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Background. Results regarding the associations between hypertension-related parameters and physical performance in older adults are conflicting. A possible explanation for these divergent results is that investigations may not have adjusted their analyses according to the use of angiotensin-converting enzyme inhibitors (ACEIs). Objectives. To examine the associations between hypertension-related parameters, ACEI use, and a set of physical performance tests in very old adults. Design. Cross-sectional study from the ilSIRENTE database. Setting. Mountain community of the Sirente geographic area (L’Aquila, Abruzzo, Italy). Participants. All persons born in the Sirente area (13 municipalities) before 1 January 1924 and living in that region at the time of study were identified and invited to participate. The final sample included 364 older adults (mean age: 85.8 ± standard deviation [SD] 4.8). Measurements. Physical performance was assessed using isometric handgrip strength (IHG), walking speed (WS) at normal and fast pace, 5-time sit-to-stand test (5STS), and muscle power measures. Blood pressure (BP) was measured after 20 to 40 min of rest, while participants sat in an upright position. Drugs were coded according to the Anatomical Therapeutic and Chemical codes. ACEIs were categorized in centrally (ACEI-c) and peripherally (ACEI-p) acting. Blood inflammatory markers, free insulin-like growth factor 1 (IGF-1), and IGF-binding protein 3 (IGFBP-3) were assayed. Results. Results indicated that 5STS test was significantly and negatively associated with diastolic BP values. However, significance was lost when results were adjusted for ACEI use. Participants on ACEIs were more likely to have greater specific muscle power and higher blood levels of IGFBP-3 than non-ACEI users. When participants were categorized according to ACEI subtypes, those on ACEI-p had higher blood IGF-1 levels compared with ACEI-c users. Conclusions. The main findings of the present study indicate that

Sarcopenia has a complex pathophysiology that encompasses metabolic dysregulation and muscle ultrastructural changes. Among the drivers of intracellular and ultrastructural changes of muscle fibers in sarcopenia, mitochondria and their quality control pathways play relevant roles. Mononucleated muscle stem cells/satellite cells (MSCs) have been attributed a critical role in muscle repair after an injury. The involvement of mitochondria in supporting MSC-directed muscle repair is unclear. There is evidence that a reduction in mitochondrial biogenesis blunts muscle repair, thus indicating that the delivery of functional mitochondria to injured muscles can be harnessed to limit muscle fibrosis and enhance restoration of muscle function. Injection of autologous respiration-competent mitochondria from uninjured sites to damaged tissue has been shown to reduce infarct size and enhance cell survival in preclinical models of ischemia–reperfusion. Furthermore, the incorporation of donor mitochondria into MSCs enhances lung and cardiac tissue repair. This strategy has also been tested for regeneration purposes in traumatic muscle injuries. Indeed, the systemic delivery of mitochondria promotes muscle regeneration and restores muscle mass and function while reducing fibrosis during recovery after an injury. In this review, we discuss the contribution of altered MSC function to sarcopenia and illustrate the prospect of harnessing mitochondrial delivery and restoration of MSCs as a therapeutic strategy against age-related sarcopenia.

Sarcopenia is an age-related neuromuscular disease characterized by substantial muscle atrophy, dynapenia and/or loss of physical function. Sarcopenia progression increases the risk for numerous negative events, including falls, disability, hospitalization, nursing home placement, and death. As such, this condition is recognized as an important topic in gerontology and geriatrics. The best approach to counteract the development and progression of sarcopenia is actively debated. Resistance training (RT) has received special attention in this context, owing to the large number of studies showing its ability to produce significant improvements in sarcopenia-related parameters. Recommendations to guide RT prescription for older adults with different conditions, including people who have traits of sarcopenia, have been published. Some authors have argued that RT guidelines for older adults are similar to one another, which may indicate that the presence of sarcopenia does not require specific physical exercise programs. However, older people with sarcopenia might present with peculiar physical, biomechanical, physiological, and psychosocial characteristics that, in our view, are not taken into adequate consideration in existing exercise guidelines. Here, we present evidence to support the view that RT prescription for older adults with sarcopenia is complex, multifactorial, and still needs more evidence.

