIALS: gov under NCT04768998.

The prognostic signature of health-related quality of life in older patients admitted to the emergency department: a 6-month follow-up study.

BACKGROUND: The management of older and multimorbid patients with complex care requires a personalised and comprehensive approach. The main diagnosis is often registered as the cause of hospitalisation, yet poor health-related quality of life (HRQoL) as well as multimorbidity may represent the underlying cause and markedly influence prognosis. AIMS: To analyse the association of HRQoL and clinical prognosis over time as assessed by a Comprehensive Geriatric Assessment (CGA)-based Multidimensional Prognostic Index (MPI) in older patients admitted to the emergency department (ED). METHODS: We used data from the prospective MPI-HOPE (Influence of the MPI on the Hospitalisation of Older Patients admitted to the Emergency department) study. Data from 165 patients (≥ 75 years) admitted to the ED of the University Hospital of Cologne, Germany, between Oct 2017 and Jan 2018 were included. Clinical prognosis was calculated by the MPI and HRQoL by the EQ5D-5L. Follow-up interviews assessed HRQoL up to 6 months after discharge. RESULTS: Most patients were multimorbid and presented with several geriatric syndromes. At admission, HRQoL was highest in patients with the best clinical prognosis. The MPI showed a negative correlation with the EQ-Index at admission (rs(86) = - 0.50, p < 0.0001) and follow-up assessments after 3 and 6 months (rs(86) = - 0.55 and rs(86) = - 0.47, p < 0.0001). DISCUSSION: Our results suggest that patients' self-perceived HRQoL in the ED is related to functional health status and clinical prognosis. CONCLUSION: The MPI as a multidimensional snapshot provides information on clinical health indicators and informs about subjective HRQoL, thereby helping in identifying patients who would benefit from a specific treatment within the frame of a patient-centered, value-based care strategy geriatric treatment.

Using the Multidimensional Prognostic Index (MPI) to improve cost-effectiveness of interventions in multimorbid frail older persons: results and final recommendations from the MPI_AGE European Project.

MPI_AGE is a European Union co-funded research project aimed to use the Multidimensional Prognostic Index (MPI), a validated Comprehensive Geriatric Assessment (CGA)-based prognostic tool, to develop predictive rules that guide clinical and management decisions in older people in different European countries. A series of international studies performed in different settings have shown that the MPI is useful to predict mortality and risk of hospitalization in community-dwelling older subjects at population level. Furthermore, studies performed in older people who underwent a CGA before admission to a nursing home or receiving homecare services showed that the MPI successfully identified groups of persons who could benefit, in terms of reduced mortality, of specific therapies such as statins in diabetes mellitus and coronary artery disease, anticoagulants in atrial fibrillation and antidementia drugs in cognitive decline. A prospective trial carried out in nine hospitals in Europe and Australia demonstrated that the MPI was able to predict not only in-hospital and long-term mortality, but also institutionalization, re-hospitalization and receiving homecare services during the one-year follow-up after hospital discharge. The project also explored the association between MPI and mortality in hospitalized older patients in need of complex procedures such as transcatheter aortic valve implantation or enteral tube feeding. Evidence from these studies has prompted the MPI_AGE Investigators to formulate recommendations for healthcare providers, policy makers and the general population which may help to improve the cost-effectiveness of appropriate health care interventions for older patients.

Neurogeriatrics-a vision for improved care and research for geriatric patients with predominating neurological disabilities.

Geriatric medicine is a rapidly evolving field that addresses diagnostic, therapeutic and care aspects of older adults. Some disabilities and disorders affecting cognition (e.g. dementia), motor function (e.g. stroke, Parkinson's disease, neuropathies), mood (e.g. depression), behavior (e.g. delirium) and chronic pain disorders are particularly frequent in old subjects. As knowledge about these age-associated conditions and disabilities is steadily increasing, the integral implementation of neurogeriatric knowledge in geriatric medicine and specific neurogeriatric research is essential to develop the field. This article discusses how neurological know-how could be integrated in academic geriatric medicine to improve care of neurogeriatric patients, to foster neurogeriatric research and training concepts and to provide innovative care concepts for geriatric patients with predominant neurological conditions and disabilities.

