Intestinal Microbiota and Derived Metabolites in Myocardial Fibrosis and Postoperative Atrial Fibrillation.

The high incidence of atrial fibrillation (AFib) following cardiac surgery (postoperative atrial fibrillation, POAF) relies on specific surgical features. However, in the setting of POAF, the role of the microbiome in the modulation of cardiac fibrosis is still not clear. This study aimed to analyze the effect of the microbiome and its main metabolic product (trimethylamine-N-oxide, TMAO) in the fibrosis of myocardial tissue, to investigate its role in POAF. Patients undergoing elective cardiac surgery with cardiopulmonary bypass, central atrio-caval cannulation and no history of AFib, were included. A fragment of the right atrium was analyzed for qualitative and mRNA-quantitative evaluation. A preoperative blood sample was analyzed with enzyme-linked immunosorbent assay (ELISA). A total of 100 patients have been included, with POAF occurring in 38%. Histologically, a higher degree of fibrosis, angiogenesis and inflammation has been observed in POAF. Quantitative evaluation showed increased mRNA expression of collagen-1, collagen-3, fibronectin, and transforming growth factor beta (TGFb) in the POAF group. ELISA analysis showed higher levels of TMAO, lipopolysaccharide and TGFb in POAF, with similar levels of sP-selectin and zonulin. TMAO ≥ 61.8 ng/mL (odds ratio, OR 2.88 [1.35-6.16], p = 0.006), preoperative hemoglobin < 13.1 g/dL (OR 2.37 [1.07-5.24], p = 0.033) and impaired right ventricular function (OR 2.38 [1.17-4.83], p = 0.017) were independent predictors of POAF. Also, TMAO was significantly associated with POAF by means of increased fibrosis. Gut microbiome product TMAO is crucial for myocardial fibrosis, which is a key factor for POAF. Patients in preoperative sinus rhythm who will develop POAF have increased genetic expression of pro-fibrotic genes and enhanced fibrosis in histological staining. Elevated TMAO level (≥61.8 ng/mL) is an independent risk factor for POAF.

Assessment of cardiopulmonary capacity in deconditioned athletes because of knee injury.

BACKGROUND: An athlete's career inevitably goes through periods of forced physical exercise interruption like a knee injury. Advanced echocardiographic methods and cardiopulmonary exercise testing (CPET) are essential in evaluating athletes in the period elapsing after the injury. However, the feasibility of a maximal pre-surgery CPET and the capacity of resting advanced echocardiographic techniques to predict cardiorespiratory capacity still need to be clarified. METHODS: We evaluated 28 non-professional athletes aged 18-52, involved in prevalently aerobic or alternate aerobic/anaerobic sports activities, affected by a knee pathology with indications for surgical treatment. The evaluation was performed at rest by trans-thoracic echocardiography, including global longitudinal strain (GLS) and myocardial work (MW) assessment, and during exercise by CPET. RESULTS: The percent-predicted peak oxygen consumption (peak VO2%) was 82.8±13.7%, the mean respiratory exchange ratio was 1.16±0.08, and the mean ventilation/carbon dioxide (VE/VCO2) slope was 24.23±3.36. Peak VO2% negatively correlated with GLS (r=-0.518, P=0.003) and global wasted work (GWW) (r =-0.441, P=0.015) and positively correlated with global work efficiency (GWE) (r=0.455, P=0.012). Finally, we found that the VE/VCO2 slope during exercise was negatively correlated with GWE (r=-0.585, P=0.001) and positively correlated with GWW (r=0.499, P=0.005). CONCLUSIONS: A maximal CPET can be obtained in deconditioned athletes because of a knee injury, allowing a comprehensive functional pre-surgery evaluation. In these patients, peak VO2 is reduced due to decreased physical activity after injury; however, a lower cardiopulmonary efficiency may be a concause of the injury itself. In addition, we demonstrated that the MW indexes obtained at rest could predict exercise capacity and ventilatory efficiency as evaluated by CPET.

Clinical outcomes and phenotypes of respiratory failure in older subjects admitted to an acute care geriatric hospital ward.