Aging induces substantial remodeling of glia, including density, morphology, cytokine expression, and phagocytic capacity. Alterations of glial cells, such as hypertrophy of lysosomes, endosomes and peroxisomes, and the progressive accumulation of lipofuscin, lipid droplets, and other debris have also been reported. These abnormalities have been associated with significant declines of microglial processes and reduced ability to survey the surrounding tissue, maintain synapses, and recover from injury. Similarly, aged astrocytes show reduced capacity to support metabolite transportation to neurons. In the setting of reduced glial activity, stressors and/or injury signals can trigger a coordinated action of microglia and astrocytes that may amplify neuroinflammation and contribute to the release of neurotoxic factors. Oxidative stress and proteotoxic aggregates may burst astrocyte-mediated secretion of pro-inflammatory cytokines, thus activating microglia, favoring microgliosis, and ultimately making the brain more susceptible to injury and/or neurodegeneration. Here, we discuss the contribution of microglia and astrocyte oxidative stress to neuroinflammation and neurodegeneration, highlight the pathways that may help gain insights into their molecular mechanisms, and describe the benefits of antioxidant supplementation-based strategies.

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Purpose: Hip fracture is a public health problem worldwide. Traditional prognostic models do not include blood biomarkers, such as those obtained by proteomics. This study aimed to investigate the relationships between serum inflammatory biomarkers and frailty in older adults with hip fracture as well as adverse outcomes at one and three months after discharge. Methods: A total of 45 patients aged 75 or older who were admitted for hip fracture were recruited. At admission, a Comprehensive Geriatric Assessment (CGA) was conducted, which included a frailty assessment using the Clinical Frailty Scale (CFS). Blood samples were collected before surgery. Participants were followed up at one and three months after discharge. The levels of 45 cytokines were analyzed using a high-throughput proteomic approach. Binary logistic regression was used to determine independent associations with outcomes, such as functional recovery, polypharmacy, hospital readmission, and mortality. Results: The results showed that IL-7 (OR 0.66 95% CI 0.46-0.94, p = 0.022) and CXCL-12 (OR 0.97 95% CI 0.95-0.99, p = 0.011) were associated with better functional recovery at three months after discharge, while CXCL-8 (OR 1.07 95% CI 1.01-1.14, p = 0.019) was associated with an increased risk of readmission. Conclusions: These findings suggest that immunology biomarkers may represent useful predictors of clinical outcomes in hip fracture patients.

Background: COVID-19 has disproportionately affected older adults. Yet, healthcare trajectories experienced by older persons hospitalized for COVID-19 have not been investigated. This study aimed at estimating the probabilities of transitions between severity states in older adults admitted in COVID-19 acute wards and at identifying the factors associated with such dynamics. Methods: COVID-19 patients aged ≥60 years hospitalized between March and December 2020 were involved in the multicentre GeroCovid project–acute wards substudy. Sociodemographic and health data were obtained from medical records. Clinical states during hospitalization were categorized on a seven-category scale, ranging from hospital discharge to death. Based on the transitions between these states, first, we defined patients’ clinical course as positive (only improvements), negative (only worsening), or fluctuating (both improvements and worsening). Second, we focused on the single transitions between clinical states and estimated their probability (through multistage Markov modeling) and associated factors (with proportional intensity models). Results: Of the 1024 included patients (mean age 78.1 years, 51.1% women), 637 (62.2%) had a positive, 66 (6.4%) had a fluctuating, and 321 (31.3%) had a negative clinical course. Patients with a fluctuating clinical course were younger, had better mobility and cognitive levels, fewer diseases, but a higher prevalence of cardiovascular disease and obesity. Considering the single transitions, the probability that older COVID-19 patients experienced clinical changes was higher within a 10-day timeframe, especially for milder clinical states. Older age, male sex, lower mobility level, multimorbidity, and hospitalization during the COVID-19 first wave (compared with the second one) were associated with an increased probability of progressing towards worse clinical states or with a lower recovery. Conclusion: COVID-19 in older inpatients has a complex and dynam

The present study was conducted to test the association between protein intake and blood pressure, glucose levels, and blood cholesterol in a large sample of Italian older adults. Longevity Check-up 7+ (Lookup 7+) is an ongoing project that started in June 2015. The project is conducted in unconventional settings (e.g., exhibitions, malls, health promotion campaigns) across Italy with the aim of fostering adoption of healthy lifestyles in the general population. For the present study, participants were eligible if they were 65+ years and provided written informed consent. Systolic (SBP) and diastolic blood pressure (DBP), and blood glucose and cholesterol levels were assessed. Protein intake was estimated using a 12-item food frequency questionnaire. Three-thousand four-hundred and four older adults were included in the study. The results of the linear regression showed an inverse association between protein intake (as a continuous variable) and DBP, and a positive correlation with blood cholesterol levels. The findings of the present study indicate that a high intake of protein was negatively associated with DBP and positively associated with total blood cholesterol levels in a large cohort of Italian older adults, after adjustment for numerous covariates.

