Respiratory Syncytial Virus Prefusion F Protein Vaccine Is Efficacious in Older Adults With Underlying Medical Conditions.

BACKGROUND: Older adults with chronic cardiorespiratory or endocrine/metabolic conditions are at increased risk of respiratory syncytial virus (RSV)-related acute respiratory illness (RSV-ARI) and severe respiratory disease. In an ongoing, randomized, placebo-controlled, multicountry, phase 3 trial in ≥60-year-old participants, an AS01E-adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD), severe RSV-LRTD, and RSV-ARI. We evaluated efficacy and immunogenicity among participants with coexisting cardiorespiratory or endocrine/metabolic conditions that increase the risk of severe RSV disease ("conditions of interest"). METHODS: Medically stable ≥60-year-old participants received 1 dose of RSVPreF3 OA or placebo. Efficacy against first RSV-LRTD and RSV-ARI episodes was assessed in subgroups with/without coexisting cardiorespiratory or endocrine/metabolic conditions of interest. Immunogenicity was analyzed post hoc in these subgroups. RESULTS: In total, 12 467 participants received RSVPreF3 OA and 12 499 received placebo. Of these, 39.6% (RSVPreF3 OA) and 38.9% (placebo) had ≥1 coexisting condition of interest. The median efficacy follow-up was 6.7 months. Efficacy against RSV-LRTD was high in participants with ≥1 condition of interest (94.6%), ≥1 cardiorespiratory (92.1%), ≥1 endocrine/metabolic (100%), and ≥2 conditions of interest (92.0%). Efficacy against RSV-ARI was 81.0% in participants with ≥1 condition of interest (88.1% for cardiorespiratory, 79.4% for endocrine/metabolic conditions) and 88.0% in participants with ≥2 conditions of interest. Postvaccination neutralizing titers were at least as high in participants with ≥1 condition of interest as in those without. CONCLUSIONS: RSVPreF3 OA was efficacious against RSV-LRTD and RSV-ARI in older adults with coexisting medical conditions associated with an increased risk of severe RSV disease. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov: NCT04886596.

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.

Kodamaea ohmeri Leg Skin Ulcer Infection in an Immunocompetent Patient: A Case Report.

INTRODUCTION: Kodamaea ohmeri is an emerging fungus recognised as an important pathogen in immunocompromised hosts, responsible for life-threatening infections. CASE PRESENTATION: We describe a case of a 69-year-old immunocompetent man with a long history of leg skin ulcers infected by K. ohmeri. This is the first case of leg wounds infected by K. ohmeri in an immunocompetent patient. The infection was successfully treated with voriconazole 200 mg daily. CONCLUSION: Though rare, K. ohmeri should be considered in patients with skin ulcers that are poorly responsive to medical treatment, even if not immunocompromised.

Prevalence, clinical characteristics, and disease burden of chronic cough in Italy: a cross-sectional study.

BACKGROUND: Chronic cough has been associated with reduced health-related quality of life, negative impacts on sleep, work, and other daily activities, and increased use of health care resources. Little is known about the prevalence of chronic cough in Italy. In the present study we sought to estimate the prevalence of chronic cough in Italy, describe sociodemographic and clinical characteristics associated with chronic cough, and characterize the impact of chronic cough on overall health and wellness, work and other daily activities, and health care resource use. METHODS: We conducted a cross-sectional study to collect sociodemographic and health-related data from Italian residents who participated in the 2020 National Health and Wellness Survey (N = 10,026). To assess the characteristics and burden of chronic cough, adults who indicated that they had experienced chronic cough during the prior 12 months were compared with propensity score-matched controls without chronic cough. RESULTS: The estimated weighted lifetime and 12-month prevalence of chronic cough were estimated as 9.2% and 6.3%, respectively. Compared with matched controls, respondents with chronic cough had significantly lower measures of overall physical and mental health (P < .001 for both comparisons), and significantly higher rates of anxiety, depression, and sleep disorders (P < .001 for all comparisons). Chronic cough was significantly associated with higher rates of impairment of work and other activities (P < .001 for all comparisons) in the past 7 days, any-cause emergency department visits and hospitalizations in the prior 6 months (P < .001 for both comparisons), and more visits to general and specialist health care providers (P < .001 for both comparisons) in the prior 6 months. CONCLUSIONS: In Italy, chronic cough affects an estimated 3.3 million adults annually and represents a significant burden to individuals and the health care system. TAKE HOME MESSAGE: Little is known about the prevalence of chronic cough in Italy. We found that, in Italy chronic cough represents a significant burden to individuals and the health care system, affecting an estimated 3.3 million adults annually.

