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 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.

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.

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.

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.

Untangling the link between the human gut microbiota composition and the severity of the symptoms of the COVID-19 infection.

Recent pandemic infection caused by SARS-CoV-2 (COVID-19) led the scientific community to investigate the possible causes contributing to the physiopathology of this disease. In this context, analyses of the intestinal microbiota highlighted possible correlation between host-associated bacterial communities and development of the COVID-19. Nevertheless, a detailed investigation of the role of the human microbiota in the severity of the symptoms of this disease is still lacking. This study performed a comprehensive meta-analysis of 323 faecal samples from public and novel Italian data sets based on the shotgun metagenomic approach. In detail, the comparative analyses revealed possible differences in the microbial biodiversity related to the individual health status, highlighting a species richness decrease in COVID-19 patients with a severe prognosis. Moreover, healthy subjects resulted characterized by a higher abundance of protective and health-supporting bacterial species, while patients affected by COVID-19 disease displayed a significant increase of opportunistic pathogen bacteria involved in developing putrefactive dysbiosis. Furthermore, prediction of the microbiome functional capabilities suggested that individuals affected by COVID-19 subsist in an unbalanced metabolism characterized by an overrepresentation of enzymes involved in the protein metabolism at the expense of carbohydrates oriented pathways, which can impact on disease severity and in excessive systemic inflammation.

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.

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 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.

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).

Lung Ultrasound in COVID-19 Pneumonia: Correlations with Chest CT on Hospital admission.

BACKGROUND: Lung ultrasound (LUS) is an accurate, safe, and cheap tool assisting in the diagnosis of several acute respiratory diseases. The diagnostic value of LUS in the workup of coronavirus disease-19 (COVID-19) in the hospital setting is still uncertain. OBJECTIVES: The aim of this observational study was to explore correlations of the LUS appearance of COVID-19-related pneumonia with CT findings. METHODS: Twenty-six patients (14 males, age 64 ± 16 years) urgently hospitalized for COVID-19 pneumonia, who underwent chest CT and bedside LUS on the day of admission, were enrolled in this observational study. CT images were reviewed by expert chest radiologists, who calculated a visual CT score based on extension and distribution of ground-glass opacities and consolidations. LUS was performed by clinicians with certified competency in thoracic ultrasonography, blind to CT findings, following a systematic approach recommended by ultrasound guidelines. LUS score was calculated according to presence, distribution, and severity of abnormalities. RESULTS: All participants had CT findings suggestive of bilateral COVID-19 pneumonia, with an average visual scoring of 43 ± 24%. LUS identified 4 different possible -abnormalities, with bilateral distribution (average LUS score 15 ± 5): focal areas of nonconfluent B lines, diffuse confluent B lines, small subpleural microconsolidations with pleural line irregularities, and large parenchymal consolidations with air bronchograms. LUS score was significantly correlated with CT visual scoring (r = 0.65, p < 0.001) and oxygen saturation in room air (r = -0.66, p < 0.001). CONCLUSION: When integrated with clinical data, LUS could represent a valid diagnostic aid in patients with suspect COVID-19 pneumonia, which reflects CT findings.

Delirium in COVID-19: epidemiology and clinical correlations in a large group of patients admitted to an academic hospital.