Respiratory failure (RF) is frequent in hospitalized older patients, but was never systematically investigated in large populations of older hospitalized patients. We conducted a retrospective administrative study based on hospitalizations of a Geriatrics Unit regarding 2014, 2015, and 2016. Patients underwent daily screening for hypoxia. Hospital discharge records were coded through a standardized methodology. RF, defined as documented hypoxia on room air, was always coded, whenever present. We investigated how RF affected clinical outcomes, whether RF grouped into specific comorbidity phenotypes, and how phenotypes associated with the outcomes. RF was coded in 48.6% of the 1,810 hospitalizations. RF patients were older and more frequently had congestive heart failure (CHF: 49 vs 23%), chronic obstructive pulmonary disease (COPD: 27 vs 6%), pneumonia (14 vs 4%), sepsis (12 vs 7%), and pleural effusion (6 vs 3%), than non-RF patients. RF predicted longer length of stay (a-Beta 2.05, 95% CI 1.4-2.69; p < 0.001) and higher in-hospital death/intensive care units (ICU) need (aRR 7.12, 5-10.15; p < 0.001) after adjustment for confounders (linear and Poisson regression with robust error variance). Among RF patients, cerebrovascular disease, cancer, electrolyte disturbances, sepsis, and non-invasive ventilation predicted increased, while CHF and COPD predicted decreased in-hospital death/ICU need. The ONCO (cancer) and Mixed (cerebrovascular disease, dementia, pneumonia, sepsis, electrolyte disturbances, bedsores) phenotypes displayed higher in-hospital death/ICU need than CARDIO (CHF) and COPD phenotypes. In this study, RF predicted increased hospital death/ICU need and longer hospital stay, but also reflected diverse underlying conditions and clinical phenotypes that accounted for different clinical courses.

Poor accuracy and sustainability of the first-step FIB4 EASL pathway for stratifying steatotic liver disease risk in the general population.

BACKGROUND AND AIMS: The European Association for the Study of the Liver introduced a clinical pathway (EASL CP) for screening significant/advanced fibrosis in people at risk of steatotic liver disease (SLD). We assessed the performance of the first-step FIB4 EASL CP in the general population across different SLD risk groups (MASLD, Met-ALD and ALD) and various age classes. METHODS: We analysed a total of 3372 individuals at risk of SLD from the 2017-2018 National Health and Nutrition Examination Survey (NHANES17-18), projected to 152.3 million U.S. adults, 300,329 from the UK Biobank (UKBB) and 57,644 from the Biobank Japan (BBJ). We assessed liver stiffness measurement (LSM) ≥8 kPa and liver-related events occurring within 3 and 10 years (3/10 year-LREs) as outcomes. We defined MASLD, MetALD, and ALD according to recent international recommendations. RESULTS: FIB4 sensitivity for LSM ≥ 8 kPa was low (27.7%), but it ranged approximately 80%-90% for 3-year LREs. Using FIB4, 22%-57% of subjects across the three cohorts were identified as candidates for vibration-controlled transient elastography (VCTE), which was mostly avoidable (positive predictive value of FIB4 ≥ 1.3 for LSM ≥ 8 kPa ranging 9.5%-13% across different SLD categories). Sensitivity for LSM ≥ 8 kPa and LREs increased with increasing alcohol intake (ALD>MetALD>MASLD) and age classes. For individuals aged ≥65 years, using the recommended age-adjusted FIB4 cut-off (≥2) substantially reduced sensitivity for LSM ≥ 8 kPa and LREs. CONCLUSIONS: The first-step FIB4 EASL CP is poorly accurate and feasible for individuals at risk of SLD in the general population. It is crucial to enhance the screening strategy with a first-step approach able to reduce unnecessary VCTEs and optimise their yield.

Appropriateness of direct oral anticoagulant prescribing in older subjects with atrial fibrillation discharged from acute medical wards.

AIMS: Knowledge on the prescriptive practice of direct oral anticoagulants (DOACs) in older subjects with atrial fibrillation (AF) hospitalized in acute medical wards is limited. This study aimed to evaluate the prevalence and appropriateness of DOAC prescriptions in hospitalized older subjects with AF, discharged from acute medical wards. METHODS: We analysed a cohort of 609 subjects with AF, aged ≥65 years (mean age 85 years) enrolled from 39 geriatric and nephrology wards in Italy. DOAC prescriptive appropriateness was evaluated according to the summary of product characteristics (smPC), 2019 Beers and STOPP criteria, and drug-drug interactions (DDIs). RESULTS: At hospital discharge, 33% of patients with AF were prescribed with DOAC, 26% with vitamin-K antagonist, while 41% did not receive any anticoagulant. Among subjects on DOAC therapy, 31% presented a violation of the smPC criteria (mainly underdosage-17%), while 48% and 18% presented a Beers/STOPP inappropriate prescription, or a DDI, respectively. Older age, lower body mass index (BMI), cancer and higher estimated glomerular filtration rate (eGFR) were independently associated with DOAC underdosage or missed prescription (age: adjusted odds ratio [aOR] 1.06, 95% confidence interval [95% CI] 1.00-1.12 for underdosage; eGFR: aOR 1.04, 95% CI 1.02-1.07 for underdosage; BMI: aOR 0.95, 95% CI 0.91-0.99 for missed prescription; cancer: aOR 1.93, 95% CI 1.19-3.13 for missed prescription). CONCLUSIONS: This study showed a suboptimal DOAC prescriptive practice in older in-patients, with frequent missed prescription and DOAC underdosage. Contrary to current recommendations, physicians appear overly concerned by bleeding risk in real-life older and frailer subjects. Strategies should be developed to promote appropriate DOAC prescription in the hospital setting.