Muscle strength is a relevant metric of aging. Greater adherence to Mediterranean diet is associated with better health outcomes across all life stages; however, evidence on the relationship between Mediterranean diet and muscle strength in older adults is inconclusive. In this study, we evaluated the relationship between adherence to Mediterranean diet and handgrip strength in a large sample of community-dwelling older adults from the Longevity Check-up 7+ project. A total of 2963 participants (mean age 72.8 +/- 5.7 years; 54.4% women) were analyzed. Mediterranean diet adherence was evaluated using a modified Medi-Lite score and categorized as low (<= 8), good (9 to 11), or high (>= 12). Handgrip strength was categorized as normal or low according to cut-points by the European Working Group on Sarcopenia in Older People 2. Older adults with lower Mediterranean diet adherence had a significantly higher prevalence of probable sarcopenia (25.9%) than those with good (19.1%) or high (15.5%) adherence. The proportion of participants with probable sarcopenia increased with age, but it remained lower in the good and high adherence groups. Logistic regression showed that greater Mediterranean diet adherence was associated with a lower risk of probable sarcopenia. Older age, female sex, and physical inactivity were associated with a greater risk of probable sarcopenia. Our findings emphasize the positive association between healthy lifestyles, including adherence to Mediterranean diet, and physical function in old age.

Introduction: Arginine metabolism is involved in the regulation of several biological processes. Many liquid chromatography tandem-mass spectrometry methods for the determination of arginine and its metabolites have been developed but they are time consuming and imply long pre-analytical procedures. The purpose of this study was to develop a rapid method for the simultaneous determination of arginine, citrulline, ornithine, symmetric and asymmetric dimethylarginine and monomethylarginine in human plasma. Materials and methods: The pre-analytical procedure consisted in a simple deproteinization. The chromatographic separation was performed using hydrophilic interaction liquid chromatography. Analytes detection was performed with a triple quadrupole equipped with electrospray ion source operating in positive ion mode. Mass spectrometry experiments were conducted in multiple reaction monitoring mode. Results and conclusions: Recovery ranged from 92.2 to 108.0%. The within-run imprecision and between-run imprecision ranged from 1.5 to 6.8 % and 3.8 to 11.9%, respectively. Carry over and matrix effect did not affect quantitative analysis. Extraction recovery was between 95 and 105 %. Stability after pre-analytical procedure was tested and all the metabolites were stable after 48 h at 4 °C. In conclusion, our novel method allow a rapid and easy determination of arginine and its metabolites both for research and clinical routine use.

Background-Analgesics could be used to manage painful symptoms during and after COVID-19. Materials and methods-Persistence of painful symptoms was assessed during and after COVID-19 in a sample of patients admitted to a post-acute COVID-19 outpatient service in Rome, Italy. Data on type and frequency of use of first-line analgesics were collected. Pain severity was evaluated with a numeric rating scale (NRS) from 0 to 10. Results-Mean age of 696 participants was 57.1 ± 20.3 years and 61.7% were women. During COVID-19, the most prevalent symptoms were fever, fatigue, arthralgia, myalgia and headache. Acetaminophen was used by 40% of the sample. Only 6.7% needed to continue analgesic therapy after COVID-19. Frequent causes of analgesics consumption were persistent arthralgia and myalgia. The most common analgesics used amongst those who continued taking analgesics in the post-acute phase of COVID-19 were the following: acetaminophen (31%), ibuprofen (31%) and other non-steroidal anti-inflammatory drug (NSAID) (29.5%); in older subjects the most common analgesic used was acetaminophen (54%). Most of the subjects in this group said there was an improvement in pain perception after taking analgesic therapy (84%). Conclusions-Use of analgesics in the post-acute COVID-19 is common in subjects with persistent arthralgia and myalgia, and common analgesics were acetaminophen and ibuprofen. Further research on the safety and efficacy of those medications in COVID-19 is warranted.