Electrocardiographic alterations in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality, and its incidence has grown within several years, quickly becoming the third leading cause of mortality. The disease is characterized by alveolar destruction, air-trapping, and chronic inflammation due to persistent exposure to a large spectrum of harmful particles. The diagnosis of COPD is made by demonstration of persistent and not fully reversible airflow limitation, and different phenotypes may be recognized based on pathophysiological, clinical, and radiological features. However, COPD is a systemic disease with effects involving several organs. For example, mechanical and functional alterations secondary to COPD involve heart function. Indeed, cardiovascular diseases are highly prevalent in patients affected by COPD and represent the primary cause of mortality in such patients. An electrocardiogram is a simple and cheap test that gives much information about the heart status of COPD patients. Consequently, variations from "normality" can be appreciated in these patients, with the most frequent abnormalities being P-wave, QRS axis, and ventricular repolarization abnormalities, in addition to conduction alterations and a vast number of arrhythmias. As a result, ECG should be routinely performed as a valuable tool to recognize alterations due to COPD (i.e., mechanical and functional) and possible associated heart diseases. This review aims to describe the typical ECG features in most COPD patients and to provide a systematic summary that can be used in clinical practice.

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.

Incidence and Outcome of Pneumomediastinum in Non-ICU Hospitalized COVID-19 Patients.

OBJECTIVES: Pneumomediastinum (PNM) is a rare complication of mechanical ventilation, but its reported occurrence in patients with acute respiratory distress syndrome secondary to COVID-19 is significant. The objective is to determine the incidence, risk factors, and outcome of PNM in non-ICU hospitalized patients with severe-to-critical COVID-19 pneumonia. DESIGN: Retrospective observational study. SETTING: Population-based, single-setting, tertiary-care level COVID treatment center. PATIENTS: Individuals hospitalized with a diagnosis of COVID-19 pneumonia and severe to critical illness were included. Those hospitalized without respiratory failure, observed for less than 24 hours, or admitted from an ICU were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients underwent a complete clinical assessment and chest CT scan, and were followed up from hospitalization to discharge or death. The outcome was the number of cases of PNM, defined as the presence of free air in the mediastinal tissues diagnosed by chest CT scan, in non-ICU hospitalized patients and the subsequent risk of intubation and mortality. PNM occurred in 48 out of 331 participants. The incidence was 14.5% (95% CI, 10.9-18.8%). A CT-Scan Severity score greater than 15 was positively associated with PNM (odds ratio [OR], 4.09; p = 0.002) and was observed in 35.2% of the participants (95% CI, 26.2-44.9%). Noninvasive ventilation was also positively associated with PNM (OR, 4.46; p = 0.005), but there was no positive association with airway pressures. Fifty patients (15%) were intubated, and 88 (27%) died. Both the risk for intubation and mortality were higher in patients with PNM, with a hazard ratio of 3.72 ( p < 0.001) and 3.27 ( p < 0.001), respectively. CONCLUSIONS: Non-ICU hospitalized patients with COVID-19 have a high incidence of PNM, increasing the risk for intubation and mortality three- to four-fold, particularly in those with extensive lung damage. These findings help define the risk and outcome of PNM in severe-to-critical COVID-19 pneumonia in a non-ICU setting.

Frailty and hyperactive delirium in hospitalized older patients with COVID-19: an insight from GeroCovid registry.