The specialized pro-resolving lipid mediator Protectin D1 affects macrophages differentiation and activity in Adult-onset Still's disease and COVID-19, two hyperinflammatory diseases sharing similar transcriptomic profiles.

Introduction: COVID-19 and autoinflammatory diseases, such as Adult-onset Still's Disease (AOSD), are characterized by hyperinflammation, in which it is observed massive production and uncontrolled secretion of pro-inflammatory cytokines. The specialized pro-resolving lipid mediators (SPMs) family is one the most important processes counteracting hyperinflammation inducing tissue repair and homeostasis restoration. Among SPMs, Protectin D1 (PD1) is able to exert antiviral features, at least in animal models. The aim of this study was to compare the transcriptome of peripheral blood mononuclear cells (PBMCs) from patients with AOSD and COVID-19 and to evaluate the role of PD1 on those diseases, especially in modulating macrophages polarization. Methods: This study enrolled patients with AOSD, COVID-19, and healthy donors HDs, undergoing clinical assessment and blood sample collection. Next-generation deep sequencing was performed to identify differences in PBMCs transcripts profiles. Plasma levels of PD1 were assessed by commercial ELISA kits. Monocyte-derived macrophages were polarized into M1 and M2 phenotypes. We analyzed the effect of PD1 on macrophages differentiation. At 10 days, macrophages were analyzed for surface expression of subtypes markers by flow cytometry. Cytokines production was measured in supernatants by Bio-Plex Assays. Results: In the transcriptomes from AOSD patients and COVID-19 patients, genes involved in inflammation, lipid catabolism, and monocytes activation were specifically dysregulated in AOSD and COVID-19 patients when compared to HDs. Patients affected by COVID-19, hospitalized in intensive care unit (ICU), showed higher levels of PD1 when compared to not-ICU hospitalized patients and HDs (ICU COVID-19 vs not-ICU COVID-19, p= 0.02; HDs vs ICU COVID-19, p= 0.0006). PD1 levels were increased in AOSD patients with SS ≥1 compared to patients with SS=0 (p=0.028) and HDs (p=0.048). In vitro treatment with PD1 of monocytes-derived macrophages from AOSD and COVID-19 patients induced a significant increase of M2 polarization vs control (p<0.05). Furthermore, a significant release of IL-10 and MIP-1ß from M2 macrophages was observed when compared to controls (p<0.05). Discussion: PD1 is able to induce pro-resolutory programs in both AOSD and COVID-19 increasing M2 polarization and inducing their activity. In particular, PD1-treated M2 macrophages from AOSD and COVID-19 patients increased the production of IL-10 and enhanced homeostatic restoration through MIP-1ß production.

A focus on CKD reporting and inappropriate prescribing among older patients discharged from geriatric and nephrology units throughout Italy: A nationwide multicenter retrospective cross-sectional study.

Older hospitalized patients with chronic kidney disease (CKD) are part of the geriatric population with a substantial risk of potentially inappropriate medication (PIM) use. The high rates of multimorbidity and polypharmacy, along with the progressive decline of eGFR, contribute to increasing the risk of drug-drug and drug-disease interactions, overdosing, and adverse drug reactions (ADRs). In this multicenter cross-sectional study, we aimed to evaluate the prevalence of CKD under-reporting and PIMs among older patients discharged from acute geriatric and nephrology units throughout Italy. Renal function was determined by estimated glomerular filtration rate (eGFR) through the Berlin Initiative Study (BIS) equation; the prevalence of PIMs was calculated by revising drug prescriptions at discharge according to STOPP criteria, Beers criteria, and summaries of product characteristics (smPCs). A descriptive analysis was performed to compare the clinical and pharmacological characteristics of patients in the two distinct settings; univariate and multivariate logistic regression models were performed to explore factors associated with CKD under-reporting in the discharge report forms and PIM prevalence. Overall, the study population consisted of 2,057 patients, aged 83 (77-89) years, more commonly women, with a median of seven (5-10) drugs prescribed at discharge. CKD under-reporting was present in 50.8% of the study population, with higher rates in geriatric vs. nephrology units (71.1% vs. 10.2%, p < 0.001). 18.5% of the study population was discharged with at least one renally inappropriate medication; factors associated with at least one contraindicated drug at discharge were the number of drugs (PR 1.09, 95% CI 1.14-1.19); atrial fibrillation (PR 1.35, 95% CI 1.01-1.81); diabetes (PR 1.61, 95% CI 1.21-2.13); being hospitalized in nephrology units (PR 1.62, 95% CI 1.14-2.31), CKD stage 3b (PR 2.35, 95% CI 1.34-4.13), and stage 4-5 (PR 14.01, 95% CI 7.36-26.72). Conversely, CKD under-reporting was not associated with the outcome. In summary, CKD under-reporting and inappropriate medication use were common in older patients discharged from hospital; the relatively high number of PIMs in both nephrology and geriatric settings underlines the need to improve appropriate prescribing during hospital stay and to decrease the risk of ADRs and side effects in this highly vulnerable population.

