The Multidisciplinary Mobile Unit (MMU) Program Bringing Hospital Specialist Geriatric Competencies at Home: A Feasible Alternative to Admission in Older Patients with Urgent Complaints.

Background/Objectives: Older patients are subject to a high number of Emergency Department (ED) visits and hospitalizations. Innovative strategies to manage geriatric urgencies in the community are thus needed. Methods: In this prospective observational study, we examined the case mix of a hospital-based domiciliary urgent care service tailored to older patients, called Multidisciplinary Mobile Unit (MMU), from January to September 2023. The service, activated by general practitioners or territorial specialists during workdays, provided domiciliary geriatric assessment, point-of-care diagnostics, including multi-site ultrasound and lab tests, and therapeutical measures, including intravenous treatment and insertion of invasive devices, with the goal of reaching on-site stabilization and avoiding ED referral. We collected data regarding multimorbidity, polypharmacy, and frailty according to the Clinical Frailty Scale (CFS), reasons for MMU activation, and diagnostic and therapeutical services provided. The assessed outcomes were immediate hospitalization after a visit, 30-day admission, and 30-day mortality. Results: Participants (n = 205, 102 M) were mostly aged (median age 83 years old), with multimorbidity and frailty (CFS median 6). The most frequent reasons for MMU activation were dyspnea (49%), cough (34%), and musculoskeletal pain (17%), while the commonest diagnostic test provided was thoracic ultrasound (81%). Only five patients (2.4%) were hospitalized immediately after MMU visit. The 30-day rate of hospitalization was 10.2%, with age, cancer, and abdominal pain as independent predictors on a stepwise binary logistic regression model. 30-day mortality was 4.9%. Conclusions: The MMU model is a feasible strategy to manage geriatric urgencies, especially involving the cardiorespiratory system, is associated with good outcomes and may prevent ED visits.

Cardiovascular Disease from Pathophysiology to Risk Estimation: Is Inflammation Estimated through Perivascular Attenuation on Computed Tomography the Key?

(1) Background: Systemic inflammation stands as a well-established risk factor for ischemic cardiovascular disease, as well as a contributing factor in the development of cardiac arrhythmias, notably atrial fibrillation. Furthermore, scientific studies have brought to light the pivotal role of localized vascular inflammation in the initiation, progression, and destabilization of coronary atherosclerotic disease. (2) Methods: We comprehensively review recent, yet robust, scientific evidence elucidating the use of perivascular adipose tissue attenuation measurement on computed tomography applied to key anatomical sites. Specifically, the investigation extends to the internal carotid artery, aorta, left atrium, and coronary arteries. (3) Conclusions: The examination of perivascular adipose tissue attenuation emerges as a non-invasive and indirect means of estimating localized perivascular inflammation. This measure is quantified in Hounsfield units, indicative of the inflammatory response elicited by dense adipose tissue near the vessel or the atrium. Particularly noteworthy is its potential utility in assessing inflammatory processes within the coronary arteries, evaluating coronary microvascular dysfunction, appraising conditions within the aorta and carotid arteries, and discerning inflammatory states within the atria, especially in patients with atrial fibrillation. The widespread applicability of perivascular adipose tissue attenuation measurement underscores its significance as a diagnostic tool with considerable potential for enhancing our understanding and management of cardiovascular diseases.

Taxonomic and metabolic development of the human gut microbiome across life stages: a worldwide metagenomic investigation.