BACKGROUND: Delirium is an acute neuropsychiatric condition associated with unfavourable outcomes, frequent in older hospitalized people. In the context of the SARS-CoV-2 pandemic, few studies have specifically focused on the inflammatory status of older, frail patients with hyperactive delirium (HD) hospitalized for COVID-19. AIM: To identify biological correlates of HD at hospital admission and to assess the independent effect of delirium and physical frailty on in-hospital mortality. METHODS: Data were retrospectively extracted by the multicenter registry GeroCovid Observational Study. Individuals aged ≥ 60 years were included if the information on the presence of HD, frailty based on the modified Fried criteria and inflammatory status had been collected. The risk of mortality was evaluated using a Kaplan-Meier estimator, according to frailty and delirium. Logistic and restricted cubic-spline regressions were employed to assess the relationship between inflammatory markers and HD. RESULTS: Three-hundred-thirty-seven older adults were included in the analysis [mean age (SD) 77.1 (9.5) years, 50.1% females], and 11.5% presented with HD. A significant association of both PaO2/FiO2 ratio (p = 0.015) and serum lactate dehydrogenase (p = 0.04) with delirium was observed. By Cox multivariable regression, frail and non-frail patients with HD had a 4.42 and 2.85 higher mortality risk compared with non-frail, non-delirious patients. CONCLUSIONS: Hyperactive delirium at hospital admission is related with markers of lung failure among older adults, especially when physical frailty coexists. Delirium is associated with increased in-hospital mortality risk, which is doubled by the coexistence of physical frailty.

Frailty in the chronic respiratory patient: association with mortality and clinical features in obstructive, restrictive, and mixed spirometric patterns.

BACKGROUND: Frailty associates with increased vulnerability to adverse health outcomes and reduced tolerance to medical interventions. Its impact on patients with chronic respiratory diseases, particularly beyond chronic obstructive pulmonary disease (COPD), remains poorly understood. AIMS: To evaluate the association between frailty index and 5-year mortality across different "spirometric" patterns and the variation in their occurring frailty determinants. METHODS: This study analyzed data from the SARA study, which enrolled 1968 older adults, to evaluate the association between frailty and 5-year mortality across different spirometric patterns. Frailty was assessed using the frailty index (FI), and spirometry was performed to determine lung function patterns. Hazard ratios (HRs) were calculated using Cox regression models, adjusting for age and sex. RESULTS: Among the study participants, 16% were classified as frail. Frailty was associated with a significantly increased risk of mortality across all spirometric patterns. The 5-year mortality rates were 34.3% in subjects with normal spirometry, 45.1% in those with obstructive defects, 55% in those with restrictive defects, and 42.6% in those with mixed airflow defects. The unadjusted HRs for mortality were 2.64 (95% CI 2.10-3.32) for the overall cohort, 2.24 (95% CI 1.48-3.40) for obstructive defects, 2.45 (95% CI 1.12-5.36) for restrictive defects, and 2.79 (95% CI 1.41-3.17) for mixed airflow defects. After adjusting for age and sex, the HRs remained statistically significant: 2.25 (95% CI 1.37-2.84) for the overall cohort, 2.08 (95% CI 1.37-3.18) for obstructive defects, 2.27 (95% CI 1.04-1.17) for restrictive defects, and 2.21 (95% CI 1.20-3.08) for mixed airflow defects. CONCLUSION: Frailty is a common syndrome and is associated with a significantly increased risk of mortality. The FI provides valuable information for risk profiling and personalized interventions beyond age and lung function parameters. Including frailty assessment in clinical evaluations can aid in resource allocation and improve patient care in respiratory diseases.

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.

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.

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.

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.

Chronic cough in adults: recommendations from an Italian intersociety consensus.

