Older adults represent most patients with cancer, yet geriatric expertise remains underrepresented in oncology practice. This review explores practical strategies to integrate geriatricians throughout the continuum of cancer care, from diagnosis to survivorship and palliative care. We discuss models of interdisciplinary collaboration, optimal timing of geriatric involvement, and innovative solutions to address the global shortage of geriatricians. Evidence demonstrates that comprehensive geriatric assessment enhances treatment tolerance, quality of life, and survival among older adults with cancer [1-5]. Despite widespread endorsement, implementation barriers persist due to workforce limitations, time constraints, and lack of institutional support. Emerging strategies include task-shifting, telehealth-enabled assessments, and education programs that empower oncologists and allied health professionals to apply geriatric principles in daily practice [6-10]. Integrating geriatricians into multidisciplinary oncology teams is essential to deliver equitable, personalized, and value-based care for aging populations. We advocate for structured collaboration models, institutional prioritization of geriatric oncology, and policy-level initiatives that reinforce the indispensable role of geriatricians in modern cancer care.

OBJECTIVES AND BACKGROUND:Older adults with multimorbidity and frailty frequently require palliative care, yet prescribing practices often remain focused on primary or secondary disease prevention rather than symptom relief. Polypharmacy and potentially inappropriate medications (PIMs) may undermine quality of life and alter the benefit-to-harm ratio in this population. This study evaluated the prevalence of polypharmacy, pharmacological prescribing patterns and PIMs in hospitalized older adults requiring palliative care. STUDY DESIGN:This nested study of the Italian multicenter point-prevalence study (Palliative Care 2.0) included patients aged ≥65 years from three metropolitan hospitals and three nursing homes in Genoa, Liguria, Italy. Needs for palliative care were assessed using the NECPAL CCOMS-ICO© tool and those categorized as 'positive' were staged I-III. Polypharmacy (≥5 drugs) and five PIMs were evaluated according to STOPP-Frail criteria. Data were analyzed through appropriate hypothesis tests (Mann-Whitney, Anova, chi-squared) comparing NECPAL positive and negative participants, while associations with number of PIMs were explored through regression analysis. RESULTS:Of 558 patients initially screened, 294 were administered the NECPAL tool, of whom 254 (45.5% of the sample screened) had PC needs (mean age 85 ± 11 years; 61% female). Polypharmacy was reported in 93.9% (276/294), with a median of 9 drugs (IQR 5). PIMs were identified in 68.2% of patients and were strongly associated with polypharmacy (p < 0.001), but were less common in nursing home residents compared with hospital patients (p < 0.001). Drug burden and the prevalence of PIMs did not decline with advancing NECPAL stage, except for increased antidiabetic use in stage III. CONCLUSIONS:Polypharmacy and PIM use are highly prevalent in older adults who require palliative care, persisting even in advanced stages of illness. Current practice appears to fall short of both effective deprescribing and fully aligning pharmacological therapy with goals of care and overall quality of life. Systematic efforts to align pharmacotherapy with patients' care goals and clinical status are essential to minimize harm and promote quality of life in the final stages of life.

BackgroundDespite a shared conceptual framework linking both components to impaired inhibitory control, clinical evidence suggests that facilitatory and oppositional paratonia are not equally related to cognitive deterioration, with facilitatory paratonia showing a stronger association with cognitive impairment. Whether this apparent divergence reflects true neurophysiological differences or arises from limitations intrinsic to clinical assessment remains unclear. Electromyography (EMG)-based assessment offers a direct approach to quantify involuntary muscle activation and reduce measurement-related confounding factors.ObjectiveTo determine whether the reported clinical divergence between facilitatory and oppositional paratonia reflects distinct neurophysiological mechanisms or is primarily driven by measurement-related factors.MethodsEighty-six participants (46 cognitively impaired and 40 cognitively healthy) underwent clinical and EMG-based assessment of paratonia during passive elbow movements. Associations with global cognitive status (Mini-Mental State Examination) and discriminative performance between cognitively impaired and healthy subjects were evaluated.ResultsClinically assessed facilitatory paratonia showed stronger associations with cognitive status and better discriminative performance than oppositional paratonia. In contrast, EMG-based assessment revealed comparable associations with cognitive status and similar discriminative performance for both paratonia components.ConclusionsEMG assessment reveals a neurophysiological convergence between facilitatory and oppositional paratonia, supporting a shared central inhibitory mechanism. Our findings indicate that the apparent clinical distinction between facilitatory and oppositional paratonia does not reflect a true pathophysiological separation, but is largely driven by limitations inherent to clinical assessment. In this context, facilitatory paratonia emerges as the most informative bedside marker of cognitive impairment.

