Background: Acute sarcopenia refers to the swift decline in muscle function and mass following acute events such as illness, surgery, trauma, or burns that presents significant challenges in hospitalized older adults. Methods: narrative review to describe the mechanisms and management of acute sarcopenia. Results: The prevalence of acute sarcopenia ranges from 28% to 69%, likely underdiagnosed due to the absence of muscle mass and function assessments in most clinical settings. Systemic inflammation, immune–endocrine dysregulation, and anabolic resistance are identified as key pathophysiological factors. Interventions include early mobilization, resistance exercise, neuromuscular electrical stimulation, and nutritional strategies such as protein supplementation, leucine, β-hydroxy-β-methyl-butyrate, omega-3 fatty acids, and creatine monohydrate. Pharmaceuticals show variable efficacy. Conclusions: Future research should prioritize serial monitoring of muscle parameters, identification of predictive biomarkers, and the involvement of multidisciplinary teams from hospital admission to address sarcopenia. Early and targeted interventions are crucial to improve outcomes and prevent long-term disability associated with acute sarcopenia.

Background: Coronavirus disease (COVID-19) is correlated with a variety of long-term sequelae that affect different aspects of health, including physical function. This study investigated the longitudinal changes in handgrip strength (HGS) over six months post-hospital discharge in COVID-19 patients and explores the associations between HGS, health-related quality of life, dyspnoea, exercise capacity, and body mass index (BMI). Methods: Adult COVID-19 patients were followed up at one, three, and six months after hospital discharge. HGS, BMI, exercise capacity, and health-related quality of life were assessed. Data from patients with HGS measurements at all three time points were analysed. Results: Low HGS was prevalent one month post-discharge (35%). Participants with low HGS exhibited more severe disease (30.5% vs. 5.9% were admitted to the intensive care unit, p < 0.01), longer hospital stays (median [IQR] 21 [10.0; 40.5] vs. 12.0 [8.0; 20.0] days, p < 0.01), greater weight loss (−5.7 [−9.1; −0.6] vs. −3.2 [−5.7; −0.0] kg, p = 0.004), and reduced exercise capacity (6 min walking test [6 MWT], 95.7 [84.0; 102.0] vs. 100.0 [92.9; 105.0]% predicted, p = 0.007). Those with persistently low HGS (40% of the initial low HGS group) had worse exercise capacity (6-MWT 93.3 [78.3; 101.0] vs. 101.0 [95.0; 107.0]% predicted, p < 0.001), more dyspnoea (29.0% vs. 2.0% of participants, p < 0.001), poorer quality of life (visual analogue scale score, 75 [50; 75] vs. 85 [75; 95], p < 0.001), and higher rates of problems in various health dimensions. HGS at 1 month was the only significant predictor of HGS improvement from 1 month to 6 months (odds ratio [95% CI] 1.11 [1.03; 1.20], p = 0.008). Conclusions: This study highlights the prevalence of reduced physical function among COVID-19 survivors and emphasises the importance of early identification and intervention to optimise their long-term health. Monitoring HGS, a simple and reliable tool, can provide valuable insights into patients’ overall physical function, aiding in tailored care and improved outcomes.

