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.

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.

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.

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.

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.

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.

Thoracic Ultrasound Strain Elastosonography as a Noninvasive Biomarker of Chronic Obstructive Pulmonary Disease-Associated Lung Injury: A Feasibility Study.

BACKGROUND: Transthoracic strain elastosonography (TSE) is being increasingly studied for estimating lung-pleura interface stiffness in pulmonary fibrosis. To date, no data exist on its application in chronic obstructive pulmonary disease (COPD). OBJECTIVES: The aim of this article was to describe the TSE pattern in patients with COPD and healthy subjects, either smokers or nonsmokers, and evaluate the feasibility of this technique for early detection of COPD in smokers. METHODS: Nineteen patients with COPD, twenty-one healthy smokers, and twenty healthy nonsmokers underwent spirometry and TSE. Elastosonography was performed by one ultrasound-certified operator on 12 different scans for each participant, on right and left sides, anteriorly and posteriorly, on upper and lower lobes. For each scan, lung-pleura interface stiffness index (SI) was calculated, and the average SI on all 12 scans (SI-12) and on posterior basal scans (SI-PB) was calculated and used for comparisons among groups of participants and correlations with spirometric parameters. RESULTS: Patients with lung injury (i.e., with COPD or healthy smokers) exhibited significantly increased lung-pleura interface stiffness on TSE, measured by SI-12 and SI-PB, than healthy nonsmokers (p < 0.05). Unlike SI-12, SI-PB was able to discriminate between subjects with lung injury and healthy nonsmokers on receiver operating characteristics analysis (area under the curve 0.846, 95% confidence interval 0.730-0.926, p < 0.001) and correlated with forced expiratory volume in the first second (r = -0.31, p = 0.018). CONCLUSION: The measurement of lung-pleura interface stiffness by TSE in posterior basal scans was able to discriminate patients with lung injury from healthy nonsmokers. The role of TSE for detecting early lung damage in COPD should be further investigated.

Interaction Between Diet and Microbiota in the Pathophysiology of Alzheimer's Disease: Focus on Polyphenols and Dietary Fibers.

Animal studies increasingly indicate that the gut microbiota composition and function can be involved in the pathophysiology and progression of Alzheimer's disease (AD) at multiple levels. However, few studies have investigated this putative gut-brain axis in human beings, and none of them considered diet as a determinant of intestinal microbiota composition. Epidemiological studies highlight that a high intake of fruit and vegetables, such as that typical of the Mediterranean diet, can modulate AD progression. Thus, nutritional interventions are being increasingly studied as a possible non-pharmacological strategy to slow down the progression of AD. In particular, polyphenols and fibers represent the nutritional compounds with the higher potential of counterbalancing the pathophysiological mechanisms of dementia due to their antioxidant, anti-inflammatory, and anti-apoptotic properties. These actions are mediated by the gut microbiota, that can transform polyphenols and fibers into biologically active compounds including, among others, phenyl-γ-valerolactones, urolithins, butyrate, and other short-chain fatty acids. In this review, the complex mechanisms linking nutrition, gut microbiota composition, and pathophysiology of cognitive decline in AD are discussed, with a particular focus on the role of polyphenols and fibers. The gaps between pre-clinical and clinical studies are particularly emphasized, as well as the urgent need for studies comprehensively evaluating the link between nutrition, microbiome, and clinical aspects of AD.

Implementing a multidisciplinary rapid geriatric observation unit for non-critical older patients referred to hospital: observational study on real-world data.