The human gut microbiota is a dynamic community of microorganisms that undergo variable changes over the entire life span. To thoroughly investigate the possible fluctuations of the microbiota throughout human life, we performed a pooled analysis of healthy fecal samples across different age groups covering the entire human life span. Our study integrated data from 79 publicly available studies and new stool samples from an Italian cohort, i.e., the Parma Microbiota project, resulting in 6,653 samples processed through the shotgun metagenomic approach. This approach has allowed species-level taxonomic reconstruction of the gut microbiota and investigation of its metabolic potential across the human life span. From a taxonomic point of view, our findings confirmed and detailed at species-level accuracy that the microbial richness of the gut microbiota gradually increases in the first stage of life, becoming relatively stable during adolescence. Moreover, the analysis identified the potential core microbiota representative of distinct age groups, revealing age-related bacterial patterns and the continuous rearrangement of the microbiota in terms of relative abundances across the life span rather than the acquisition and loss of taxa. Furthermore, the shotgun approach provided insights into the functional contribution of the human gut microbiome. The metagenomic analysis revealed functional age-related differences, particularly in carbohydrate and fiber metabolism, suggesting a co-evolution of the microbiome assembly with diet. Additionally, we identified correlations between vitamin synthesis, such as thiamine and niacin, and early life, suggesting a potential role of the microbiome in human physiology, in particular in the functions of the host's nervous and immune systems. IMPORTANCE: In this study, we provided comprehensive insights into the dynamic nature of the human gut microbiota across the human life span. In detail, we analyzed a large data set based on a shotgun metagenomic approach, combining public data sets and new samples from the Parma Microbiota project and obtaining a detailed overview of the possible relationship between gut microbiota development and aging. Our findings confirmed the main stages in microbial richness development and revealed specific core microbiota associated with different age stages. Moreover, the shotgun metagenomic approach allowed the disentangling of the functional changes in the microbiome across the human life span, particularly in diet-related metabolism, which is probably correlated to bacterial co-evolution with dietary habits. Notably, our study also uncovered positive correlations with vitamin synthesis in early life, suggesting a possible impact of the microbiota on human physiology.

The interaction between Mediterranean diet and intestinal microbiome: relevance for preventive strategies against frailty in older individuals.

Age-related changes in intestinal microbiome composition and function are increasingly recognized as pivotal in the pathophysiology of aging and are associated with the aging phenotype. Diet is a major determinant of gut-microbiota composition throughout the entire lifespan, and several of the benefits of a healthy diet in aging could be mediated by the microbiome. Mediterranean diet (MD) is a traditional dietary pattern regarded as the healthy diet paradigm, and a large number of studies have demonstrated its benefits in promoting healthy aging. MD has also a positive modulatory effect on intestinal microbiome, favoring bacterial taxa involved in the synthesis of several bioactive compounds, such as short-chain fatty acids (SCFAs), that counteract inflammation, anabolic resistance, and tissue degeneration. Intervention studies conducted in older populations have suggested that the individual response of older subjects to MD, in terms of reduction of frailty scores and amelioration of cognitive function, is significantly mediated by the gut-microbiota composition and functionality. In this context, the pathophysiology of intestinal microbiome in aging should be considered when designing MD-based interventions tailored to the needs of geriatric patients.

Factors associated with delirium in a real-world acute-care setting: analysis considering the interdependence of clinical variables with the frailty syndrome.

PURPOSE: Delirium risk assessment in the acute-care setting generally does not account for frailty. The objective of this retrospective study was to identify factors associated with delirium, considering the interdependency of clinical variables with frailty syndrome in complex older patients. METHODS: The clinical records of 587 participants (248 M, median age 84) were reviewed, collecting clinical, anamnestic and pharmacological data. Frailty syndrome was assessed with the Clinical Frailty Scale (CFS). Delirium was the main study endpoint. The correlations of the considered anamnestic and clinical variables with delirium and its subtypes were investigated selecting only those variables not showing a high overlap with frailty. Correlations associated with a 25% excess of frequency of delirium in comparison with the average of the population were considered as statistically significant. RESULTS: Delirium was detected in 117 (20%) participants. The presence of one among age > 85 years old, CFS > 4 and invasive devices explained 95% of delirium cases. The main factors maximizing delirium incidence at the individual level were dementia, other psychiatric illness, chronic antipsychotic treatment, and invasive devices. The coexistence of three of these parameters was associated with a peak frequency of delirium, ranging from 57 to 61%, mostly hypoactive forms. CONCLUSIONS: In acute-care wards, frailty exhibited a strong association with delirium during hospitalization, while at the individual level, dementia and the use of antipsychotics remained important risk factors. Modern clinical prediction tools for delirium should account for frailty syndrome.

Coronary inflammation on chest computed tomography and COVID-19 mortality.