Predictors of undernutrition in COPD patients.

BACKGROUND & AIMS: Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by persistent respiratory symptoms and airflow limitation. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) report recommends smoking cessation, pharmacological therapy and pulmonary rehabilitation, but this clinical course can be negatively influenced by undernutrition, a condition documented in about 20% of COPD patients. An altered energy balance characterized by an insufficient intake of energy and nutrients is the primary cause of undernutrition, therefore the aim of this study is to investigate whether clinical and instrumental variables collected during a routine respiratory assessment associate with an altered energy balance in order to identify COPD patients at higher risk of undernutrition worth of further assessment. METHODS: A total of forty-nine participants with a diagnosis of stable COPD were included in this mono-center and longitudinal study. Subjects underwent a multidimensional assessment including evaluation of medical history, evaluation of pulmonary function, evaluation of nutritional status, evaluation of energy intake and resting energy expenditure (REE) using EPIC questionnaire and indirect-calorimetry (IC), respectively, evaluation of physical impairment and mood status. RESULTS: The 24% of participants was at risk of undernutrition with a mean energy intake, total protein intake and lipid intake significantly lower than not at risk subjects, while REE was significantly higher. Age, sex, multimorbidity, disability and depression, and pulmonary function tests were not associated with a negative energy balance, with the exception of the Cumulative Illness Rating Scale (CIRS) severity index, which showed a significant association. CONCLUSION: Clinical evaluation and pulmonary function tests are unable to reliably predict undernutrition in COPD patients, so a nutritional screening should always be forecast in this population based on an accurate evaluation of energy intake and expenditure and body composition.

Exploring Cost-Effectiveness of the Comprehensive Geriatric Assessment in Geriatric Oncology: A Narrative Review.

The Comprehensive Geriatric Assessment (CGA) and the corresponding geriatric interventions are beneficial for community-dwelling older persons in terms of reduced mortality, disability, institutionalisation and healthcare utilisation. However, the value of CGA in the management of older cancer patients both in terms of clinical outcomes and in cost-effectiveness remains to be fully established, and CGA is still far from being routinely implemented in geriatric oncology. This narrative review aims to analyse the available evidence on the cost-effectiveness of CGA adopted in geriatric oncology, identify the relevant parameters used in the literature and provide recommendations for future research. The review was conducted using the PubMed and Cochrane databases, covering published studies without selection by the publication year. The extracted data were categorised according to the study design, participants and measures of cost-effectiveness, and the results are summarised to state the levels of evidence. The review conforms to the SANRA guidelines for quality assessment. Twenty-nine studies out of the thirty-seven assessed for eligibility met the inclusion criteria. Although there is a large heterogeneity, the overall evidence is consistent with the measurable benefits of CGA in terms of reducing the in-hospital length of stay and treatment toxicity, leaning toward a positive cost-effectiveness of the interventions and supporting CGA implementation in geriatric oncology clinical practice. More research employing full economic evaluations is needed to confirm this evidence and should focus on CGA implications both from patient-centred and healthcare system perspectives.

Sarcopenia in Hepatocellular Carcinoma: Pathogenesis and Management.

BACKGROUND: Sarcopenia is almost constantly observed in patients with cirrhosis and hepatocellular carcinoma (HCC). SUMMARY: Chronic liver disease represents a unique pathophysiological scenario in which sarcopenia develops and all factors involved in the pathogenesis should be taken into account for an appropriate management of the disease. No properly designed intervention studies on this topic are available and, thus, no effective strategies have been developed for clinical practice. Apart from any targeted intervention, treatment, and optimization of liver disease is crucial. KEY MESSAGES: In patients with cirrhosis and HCC, nutritional support to maintain and restore nutrition status, a targeted use of branched-chain amino acids and a guided physical exercise, should all be an integral part of the multidimensional assessment and tailored interventions.

Metabolic and genetic determinants for progression to severe liver disease in subjects with obesity from the UK Biobank.