BACKGROUND: Delirium incidence and clinical correlates in coronavirus disease-19 (COVID-19) pneumonia are still poorly investigated. AIM: To describe the epidemiology of delirium in patients hospitalized for suspect COVID-19 pneumonia during the pandemic peak in an academic hospital of Northern Italy, identify its clinical correlations and evaluate the association with mortality. METHODS: The clinical records of 852 patients admitted for suspect COVID-19 pneumonia, defined as respiratory symptoms or fever or certain history of contact with COVID-19 patients, plus chest CT imaging compatible with alveolar-interstitial pneumonia, were retrospectively analyzed. Delirium was defined after careful revision of daily clinical reports in accordance with the Confusion Assessment Method criteria. Data on age, clinical presentation, comorbidities, drugs, baseline lab tests and outcome were collected. The factors associated with delirium, and the association of delirium with mortality, were evaluated through binary logistic regression models. RESULTS: Ninety-four patients (11%) developed delirium during stay. They were older (median age 82, interquartile range, IQR 78-89, vs 75, IQR 63-84, p < 0.001), had more neuropsychiatric comorbidities and worse respiratory exchanges at baseline. At multivariate models, delirium was independently and positively associated with age [odds ratio (OR) 1.093, 95% confidence interval (CI) 1.046-1.143, p < 0.001], use of antipsychotic drugs (OR 4.529, 95% CI 1.204-17.027, p = 0.025), serum urea and lactate-dehydrogenase at admission. Despite a higher mortality in patients with delirium (57% vs 30%), this association was not independent of age and respiratory parameters. CONCLUSIONS: Delirium represents a common complication of COVID-19 and a marker of severe disease course, especially in older patients with neuropsychiatric comorbidity.

The Gut-Muscle Axis in Older Subjects with Low Muscle Mass and Performance: A Proof of Concept Study Exploring Fecal Microbiota Composition and Function with Shotgun Metagenomics Sequencing.

The gut microbiota could influence the pathophysiology of age-related sarcopenia through multiple mechanisms implying modulation of chronic inflammation and anabolic resistance. The aim of this study was to compare the fecal microbiota composition and functionality, assessed by shotgun metagenomics sequencing, between two groups of elderly outpatients, differing only for the presence of primary sarcopenia. Five sarcopenic elderly subjects and twelve non-sarcopenic controls, classified according to lower limb function and bioimpedance-derived skeletal muscle index, provided a stool sample, which was analyzed with shotgun metagenomics approaches, to determine the overall microbiota composition, the representation of bacteria at the species level, and the prediction of bacterial genes involved in functional metabolic pathways. Sarcopenic subjects displayed different fecal microbiota compositions at the species level, with significant depletion of two species known for their metabolic capacity of producing short-chain fatty acids (SCFAs), Faecalibacterium prausnitzii and Roseburia inulinivorans, and of Alistipes shahii. Additionally, their fecal metagenome had different representation of genes belonging to 108 metabolic pathways, namely, depletion of genes involved in SCFA synthesis, carotenoid and isoflavone biotransformation, and amino acid interconversion. These results support the hypothesis of an association between microbiota and sarcopenia, indicating novel possible mediators, whose clinical relevance should be investigated in future studies.

Gut microbiome and kidney stone disease: not just an Oxalobacter story.

Intestinal regulation of oxalate absorption is a complex mechanism, not exclusively reliant on the oxalate-degrading anaerobe Oxalobacter formigenes. Using metagenomics, Miller et al. were able to describe a network of bacterial taxa co-occurring with Oxalobacter formigenes in fecal samples from non-stone forming controls and less represented in stone formers. These findings may help to illuminate why previous intervention studies with probiotics have failed to reduce the risk of hyperoxaluria, opening new possibilities for future research.

The intestinal microbiome and its relevance for functionality in older persons.

PURPOSE OF REVIEW: This article summarizes the advances of research on the role of the intestinal microbiota in influencing sarcopenia, frailty, and cognitive dysfunction in older individuals, and thus its relevance for healthy active ageing. RECENT FINDINGS: Age-related alterations of intestinal microbiota composition may negatively influence muscle protein synthesis and function by promoting chronic systemic inflammation, insulin resistance, oxidative stress, and reducing nutrient bioavailability. However, this 'gut-muscle axis' hypothesis is not supported by human data to date. Some observational studies have instead demonstrated that, in older individuals, frailty and Alzheimer-type dementia are associated with fecal microbiota dysbiosis, that is, reduced biodiversity and overexpression of pathobionts. The main possible mechanisms of the 'gut-brain axis' in cognitive function modulation include effects on neurotransmission, neuroinflammation, and amyloid deposition. Conversely, longevity in good health may be associated with the maintenance of a fecal microbiota composition similar to that of healthy young adults. However, the role of gut microbiota as an independent modulator of frailty and cognition still remains uncertain, being influenced by several physiological factors, including diet and exercise. SUMMARY: The intestinal microbiome composition represents a possible determinant of functional performance in older people, and a promising target for antiaging therapeutic interventions.