OBJECTIVES: The main factors associated with coronavirus disease-19 (COVID-19) mortality are age, comorbidities, pattern of inflammatory response, and SARS-CoV-2 lineage involved in infection. However, the clinical course of the disease is extremely heterogeneous, and reliable biomarkers predicting adverse prognosis are lacking. Our aim was to elucidate the prognostic role of a novel marker of coronary artery disease inflammation, peri-coronary adipose tissue attenuation (PCAT), available from high-resolution chest computed tomography (HRCT) in COVID-19 patients with severe disease requiring hospitalization. METHODS: Two distinct groups of patients were admitted to Parma University Hospital in Italy with COVID-19 in March 2020 and March 2021 (first- and third-wave peaks of the COVID-19 pandemic in Italy, with the prevalence of wild-type and B.1.1.7 SARS-CoV-2 lineage, respectively) were retrospectively enrolled. The primary endpoint was in-hospital mortality. Demographic, clinical, laboratory, HRCT data, and coronary artery HRCT features (coronary calcium score and PCAT attenuation) were collected to show which variables were associated with mortality. RESULTS: Among the 769 patients enrolled, 555 (72%) were discharged alive, and 214 (28%) died. In multivariable logistic regression analysis age (p < 0.001), number of chronic illnesses (p < 0.001), smoking habit (p = 0.006), P/F ratio (p = 0.001), platelet count (p = 0.002), blood creatinine (p < 0.001), non-invasive mechanical ventilation (p < 0.001), HRCT visual score (p < 0.001), and PCAT (p < 0.001), but not the calcium score, were independently associated with in-hospital mortality. CONCLUSION: Coronary inflammation, measured with PCAT on non-triggered HRCT, appeared to be independently associated with higher mortality in patients with severe COVID-19, while the pre-existent coronary atherosclerotic burden was not associated with adverse outcomes after adjustment for covariates. CLINICAL RELEVANCE STATEMENT: The current study demonstrates that a relatively simple measurement, peri-coronary adipose tissue attenuation (PCAT), available ex-post from standard high-resolution computed tomography, is strongly and independently associated with in-hospital mortality. KEY POINTS: • Coronary inflammation can be measured by the attenuation of peri-coronary adipose tissue (PCAT) on high-resolution CT (HRCT) without contrast media. • PCAT is strongly and independently associated with in-hospital mortality in SARS-CoV-2 patients. • PCAT might be considered an independent prognostic marker in COVID-19 patients if confirmed in other studies.

The possible role of gut microbiota dysbiosis in the pathophysiology of delirium in older persons.

Delirium is a clinical syndrome characterized by an acute change in attention, awareness and cognition with fluctuating course, frequently observed in older patients during hospitalization for acute medical illness or after surgery. Its pathogenesis is multifactorial and still not completely understood, but there is general consensus on the fact that it results from the interaction between an underlying predisposition, such as neurodegenerative diseases, and an acute stressor acting as a trigger, such as infection or anesthesia. Alterations in brain insulin sensitivity and metabolic function, increased blood-brain barrier permeability, neurotransmitter imbalances, abnormal microglial activation and neuroinflammation have all been involved in the pathophysiology of delirium. Interestingly, all these mechanisms can be regulated by the gut microbiota, as demonstrated in experimental studies investigating the microbiota-gut-brain axis in dementia. Aging is also associated with profound changes in gut microbiota composition and functions, which can influence several aspects of disease pathophysiology in the host. This review provides an overview of the emerging evidence linking age-related gut microbiota dysbiosis with delirium, opening new perspectives for the microbiota as a possible target of interventions aimed at delirium prevention and treatment.

Advancing healthcare through thoracic ultrasound research in older patients.

This paper reports the proceedings of a meeting convened by the Research Group on Thoracic Ultrasound in Older People of the Italian Society of Gerontology and Geriatrics, to discuss the current state-of-the-art of clinical research in the field of geriatric thoracic ultrasound and identify unmet research needs and potential areas of development. In the last decade, point-of-care thoracic ultrasound has entered clinical practice for diagnosis and management of several respiratory illnesses, such as bacterial and viral pneumonia, pleural effusion, acute heart failure, and pneumothorax, especially in the emergency-urgency setting. Very few studies, however, have been specifically focused on older patients with frailty and multi-morbidity, who frequently exhibit complex clinical pictures needing multidimensional evaluation. At the present state of knowledge, there is still uncertainty on the best requirements of ultrasound equipment, methodology of examination, and reporting needed to optimize the advantages of thoracic ultrasound implementation in the care of geriatric patients. Other issues regard differential diagnosis between bacterial and aspiration pneumonia, objective grading of interstitial syndrome severity, quantification and monitoring of pleural effusions and solid pleural lesions, significance of ultrasonographic assessment of post-COVID-19 sequelae, and prognostic value of assessment of diaphragmatic thickness and motility. Finally, application of remote ultrasound diagnostics in the community and nursing home setting is still poorly investigated by the current literature. Overall, the presence of several open questions on geriatric applications of thoracic ultrasound represents a strong call to implement clinical research in this field.