Background: The present study was conducted to explore the association between protein intake across the main meals and hypertension (HTN)-related parameters in community-dwelling Brazilian older adults. Methods: Brazilian community-dwelling older adults were recruited in a senior center. Dietary habits were assessed through 24 h recall. Protein intake was classified as high and low according to median and recommended dietary allowance values. Absolute and body weight (BW)–adjusted protein consumption levels were quantified and analyzed according to ingestion across the main meals. Systolic (SBP) and diastolic blood pressure (DBP) were measured using an oscilometric monitor. Participants were categorized as hypertensive according to physician diagnosis or the detection of high SBP and/or DBP values. Results: One hundred ninety-seven older adults were enrolled in the present study. Protein intake at lunch was independently and negatively associated with SBP. Furthermore, a lower prevalence of HTN (diagnosed by a physician) was observed in participants with higher intakes of protein. These results remained significant after adjustment for many covariates. However, significance was lost when kilocalories and micronutrients were included in the model. Conclusions: Findings of the present study indicate that protein intake at lunch was independently and negatively associated with systolic BP in community-dwelling older adults.

Background: Ageing is accompanied by a progressive loss of skeletal muscle mass and strength, potentially determining the insurgence of sarcopenia. Evidence suggests that motoneuron and neuromuscular junction (NMJ) degeneration contribute to sarcopenia pathogenesis. Seeking for strategies able to slow down sarcopenia insurgence and progression, we investigated whether a 2-year mixed-model training involving aerobic, strength and balance exercises would be effective for improving or preserving motoneuronal health and NMJ stability, together with muscle mass, strength and functionality in an old, sarcopenic population. Methods: Forty-five sarcopenic elderly (34 females; 11 males) with low dual-energy X-ray absorptiometry (DXA) lean mass and Short Physical Performance Battery (SPPB) score <9 were randomly assigned to either a control group [Healthy Aging Lifestyle Education (HALE), n = 21] or an intervention group [MultiComponent Intervention (MCI), n = 24]. MCI trained three times per week for 2 years with a mix of aerobic, strength and balance exercises matched with nutritional advice. Before and after the intervention, ultrasound scans of the vastus lateralis (VL), SPPB and a blood sample were obtained. VL architecture [pennation angle (PA) and fascicle length (Lf)] and cross-sectional area (CSA) were measured. As biomarkers of neuronal health and NMJ stability status, neurofilament light chain (NfL) and C-terminal agrin fragment (CAF) concentrations were measured in serum. Differences in ultrasound parameters, NfL and CAF concentration and physical performance between baseline and follow-up were tested with mixed ANOVA or Wilcoxon test. The relationship between changes in physical performance and NfL or CAF concentration was assessed through correlation analyses. Results: At follow-up, MCI showed preserved VL architecture (PA, Lf) despite a reduced CSA (−8.4%, P < 0.001), accompanied by maintained CAF concentration and ameli

Traditional healthcare paradigms rely on the disease-centered approach aiming at reducing human nature by discovering specific drivers and biomarkers that cause the advent and progression of diseases. This reductive approach is not always suitable to understand and manage complex conditions, such as multimorbidity and cancer. Multimorbidity requires considering heterogeneous data to tailor preventing and targeting interventions. Personalized Medicine represents an innovative approach to address the care needs of multimorbid patients considering relevant patient characteristics, such as lifestyle and individual preferences, in opposition to the more traditional “one-size-fits-all” strategy focused on interventions designed at the population level. Integration of omic (e.g., genomics) and non-strictly medical (e.g., lifestyle, the exposome) data is necessary to understand patients’ complexity. Artificial Intelligence can help integrate and manage heterogeneous data through advanced machine learning and bioinformatics algorithms to define the best treatment for each patient with multimorbidity and cancer. The experience of an Italian research hospital, leader in the field of oncology, may help to understand the multifaceted issue of managing multimorbidity and cancer in the framework of Personalized Medicine.