BACKGROUND:Frailty is defined as a state of increased vulnerability to stressors resulting from reduced physiological homeostasis. The need to identify biomarkers capable of offering insight into the biological underpinnings of frailty and supporting early detection, diagnosis, and prognostic evaluation has grown in recent years. Heart rate variability (HRV), defined as the temporal variability between consecutive R waves of the electrocardiogram (R-R intervals), has emerged as a promising physiological biomarker in this context. METHODS:We conducted a narrative review of studies to synthesize evidence on HRV and frailty, examining analytical domains of HRV and situating findings within the current biomarker framework. Relevant literature was assessed across time-domain, frequency-domain, geometric and non-linear measures of HRV, together with reported associations involving clinical, functional and cognitive outcomes. RESULTS:Within the landscape of frailty biomarkers, HRV provides a non-invasive index of autonomic nervous system function. Reduced HRV has been associated with frailty status, diminished physiological reserve, adverse clinical outcomes, and cognitive decline, with particularly notable findings when assessed during physiological challenges rather than at rest. It should be noted, however, that the literature is heterogeneous and methodologically inconsistent, especially regarding recording duration and the specific HRV parameters analysed. CONCLUSIONS:HRV is a highly promising physiological biomarker in the context of frailty, but further research is needed to clarify several aspects of its role. Its potential integration with other biomarkers may help confirm its validity and could contribute to identifying biomarker clusters relevant to personalized approaches.

By 2030, one in six people globally will be over 60, potentially increasing the burden of frailty, a condition characterized by reduced physiological resilience and poor clinical outcomes. Although frailty affects up to 49 % of hospitalized patients, it is frequently under-recognized. Tools like the Clinical Frailty Scale (CFS) and the FI-Lab aim to assess frailty, though each has limitations. This retrospective cohort study evaluated the predictive value of CFS and FI-Lab, separately and in combination, for in-hospital and three-month post-discharge mortality in older adults. The study included 410 hospitalized patients (median age 87) admitted to two geriatric units between 2023 and 2025. Frailty was assessed using the CFS and a 22-item FI-Lab derived from blood tests within 48 h of admission. In-hospital and post-discharge mortality rates were 12.6 % and 24.7 %, respectively. Both FI-Lab and CFS were independently associated with increased mortality risk. A weak correlation between the two tools (r = 0.19, p < 0.001) suggests they capture distinct but complementary aspects of frailty. These findings support the combined use of FI-Lab and CFS for more accurate risk stratification in acutely ill older adults. FI-Lab may reflect acute physiological stress not captured by clinical measures alone, aiding early identification of vulnerable patients. Despite limitations, including modest sample size and lack of adjustment for multimorbidity, this study highlights the potential utility of integrating lab-based frailty assessments into routine hospital care for personalized geriatric management.

Frailty, reflecting diminished physiological reserve, may influence how Alzheimer's disease (AD) pathology manifests. This study evaluated the prognostic relevance of frailty in mild cognitive impairment due to AD (MCI-AD). 50 patients underwent frailty assessment using the Clinical Frailty Scale (CFS), with multimorbidity, polypharmacy, and cognition (Mini-Mental State Examination, MMSE) recorded. Participants (median age 74 years; 76% women) exhibited low frailty (median CFS 3). Higher CFS scores correlated with lower baseline MMSE and faster annual decline. In adjusted analyses, CFS independently predicted both poorer cognition and steeper decline, whereas CSF P-tau did not. Frailty thus provides complementary prognostic information to biomarkers in the early stages of AD.

Abstract Elevated levels of the NAD+-generating enzyme nicotinamide phosphoribosyltransferase (NAMPT) are a common feature across numerous cancer types. Accordingly, we previously reported pervasive NAD+ dysregulation in multiple myeloma (MM) cells in association with upregulated NAMPT expression. Unfortunately, albeit being effective in preclinical models of cancer, NAMPT inhibition has proven ineffective in clinical trials because of the existence of alternative NAD+ production routes using NAD+ precursors other than nicotinamide. Here, by leveraging mathematical modeling approaches integrated with transcriptome data, we defined the specific NAD+ landscape of MM cells and established that the Preiss-Handler pathway for NAD+ biosynthesis, which uses nicotinic acid as a precursor, supports NAD+ synthesis in MM cells via its key enzyme nicotinate phosphoribosyltransferase (NAPRT). Accordingly, we found that NAPRT confers resistance to NAD+-depleting agents. Transcriptomic, metabolic, and bioenergetic profiling of NAPRT-knockout (KO) MM cells showed these to have weakened endogenous antioxidant defenses, increased propensity to oxidative stress, and enhanced genomic instability. Concomitant NAMPT inhibition further compounded the effects of NAPRT-KO, effectively sensitizing MM cells to the chemotherapeutic drug, melphalan; NAPRT added-back fully rescues these phenotypes. Overall, our results propose comprehensive NAD+ biosynthesis inhibition, through simultaneously targeting NAMPT and NAPRT, as a promising strategy to be tested in randomized clinical trials involving transplant-eligible patients with MM, especially those with more aggressive disease.