BACKGROUND: Obesity is among the main determinants of nonalcoholic fatty liver disease progression towards severe liver disease (SLD). However, risk factors for SLD in individuals with obesity have not been examined. OBJECTIVES: To identify the independent risk factors for SLD among participants with obesity from the UK Biobank. METHODS: A total of 80,224 UK Biobank participants with obesity (body mass index[BMI] > 30 kg/m2) and 242,822 without obesity, of European descent without clinical history of liver disease and liver cancer were prospectively followed for the onset of SLD, defined as a composite diagnosis of cirrhosis, decompensated liver disease, hepatocellular carcinoma and/or liver transplantation. Risk factors for incident SLD were assessed by Cox proportional hazards models. Different clinical phenotypes were derived by latent class analysis (LCA). RESULTS: Obesity conferred a 2.6-fold increased risk for SLD that was abolished after the inclusion of waist circumference (WC) in the model. Among individuals with obesity, age (adjusted hazard ratio [aHR] 1.05, 95%CI 1.03-1.07, p = 3.9 * 10-7), type 2 diabetes (aHR 2.18, 95%CI 1.55-3.05, p = 6.2 * 10-6), PNPLA3 rs738409 (aHR 1.59, 95%CI 1.33-1.9, p = 3.1 * 10-7) and WC (aHR 1.04, 95%CI 1.02-1.06, p = 8.5 * 10-6) were independent predictors of SLD. BMI category-specific WC thresholds allowed a better risk stratification compared to traditional ones. By LCA, the clinical phenotype at highest risk for SLD was that with BMI < 35 kg/m2 and WC above BMI-category specific thresholds. CONCLUSIONS: Age, WC, type 2 diabetes, and the PNPLA3 variant are the main risk factors for SLD in individuals with obesity. WC is the principal mediator of SLD risk conveyed by increased BMI. BMI category-specific WC-thresholds may refine the SLD risk more accurately than traditional thresholds.

A Polygenic Risk Score to Refine Risk Stratification and Prediction for Severe Liver Disease by Clinical Fibrosis Scores.

BACKGROUND & AIMS: A polygenic risk score based on well-known genetic variants in PNPLA3, TM6SF2, MBOAT7, and GCKR predicts hepatic fat content (polygenic risk score-hepatic fat content [PRS-HFC]). Here, we hypothesized that the addition of PRS-HFC to clinical fibrosis scores may improve risk stratification and prediction of severe liver disease (SLD). METHODS: We used data from 266,687 individuals in the UK Biobank, evaluating the incidence of cirrhosis, decompensated liver disease, hepatocellular carcinoma, and/or liver transplantation during a median follow-up period of 9 years. Nonalcoholic fatty liver disease fibrosis score, Fibrosis-4, aspartate aminotransferase-to-platelet ratio, BARD, and Forns scores, and PRS-HFC, were computed. All analyses were stratified according to the presence of diabetes, obesity, and a positive fatty liver index (≥60). RESULTS: Unfavorable genetics (PRS-HFC, ≥0.396) further stratified the risk of SLD in subjects in intermediate-/high-risk classes of fibrosis scores, with a higher effect in those with metabolic risk factors, and the prediction was improved by integrating PRS-HFC (areas under the receiver operating characteristic increased for all scores with a P value of approximately 10-2 to 10-4, except for the aspartate aminotransferase-to-platelet ratio in the overall population and in subjects with obesity). PRS-HFC improved diagnostic accuracies and positive predictive values for SLD in intermediate-high clinical score risk classes. Risk stratification and prediction were not affected or were poorly affected by unfavorable genetics in subjects without metabolic risk factors. CONCLUSIONS: Integration of genetics with clinical fibrosis scores refines individual risk and prediction for SLD, mainly in individuals at risk for nonalcoholic fatty liver disease. These data provide evidence from a prospective cohort that common genetic variants capture additional prognostic insights not conveyed by validated clinical/biochemical parameters.

Combined evaluation of aminotransferases improves risk stratification for overall and cause-specific mortality in older patients.