Approach to COVID-19 in older adults and indications for improving the outcomes.

Background: COVID-19 continues to present challenges in the care of older adults with frailty and/or comorbidities and very old patients, who can be hospitalized with severe COVID-19 despite full vaccination. Frailty is a heterogeneous syndrome characterized by an increased aging-related vulnerability due to a reduced physiological reserve and function of systemic organs, and is associated with an impairment of activities of daily living. Frail older adults remain at elevated risk of mortality from COVID-19 compared to older adults without frailty, and some pre-existing risk factors such as malnutrition, prolonged bed rest, and the association with comorbidities can aggravate the SARS-CoV-2 infection. Furthermore, the severity of COVID-19 can impact on long-term functioning of older patients surviving from the infection. Persistent symptoms are another emerging problem of the post-vaccination phase of pandemic, as most patients suffer from chronic symptoms which can become debilitating and affect the daily routine. Aim of this review: In this complex relationship, the evaluation of COVID-19 in vulnerable categories is still a matter of high interest and personalized care plans based on a comprehensive geriatric assessment, tailored interventions; specific therapeutic algorithms among older adults are thus recommended in order to improve the outcomes.

Disentangling the interactions between nasopharyngeal and gut microbiome and their involvement in the modulation of COVID-19 infection.

The human organism is inhabited by trillions of microorganisms, known as microbiota, which are considered to exploit a pivotal role in the regulation of host health and immunity. Recent investigations have suggested a relationship between the composition of the human microbiota and COVID-19 infection, highlighting a possible role of bacterial communities in the modulation of the disease severity. In this study, we performed a shotgun metagenomics analysis to explore and compare the nasopharyngeal microbiota of 38 hospitalized Italian patients with and without COVID-19 infection during the third and fourth pandemic waves. In detail, the metagenomic analysis combined with specific correlation analyses suggested a positive association of several microbial species, such as S. parasanguinis and P. melaninogenica, with the severity of COVID-19 infection. Furthermore, the comparison of the microbiota composition between the nasopharyngeal and their respective fecal samples highlighted an association between these different compartments represented by a sharing of several bacterial species. Additionally, lipidomic and deep-shotgun functional analyses of the fecal samples suggested a metabolic impact of the microbiome on the host's immune response, indicating the presence of key metabolic compounds in COVID-19 patients, such as lipid oxidation end products, potentially related to the inflammatory state. Conversely, the patients without COVID-19 displayed enzymatic patterns associated with the biosynthesis and degradation of specific compounds like lysine (synthesis) and phenylalanine (degradation) that could positively impact disease severity and contribute to modulating COVID-19 infection. IMPORTANCE The human microbiota is reported to play a major role in the regulation of host health and immunity, suggesting a possible impact on the severity of COVID-19 disease. This preliminary study investigated the possible correlation between nasopharyngeal microbiota and COVID-19 infection. In detail, the analysis of the nasopharyngeal microbiota of hospitalized Italian patients with and without COVID-19 infection suggested a positive association of several microbial species with the severity of the disease and highlighted a sharing of several bacteria species with the respective fecal samples. Moreover, the metabolic analyses suggested a possible impact of the microbiome on the host's immune response and the disease severity.

Natural heteroclitic-like peptides are generated by SARS-CoV-2 mutations.

Humoral immunity is sensitive to evasion by SARS-CoV-2 mutants, but CD8 T cells seem to be more resistant to mutational inactivation. By a systematic analysis of 30 spike variant peptides containing the most relevant VOC and VOI mutations that have accumulated overtime, we show that in vaccinated and convalescent subjects, mutated epitopes can have not only a neutral or inhibitory effect on CD8 T cell recognition but can also enhance or generate de novo CD8 T cell responses. The emergence of these mutated T cell function enhancing epitopes likely reflects an epiphenomenon of SARS-CoV-2 evolution driven by antibody evasion and increased virus transmissibility. In a subset of individuals with weak and narrowly focused CD8 T cell responses selection of these heteroclitic-like epitopes may bear clinical relevance by improving antiviral protection. The functional enhancing effect of these peptides is also worth of consideration for the future development of new generation, more potent COVID-19 vaccines.