Background/Objectives: The Rapid Geriatric Assessment (RGA) is a tool designed to screen for frailty, sarcopenia, anorexia related to aging, and cognitive impairment. This study aimed to translate and validate the RGA for use among Italian community-dwelling older adults. Methods: This cross-cultural study involved 100 community-dwelling older adults randomly recruited through convenience sampling from general practitioner offices in Genoa (Italy), between January and June 2019. The RGA includes the Simple FRAIL Questionnaire Screening Tool, SARC-F Screening for Sarcopenia, Simplified Nutritional Assessment Questionnaire (SNAQ), and Rapid Cognitive Screening (RCS). These were validated against gold-standard tools: the Abbreviated Comprehensive Geriatric Assessment (aCGA) and Multidimensional Prognostic Index (MPI). Additional assessments included the Timed Up and Go (TUG) and Handgrip test. The validation process included forward–backward translation, synthesis, and consensus by independent reviewers. Psychometric properties, internal consistency (Cronbach alpha), and validity correlations were analyzed. Results: The RGA demonstrated satisfactory psychometric properties, with internal consistency (Cronbach alpha = 0.59) and significant validity correlations (RGA and aCGA, rho = 0.34, p = 0.001; RGA and MPI, rho = 0.49, p < 0.001). Discriminant validity was confirmed by significant correlations between specific subitems and reference measures: FRAIL with TUG (p < 0.05), SARC-F with Handgrip strength (p = 0.013), SNAQ with BMI, and RCS with MMSE (p < 0.001). Conclusions: The Italian version of the RGA is a reliable screening tool for geriatric syndromes in community-dwelling older adults. While it does not replace a CGA, the RGA may identify individuals who may benefit from further evaluation using a complete CGA.

Background/Objectives: Multiple myeloma (MM) is a plasma cell neoplasm predominantly diagnosed in older adults. However, the significance of defining patient frailty, as well as identifying the most suitable and reliable tools for its assessment, remains to be firmly established. Methods: This retrospective observational study investigated 36 patients aged 65 or older who underwent Comprehensive Geriatric Assessment (CGA). The average patient age was 76 (SD 6.22), with 33.3% being female. Patients were evaluated using the International Myeloma Working Group Frailty Index (IMWG-FI) and the 40-item Rockwood's Frailty Index (FI) at the Oncogeriatrics clinic of the IRCCS Polyclinic San Martino Hospital, Genoa, Italy between December 2017 and August 2021. Laboratory, cancer-specific, demographic, and clinical variables were collected. Survival analysis and frailty comparison were conducted using Stata version 17.0. Results: Stepwise multivariate analysis identified the Numerical Rating Scale (NRS) (HR 1.40, 95% CI 1.09-1.78, p = 0.008) and Rockwood's Frailty Index (FI) (HR 2.23, 95% CI 1.29-3.87, p = 0.004) as significant prognostic predictors, adjusted for sex, ISS stage, and multimorbility. Comparison between Rockwood's FI and IMWG-FI using Spearman correlation coefficient showed no statistically significant correlation (r = 0.268, p = 0.114). Multivariate Cox model, adjusting for sex, International Staging System (ISS) stage, and Cumulative Illness Rating Scale (CIRS) comorbidity index demonstrated the superior predictive ability of Rockwood's FI over IMWG-FI (C-index 0.775 vs. 0.749). Conclusions: The 40-item Rockwood FI emerges as a valuable tool for prognostication in old MM patients, demonstrating non-inferiority to the traditional IMWG-FI in predictive accuracy, emphasizing the importance of a comprehensive approach considering both disease-specific and patient-related factors.