Detection of sarcopenia in primary care is a first and essential step in community-dwelling older adults before implementing preventive interventions against the onset of disabling conditions. In fact, leaving this condition undiagnosed and untreated can impact on the individual’s quality of life and function, as well as on healthcare costs. This article summarizes the many instruments today available for promoting an earlier and prompter detection of sarcopenia in primary care, combining insights about its clinical management. Primary care physicians may indeed play a crucial role in the identification of individuals exposed to the risk of sarcopenia or already presenting this condition. To confirm the suspected diagnosis, several possible techniques may be advocated, but it is important that strategies are specifically calibrated to the needs, priorities and resources of the setting where the evaluation is conducted. To tackle sarcopenia, nutritional counselling and physical activity programs are today the two main interventions to be proposed. Multicomponent and personalized exercise programs can (and should) be prescribed by primary care physicians, taking advantage of validated programs ad hoc designed for this purpose (e.g., the Vivifrail protocol). It is possible that, in the next future, new pharmacological treatments may become available for tackling the skeletal muscle decline. These will probably find application in those individuals non-responding to lifestyle interventions.

Frailty is a reversible state of reduced resilience to stressful events resulting from a multisystem impairment of the human body. As frailty progresses, people become more vulnerable to numerous adverse events, including falls and fractures, cognitive decline, disability, hospitalization, nursing home placement, and death. As such, substantial health care costs are associated with frailty. These features have led to the recognition of frailty as a public health problem. The identification of strategies for the management of frailty has, therefore, become a topic of extensive instigation. In this context, resistance (RT) and power training (PT) have received considerable attention, and experts in the field have recently suggested that both training modalities may improve frailty-related parameters. However, most studies have only included robust people and investigated frailty as a secondary outcome, so that current literature only allows RT and PT preventive programs against frailty to be designed. Here, we provide evidence-based critical recommendations for the prescription of RT and PT programs against incident frailty in community-dwellers.

Primary mitochondrial myopathies (PMM) are a group of mitochondrial disorders characterized by a predominant skeletal muscle involvement. The aim of this study was to evaluate whether the biochemical profile determined by Fourier-transform infrared (FTIR) spectroscopic technique would allow to distinguish among patients affected by progressive external ophthalmoplegia (PEO), the most common PMM presentation, oculopharyngeal muscular dystrophy (OPMD), and healthy controls. Thirty-four participants were enrolled in the study. FTIR spectroscopy was found to be a sensitive and specific diagnostic marker for PEO. In particular, FTIR spectroscopy was able to distinguish PEO patients from those affected by OPMD, even in the presence of histological findings similar to mitochondrial myopathy. At the same time, FTIR spectroscopy differentiated single mtDNA deletion and mutations in POLG, the most common nuclear gene associated with mitochondrial diseases, with high sensitivity and specificity. In conclusion, our data suggest that FTIR spectroscopy is a valuable biodiagnostic tool for the differential diagnosis of PEO with a high ability to also distinguish between single mtDNA deletion and mutations in POLG gene based on specific metabolic transitions.

For survivors of severe COVID-19 disease, having defeated the virus is just the beginning of an uncharted recovery path. What follows after the acute phase of SARS-CoV-2 infection depends on the extension and severity of viral attacks in different cell types and organs. Despite the ridiculously large number of papers that have flooded scientific journals and preprint-hosting websites, a clear clinical picture of COVID-19 aftermath is vague at best. Without larger prospective observational studies that are only now being started, clinicians can retrieve information just from case reports and or small studies. This is the time to understand how COVID-19 goes forward and what consequences survivors may expect to experience. To this aim, a multidisciplinary post-acute care service involving several specialists has been established at the Fondazione Policlinico Universitario A. Gemelli IRCSS (Rome, Italy). Although COVID-19 is an infectious disease primarily affecting the lung, its multi-organ involvement requires an interdisciplinary approach encompassing virtually all branches of internal medicine and geriatrics. In particular, during the post-acute phase, the geriatrician may serve as the case manager of a multidisciplinary team. The aim of this article is to describe the importance of the interdisciplinary approach––coordinated by geriatrician––to cope the potential post-acute care needs of recovered COVID-19 patients.