BACKGROUND: Recent studies identified low levels of alanine aminotransferase (ALT) as strong predictors of mortality in older people. AIMS: Here we verified if the combined evaluation of aminotransferases may improve risk stratification for adverse outcomes in older patients. METHODS: Data are from 761 participants aged more than 65 years from a prospective population-based database (InCHIANTI study), without known baseline chronic liver disease or malignancies. Associations between aminotransferase levels and the risk of all-cause, cardiovascular- and cancer-death were assessed by Cox-models with time-dependent covariates. RESULTS: The association of ALT and aspartate aminotransferase (AST) with mortality was non-linear, mirroring a J- and a U-shaped curve, respectively. Based on quintiles of transaminase activities and on their association with overall mortality, low, intermediate (reference group) and high levels were defined. Having at least one transaminase in the low range [aHR 1.76 (1.31-2.36), p < 0.001], mainly if both [(aHR 2.39 (1.81-3.15), p < 0.001], increased the risk of overall mortality, as well as having both enzymes in the high range [aHR 2.14 (1.46-3.15), p < 0.001]. While similar trends were confirmed with respect to cardiovascular mortality, subjects with the highest risk of cancer mortality were those with both enzymes in the high range [aHR 3.48 (1.43-8.44), p = 0.006]. Low levels of transaminases were associated with frailty, sarcopenia and disability, while high levels did not capture any known proxy of adverse outcome. Conclusions and discussion The prognostic information is maximized by the combination of the 2 liver enzymes. While both aminotransferases in low range are characteristically found in the most fragile phenotype, both enzymes in high range are more likely to identify new-onset vascular/infiltrative diseases with adverse outcome.

Association Between Smoking and SARS-CoV-2 Infection: Cross-sectional Study of the EPICOVID19 Internet-Based Survey.

BACKGROUND: Several studies have reported a low prevalence of current smoking among hospitalized COVID-19 cases; however, no definitive conclusions can be drawn. OBJECTIVE: We investigated the association of tobacco smoke exposure with nasopharyngeal swab (NPS) test results for SARS-CoV-2 infection and disease severity accounting for possible confounders. METHODS: The nationwide, self-administered, cross-sectional web-based Italian National Epidemiological Survey on COVID-19 (EPICOVID19) was administered to an Italian population of 198,822 adult volunteers who filled in an online questionnaire between April 13 and June 2, 2020. For this study, we analyzed 6857 individuals with known NPS test results. The associations of smoking status and the dose-response relationship with a positive NPS test result and infection severity were calculated as odds ratios (ORs) with 95% CIs by means of logistic and multinomial regression models adjusting for sociodemographic, clinical, and behavioral characteristics. RESULTS: Out of the 6857 individuals (mean age 47.9 years, SD 14.1; 4516/6857, 65.9% female), 63.2% (4334/6857) had never smoked, 21.3% (1463/6857) were former smokers, and 15.5% (1060/6857) were current smokers. Compared to nonsmokers, current smokers were younger, were more educated, were less affected by chronic diseases, reported COVID-19-like symptoms less frequently, were less frequently hospitalized, and less frequently tested positive for COVID-19. In multivariate analysis, current smokers had almost half the odds of a positive NPS test result (OR 0.54, 95% CI 0.45-0.65) compared to nonsmokers. We also found a dose-dependent relationship with tobacco smoke: mild smokers (adjusted OR [aOR] 0.76, 95% CI 0.55-1.05), moderate smokers (aOR 0.56, 95% CI 0.42-0.73), and heavy smokers (aOR 0.38, 95% CI 0.27-0.53). This inverse association also persisted when considering the severity of the infection. Current smokers had a statistically significantly lower probability of having asymptomatic (aOR 0.50, 95% CI 0.27-0.92), mild (aOR 0.65, 95% CI 0.53-0.81), and severe infections (aOR 0.27, 95% CI 0.17-0.42) compared to those who never smoked. CONCLUSIONS: Current smoking was negatively associated with SARS-CoV-2 infection with a dose-dependent relationship. Ad hoc experimental studies are needed to elucidate the mechanisms underlying this association. TRIAL REGISTRATION: ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701.

Comprehensive geriatric assessment in older adults with cancer: Recommendations by the Italian Society of Geriatrics and Gerontology (SIGG).

INTRODUCTION: Optimizing the approach to older adults with cancer is now a priority given the increasing frequency of new cancer diagnoses that are made in the older population. The comprehensive geriatric assessment (CGA) represents the gold-standard for (1) defining prognosis and ability to withstand cancer treatments, (2) exploring the multiple aspects that define the complexity of frail older persons, and (3) designing person-tailored interventions. MATERIALS AND METHODS: In this document, based on a comprehensive revision of the literature, the Italian Society for Geriatrics and Gerontology proposes a CGA model (ONCOGER CGA) to be adopted by oncology centers for their routine approach to older patients with cancer. RESULTS AND DISCUSSION: A widespread use of this standardized CGA format will facilitate comparisons across institutions, promote studies based on a multidimensional patient assessment, and foster the inclusion of geriatric endpoints in oncological clinical trials. Furthermore, we predict that the use of a standardized CGA approach will increase the integration of geriatricians into oncology care teams with the final result of improving therapeutic choices and clinical outcomes.

Rapid COVID-19 Screening Based on Self-Reported Symptoms: Psychometric Assessment and Validation of the EPICOVID19 Short Diagnostic Scale.