BACKGROUND: Chronic cough (CC) is a burdensome health problem in adult and older people, with a major impact on quality of life. Its management is often troublesome, and many guidelines have been released. Notwithstanding, a proportion of cases still do not reach a definite diagnosis and resolutive treatment. A coordinated approach between different specialists would be highly recommended, but its implementation in clinical practice suffers from the lack of shared protocols and poor awareness of the problem. The present consensus document has been implemented to address these issues. AIMS: To develop evidence-based recommendations for the management of adults with CC. METHODS: A 12-member expert task force of general practitioners, geriatricians, pneumologists, allergologists, otorhynolaringologists and gastroenterologists was established to develop evidence-based recommendations for the diagnostic and therapeutic approach to subjects with CC. A modified Delphi approach was used to achieve consensus, and the US Preventive Services Task Force system was used to rate the strength of recommendations and the quality of evidence. RESULTS: A total of 56 recommendations were proposed, covering 28 topics and concerning definitions and epidemiology, pathogenesis and etiology, diagnostic and therapeutic approach along with the consideration of specific care settings. CONCLUSION: These recommendations should ease the management of subjects with CC by coordinating the expertise of different specialists. By providing a convenient list of topics of interest, they might assist in identifying unmet needs and research priorities.

Atrial fibrillation and COVID-19 in older patients: how disability contributes to shape the risk profile. An analysis of the GeroCovid registry.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is often complicated by disabling conditions in the elderly. COVID-19 has high mortality in older people. This study aimed at evaluating the relationship of pre-infection AF with characteristics and survival of older COVID-19 patients. METHODS: We retrospectively analyzed inpatients aged ≥ 60 years enrolled in GeroCovid Observational, a multicenter registry endorsed by the Italian and the Norwegian Societies of Gerontology and Geriatrics. Pre-COVID-19 sociodemographic, functional, and medical data were systematically collected, as well as in-hospital mortality. RESULTS: Between March and June 2020, 808 COVID-19 subjects were enrolled (age 79 ± 9 years; men 51.7%). The prevalence of AF was 21.8%. AF patients were older (82 ± 8 vs. 77 ± 9 years, p < 0.001), had a higher CHA2DS2-VASc score (4.1 ± 1.5 vs. 3.2 ± 1.5, p < 0.001) and were more likely to present almost all comorbidities. At multivariable analysis, advanced age, white blood cell count, the presence of heart and peripheral artery diseases were significantly associated with the presence of AF. In-hospital mortality was higher in AF patients (36.9 vs. 27.5%; OR = 1.55, 95% CI = 1.09-2.20; p = 0.015). A decision tree analysis showed that, in AF subjects, preserved functional status at admission was the most important factor associated with survival. In patients without AF, baseline COVID-19 severity was the most relevant variable related to clinical prognosis. CONCLUSIONS: AF is frequent in older patients with COVID-19, in whom it associates with clinical complexity and high mortality. Pre-infection disability shapes the prognosis of this extremely vulnerable segment of hospitalized subjects. CLINICAL TRIAL REGISTRATION: GeroCovid Observational was registered at www.clinicaltrials.gov (NCT04379440).

Humoral immunity induced by mRNA COVID-19 vaccines in Nursing Home Residents previously infected with SARS-CoV-2.

BACKGROUND: Nursing home (NH) residents suffered the greatest impact of the COVID-19 pandemic. Limited data are available on vaccine-induced immunity and on the protection ensured by a prior infection in this population. AIMS: The present study aims to monitor antibody levels and their persistence over a 6-month period in NH residents according to the history of prior SARS-CoV-2 infection. METHODS: We measured anti-trimeric Spike IgG antibody levels in a sample of 395 residents from 25 NHs in 6 Italian Regions at study enrolment (prior to the first dose of vaccine, T0) and then after 2 (T1) and 6 months (T2) following the first vaccine dose. All participants received mRNA vaccines (BNT162b2 or mRNA-1273). Analyses were performed using log-transformed values of antibody concentrations and geometric means (GM) were calculated. RESULTS: Superior humoral immunity was induced in NH residents with previous SARS-CoV-2 infection. (T0: GM 186.6 vs. 6.1 BAU/ml, p < 0.001; T1: GM 5264.1 vs. 944.4 BAU/ml, p < 0.001; T2: GM 1473.6 vs. 128.7 BAU/ml, p < 0.001). Residents with prior SARS-CoV-2 infection receiving two vaccine doses presented significantly higher antibody concentration at T1 and T2. A longer interval between previous infection and vaccination was associated with a better antibody response over time. DISCUSSION: In a frail sample of NH residents, prior SARS-CoV-2 infection was associated with a higher humoral response to vaccination. Number of vaccine doses and the interval between infection and vaccination are relevant parameters in determining humoral immunity. CONCLUSIONS: These findings provide important information to plan future immunization policies and disease prevention strategies in a highly vulnerable population.