BACKGROUND: Geriatric rapid observation units may represent an alternative to hospitalization in older patients with non-critical acute illness. AIMS: To describe the characteristics and outcomes of patients admitted to a geriatric observation unit called URGe (Unità Geriatrica Rapida), implemented in an Italian hospital and characterized by multidisciplinary medical staff with geriatric expertise, fast-track access to diagnostic resources, regular use of point-of-care ultrasound and predicted length of stay (LOS) < 72 h. METHODS: The medical records of patients admitted to URGe during a 3-month period (452 subjects, 247 F and 205 M, median age 82 years, IQR 77-87) were retrospectively examined. The primary study endpoint was transferral from URGe to regular wards. Baseline covariates included demographics, comprehensive geriatric assessment, acute illnesses, comorbidities, vital signs and routine laboratory tests. RESULTS: Despite elevated burden of multimorbidity (median number of chronic diseases 4, IQR 2-5) and frailty (median Rockwood Clinical Frailty Scale score 4, IQR 3-6), only 137 patients (30.3%) required transferral from URGe to regular wards. The main factors positively associated with this outcome were Rockwood score, fever, cancer and red cell distribution width (P < 0.05 on multivariate logistic regression model). The rate of complications (mortality, delirium, and falls) during URGe stay was low (0.5%, 7% and 2%, respectively). Overall duration of hospital stay was lower than that of a group of historical controls matched by age, sex, main diagnosis, multimorbidity and frailty. CONCLUSIONS: The URGe model of acute geriatric care is feasible, safe and has the potential of reducing unnecessary hospitalizations of older patients.

The Effects of Lifestyle and Diet on Gut Microbiota Composition, Inflammation and Muscle Performance in Our Aging Society.

Living longer is associated with an increased risk of chronic diseases, including impairments of the musculoskeletal and immune system as well as metabolic disorders and certain cancers, each of which can negatively affect the relationship between host and microbiota up to the occurrence of dysbiosis. On the other hand, lifestyle factors, including regular physical exercise and a healthy diet, can affect skeletal muscle and immune aging positively at all ages. Accordingly, health benefits could partly depend on the effect of such interventions that influence the biodiversity and functionality of intestinal microbiota. In the present review, we first discuss the physiological effects of aging on the gut microbiota, immune system, and skeletal muscle. Secondly, we describe human epidemiological evidence about the associations between physical activity and fitness and the gut microbiota composition in older adults. The third part highlights the relevance and restorative mechanisms of immune protection through physical activity and specific exercise interventions during aging. Fourth, we present important research findings on the effects of exercise and protein as well as other nutrients on skeletal muscle performance in older adults. Finally, we provide nutritional recommendations to prevent malnutrition and support healthy active aging with a focus on gut microbiota. Key nutrition-related concerns include the need for adequate energy and protein intake for preventing low muscle mass and a higher demand for specific nutrients (e.g., dietary fiber, polyphenols and polyunsaturated fatty acids) that can modify the composition, diversity, and metabolic capacity of the gut microbiota, and may thus provide a practical means of enhancing gut and systemic immune function.

The Clinical Significance of Procalcitonin Elevation in Patients over 75 Years Old Admitted for COVID-19 Pneumonia.

AIM: To investigate the clinical significance of procalcitonin (PCT) elevation on hospital admission for coronavirus disease-19 (COVID-19) and its association with mortality in oldest old patients (age > 75 years). METHODS: The clinical records of 1074 patients with chest high-resolution computed-tomography (HRCT) positive for interstitial pneumonia and symptoms compatible for COVID-19, hospitalized in medical wards during the first pandemic wave in a single academic center in Northern Italy, were retrospectively analyzed. All patients had serum PCT testing performed within six hours from admission. Information on COVID-19-related symptoms, comorbidities, drugs, autonomy in daily activities, respiratory exchanges, other routine lab tests, and outcomes were collected. Clinical characteristics were compared across different admission PCT levels and ages. The association of admission PCT with mortality was tested separately in participants aged > 75 and ≤75 years old by stepwise multivariate Cox regression model with forward selection. RESULTS: With increasing classes of PCT levels (<0.05, 0.05-0.49, 0.5-1.99, and ≥2 ng/ml), there was a significant trend (P < 0.0001) towards older age, male gender, wider extension of lung involvement on HRCT, worse respiratory exchanges, and several other laboratory abnormalities. Each incremental PCT class was associated with increased risk of hospital death at multivariate models in subjects older than 75 (hazard ratio for PCT ≥ 2 vs. <0.05 ng/ml: 30.629, 95% confidence interval 4.176-224.645, P = 0.001), but not in subjects aged 75 or younger. CONCLUSIONS: In patients admitted for COVID-19, PCT elevation was associated with several clinical, radiological, and laboratory characteristics of disease severity. However, PCT elevation was strongly associated with hospital mortality only in oldest old subjects (age > 75).