BACKGROUND: Confirmed COVID-19 cases have been registered in more than 200 countries, and as of July 28, 2020, over 16 million cases have been reported to the World Health Organization. This study was conducted during the epidemic peak of COVID-19 in Italy. The early identification of individuals with suspected COVID-19 is critical in immediately quarantining such individuals. Although surveys are widely used for identifying COVID-19 cases, outcomes, and associated risks, no validated epidemiological tool exists for surveying SARS-CoV-2 infection in the general population. OBJECTIVE: We evaluated the capability of self-reported symptoms in discriminating COVID-19 to identify individuals who need to undergo instrumental measurements. We defined and validated a method for identifying a cutoff score. METHODS: Our study is phase II of the EPICOVID19 Italian national survey, which launched in April 2020 and included a convenience sample of 201,121 adults who completed the EPICOVID19 questionnaire. The Phase II questionnaire, which focused on the results of nasopharyngeal swab (NPS) and serological tests, was mailed to all subjects who previously underwent NPS tests. RESULTS: Of 2703 subjects who completed the Phase II questionnaire, 694 (25.7%) were NPS positive. Of the 472 subjects who underwent the immunoglobulin G (IgG) test and 421 who underwent the immunoglobulin M test, 22.9% (108/472) and 11.6% (49/421) tested positive, respectively. Compared to NPS-negative subjects, NPS-positive subjects had a higher incidence of fever (421/694, 60.7% vs 391/2009, 19.5%; P<.001), loss of taste and smell (365/694, 52.6% vs 239/2009, 11.9%; P<.001), and cough (352/694, 50.7% vs 580/2009, 28.9%; P<.001). With regard to subjects who underwent serological tests, IgG-positive subjects had a higher incidence of fever (65/108, 60.2% vs 43/364, 11.8%; P<.001) and pain in muscles/bones/joints (73/108, 67.6% vs 71/364, 19.5%; P<.001) than IgG-negative subjects. An analysis of self-reported COVID-19 symptom items revealed a 1-factor solution, the EPICOVID19 diagnostic scale. The following optimal scores were identified: 1.03 for respiratory problems, 1.07 for chest pain, 0.97 for loss of taste and smell 0.97, and 1.05 for tachycardia (ie, heart palpitations). These were the most important symptoms. For adults aged 18-84 years, the cutoff score was 2.56 (sensitivity: 76.56%; specificity: 68.24%) for NPS-positive subjects and 2.59 (sensitivity: 80.37%; specificity: 80.17%) for IgG-positive subjects. For subjects aged ≥60 years, the cutoff score was 1.28, and accuracy based on the presence of IgG antibodies improved (sensitivity: 88.00%; specificity: 89.58%). CONCLUSIONS: We developed a short diagnostic scale to detect subjects with symptoms that were potentially associated with COVID-19 from a wide population. Our results support the potential of self-reported symptoms in identifying individuals who require immediate clinical evaluations. Although these results come from the Italian pandemic period, this short diagnostic scale could be optimized and tested as a screening tool for future similar pandemics.

Perioperative Management of Elderly patients (PriME): recommendations from an Italian intersociety consensus.

BACKGROUND: Surgical outcomes in geriatric patients may be complicated by factors such as multiple comorbidities, low functional performance, frailty, reduced homeostatic capacity, and cognitive impairment. An integrated multidisciplinary approach to management is, therefore, essential in this population, but at present, the use of such an approach is uncommon. The Perioperative Management of Elderly patients (PriME) project has been established to address this issue. AIMS: To develop evidence-based recommendations for the integrated care of geriatric surgical patients. METHODS: A 14-member Expert Task Force of surgeons, anesthetists, and geriatricians was established to develop evidence-based recommendations for the pre-, intra-, and postoperative care of hospitalized older patients (≥ 65 years) undergoing elective surgery. A modified Delphi approach was used to achieve consensus, and the strength of recommendations and quality of evidence was rated using the U.S. Preventative Services Task Force criteria. RESULTS: A total of 81 recommendations were proposed, covering preoperative evaluation and care (30 items), intraoperative management (19 items), and postoperative care and discharge (32 items). CONCLUSIONS: These recommendations should facilitate the multidisciplinary management of older surgical patients, integrating the expertise of the surgeon, the anesthetist, the geriatrician, and other specialists and health care professionals (where available) as needed. These roles may vary according to the phase and setting of care and the patient's conditions.

Self-Reported Symptoms of SARS-CoV-2 Infection in a Nonhospitalized Population in Italy: Cross-Sectional Study of the EPICOVID19 Web-Based Survey.