To investigate the independent and combined impact of pressure ulcers (PU) and frailty on long-term survival in hospitalized older adults. Both PU and frailty were independently associated with increased long-term mortality. Each one-point increase in the Clinical Frailty Scale was linked to a 53

In recent years, there has been a significant change in the type of patients referred to memory clinics, characterized by an increase in mildly symptomatic individuals and potentially even healthy people at risk of cognitive decline due to Alzheimer's disease and other neurodegenerative diseases in this context. Additionally, there is growing interest in developing health services focused on brain health throughout the lifespan, particularly within a primary prevention framework. This effort has led to proposing dedicated "brain health services" for dementia risk reduction. However, in the context of cognitive disorders, distinguishing between primary and secondary prevention poses significant challenges, particularly in identifying individuals within the general population who may exhibit subtle cognitive decline or early-stage neurodegeneration. We propose seven key dimensions for assessing "brain health": cognitive reserve along with social and functional status, cognitive decline, mood and sleep disorders, general dementia risk factors, geriatric syndromes in older adults, structural brain damage, and neurodegenerative proteinopathies. Together, these dimensions form a comprehensive "brain health chart". We review the known evidence for each dimension's role in assessing brain health, emphasizing approaches that can be applied in a community setting. We believe that by identifying broadly applicable assessment methods for these dimensions, the development of personalized strategies for maintaining brain health could be facilitated.

Introduction:Cognitive reserve (CR) is a multidimensional construct based on lifelong engagement in cognitively stimulating domains, including education, occupation and leisure activities, that plays a crucial role in mitigating the presentation of dementia. To date, the contribution of each CR subdomain in the development of dementia is under-investigated. This study is aimed at assessing the association of CR subdomains with cognitive status, accounting for sex and age in an old-age population. Methods:317 older adults were recruited with a diagnosis of subjective cognitive impairment, mild cognitive impairment, and dementia due to Alzheimer's disease or mixed-type dementia. Cognitive Reserve Index questionnaire (CRIq) was used to assess CR. Patients were stratified based on sex and dementia staging (CDR). Significant variables from univariate analysis entered a multivariate ordinal regression model, using CDR as the dependent variable. Results:The results showed that the leisure activities subdomain was the main determinant of cognitive status (OR 0.90, 95%CI 0.82-1.00, p = 0.003); CR and sex did not show any interaction. Discussion:Unlike education and occupation, leisure activities may be considered a lifelong, dynamic contributor to CR. These findings highlight the importance of refining CR assessment, with particular attention to leisure activities as a potentially modifiable target for dementia prevention.

Purpose: In recent times, growing uncertainty has emerged regarding the effectiveness of standard pressure ulcer (PU) risk assessment tools, which are suspected to be no better than clinical judgment, especially in the frail and comorbid elderly population. This study aimed to identify the primary clinical predictive variables for PU development and severity in hospitalized older adults, utilizing a multidimensional frailty assessment, and compare them with the Braden scale. Patients and methods: The population consisted of 316 patients, admitted to the Geriatric Unit and Transitional Care of San Bartolomeo Hospital in Sarzana (Italy) during the period 21/02/22-01/07/22. The collected information included both anamnestic and laboratory data. A comprehensive geriatric assessment was performed, including also anthropometric and physical performance measurements. Multivariate logistic analysis was used, both in a binary classification test and in the subsequent ordinal classification test of severity levels. The final performance of the model was assessed by ROC curve estimation and AUC comparison with the Results: Within the population, 152 subjects (48%) developed PU at different levels of severity. The results showed that age, Braden scale (subscales of mobility and friction/shear), Barthel scale, Mini Nutritional Assessment, hemoglobin, and albumin are predictors associated with the development of PU (AUC 85%). The result is an improvement over the use of the Braden scale alone (AUC 75%). Regarding the identification of predictive factors for PU severity, 4AT also emerges as potentially relevant. Conclusion: Assessing the subject's nutritional status, physical performance, and functional autonomies enables the effective integration of the Braden scale in identifying patients most susceptible to developing PU. Our findings support the integration of a comprehensive set of methodologically robust frailty determinants into traditional risk assessment tools. This integration reflects the mutual interplay between patients' frailty, skin frailty, and PU development in very old hospitalized patients.

Purpose. Hip fractures in older adults are a major challenge for public health, it is associated with increased morbidity and mortality, especially in frailty older adults. An accurate evaluation of preventable perioperative risk factors is essential to optimize care pathways and clinical outcomes. This study aims to gauge evidence on the predictive accuracy of perioperative variables, including the Nottingham Hip Fracture Score (NHFS), on overall long-term survival (OS) in frail, hospitalized hip-fractured older adults. Methods. From March 2020 to September 2021, 433 elderly patients with hip fractures received multidisciplinary orthogeriatric care in Policlinic San Martino Hospital (Genova, Italy). Enrolled patients received geriatric assessment (CGA) within 24 hours from hospital admission and their medical conditions were assessed alongside post-operative complications and survival rates. Statistical analyses, including Cox models, evaluated factor influencing overall survival. Results. The patients' most prevalent clinical phenotype was frailty, sustained by loss of muscle strength, malnutrition and functional disability. This phenotype reflects the unique demographic of the Liguria region (Italy) with the highest proportion of oldest-old (>= 85 years) and frail individuals in the nation. Results showed NHFS > 5, vitamin D deficiency and delayed verticalization as key predictive determinants of long-term mortality (up to 21 months). Resilience to perioperative stressors in frail hip-fractured patients is crucial to the success of treatments aimed at improving their physical recovery. Conclusions. Our research showed that targeting preventable factors during surgery can greatly impact the functional reserve of frail elderly patients, influencing their recovery and long-term outcomes, including mortality rates.