The Multidimensional Prognostic Index in general practice: One-year follow-up study.

BACKGROUND: Older patients' health problems in general practice (GP) can often not be assigned to a specific disease, requiring a paradigm shift to goal-oriented, personalised care for clinical decision making. PURPOSE: To investigate the predictive value of the comprehensive geriatric assessment (CGA)-based Multidimensional Prognostic Index (MPI) in a GP setting with respect to the main healthcare indicators during the 12 months following initial evaluation. METHODS: One hundred twenty-five consecutive patients aged 70 years and older were enrolled in a GP and followed up to one year. All patients underwent a CGA based on which the MPI was calculated and subdivided into three risk groups (MPI-1, 0-0.33 = low risk, MPI-2, 0.34-0.66 = moderate risk and MPI-3, 0.67-1, severe risk). Grade of Care (GC), hospitalization rate, mortality, nursing home admission, use of home care services, falls, number of general practitioner contacts (GPC), of geriatric resources (GR) and geriatric syndromes (GS) during the 12 months following initial evaluation were collected. RESULTS: The MPI was significantly associated with number of GS (P < .001), GR (P < .001), GC (P < .001) as well as with the average number of GPC per year (mean 10.4, P = .046). Interestingly, the clinical judgement of the general practitioner, in this case knowing his patients for 16 years on average, was associated with adverse outcomes to a similar extent than the prediction offered by the MPI (GP/adverse outcomes and MPI/adverse outcomes P < .001). CONCLUSION: The MPI is strongly associated with adverse outcomes in older GP patients and strongly predicts the number of GPC up to one year after initial evaluation. Considering the feasibility and the strong clinimetric properties of the MPI, its collection should be encouraged as early as possible to disclose risk conditions, implement tailored preventive strategies and improve cost-effectiveness of healthcare resources use.

Burden of multimorbidity and outcome in ambulatory geriatric hemodialysis patients : Report from the QiN registry in Germany.

BACKGROUND: Patients with end-stage renal disease (ESRD) requiring hemodialysis are typically characterized by multimorbidity and increasingly by advanced age; however, there are few data on their geriatric needs. OBJECTIVE: The aim of the study was to evaluate the clinical characteristics of a large cohort of incident patients in ambulatory hemodialysis units with a particular focus on those aged over 80 years in Germany. METHODS: The electronic patient registry of the Board of Trustees (Kuratorium) for Dialysis and Kidney Transplantation (KfH) was searched for all patients who began hemodialysis in 1 of the 191 units between 2007 and 2013 and were 65 years and older. Patients were analyzed by age (65-79 years and ≥80 years) for clinical and biochemical characteristics, mortality, quality of life and hospitalizations. RESULTS: Of the 21,355 incident patients, a total of 13,872 (65%) were over 65 years old, with 9998 (46.8%) aged between 65 and 79 years and 3874 (18.1%) patients 80 years or older (oldest old). The spectrum of morbidity was comparable between the two age groups but there was a significantly higher prevalence of anemia, hypoalbuminemia and multimorbidity (>four comorbidities) in the older age group. Median survival was 4.5 years (1638 days) in the younger age group and 2.7 years (978 days) in the older group. Almost half of the patients experienced at least one episode of hospitalization during the first year but there were no significant differences between the age groups (45.9% in younger vs. 47% in older patients). In the older age group 463 (12%) patients survived more than 5 years after initiation of hemodialysis despite the presence of multiple risk factors for adverse clinical outcome. CONCLUSION: More than half of the chronic ambulatory hemodialysis patients were of advanced age and had a very high burden of multimorbidity. Nevertheless, a subgroup of ERSD patients over 80 years old survived at least 5 years on hemodialysis despite the presence of multiple risk factors for adverse clinical outcome. Identification of these patients as well as optimized care for frail hemodialysis patients will require application of geriatric assessment tools in addition to traditional parameters in nephrology. The development and validation of such tools should be the subject of further clinical studies.