Background: Adverse drug reactions (ADRs) represent a major and often underestimated source of morbidity, hospitalization, and functional decline in older adults. The convergence of age-related pharmacokinetic and pharmacodynamic changes, multimorbidity, polypharmacy, and frailty creates a clinical environment in which ADR risk is not static but evolves along progressive trajectories—from mild, early manifestations toward severe, potentially irreversible outcomes. Understanding these trajectories is essential for rational geriatric prescribing. Methods: This narrative review synthesizes evidence from epidemiological studies, systematic reviews, Cochrane analyses, and clinical trials published between 2000 and 2025, focusing on adults aged 65 years and older with two or more chronic conditions. Sources were identified through a structured, non-systematic literature search of PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus using the terms ‘adverse drug reactions’, ‘polypharmacy’, ‘multimorbidity’, ‘frailty’, ‘deprescribing’, and ‘pharmacokinetics’ in older adults, alone and in combination. Evidence quality was assessed narratively, distinguishing trial evidence from observational and expert consensus data. Results: ADRs in older adults are best classified using complementary frameworks—the augmented Type A to withdrawal Type E and failure-of-therapy Type F taxonomy (Types A–F), the Dose-Time-Susceptibility (DoTS) classification, and the EIDOS mechanistic scheme—which together capture the heterogeneity of drug-related harm in this population. Age-related pharmacokinetic changes (altered absorption, increased volume of distribution of lipophilic drugs, reduced hepatic and renal clearance) and pharmacodynamic shifts (heightened receptor sensitivity, baroreflex impairment, increased blood–brain barrier permeability) interact with polypharmacy and frailty to amplify ADR trajectories from mild to severe. Anticholinergic burden, prescribing cascades, and inappropriate polypharmacy function as structural accelerators of these trajectories. Medication review and deprescribing improve prescribing quality but evidence for hard outcome benefits remains of low to very low certainty. Emerging AI-enabled digital tools show promising accuracy for identifying frailty and pharmacological vulnerability, but this performance relates to frailty classification and has not yet been shown to prevent ADR trajectories; they require validation for routine clinical use. Conclusions: Recognizing ADRs in older adults as dynamic trajectories rather than isolated events repositions prescribing review and deprescribing from optional to essential clinical acts. An integrated approach combining pharmacological vigilance, comprehensive geriatric assessment, structured deprescribing, and emerging digital decision-support tools offers the most realistic pathway to reduce the trajectory-related burden of drug-related harm in complex older patients.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome driven by frequent coexistence of cardio-renal-metabolic comorbidities. It has growing epidemiological relevance as global populations age. At its pathophysiological core lies a state of chronic systemic inflammation, coronary microvascular dysfunction and myocardial remodelling, a cascade where epicardial adipose tissue plays a pivotal amplifying role. This complexity is driving a fundamental shift in HFpEF management towards integrated cardiometabolic targeting. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the dual GLP1/glucose-dependent insulinotropic polypeptide (GIP)-RA tirzepatide have emerged as compelling multi-system agents, simultaneously addressing several key pathophysiological drivers of the syndrome with consistent improvements in symptoms, functional capacity and clinical outcomes. Nevertheless, questions remain regarding the long-term impact on cardiovascular outcomes, consequences of discontinuing treatment and the potential loss of muscle mass. This review examines the pathophysiological basis of HFpEF within the cardio-renal-metabolic continuum, appraising the clinical evidence, benefits and limitations of GLP-1RAs in HFpEF and discussing future directions including phenotype-directed therapy, mechanism-based combination strategies and next-generation molecules.

Aim: Dyslipidemia encompasses various forms of lipid abnormalities and represents a central component of metabolic syndrome. The relationship between dyslipidemia subtypes and broader metabolic profiles is poorly characterized in modern populations. This study provides a comprehensive metabolic characterization of patients presenting with distinct dyslipidemic patterns – low high-density lipoprotein cholesterol (HDL-c) and elevated low-density lipoprotein cholesterol (LDL-c) – at a dedicated tertiary-center outpatient clinic. Methods: Patients evaluated at the Metabolic Health Clinic of San Raffaele Hospital, Milan, between January 2023 and October 2024, were included. Medical history, anthropometrics (i.e. body mass index, BMI, and waist circumference), serum lipids and liver enzymes were recorded. Patients with low HDL-c or high LDL-c, as defined according to current guidelines, were compared to patients with normal values. Network analysis identified patient distinct metabolic clusters. Results: A total of 496 individuals were included. Patients with low HDL-c levels (n=193, 38.9%) exhibited higher BMI (28.6 vs 25.6 kg/m², p<0.001), waist circumference (100.0 vs 94.0 cm, p<0.001), ALT levels (28.0 vs. 23.0 U/L, p<0.001), and triglycerides (146.0 vs. 99.0 mg/dL, p<0.001), and a greater prevalence of fatty liver disease (33% vs. 21%, p 0.006) and arterial hypertension (51% vs. 39%, p 0.012) than those with normal HDL-c levels. HDL-c showed significant inverse correlations with both BMI (R coefficient -0.272, p<0.0001) and waist circumference (R coefficient -0.325, p<0.0001). Network analysis highlighted strong associations among HDL-c, triglycerides, ALT levels, BMI, and waist circumference. Conversely, high LDL-c levels, found in 382 (77%) patients, showed no association with metabolic parameters. Conclusions: Low HDL-c was associated with obesity, central adiposity, hypertriglyceridemia, and fatty liver disease. In striking contrast, LDL-c appears to be independent of these metabolic alterations. These findings underscore the interconnectedness of HDL-c with the metabolic landscape, while emphasizing the importance of assessing LDL-c levels regardless of patient anthropometrics and metabolic phenotype.