Dementia, infections and vaccines: 30 years of controversy.

This paper reports the proceedings of a virtual meeting convened by the European Interdisciplinary Council on Ageing (EICA), to discuss the involvement of infectious disorders in the pathogenesis of dementia and neurological disorders leading to dementia. We recap how our view of the infectious etiology of dementia has changed over the last 30 years in light of emerging evidence, and we present evidence in support of the implication of infection in dementia, notably Alzheimer's disease (AD). The bacteria and viruses thought to be responsible for neuroinflammation and neurological damage are reviewed. We then review the genetic basis for neuroinflammation and dementia, highlighting the genes that are currently the focus of investigation as potential targets for therapy. Next, we describe the antimicrobial hypothesis of dementia, notably the intriguing possibility that amyloid beta may itself possess antimicrobial properties. We further describe the clinical relevance of the gut-brain axis in dementia, the mechanisms by which infection can move from the intestine to the brain, and recent findings regarding dysbiosis patterns in patients with AD. We review the involvement of specific pathogens in neurological disorders, i.e. SARS-CoV-2, human immunodeficiency virus (HIV), herpes simplex virus type 1 (HSV1), and influenza. Finally, we look at the role of vaccination to prevent dementia. In conclusion, there is a large body of evidence supporting the involvement of various infectious pathogens in the pathogenesis of dementia, but large-scale studies with long-term follow-up are needed to elucidate the role that infection may play, especially before subclinical or clinical disease is present.

Accounting Gut Microbiota as the Mediator of Beneficial Effects of Dietary (Poly)phenols on Skeletal Muscle in Aging.

Sarcopenia, the age-related loss of muscle mass and function increasing the risk of disability and adverse outcomes in older people, is substantially influenced by dietary habits. Several studies from animal models of aging and muscle wasting indicate that the intake of specific polyphenol compounds can be associated with myoprotective effects, and improvements in muscle strength and performance. Such findings have also been confirmed in a smaller number of human studies. However, in the gut lumen, dietary polyphenols undergo extensive biotransformation by gut microbiota into a wide range of bioactive compounds, which substantially contribute to bioactivity on skeletal muscle. Thus, the beneficial effects of polyphenols may consistently vary across individuals, depending on the composition and metabolic functionality of gut bacterial communities. The understanding of such variability has recently been improved. For example, resveratrol and urolithin interaction with the microbiota can produce different biological effects according to the microbiota metabotype. In older individuals, the gut microbiota is frequently characterized by dysbiosis, overrepresentation of opportunistic pathogens, and increased inter-individual variability, which may contribute to increasing the variability of biological actions of phenolic compounds at the skeletal muscle level. These interactions should be taken into great consideration for designing effective nutritional strategies to counteract sarcopenia.

Disentangling the Complexity of Nutrition, Frailty and Gut Microbial Pathways during Aging: A Focus on Hippuric Acid.

Hippuric acid (HA) is a metabolite resulting from the hepatic glycine conjugation of benzoic acid (BA) or from the gut bacterial metabolism of phenylalanine. BA is generally produced by gut microbial metabolic pathways after the ingestion of foods of vegetal origin rich in polyphenolic compounds, namely, chlorogenic acids or epicatechins. It can also be present in foods, either naturally or artificially added as a preservative. The plasma and urine HA levels have been used in nutritional research for estimating the habitual fruit and vegetable intake, especially in children and in patients with metabolic diseases. HA has also been proposed as a biomarker of aging, since its levels in the plasma and urine can be influenced by the presence of several age-related conditions, including frailty, sarcopenia and cognitive impairment. Subjects with physical frailty generally exhibit reduced plasma and urine levels of HA, despite the fact that HA excretion tends to increase with aging. Conversely, subjects with chronic kidney disease exhibit reduced HA clearance, with HA retention that may exert toxic effects on the circulation, brain and kidneys. With regard to older patients with frailty and multimorbidity, interpreting the HA levels in the plasma and urine may result particularly challenging because HA is at the crossroads between diet, gut microbiota, liver and kidney function. Although these considerations may not make HA the ideal biomarker of aging trajectories, the study of its metabolism and clearance in older subjects may provide valuable information for disentangling the complex interaction between diet, gut microbiota, frailty and multimorbidity.