Effects of the COVID-19 Epidemic on Hospital Admissions for Non-Communicable Diseases in a Large Italian University-Hospital: A Descriptive Case-Series Study.

BACKGROUND: Concern is growing about the negative consequences that response measures to the COVID-19 epidemic may have on the management of other medical conditions. METHODS: A retrospective descriptive case-series study conducted at a large University-hospital in northern Italy, an area severely hit by the epidemic. RESULTS: Between 23 February and 14 May 2020, 4160 (52%) COVID-19 and 3778 (48%) non-COVID-19 patients were hospitalized. COVID-19 admissions peaked in the second half of March, a period characterized by an extremely high mortality rate (27.4%). The number of admissions in 2020 was similar to 2019, but COVID-19 patients gradually occupied all available beds. Comparison between COVID-19 and non-COVID-19 admissions in 2020 revealed significant differences concerning all age classes and gender. Specifically, COVID-19 patients were older, predominantly male, and exhibited more comorbidities. Overall, admissions for non-communicable diseases (NCDs) in 2020 vs. 2019 dropped by approximately one third. Statistically significant reductions were observed for acute myocardial infarction (-78, -33.9%), cerebrovascular disease (-235, -41.5%), and cancer (-368, -31.9%). While the first two appeared equally distributed between COVID-19 and non-COVID-19 patients, chronic NCDs were statistically significantly more frequent in the former, except cancer, which was less frequent in COVID-19 patients. CONCLUSIONS: Prevention of collateral damage to patients with other diseases should be an integral part of epidemic response plans. Prospective cohort studies are needed to understand the long-term impact.

The right immune-modulation at the right time: thymosin α1 for prevention of severe COVID-19 in cancer patients.

We presented the rationale for the use of thymosin α1 as prophylaxis of severe COVID-19 in cancer patients undergoing active treatment, constituting the background for the PROTHYMOS study, a prospective, multicenter, open-label, Phase II randomized study, currently in its start-up phase (Eudract no. 2020-006020-13). We aim to offer new hope for this incurable disease, especially to frail patient population, such as patients with cancer. The hypothesis of an effective prophylactic approach to COVID-19 would have immediate clinical relevance, especially given the lack of curative approaches. Moreover, in the 'COVID-19 vaccine race era' both clinical and biological results coming from the PROTHYMOS trials could even support the rationale for future combinatorial approaches, trying to rise vaccine efficacy in frail individuals.

Clinical Features, Histopathology and Differential Diagnosis of Sarcoidosis.

Sarcoidosis is a chameleon disease of unknown etiology, characterized by the growth of non-necrotizing and non-caseating granulomas and manifesting with clinical pictures that vary on the basis of the organs that are mainly affected. Lungs and intrathoracic lymph nodes are the sites that are most often involved, but virtually no organ is spared from this disease. Histopathology is distinctive but not pathognomonic, since the findings can be found also in other granulomatous disorders. The knowledge of these findings is important because it could be helpful to differentiate sarcoidosis from the other granulomatous-related diseases. This review aims at illustrating the main clinical and histopathological findings that could help clinicians in their routine clinical practice.

Gut Microbiota, Muscle Mass and Function in Aging: A Focus on Physical Frailty and Sarcopenia.