[Current insights into anemia in old age : Summary of the symposium "Anemia in old age" on the occasion of the annual congress of the German Society for Geriatrics (DGG) 2016 in Stuttgart]. / Aktuelle Einblicke in die Anämie im Alter : Zusammenfassung zum Symposium "Anämie im Alter" anlässlich der DGG-Jahrestagung 2016 in Stuttgart.

Anemia in advanced age is often a multifactorial condition requiring an interdisciplinary approach. The contributions to the opening interdisciplinary symposium on anemia in older subjects focused on physiological and histopathological as well as on nephrological and neurogeriatric aspects and on the therapeutic implications of this underdiagnosed, yet highly frequent disease. The symposium was the kick-off event for the founding of the German Geriatric Society special interest group on anemia in advanced age.

[Geriatric inpatients with iron deficiency-associated Restless Legs Syndrome. A retrospective analysis]. / Stationär behandelte geriatrische Patienten mit Eisenmangel-assoziiertem Restless-Legs-Syndrom : Eine retrospektive Analyse.

OBJECTIVE: The Restless Legs Syndrome (RLS) is a clinically relevant condition in geriatric patients. An association between iron deficiency and RLS is largely acknowledged. The clinical and therapeutic management of iron deficiency-associated RLS has been, however, poorly evaluated in geriatric patients. METHODS: Data from all RLS inpatients admitted to a geriatric unit between 2009 and 2011 were retrospectively collected on demographics and clinical characteristics, iron status, drug treatment including iron substitution, as well as comprehensive geriatric assessment (CGA) scores. RESULTS: RLS was diagnosed in 56 of the 4,063 admitted patients during the two years. Of the RLS cases, 20 (36%) showed iron deficiency. Thirteen of these were treated with iron substitution according to the existing guidelines. Both RLS patients with and without iron deficiency showed a significant clinical improvement between admission to discharge according to the CGA scores. CONCLUSION: Iron substituted geriatric patients with iron deficiency-associated RLS substantially benefited from the treatment, similarly to RLS patients without iron deficiency. A multidimensional assessment, careful iron metabolism examination and adequate treatment choice should be equally importantly considered in geriatric patients with RLS.

Intravenous iron administration in restless legs syndrome : An observational study in geriatric patients.

BACKGROUND: This observational study was carried out to investigate the effect of intravenous (i.v.) iron administration on the clinical symptoms of restless legs syndrome (RLS) in geriatric outpatients over 65 years old. METHODS: In this study geriatric outpatients (mean 4.5 ± 3.4 comorbidities and 5.7 ± 4.4 drugs taken) were recruited according to the following inclusion criteria: ≥ 65 years, diagnosis of RLS due to iron deficiency, i.e. ferritin < 50 µg/l or transferrin saturation (TFS) < 16 %) as well as no other iron therapy within 2 weeks prior to the study. Of the patients 7 (41 %) received 500 mg ferric carboxymaltose (FCM) and 10 patients (59 %) received iron gluconate (62.5 mg) based on the degree of iron deficiency. As assessed by the international RLS severity scale (IRLS) symptoms were recorded 3 times: at the beginning of iron therapy (t0), after 2 weeks (t1) and after 12 weeks (t2). RESULTS: A total of 17 patients (13 female, 4 male, mean age 73.2 ± 5.9 years) were included. The IRLS score significantly improved in all patients as shown by an average decrease from 30.2 (± 4.3) to 20.2 (± 4.7) (p < 0.001) after 2 weeks of i.v. iron treatment and to 23.2 ± 6.6 (p < 0.001) after 12 weeks. There was a high correlation between ferritin values and the IRLS score (C 0.729, p < 0.001). The part of the IRLS referring to activities of daily living (ADL) improved from a median of 3 (scores 3-4) to 2 (scores 2-3, p = 0.001) after 2 weeks (effect size - 0.6). CONCLUSION: In this study group of geriatric outpatients i.v. administration of iron was associated with a significant improvement of symptoms in RLS as assessed by the IRLS score 2 weeks after treatment. In geriatric patients with RLS associated with iron deficiency, i.v. iron administration should be considered regarding improvement of RLS symptoms and ADL.

