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.

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.

BackgroundSerum procalcitonin and high-sensitivity C-reactive protein (hs-CRP) elevations have been associated with pneumonia in adults. Our aim was to establish their diagnostic usefulness in a cohort of hospitalized multimorbid patients ≥65 years old admitted to hospital with acute respiratory symptoms.MethodsWith a retrospective cohort study design, all multimorbid patients ≥65 years-old with acute respiratory symptoms admitted to an internal medicine hospital ward in Italy from January to August 2013 were evaluated. Pneumonia diagnosis, comorbidities expressed through Cumulative Illness Rating Scale (CIRS), setting of living, length of stay, serum hs-CRP and procalcitonin at admission were collected for each patient. Data were analyzed with Mann-Whitney’s U test and multivariate Cox logistic regression analysis. A Receiver Operating Characteristic (ROC) curve was used to verify each biomarker’s association with pneumonia diagnosis.ResultsFour hundred fifty five patients (227 M) were included in the study, of whom 239 with pneumonia (138 M, mean age 80 ± 13) and 216 without pneumonia (89 M, mean age 80 ± 14). After adjustment for age and sex, median levels of hs-CRP were significantly higher in patients with pneumonia (116 mg/L, IQR 46.5–179.0, vs 22.5 mg/dl, IQR 6.9–84.4, p < 0.0001), while procalcitonin median levels were not (0.22 ng/ml IQR 0.12–0.87, vs 0.15 ng/ml, IQR 0.10–0.35, p = 0.08). The ROC analysis showed that, unlike procalcitonin, hs-CRP values were predictive of pneumonia (AUC 0.76, 95 % CI 0.72–0.79, p < 0.0001, cut-off value 61 mg/L), even after adjustment for possible confounders including nursing home residence and dementia. Serum hs-CRP levels >61 mg/L were independently associated with a 3.59-fold increased risk of pneumonia (OR 3.59, 95 % CI 2.35–5.48, p < 0.0001).ConclusionIn elderly multimorbid patients who require hospital admission for respiratory symptoms, serum hs-CRP testing seems to be more useful than procalcitonin for guiding the diagnostic process when clinical suspicion of pneumonia is present. Procalcitonin testing might hence be not recommended in this setting.

Objectives Effective treatments for coronavirus disease 2019 (COVID-19) are urgently needed. We hypothesized that colchicine, by counteracting proinflammatory pathways implicated in the uncontrolled inflammatory response of COVID-19 patients, reduces pulmonary complications, and improves survival. Methods This retrospective study included 71 consecutive COVID-19 patients (hospitalized with pneumonia on CT scan or outpatients) who received colchicine and compared with 70 control patients who did not receive colchicine in two serial time periods at the same institution. We used inverse probability of treatment propensity-score weighting to examine differences in mortality, clinical improvement (using a 7-point ordinary scale), and inflammatory markers between the two groups. Results Amongst the 141 COVID-19 patients (118 [83.7%] hospitalized), 70 (50%) received colchicine. The 21-day crude cumulative mortality was 7.5% in the colchicine group and 28.5% in the control group (P = 0.006; adjusted hazard ratio: 0.24 [95%CI: 0.09 to 0.67]); 21-day clinical improvement occurred in 40.0% of the patients on colchicine and in 26.6% of control patients (adjusted relative improvement rate: 1.80 [95%CI: 1.00 to 3.22]). The strong association between the use of colchicine and reduced mortality was further supported by the diverging linear trends of percent daily change in lymphocyte count (P = 0.018), neutrophil-to-lymphocyte ratio (P = 0.003), and in C-reactive protein levels (P = 0.009). Colchicine was stopped because of transient side effects (diarrhea or skin rashes) in 7% of patients. Conclusion In this retrospective cohort study colchicine was associated with reduced mortality and accelerated recovery in COVID-19 patients. This support the rationale for current larger randomized controlled trials testing the safety/efficacy profile of colchicine in COVID-19 patients.

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The prognostic value of quick Sepsis-related Organ Failure Assessment (qSOFA) score in geriatric patients is uncertain. We aimed to compare qSOFA vs. Systemic Inflammatory Response Syndrome (SIRS) criteria for mortality prediction in older multimorbid subjects, admitted for suspected sepsis in a geriatric ward. We prospectively enrolled 272 patients (aged 83.7 ± 7.4). At admission, qSOFA and SIRS scores were calculated. Mortality was assessed during hospital stay and three months after discharge. The predictive capacity of qSOFA and SIRS was assessed by calculating the Area Under the Receiver Operating Characteristic Curve (AUROC), through pairwise AUROC comparison, and multivariable logistic regression analysis. Both qSOFA and SIRS exhibited a poor prognostic performance (AUROCs 0.676, 95% CI 0.609–0.738, and 0.626, 95% CI 0.558–0.691 for in-hospital mortality; 0.684, 95% CI 0.614–0.748, and 0.596, 95% CI 0.558–0.691 for pooled three-month mortality, respectively). The predictive capacity of qSOFA showed no difference to that of SIRS for in-hospital mortality (difference between AUROCs 0.05, 95% CI −0.05 to 0.14, p = 0.31), but was superior for pooled three-month mortality (difference between AUROCs 0.09, 95% CI 0.01–0.17, p = 0.029). Multivariable logistic regression analysis, accounting for possible confounders, including frailty, showed that both scores were not associated with in-hospital mortality, although qSOFA, unlike SIRS, was associated with pooled three-month mortality. In conclusion, neither qSOFA nor SIRS at admission were strong predictors of mortality in a geriatric acute-care setting. Traditional geriatric measures of frailty may be more useful for predicting adverse outcomes in this setting.

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Older multimorbid frail subjects have been severely involved in the coronavirus disease-19 (COVID-19) pandemic. The aim of this retrospective study is to compare the clinical features and outcomes of patients admitted in different phases of the outbreak in a COVID-19 hospital hub, with a particular focus on age, multimorbidity, and functional dependency. The clinical records of 1264 patients with clinical and radiological features compatible with COVID-19 pneumonia admitted in February–June, 2020, were analyzed, retrieving demographical, clinical, laboratory data, and outcomes. All variables were compared after stratification by the period of admission (first phase: rising slope of pandemic wave; second phase: plateau and falling slope), age, results of the first reverse transcriptase-polymerase chain reaction (RT-PCR) test for detection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), multimorbidity (≥2 chronic diseases), and presence of disability. Factors independently associated with hospital mortality were determined by multivariate forward-selection logistic regression. Patients admitted during the second phase were older, more frequently multimorbid, disabled, and of female gender. However, on admission they exhibited milder respiratory impairment (PaO2/FiO2 268, IQR 174–361, vs. 238, IQR 126–327 mmHg, p < 0.001) and lower mortality (22% vs. 27%, p < 0.001). Age, respiratory exchanges, positive RT-PCR test, number of chronic diseases (odds ratio (OR) 1.166, 95% confidence interval (CI) 1.036–1.313, p = 0.011), and disability (OR 1.927, 95% CI 1.027–3.618, p = 0.022) were positively associated with mortality, while admission during the second phase exhibited an inverse association (OR 0.427, 95% CI 0.260–0.700, p = 0.001). In conclusion, older multimorbid patients were mainly hospitalized during the second phase of the pandemic wave. The prognosis was strongly influenced by the COVID-19 phenotype and period of admission, not just by age, multimorbidity, and disability.