In the past the right ventricle (RV) has been traditionally regarded as a simple conduit between the venous system and the pulmonary circulation and it has aroused little interest in both clinical and echocardiographic cardiologists to such an extent that it has been defined as the "forgotten chamber." Subsequently it was clearly shown that the right heart (RH) plays an important physiologic role in cardiac activity, and that congenital or acquired alterations in its structure and function have an important prognostic value. Aim of this review is to shed the light on the echocardiographic approach to this cardiac chamber. In this narrative review we critically explored the most recent literature on this topic using PubMed and Medline and examining the most recent guidelines on the echocardiographic approach to the RV. Echocardiographic approach to RV presents some technical difficulties, which stem from the position of the RV inside the thorax and around the LV and from its particular anatomy, which precludes geometric assumptions. However, RV may now be evaluated quantitatively and qualitatively in many ways, and some new methods can partially overcome some of the limits imposed by its complex anatomy, thereby yielding a quantitative evaluation. Furthermore, due to the wide range of pathologies which may involve the RV a disease-oriented approach should be considered in the echocardiographic investigation of right heart disease.

The addiction of tumors to elevated nicotinamide adenine dinucleotide (NAD+) levels is a hallmark of cancer metabolism. Obstructing NAD+ biosynthesis in tumors is a new and promising antineoplastic strategy. Inhibitors developed against nicotinamide phosphoribosyltransferase (NAMPT), the main enzyme in NAD+ production from nicotinamide, elicited robust anticancer activity in preclinical models but not in patients, implying that other NAD+-biosynthetic pathways are also active in tumors and provide sufficient NAD+ amounts despite NAMPT obstruction. Recent studies show that NAD+ biosynthesis through the so-called “Preiss-Handler (PH) pathway”, which utilizes nicotinate as a precursor, actively operates in many tumors and accounts for tumor resistance to NAMPT inhibitors. The PH pathway consists of three sequential enzymatic steps that are catalyzed by nicotinate phosphoribosyltransferase (NAPRT), nicotinamide mononucleotide adenylyltransferases (NMNATs), and NAD+ synthetase (NADSYN1). Here, we focus on these enzymes as emerging targets in cancer drug discovery, summarizing their reported inhibitors and describing their current or potential exploitation as anticancer agents. Finally, we also focus on additional NAD+-producing enzymes acting in alternative NAD+-producing routes that could also be relevant in tumors and thus become viable targets for drug discovery.

Background: As the population ages, the concept of frailty becomes increasingly relevant and may be considered a precursor between aging and the development of dementia in later life. Similarly, the construct of cognitive reserve (CR) is an accepted model of cognitive resilience that may account for individual differences in trajectories of brain aging, mitigating the clinical expression of dementia. Objective: We aim to estimate the role of CR and frailty in moderating the prediction of dementia in the population aged over 80 who are attending an Italian outpatient memory clinic. Methods: Comprehensive Geriatric Assessment, Clinical Frailty Scale (CFS) to screen for frailty, and Cognitive Reserve Index questionnaire (CRIq) to evaluate CR, were used to assess patients systematically. We performed multivariate logistic regression to assess associations with dementia. Model performance and interaction between frailty and cognitive reserve were then evaluated. Results: 166 patients were consecutively enrolled (mean age was 85.7 years old, females composed 68%); 25% had a diagnosis of amnestic mild cognitive impairment, and 75% had a diagnosis of dementia. Multivariate regression analysis showed that CRIq and CFS were the main clinical assessment tools associated with the presence of dementia, even after collinearity adjustment. No significant interaction of CFS*CRIq was found. Conclusions: To our knowledge, this is the first study to investigate the association between CR, frailty, dementia, and their related interacting terms in a real-world population of very old patients. Our findings may suggest that both CR and frailty shape an individual’s resilience throughout their lifetime. This may potentially counteract the effects of brain neuropathology, in line with the hypothesis that meaningful associations exist between CR, frailty, and cognition in later life.