Exercise and immune system as modulators of intestinal microbiome: implications for the gut-muscle axis hypothesis.

Exercise is a possible modulator of intestinal microbiome composition, since some investigations have shown that it is associated with increased biodiversity and representation of taxa with beneficial metabolic functions. Conversely, training to exhaustion can be associated with dysbiosis of the intestinal microbiome, promoting inflammation and negative metabolic consequences. Gut microbiota can, in turn, influence the pathophysiology of several distant organs, including the skeletal muscle. A gut-muscle axis may in fact regulate muscle protein deposition and muscle function. In older individuals, this axis may be involved in the pathogenesis of muscle wasting disorders through multiple mechanisms, involving transduction of pro-anabolic stimuli from dietary nutrients, modulation of inflammation and insulin sensitivity. The immune system plays a fundamental role in these processes, being influenced by microbiome composition and at the same time contributing to shape microbial communities. In this review, we summarize the most recent literature acquisitions in this field, disentangling the complex relationships between exercise, microbiome, immune system and skeletal muscle function and proposing an interpretative framework that will need verification in future studies.

Gut Microbiota and Microbiota-Related Metabolites as Possible Biomarkers of Cognitive Aging.

Gut microbiota composition and functionality can influence the pathophysiology of age-related cognitive impairment and dementia, according to a large number of animal studies. The translation of this concept to humans is still uncertain, due to the relatively low number of clinical studies focused on fecal microbiota and large number of environmental factors that influence the microbiota composition. However, the fecal microbiota composition of older patients with dementia is deeply different from that of healthy active controls, conditioning a different metabolic profile. The possible use of fecal microbiota-related parameters and microbiota-derived metabolites as biomarkers of cognitive performance and dementia is critically reviewed in this paper, focusing on the most promising areas of research for the future.

Short-Physical Performance Battery (SPPB) score is associated with falls in older outpatients.

BACKGROUND: The capacity of Short-Physical Performance Battery (SPPB) test to discriminate between fallers and non-fallers is controversial, and has never been compared with fall risk assessment-specific tools, such as Performance-Oriented Mobility Assessment (POMA). AIM: To verify the association of SPPB and POMA scores with falls in older outpatients. METHODS: 451 older subjects (150 males, mean age 82.1 ± 6.8) evaluated in a geriatric outpatient clinic for suspected frailty were enrolled in this cross-sectional study. Self-reported history of falls and medication history were carefully assessed. Each participant underwent comprehensive geriatric assessment, including SPPB, POMA, Geriatric Depression Scale (GDS), mini-mental state examination (MMSE) and mini-nutritional assessment-short form (MNA-SF). Multivariate logistic regression and receiver-operating characteristic (ROC) analyses were performed to determine the factors associated with the status of faller. RESULTS: 245 (54.3%) subjects were identified as fallers. They were older and had lower SPPB and POMA test scores than non-fallers. At ROC analysis, SPPB (AUC 0.676, 95% CI 0.627-0.728, p < 0.001) and POMA (AUC 0.677, 95% CI 0.627-0.726, p < 0.001) scores were both associated with falls. At multivariate logistic regression models, SPPB total score (OR 0.83, 95% CI 0.76-0.92, p < 0.001), POMA total score (OR 0.94, 95% CI 0.91-0.98, p = 0.002) and SPPB balance score alteration (OR 2.88, 95% CI 1.42-5.85, p = 0.004), but not POMA balance subscale score alteration, were independently associated with recorded falls, as also GDS, MMSE and MNA-SF scores. CONCLUSIONS: SPPB total score was independently associated with reported falls in older outpatients, resulting non-inferior to POMA scale. The use of SPPB for fall risk assessment should be implemented.