[Frailty: Prevention]. / Frailty: Prävention.

The Frailty syndrome is usually related to the aging process and chronological age, but it is not an inevitable consequence of it - at least until the final phase of life. Primary care interventions that promote physical activity and nutrition can prevent the progression from pre-frailty to frailty. This article presents the current state of knowledge on primary and secondary prevention of frailty.

Prognostic Features of Sarcopenia in Older Hospitalized Patients: A 6-Month Follow-Up Study.

Background: Sarcopenia is associated with adverse health outcomes. Understanding the association between sarcopenia, multidimensional frailty, and prognosis is essential for improving patient care. The aim of this study was to assess the prevalence and prognostic signature of sarcopenia in an acute hospital setting co-led by internists and geriatricians. Methods: Sarcopenia was assessed by applying the European Working Group on Sarcopenia in Older People (EWGSOP2) algorithm, including the SARC-F score, handgrip strength, bioelectrical impedance analysis (BIA), and Timed Up and Go (TUG) test, to 97 older multimorbid inpatients (76.5 ± 6.8 years, 55% women). The patients underwent a Comprehensive Geriatric Assessment (CGA) including an evaluation of Geriatric Syndromes (GSs) and Resources (GR) and prognosis calculation using the CGA-based Multidimensional Prognostic Index (MPI), European Quality of life-5 Dimensions (EQ-5D-5L) scale, Rosenberg Self-Esteem Scale (RSES), and Geriatric Depression Scale (GDS). Information on survival and rehospitalizations was collected 1, 3, and 6 months after discharge. Results: Sarcopenia was present in 63% (95% CI: 54-72%) of patients and categorized as probable (31%), confirmed (13%), and severe sarcopenia (18%). Sarcopenic patients showed significantly higher median MPI-values (p < 0.001), more GSs (p = 0.033), fewer GR (p = 0.003), lower EQ-5D-5L scores (p < 0.001), and lower RSES scores (p = 0.025) than non-sarcopenic patients. Six months after discharge, being sarcopenic at baseline was predictive of falls (p = 0.027) and quality of life (p = 0.043), independent of age, gender, and MPI. Conclusions: Sarcopenia is highly prevalent in older hospitalized multimorbid patients and is associated with poorer prognosis, mood, and quality of life up to 6 months after discharge, independent of age, sex, and MPI as surrogate markers of biological age.

Profiles of Geriatric Syndromes and Resources in Older Patients with Atrial Fibrillation.