Insights from comparison of the clinical presentation and outcomes of patients hospitalized with COVID-19 in an Italian internal medicine ward during first and third wave.

Background: The reasons of variability of clinical presentation of coronavirus disease-19 (COVID-19) across different pandemic waves are not fully understood, and may include individual risk profile, SARS-CoV-2 lineage and seasonal variations of viral spread. The objective of this retrospective study was to compare the characteristics and outcomes of patients admitted with confirmed coronavirus disease-19 (COVID-19) in the same season during the first (March 2020) and the third pandemic wave (March 2021, dominance of SARS-CoV-2 B.1.1.7 lineage) in an internal medicine ward of a large teaching hospital in Italy. Materials and methods: Data of 769 unvaccinated patients (399 from the first and 370 from the third wave) were collected from clinical records, including symptom type and duration, extension of lung abnormalities on chest computed tomography (CT) and PaO2/FiO2 ratio on admission arterial blood gas analysis. Results: Third wave patients were in average younger (median 65, interquartile range [IQR] 55-75, vs. 72, IQR 61-81 years old, p < 0.001), with less comorbidities and better pulmonary (CT visual score median 25, IQR 15-40, vs. 30, IQR 15-50, age- and sex-adjusted p = 0.017) and respiratory involvement (PaO2/FiO2 median 288, IQR 237-338, vs. 233, IQR 121-326 mmHg, age- and sex-adjusted p < 0.001) than first wave patients. Hospital mortality was lower (19% vs. 36%, p < 0.001), but not for subjects over 75 years old (46 vs. 49%). Age, number of chronic illnesses, PCT levels, CT visual score [Odds Ratio (OR) 1.022, 95% confidence interval (CI) 1.009-1.036, p < 0.001] and PaO2/FiO2 (OR 0.991, 95% CI 0.988-0.994, p < 0.001), but not the pandemic wave, were associated with mortality on stepwise multivariate logistic regression analysis. Conclusion: Despite the higher virulence of B.1.1.7 lineage, we detected milder clinical presentation and improved mortality in patients hospitalized during the third COVID-19 wave, with involvement of younger subjects. The reasons of this discrepancy are unclear, but could involve the population effect of vaccination campaigns, that were being conducted primarily in older frail subjects during the third wave.

Effects of a 2-year exercise training on neuromuscular system health in older individuals with low muscle function.

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 ameliorated overall SPPB performance (P = 0.007). Conversely, HALE showed 12.7% decrease in muscle CSA (P < 0.001), together with 5.1% and 5.5% reduction in PA and Lf (P < 0.001 and P = 0.001, respectively), and a 6.2% increase in CAF (P = 0.009) but improved SPPB balance score (P = 0.007). NfL concentration did not change in either group. In the population, negative correlations between changes in CAF concentration and SPPB total score were found (P = 0.047), whereas no correlation between NfL and SPPB variations was observed. CONCLUSIONS: The present findings suggest that our 2-year mixed aerobic, strength and balance training seemed effective for preventing the age and sarcopenia-related increases in CAF concentration, preserving NMJ stability as well as muscle structure (PA and Lf) and improving physical performance in sarcopenic older individuals.

The role of nutrition and the Mediterranean diet on the trajectories of cognitive decline.

The worldwide burden of dementia is immense, and set to increase to unprecedented levels in the coming decades, due to population aging. In the absence of disease-modifying treatment, there is therefore a strong rationale to support the assumption that acting on modifiable risk factors, especially in midlife, is a good strategy for reducing the burden of dementia. Among these risk factors, nutrition is key, as it is fundamental to healthy aging, and has interrelated benefits on a number of organ systems, metabolic processes and health states that can all contribute to modifying the risk of dementia. In this paper, we review the methodological challenges of comparing studies of dietary interventions. We then discuss the effect of genetics and the environment on brain health, and review in particular the literature data on the effect of nutrition on cognition. We summarize the body of data reporting the largely beneficial effects of the Mediterranean diet on brain health, and the possible mechanisms that mediate these effects. Finally, we discuss future perspectives for further research in the field, notably the "gut-brain axis", thought to be a key mediator of the effect of nutrition on brain health.