Understanding the gut-kidney axis in nephrolithiasis: an analysis of the gut microbiota composition and functionality of stone formers.

OBJECTIVES: The involvement of the gut microbiota in the pathogenesis of calcium nephrolithiasis has been hypothesised since the discovery of the oxalate-degrading activity of Oxalobacter formigenes, but never comprehensively studied with metagenomics. The aim of this case-control study was to compare the faecal microbiota composition and functionality between recurrent idiopathic calcium stone formers (SFs) and controls. DESIGN: Faecal samples were collected from 52 SFs and 48 controls (mean age 48±11). The microbiota composition was analysed through 16S rRNA microbial profiling approach. Ten samples (five SFs, five controls) were also analysed with deep shotgun metagenomics sequencing, with focus on oxalate-degrading microbial metabolic pathways. Dietary habits, assessed through a food-frequency questionnaire, and 24-hour urinary excretion of prolithogenic and antilithogenic factors, including calcium and oxalate, were compared between SFs and controls, and considered as covariates in the comparison of microbiota profiles. RESULTS: SFs exhibited lower faecal microbial diversity than controls (Chao1 index 1460±363vs 1658±297, fully adjusted p=0.02 with stepwise backward regression analysis). At multivariate analyses, three taxa (Faecalibacterium, Enterobacter, Dorea) were significantly less represented in faecal samples of SFs. The Oxalobacter abundance was not different between groups. Faecal samples from SFs exhibited a significantly lower bacterial representation of genes involved in oxalate degradation, with inverse correlation with 24-hour oxalate excretion (r=-0.87, p=0.002). The oxalate-degrading genes were represented in several bacterial species, whose cumulative abundance was inversely correlated with oxaluria (r=-0.85, p=0.02). CONCLUSIONS: Idiopathic calcium SFs exhibited altered gut microbiota composition and functionality that could contribute to nephrolithiasis physiopathology.

Short-Term Changes in Urinary Relative Supersaturation Predict Recurrence of Kidney Stones: A Tool to Guide Preventive Measures in Urolithiasis.

PURPOSE: Kidney stone disease is characterized by a relatively high rate of recurrence. In our study we analyzed the association between relative supersaturation and the risk of stone recurrence. Additionally, we examined the association between the risk of recurrence and changes in relative supersaturation and urinary composition after 1 week of medical treatment. MATERIALS AND METHODS: We performed a post hoc analysis of data from a previously published randomized controlled trial comparing the effect of 2 diets in 120 men with recurrent calcium oxalate stones and hypercalciuria. Baseline and followup 24-hour urine parameters were used to calculate the relative supersaturation of calcium oxalate, calcium phosphate and uric acid using the EQUIL2, JESS and LithoRisk computer programs. Cox models were used to calculate the estimated association between each baseline relative supersaturation, and 1-week changes and the risk of recurrence during followup. RESULTS: During a 5-year followup 35 patients (34%) experienced recurrence. A reduction in calcium oxalate relative supersaturation at 1 week was significantly associated with a lower risk of recurrence using the EQUIL2 calculation (for every 10% reduction from baseline HR 0.92, 95% CI 0.86-1.00, p = 0.044). However, there was no association for relative supersaturation calculated by other methods or for the relative supersaturation of other salts. Changes in the 24-hour urine excretion of citrate, potassium and magnesium were significantly associated with a risk of recurrence. CONCLUSIONS: In recurrent stone formers with hypercalciuria baseline values and changes in the relative supersaturation of calcium oxalate may be associated with the risk of recurrence. Changes in urinary citrate, potassium and magnesium following dietary intervention may also be predictive.