One of the most widely conserved hallmarks of aging is a decline in functional capabilities. Mobility loss is particularly burdensome due to its association with negative health outcomes, loss of independence and disability, and the heavy impact on quality of life. Recently, a new condition, physical frailty and sarcopenia, has been proposed to define a critical stage in the disabling cascade. Physical frailty and sarcopenia are characterized by weakness, slowness, and reduced muscle mass, yet with preserved ability to move indepen-dently. One of the strategies that have shown some benefits in combatting mobility loss and its consequences for older adults is physical activity. Here, we describe the opportunities and challenges for the development of physical activity interventions in people with physical frailty and sarcopenia. The aim of this article is to review age-related physio(patho)logical changes that impact mobility in old age and to provide recommendations and procedures in accordance with the available literature.

The present study investigated and compared the patterns of dietary protein intake and physical function in Brazilian and Italian older women. Seventy-five Brazilian older women were recruited in a community senior center. Fifty-three age-matched Italian older women were selected from participants of the Longevity check-up (Lookup) 7+ study. In both samples, physical performance was evaluated by isometric handgrip strength (IHG) and five-time sit-to-stand (5 × STS) tests, while diet was assessed through 24-h recall. Results indicated that Brazilian women had a higher intake of plant-based protein (52.7% vs. 30.5% kcal), while Italian women consumed greater amounts of animal-derived protein (29.7% vs. 41.5% kcal). In Brazilian women, the binary logistic regression analysis indicated that body weight-adjusted protein consumption was associated with IHG adjusted by body mass index and with 5 × STS performance. In the Italian sample, the intake of isoleucine, leucine, and valine was significantly associated with 5 × STS performance. Our findings indicate that Brazilian and Italian community-dwelling older women show different patterns of protein intake, with higher consumption of plant-based protein in the Brazilian sample and higher ingestion of animal-derived protein in the Italian subgroup. These dietary patterns may differentially impact the relationship between physical function and protein intake observed in Brazilian and Italian older women.

Fatigue is an often-neglected symptom but frequently complained of by older people, leading to the inability to continue functioning at a normal level of activity. Fatigue is frequently associated with disease conditions and impacts health status and quality of life. Yet, fatigue cannot generally be completely explained as a consequence of a single disease or pathogenetic mechanism. Indeed, fatigue mirrors the exhaustion of the physiological reserves of an older individual. Despite its clinical relevance, fatigue is typically underestimated by healthcare professionals, mainly because reduced stamina is considered to be an unavoidable corollary of aging. The incomplete knowledge of pathophysiological mechanisms of fatigue and the lack of a gold standard tool for its assessment contribute to the poor appreciation of fatigue in clinical practice. Inadequate nutrition is invoked as one of the mechanisms underlying fatigue. Modifications in food intake and body composition changes seem to influence the perception of fatigue, probably through the mechanisms of inflammation and/or mitochondrial dysfunction. Here, we present an overview on the mechanisms that may mediate fatigue levels in old age, with a special focus on nutrition.

Extracellular vesicles have been identified as pivotal mediators of intercellular communication with critical roles in physiological and pathological conditions. Via this route, several molecules (e.g., nucleic acids, proteins, metabolites) can be transferred to proximal and distant targets to convey specific information. Extracellular vesicle-associated cargo molecules have been proposed as markers of several disease conditions for their potential of tracking down the generating cell. Indeed, circulating extracellular vesicles may represent biomarkers of dysfunctional cellular quality control systems especially in conditions characterized by the accrual of intracellular misfolded proteins. Furthermore, the identification of extracellular vesicles as tools for the delivery of nucleic acids or other cargo molecules to diseased tissues makes these circulating shuttles possible targets for therapeutic development. The increasing interest in the study of extracellular vesicles as biomarkers resides mainly in the fact that the identification of peripheral levels of extracellular vesicle-associated proteins might reflect molecular events occurring in hardly accessible tissues, such as the brain, thereby serving as a 'brain liquid biopsy'. The exploitation of extracellular vesicles for diagnostic and therapeutic purposed might offer unprecedented opportunities to develop personalized approaches. Here, we discuss the bright and dark sides of extracellular vesicles in the setting of two main neurodegenerative diseases (i.e., Parkinson's and Alzheimer's diseases). A special focus will be placed on the possibility of using extracellular vesicles as biomarkers for the two conditions to enable disease tracking and treatment monitoring.