BACKGROUND: Understanding the occurrence of symptoms resembling those of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large nonhospitalized population at the peak of the epidemic in Italy is of paramount importance; however, data are currently scarce. OBJECTIVE: The aims of this study were to evaluate the association of self-reported symptoms with SARS-CoV-2 nasopharyngeal swab (NPS) test results in nonhospitalized individuals and to estimate the occurrence of symptoms associated with coronavirus disease (COVID-19) in a larger nontested population. METHODS: EPICOVID19 is a self-administered cross-sectional voluntary web-based survey of adults throughout Italy who completed an anonymous questionnaire in the period of April 13 to 21, 2020. The associations between symptoms potentially related to SARS-CoV-2 infection and NPS results were calculated as adjusted odds ratios (aORs) with 95% CIs by multiple logistic regression analysis controlling for age, sex, education, smoking habits, and number of comorbidities. Thereafter, for each symptom and for combinations of the symptoms, we calculated the sensitivity, specificity, accuracy, and areas under the curve (AUCs) in a receiver operating characteristic (ROC) analysis to estimate the occurrence of COVID-19-like infection in the nontested population. RESULTS: A total of 171,310 people responded to the survey, of whom 102,543 (59.9%) were women; mean age 47.4 years. Out of the 4785 respondents with known NPS test results, 4392 were not hospitalized. Among the 4392 nonhospitalized respondents, those with positive NPS tests (856, 19.5%) most frequently reported myalgia (527, 61.6%), olfactory and taste disorders (507, 59.2%), cough (466, 54.4%), and fever (444, 51.9%), whereas 7.7% were asymptomatic. Multiple regression analysis showed that olfactory and taste disorders (aOR 10.3, 95% CI 8.4-12.7), fever (aOR 2.5, 95% CI 2.0-3.1), myalgia (aOR 1.5, 95% CI 1.2-1.8), and cough (aOR 1.3, 95% CI 1.0-1.6) were associated with NPS positivity. Having two to four of these symptoms increased the aOR from 7.4 (95% CI 5.6-9.7) to 35.5 (95% CI 24.6-52.2). The combination of the four symptoms showed an AUC of 0.810 (95% CI 0.795-0.825) in classifying positive NPS test results and then was applied to the nonhospitalized and nontested sample (n=165,782). We found that 7739 to 20,103 of these 165,782 respondents (4.4% to 12.1%) had experienced symptoms suggestive of COVID-19 infection. CONCLUSIONS: Our results suggest that self-reported symptoms are reliable indicators of SARS-CoV-2 infection in a pandemic context. A nonnegligible number of symptomatic respondents (up to 12.1%) were undiagnosed and potentially contributed to the spread of the infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701.

Potentially Inappropriate Medications, Drug-Drug Interactions, and Anticholinergic Burden in Elderly Hospitalized Patients: Does an Association Exist with Post-Discharge Health Outcomes?

BACKGROUND: Polypharmacy is very common in elderly patients and is associated with detrimental outcomes. OBJECTIVE: Our objective was to evaluate the associations between a large panel of therapy quality indicators, including explicit lists of potentially inappropriate medications (PIMs; Beers criteria and Screening Tool of Older Persons' potentially inappropriate Prescriptions [STOPP] criteria), the Anticholinergic Cognitive Burden (ACB) score, and the number of drug-drug interactions (DDIs), with respect to mortality, rehospitalization, and physical function decline within 3 months from hospital discharge in a cohort of hospitalized elderly patients. METHODS: We studied 2631 individuals aged ≥ 65 years (median age 79.6; males 48.6%) enrolled in the REPOSI registry. The relationships with mortality and rehospitalization were evaluated using Cox regressions, and relationships with functional status change (as percentage variation of Barthel Index [BI]) were evaluated using mixed linear models. RESULTS: None of the studied indicators was associated with mortality and rehospitalization. Conversely, only ACB was associated with physical function decline, even after correction for confounders (adjusted mean BI variation of - 7.55%; 95% confidence interval [CI] - 12.37 to - 2.47). The number of medications at discharge, particularly polypharmacy (more than five drugs daily), were the only therapy-related factors associated with mortality (adjusted hazard ratio [aHR] 1.05 [95% CI 1.01-1.10] and 1.70 [95% CI 1.12-2.58], respectively) and rehospitalization (aHR 1.05 [95% CI 1.01-1.08] and 1.31 [95% CI 1.01-1.71], respectively). CONCLUSION: Polypharmacy, a very simple measure, outperformed sophisticated PIM and DDI indicators of quality of therapy as a correlate of primary clinical outcomes, whereas ACB was associated with physical function decline. Thus, innovative approaches to the definition and research of PIMs and DDIs are eagerly awaited from the perspective of averaging the quantitative burden and qualitative interaction of drugs.