Impact of probiotics on muscle mass, muscle strength and lean mass: a systematic review and meta-analysis of randomized controlled trials.

Probiotics have shown potential to counteract sarcopenia, although the extent to which they can influence domains of sarcopenia such as muscle mass and strength in humans is unclear. The aim of this systematic review and meta-analysis was to explore the impact of probiotic supplementation on muscle mass, total lean mass and muscle strength in human adults. A literature search of randomized controlled trials (RCTs) was conducted through PubMed, Scopus, Web of Science and Cochrane Library from inception until June 2022. Eligible RCTs compared the effect of probiotic supplementation versus placebo on muscle and total lean mass and global muscle strength (composite score of all muscle strength outcomes) in adults (>18 years). To evaluate the differences between groups, a meta-analysis was conducted using the random effects inverse-variance model by utilizing standardized mean differences. Twenty-four studies were included in the systematic review and meta-analysis exploring the effects of probiotics on muscle mass, total lean mass and global muscle strength. Our main analysis (k = 10) revealed that muscle mass was improved following probiotics compared with placebo (SMD: 0.42, 95% CI: 0.10-0.74, I2  = 57%, P = 0.009), although no changes were revealed in relation to total lean mass (k = 12; SMD: -0.03, 95% CI: -0.19 - 0.13, I2  = 0%, P = 0.69). Interestingly, a significant increase in global muscle strength was also observed among six RCTs (SMD: 0.69, 95% CI: 0.33-1.06, I2  = 64%, P = 0.0002). Probiotic supplementation enhances both muscle mass and global muscle strength; however, no beneficial effects were observed in total lean mass. Investigating the physiological mechanisms underpinning different ageing groups and elucidating appropriate probiotic strains for optimal gains in muscle mass and strength are warranted.

Intestinal microbiome in normal ageing, frailty and cognition decline.

PURPOSE OF REVIEW: The intestinal microbiome modulates the risk of several age-related chronic diseases and syndromes, including frailty and neurodegenerative diseases. Herein we provided an update on the influence of gut microbiota on physical and cognitive performance in older age and suggest microbiota-targeted interventions for healthy ageing. RECENT FINDINGS: Low uniqueness index of the gut microbiome and high representation of Bacteroides are independently associated with mortality in older individuals, while the centenarian microbiome is characterized by high abundance of Lactobacilli and Bifidobacteria . Frailty syndrome, sarcopenia and cognitive decline are associated with reduced faecal microbiota biodiversity, reduced abundance of bacteria able to synthetize short-chain fatty acids (SCFA), including Faecalibacterium prausnitzii , and reduced faecal butyrate levels. Dietary intervention, especially involving Mediterranean diet, and exercise training seem to be associated with improved biodiversity of the microbiota, increased capacity of SCFA synthesis and, probably, protection against the onset of frailty and cognitive decline. SUMMARY: The gut microbiota biodiversity and composition may reflect the different ageing trajectory, but further research is needed to understand potential independent and combined effects of environmental and lifestyle factors in older adults, especially from a clinical point of view.

Sarcoidosis and COVID-19: At the Cross-Road between Immunopathology and Clinical Manifestation.

Coronavirus disease 2019 (COVID-19) has been associated with dysregulation of the immune system featuring inappropriate immune responses, exacerbation of inflammatory responses, and multiple organ dysfunction syndrome in patients with severe disease. Sarcoidosis, also known as Besnier-Boeck-Schaumann disease, is an idiopathic granulomatous multisystem disease characterized by dense epithelioid non-necrotizing lesions with varying degrees of lymphocytic inflammation. These two diseases have similar clinical manifestations and may influence each other at multiple levels, eventually affecting their clinical courses and prognosis. Notably, sarcoidosis patients are at high risk of severe COVID-19 pneumonia because of the underlying lung disease and chronic immunosuppressive treatment. In this narrative review, we will discuss interactions between sarcoidosis and COVID-19 in terms of clinical manifestations, treatment, and pathogenesis, including the role of the dysregulated renin-angiotensin system, altered immune responses involving increased cytokine levels and immune system hyperactivation, and cellular death pathways.