Objective: Older patients with nonvalvular atrial fibrillation (AF) are at high risk for frailty and geriatric syndromes (GSs), which modulate their individual prognosis and are therefore relevant for further management. Because few studies have evaluated the geriatric profile of older AF patients, this secondary analysis aims to further characterize the patterns of GSs and geriatric resources (GRs) in AF patients and their association with anticoagulation use. Methods: Data from 362 hospitalized patients aged 65 years and older with AF (n = 181, 77.8 ± 5.8 years, 38% female) and without AF (non-AF [NAF]; n = 181, 77.5 ± 5.9 years, 40% female) admitted to an internal medicine and nephrology ward of a large university hospital in Germany were included. All patients underwent usual care plus a comprehensive geriatric assessment (CGA) including calculation of the Multidimensional Prognostic Index (MPI) and collection of 17 GSs and 10 GRs. Patients were followed up by telephone 6 and 12 months after discharge to collect data on their health status. Results: The mean MPI score of 0.47 indicated an average risk of poor outcome, and patients with AF had a significantly higher MPI than those without AF (p = 0.040). After adjustment for chronological age, biological sex, Cumulative Illness Rating Scale (CIRS) for relevant chronic diagnoses and MPI as a proxy for biological age, AF patients had significantly more mnestic resources (63.5% vs. 33.1%, p < 0.001), a tendency for less age-appropriate living conditions (56.4% vs. 72.9%, p = 0.051) and more sensory impairment (78.5% vs. 52.5%, p < 0.001) than NAF patients. They also had a higher number of GSs (p = 0.046). AF patients on oral anticoagulants (OACs, n = 91) had less age-appropriate living conditions (48.4% vs. 64.4%, p < 0.05) and mnestic resources (36.3% vs. 54.4%, p < 0.01), but more emotional resources (80.2% vs. 65.6%, p < 0.05) and chronic pain (56% vs. 40%, p < 0.05) than patients without OACs (n = 90). Overall, mortality at 1 year was increased in patients with a higher MPI (p < 0.009, adjusted for age, sex and CIRS), with a diagnosis of AF (p = 0.007, adjusted for age, sex, CIRS and MPI), with of male sex (p = 0.008, adjusted for age, CIRS and MPI) and those with AF and treated with hemodialysis (p = 0.022, compared to AF patients without dialysis treatment). Conclusions: Patients with AF and patients with AF and OACs show differences in their multidimensional frailty degree as well as GR and GS profiles compared to patients without AF or with AF not treated with OACs. Mortality after 1 year is increased in AF patients with a higher MPI and dialysis, independently from OAC use and overall burden of chronic disease as assessed per CIRS. GRs and GSs, especially age-appropriate living conditions, emotional resources, sensory impairment and chronic pain, can be considered as factors that may modify the individual impact of frailty, underscoring the relevance of these parameters in the management of older patients.

Antioxidant clinical trials in mild cognitive impairment and Alzheimer's disease.

Alzheimer's disease (AD) is a highly disabling progressive neurodegenerative disorder characterized by a steadily growing number of patients, by the absence of a cure for the disease and by great difficulties in diagnosing in the preclinical phase. Progresses in defining the complex etiopathogenesis of AD consider oxidative stress a core aspect as far as both AD onset and progression are concerned. However, clinical trials of antioxidants in AD have brought conflicting conclusions. In this review, we report the main results of clinical trials with antioxidants in mild cognitive impairment (MCI) and AD. Although available data do not warrant the doubtless use of antioxidants in AD, they are characterized by extremely poor comparability and the absence of a substantial clinical benefit of antioxidants in AD is not disproved to date. Furthermore, the role of vascular damage that contributes to oxidative stress in AD should be addressed in testing antioxidant treatments. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.

A multidimensional approach to older patients during COVID-19 pandemic: a position paper of the Special Interest Group on Comprehensive Geriatric Assessment of the European Geriatric Medicine Society (EuGMS).

PURPOSE: The COVID-19 pandemic has been a dramatic trigger that has challenged the intrinsic capacity of older adults and of society. Due to the consequences for the older population worldwide, the Special Interest Group on Comprehensive Geriatric Assessment (CGA) of the European Geriatric Medicine Society (EuGMS) took the initiative of collecting evidence on the usefulness of the CGA-based multidimensional approach to older people during the COVID-19 pandemic. METHODS: A narrative review of the most relevant articles published between January 2020 and November 2022 that focused on the multidimensional assessment of older adults during the COVID-19 pandemic. RESULTS: Current evidence supports the critical role of the multidimensional approach to identify older adults hospitalized with COVID-19 at higher risk of longer hospitalization, functional decline, and short-term mortality. This approach appears to also be pivotal for the adequate stratification and management of the post-COVID condition as well as for the adoption of preventive measures (e.g., vaccinations, healthy lifestyle) among non-infected individuals. CONCLUSION: Collecting information on multiple health domains (e.g., functional, cognitive, nutritional, social status, mobility, comorbidities, and polypharmacy) provides a better understanding of the intrinsic capacities and resilience of older adults affected by SARS-CoV-2 infection. The EuGMS SIG on CGA endorses the adoption of the multidimensional approach to guide the clinical management of older adults during the COVID-19 pandemic.