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.

Clustering of patients with end-stage chronic diseases by symptoms: a new approach to identify health needs.

BACKGROUND: End-stage chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) and chronic renal failure (CRF) are characterized by a high burden of daily symptoms that, irrespective of the primary organ failure, are widely shared. AIMS: To evaluate whether and to which extent symptom-based clusters of patients with end-stage COPD, CHF and CRF associate with patients' health status, mobility, care dependency and life-sustaining treatment preferences. METHODS: 255 outpatients with a diagnosis of advanced COPD (n = 95), advanced CHF (n = 80) or CRF requiring dialysis (n = 80) were visited in their home environment and underwent a multidimensional assessment: clinical characteristics, symptom burden using Visual Analog Scale (VAS), health status questionnaires, timed "Up and Go" test, Care Dependency Scale and willingness to undergo mechanical ventilation or cardiopulmonary resuscitation. Three clusters were obtained applying K-means cluster analysis on symptoms' severity assessed via VAS. Cluster characteristics were compared using non-parametric tests. RESULTS: Cluster 1 patients, with the least symptom burden, had a better quality of life, lower care dependency and were more willing to accept life-sustaining treatments than others. Cluster 2, with a high presence and severity of dyspnea, fatigue, cough, muscle weakness and mood problems, and Cluster 3, with the highest occurrence and severity of symptoms, reported similar care dependency and life-sustaining treatment preferences, while Cluster 3 reported the worst physical health status. DISCUSSION: Symptom-based clusters identify patients with different health needs and might help to develop palliative care programs. CONCLUSION: Clustering by symptoms identifies patients with different health status, care dependency and life-sustaining treatment preferences.

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 frailty index, lung function, and major clinical determinants in chronic obstructive pulmonary disease.

BACKGROUND: Airflow limitation alone is unable to capture the complexity of chronic obstructive pulmonary disease (COPD), better explained by comprehensive disease-specific indexes. Frailty is a clinical condition characterized by high vulnerability to internal and external stressors and represents a strong predictor of adverse outcomes. AIMS: Primary objective was to test the association between indexes of lung function and COPD severity with frailty index (FI), and secondary to evaluate the association between FI and comorbidities, cognitive and physical function, BODE index, and mortality. METHODS: 150 stable COPD outpatients were enrolled and followed up to 4 years. At baseline, participants performed a geriatric multidimensional assessment, pulmonary function tests, arterial blood gas analysis, 6-min walking test, and bioimpedance analysis. BODE and FI were calculated. Spearman's ρ was used to assess correlations. Mortality was assessed using Kaplan-Meier curves. RESULTS: Participants were followed up for a median of 39 months. Mean age was 73 years and median frailty index 0.15 (IQR 0.11-0.19). FI was higher in frequent exacerbators (≥ 2/year) (mean 0.18 vs 0.15, p 0.01) and dyspnoeic patients (mMRC ≥ 2) (mean 0.21 vs 0.14, p < 0.01) and correlated with lung volumes, expiratory flows, and pressure of arterial oxygen. FI was positively correlated with the number of comorbidities, depressive symptoms, cognitive decline, and BODE index. Mortality was higher in patients with BODE higher than 3 (HR 3.6, 95% CI 1.2-10.9), and not associated with FI. DISCUSSION: FI positively correlates with all clinical drivers orienting the choice of treatment in COPD. CONCLUSIONS: FI associates with lung function and COPD severity, but does not associate with mortality.