Objective: To determine whether a multicomponent intervention based on physical activity with technological support and nutritional counselling prevents mobility disability in older adults with physical frailty and sarcopenia. Design: Evaluator blinded, randomised controlled trial. Setting: 16 clinical sites across 11 European countries, January 2016 to 31 October 2019. Participants: 1519 community dwelling men and women aged 70 years or older with physical frailty and sarcopenia, operationalised as the co-occurrence of low functional status, defined as a short physical performance battery (SPPB) score of 3 to 9, low appendicular lean mass, and ability to independently walk 400 m. 760 participants were randomised to a multicomponent intervention and 759 received education on healthy ageing (controls). Interventions: The multicomponent intervention comprised moderate intensity physical activity twice weekly at a centre and up to four times weekly at home. Actimetry data were used to tailor the intervention. Participants also received personalised nutritional counselling. Control participants received education on healthy ageing once a month. Interventions and follow-up lasted for up to 36 months. Main outcome measures: The primary outcome was mobility disability (inability to independently walk 400 m in <15 minutes). Persistent mobility disability (inability to walk 400 m on two consecutive occasions) and changes from baseline to 24 and 36 months in physical performance, muscle strength, and appendicular lean mass were analysed as pre-planned secondary outcomes. Primary comparisons were conducted in participants with baseline SPPB scores of 3–7 (n=1205). Those with SPPB scores of 8 or 9 (n=314) were analysed separately for exploratory purposes. Results: Mean age of the 1519 participants (1088 women) was 78.9 (standard deviation 5.8) years. The average follow-up was 26.4 (SD 9.5) months. Among participants with SPPB scores of 3–7, mobility disability occur

The most commonly used antiviral treatment against hepatitis C virus is a combination of direct-acting antivirals (DAAs) and ribavirin (RBV), which leads to a shortened duration of therapy and a sustained virologic response until 98%. Nonetheless, several dose-related side effects of RBV could limit its applications. This study aims to measure the urinary concentration of RBV and its main metabolites in order to evaluate the drug metabolism ability of HCV patients and to evaluate the adverse effects, such as anemia, with respect to RBV metabolite levels. RBV and its proactive and inactive metabolites were identified and quantified in the urine of 17 HCV males with severe liver fibrosis using proton nuclear magnetic resonance (1H-NMR) at the fourth week (TW4) and at the twelfth week of treatment (EOT). Four prodrug urinary metabolites, including RBV, were identified and three of them were quantified. At both the TW4 and EOT stages, six HCV patients were found to maintain high concentrations of RBV, while another six patients maintained a high level of RBV proactive metabolites, likely due to nucleosidase activity. Furthermore, a negative correlation between the reduction in hemoglobin (Hb) and proactive forms was observed, according to RBV-triphosphate accumulation causing the hemolysis. These findings represent a proof of concept regarding tailoring the drug dose in relation to the specific metabolic ability of the individual, as expected by the precision medicine approach.

Background: Fatigue with reduced tolerance to exercise is a common persistent long-lasting feature amongst COVID-19 survivors. The assessment of muscle function in this category of patients is often neglected.Aim.: To evaluate the potential impact of a daily supplementation based on amino acids, minerals, vi-tamins, and plant extracts (Apportal (R)) on muscle function, body composition, laboratory parameters and self-rated health in a small group of COVID-19 survivors affected by fatigue.Methods: Thirty participants were enrolled among patients affected by physical fatigue during or after acute COVID-19 and admitted to the post-COVID-19 outpatient service at Fondazione Policlinico Gemelli in Rome between 1st March 2021 and 30th April 2021. All participants were evaluated at first visit (t0) and at control visit (t1), after taking a daily sachet of Apportal (R) for 28 days. Muscle function was analyzed using hand grip strength test, exhaustion strength time and the number of repetitions at one -minute chair stand test. Body composition was assessed with bioelectrical impedance analysis (BIA). Laboratory parameters, including standard blood biochemistry and ferritin levels, were evaluated at the first visit and during the control visit. A quick evaluation of self-rated health, before COVID-19, at t0 and t1, was obtained through a visual analogue scale (VAS). Results: Participants aged 60 years and older were 13 (43%). Females represented the 70% of the study sample. Participants hospitalized for COVID-19 with low -flow oxygen supplementation represented the 43.3% of the study sample while 3.3% received noninvasive ventilation (NIV) or invasive ventilation. Hand grip strength improved from 26.3 Kg to 28.9 Kg (p < 0.05) at t1 as compared to t0. The mean time of strength exhaustion increased from 31.7 s (sec) at t0 to 47.5 s at t1 (p < 0.05). Participants performed a higher number of repetitions (28.3 vs. 22.0; p < 0.05) during the one-minute chair stand test at