Improvement of Dietary Habits among German Medical Students by Attending a Nationwide Online Lecture Series on Nutrition and Planetary Health ("Eat This!").

Nutrition is a major influential factor in optimizing human health and environmental sustainability. Medical students often do not follow national dietary guideline recommendations. Raising awareness of a healthy lifestyle is important as physicians with healthy lifestyle behaviors are more likely to counsel on nutrition. Our study aims to evaluate a Germany-wide online lecture series on nutritional medicine, "Eat This!". Before and after the course, 520 medical students who participated and 64 who did not participate in the course (comparison group) filled out an online survey. To assess the students' dietary habits, a validated FFQ was used. According to this questionnaire, only 31% of the lecture participants consumed enough fruits and 24% consumed enough vegetables, while almost half of the students exceeded the recommended maximum amount of crisps and sweets. After attending the lecture series, guideline adherence with respect to fruits and vegetables showed a significant increase, as did awareness of healthy nutrition and percentage of students with low-risk lifestyle habits. Our results show that low-threshold approaches, such as "Eat This!", can positively influence the dietary behaviors and lifestyle habits of medical students. This can help future doctors fulfill their role in the fight against the global burden of non-communicable diseases.

Implementing nutritional medicine into medical curricula: A student-initiated course improves knowledge and attitudes.

BACKGROUND & AIMS: Although the risks and opportunities of nutrition in health trajectories are well known, it is rarely addressed in doctors' daily routine. This is partly related to physicians' lack of confidence in their ability to provide nutritional counselling, possibly due to insufficient training in medical school. Our study aimed at assessing the status quo of nutrition in the German medical curricula and the impact of a recently implemented, student-initiated online teaching initiative on perceived competence, knowledge and attitudes. METHODS: "Eat This!" was the first Germany-wide initiative for online nutritional medicine (NM) education, consisting of 11 digital lectures on nutrition basics, nutrition medicine and public health nutrition. The contact time with NM during studies as well as the effects on students' attitudes towards NM, their self-perceived competence in NM and their nutrition knowledge were assessed from October 2020 to February 2021 in a cross-sectional as well as a prospective study using online questionnaires. RESULTS: Over 1500 medical students from 42 German faculties participated in the lecture series and the online survey. One hundred and twenty-two students formed a control group. Although considering the topic relevant, students rated their training in NM as insufficient, in terms of both quality and quantity. Initially, they did not feel able to counsel patients and rated their knowledge as low. However, self-ratings and the score in a 33-item multiple-choice test knowledge improved by participating in Eat This! as did their attitude towards nutrition and planetary health. No such changes were observed in the control group of 122 students not attending the course. CONCLUSION: Our results show that education in NM at German medical schools is perceived insufficient despite high student interest. But even low-threshold educational options like "Eat This!" can improve students' perceived competence, knowledge, and attitudes, and thus be an efficient and cost-effective way to address related deficits.

Combination of the biomarkers for aging and cancer? - Challenges and current status.