Human gut microbiota is able to influence the host physiology by regulating multiple processes, including nutrient absorption, inflammation, oxidative stress, immune function, and anabolic balance. Aging is associated with reduced microbiota biodiversity, increased inter-individual variability, and over-representation of pathobionts, and these phenomena may have great relevance for skeletal muscle mass and function. For this reason, the presence of a gut-muscle axis regulating the onset and progression of age-related physical frailty and sarcopenia has been recently hypothesized. In this narrative review, we summarize the studies supporting a possible association between gut microbiota-related parameters with measures of muscle mass, muscle function, and physical performance in animal models and humans. Reduced muscle mass has been associated with distinct microbiota composition and reduced fermentative capacity in mice, and the administration of probiotics or butyrate to mouse models of muscle wasting has been associated with improved muscle mass. However, no studies have targeted the human microbiome associated with sarcopenia. Limited evidence from human studies shows an association between microbiota composition, involving key taxa such as Faecalibacterium and Bifidobacterium, and grip strength. Similarly, few studies conducted on patients with parkinsonism showed a trend towards a different microbiota composition in those with reduced gait speed. No studies have assessed the association of fecal microbiota with other measures of physical performance. However, several studies, mainly with a cross-sectional design, suggest an association between microbiota composition and frailty, mostly assessed according to the deficit accumulation model. Namely, frailty was associated with reduced microbiota biodiversity, and lower representation of butyrate-producing bacteria. Therefore, we conclude that the causal link between microbiota and physical fitness is still uncertain due to the lack of targeted studies and the influence of a large number of covariates, including diet, exercise, multimorbidity, and polypharmacy, on both microbiota composition and physical function in older age. However, the relationship between gut microbiota and physical function remains a very promising area of research for the future.

The Urinary Microbiome and Anticancer Immunotherapy: The Potentially Hidden Role of Unculturable Microbes.

Several urinary disorders, including overactive bladder, urinary incontinence, and interstitial cystitis, are often characterized by negative urine cultures. The application of metagenomics (i.e., 16S rRNA microbial profiling or whole-genome shotgun sequencing) to urine samples has enabled the identification of previously undetected bacteria, contributing to the discovery and characterization of the urinary microbiome. The most frequent species isolated are Lactobacillus (15%), Corynebacterium (14.2%), Streptococcus (11.9%), Actinomyces (6.9%), and Staphylococcus (6.9%). Although several studies are emerging in this context, the role of urinary microbiota in the pathogenesis of infections and in tumor carcinogenesis remains unclear. Furthermore, data on the activity of gut microbiota in modulating sensitivity to immune checkpoint inhibitors in advanced cancer patients suggest that the influence of urinary microbiota on tumor response to anticancer therapy should also be investigated. Moreover, its possible relationship with tumor mutational burden, which is in turn correlated with response to immunotherapy, should be the focus of future studies. Of note, the effect of antibiotics on this complex scenario seems to deserve careful consideration.

Ultrasound imaging of abdominal sarcoidosis: State of the art.

Since it has been recognized that sarcoidosis (SA) is not an exclusive disorder of the lungs but can also affect other organs such as the liver and spleen, efforts have been made to define specific imaging criteria for the diagnosis of the single organ involvement, and the concept has been reinforced that the exclusion of alternative causes is important to achieve the correct diagnosis. Ultrasound (US) is a useful tool to evaluate patients with suspected abdominal SA, such as of the liver, spleen, kidney, pancreas and other organs, showing findings such as organomegaly, focal lesions and lymphadenopathy. While the diagnosis of abdominal SA is more predictable in the case of involvement of other organs (e.g., lungs), the problem is more complex in the case of isolated abdominal SA. The recent use of contrast-enhanced ultrasound and endoscopic ultrasound elastography has provided additional information about the enhancement patterns and tissue rigidity in abdominal SA. Here we critically review the role of US in abdominal SA, reporting typical findings and limitations of current evidence and by discussing future perspectives of study.