Nonconventional clinical presentations of diseases are common in older adults. Even dramatic events, such as foreign body (FB) inhalation, can occur in a subtle and non-specific manner. Pill aspiration is a rare yet overlooked cause of airway injury. It accounts for approximately 7% of all FB aspirations. In contrast, oral dysphagia and polypharmacology, mainly administrated in solid oral dosage forms (SDOF), like tablets and pills, are common conditions in older adults. Herein, we present a case of SDOF aspiration in a 78-year-old man. FB inhalation developed with general clinical deterioration and neurological impairment (delirium) rather than overt respiratory symp-toms. Bronchoscopy provided remarkable images of this unexpected finding. Caregivers and healthcare workers must be aware of the risk of SDOF aspiration and adopt proper safety mea-sures. Early recognition and bronchoscopy for diagnostic and therapeutic purposes can be life-saving in such cases.

The diagnosis of cachexia is based on loss of body weight and low body mass index plus at least three out of five additional criteria: decrease in muscle strength, fatigue, anorexia, low lean body mass, and abnormal biochemistry. Cachexia affects 50-80% of cancer patients, accounting for up to 20% of all cancer-related deaths. Cachexia is associated with increased incidence of doselimiting chemotherapy toxicity and higher odds of treatment discontinuation. Energy wasting resulting from an imbalance between energy requirements and energy uptake is proposed to contribute to cachexia. Muscle protein breakdown, acceleration of myonuclear apoptosis, and impaired muscle regeneration contribute to nitrogen imbalance and muscle wasting in cachexia. Identifying personalised nutritional needs and developing tailored nutritional plans are pillars of cachexia treatment. Substances with muscle anabolic activities may represent a pharmacological option to contrast cachexia. Multimodal treatment protocols should involve a multidisciplinary team of health professionals as well as patients and their formal and informal caregivers.

The mammalian target of rapamycin (mTOR) is a major regulator of skeletal myocyte viability. The signaling pathways triggered by mTOR vary according to the type of endogenous and exogenous factors (e.g., redox balance, nutrient availability, physical activity) as well as organismal age. Here, we provide an overview of mTOR signaling in skeletal muscle, with a special focus on the role played by mTOR in the development of sarcopenia. Intervention strategies targeting mTOR in sarcopenia (e.g., supplementation of plant extracts, hormones, inorganic ions, calorie restriction, and exercise) have also been discussed.

Long COVID, a condition characterized by symptom and/or sign persistence following an acute COVID-19 episode, is associated with reduced physical performance and endothelial dysfunction. Supplementation of l-arginine may improve endothelial and muscle function by stimulating nitric oxide synthesis. A single-blind randomized, placebo-controlled trial was conducted in adults aged between 20 and 60 years with persistent fatigue attending a post-acute COVID-19 outpatient clinic. Participants were randomized 1:1 to receive twice-daily orally either a combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C or a placebo for 28 days. The primary outcome was the distance walked on the 6 min walk test. Secondary outcomes were handgrip strength, flow-mediated dilation, and fatigue persistence. Fifty participants were randomized to receive either l-arginine plus vitamin C or a placebo. Forty-six participants (median (interquartile range) age 51 (14), 30 [65%] women), 23 per group, received the intervention to which they were allocated and completed the study. At 28 days, l-arginine plus vitamin C increased the 6 min walk distance (+30 (40.5) m; placebo: +0 (75) m, p = 0.001) and induced a greater improvement in handgrip strength (+3.4 (7.5) kg) compared with the placebo (+1 (6.6) kg, p = 0.03). The flow-mediated dilation was greater in the active group than in the placebo (14.3% (7.3) vs. 9.4% (5.8), p = 0.03). At 28 days, fatigue was reported by two participants in the active group (8.7%) and 21 in the placebo group (80.1%; p < 0.0001). l-arginine plus vitamin C supplementation improved walking performance, muscle strength, endothelial function, and fatigue in adults with long COVID. This supplement may, therefore, be considered to restore physical performance and relieve persistent symptoms in this patient population.