The proportion of patients diagnosed with cancer has been shown to rise with the increasing aging global population. Advanced age is a major risk factor for morbidity and mortality in older adults. As individuals experience varying health statuses, particularly with age, it poses a challenge for medical professionals in the cancer field to obtain standardized treatment outcomes. Hence, relying solely on chronological age and disease-related parameters is inadequate for clinical decision-making for elderly patients. With functional, multimorbidity-related, and psychosocial changes that occur with aging, oncologic diseases may develop and be treated differently from younger patients, leading to unique challenges in treatment efficacy and tolerance. To overcome this challenge, personalized therapy using biomarkers has emerged as a promising solution. Various categories of biomarkers, including inflammatory, hematological, metabolic, endocrine, and DNA modification-related indicators, may display features related to both cancer and aging, aiding in the development of innovative therapeutic approaches for patients with cancer in old age. Furthermore, physical functional measurements as non-molecular phenotypic biomarkers are being investigated for their potential complementary role in structured multidomain strategies to combat age-related diseases such as cancer. This review provides insight into the current developments, recent discoveries, and significant challenges in cancer and aging biomarkers, with a specific focus on their application in advanced age.

Refeeding-associated AMPKγ1 complex activity is a hallmark of health and longevity.

Late-life-initiated dietary interventions show limited efficacy in extending longevity or mitigating frailty, yet the underlying causes remain unclear. Here we studied the age-related fasting response of the short-lived killifish Nothobranchius furzeri. Transcriptomic analysis uncovered the existence of a fasting-like transcriptional program in the adipose tissue of old fish that overrides the feeding response, setting the tissue in persistent metabolic quiescence. The fasting-refeeding cycle triggers an inverse oscillatory expression of genes encoding the AMP-activated protein kinase (AMPK) regulatory subunits Prkag1 (γ1) and Prkag2 (γ2) in young individuals. Aging blunts such regulation, resulting in reduced Prkag1 expression. Transgenic fish with sustained AMPKγ1 countered the fasting-like transcriptional program, exhibiting a more youthful feeding and fasting response in older age, improved metabolic health and longevity. Accordingly, Prkag1 expression declines with age in human tissues and is associated with multimorbidity and multidimensional frailty risk. Thus, selective activation of AMPKγ1 prevents metabolic quiescence and preserves healthy aging in vertebrates, offering potential avenues for intervention.

The Role of Multidimensional Prognostic Index to Identify Hospitalized Older Adults with COVID-19 Who Can Benefit from Remdesivir Treatment: An Observational, Prospective, Multicenter Study.

BACKGROUND: Data regarding the importance of multidimensional frailty to guide clinical decision making for remdesivir use in older patients with coronavirus disease 2019 (COVID-19) are largely unexplored. OBJECTIVE: The aim of this research was to evaluate if the Multidimensional Prognostic Index (MPI), a multidimensional frailty tool based on the Comprehensive Geriatric Assessment (CGA), may help physicians in identifying older hospitalized patients affected by COVID-19 who might benefit from the use of remdesivir. METHODS: This was a multicenter, prospective study of older adults hospitalized for COVID-19 in 10 European hospitals, followed-up for 90 days after hospital discharge. A standardized CGA was performed at hospital admission and the MPI was calculated, with a final score ranging between 0 (lowest mortality risk) and 1 (highest mortality risk). We assessed survival with Cox regression, and the impact of remdesivir on mortality (overall and in hospital) with propensity score analysis, stratified by MPI = 0.50. RESULTS: Among 496 older adults hospitalized for COVID-19 (mean age 80 years, female 59.9%), 140 (28.2% of patients) were treated with remdesivir. During the 90 days of follow-up, 175 deaths were reported, 115 in hospital. Remdesivir treatment significantly reduced the risk of overall mortality (hazard ratio [HR] 0.54, 95% confidence interval CI 0.35-0.83 in the propensity score analysis) in the sample as whole. Stratifying the population, based on MPI score, the effect was observed only in less frail participants (HR 0.47, 95% CI 0.22-0.96 in propensity score analysis), but not in frailer subjects. In-hospital mortality was not influenced by remdesivir use. CONCLUSIONS: MPI could help to identify less frail older adults hospitalized for COVID-19 who could benefit more from remdesivir treatment in terms of long-term survival.