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Aims Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent disease and has been repeatedly associated with an increased risk of cardiovascular disease. However, the extent of such association is unclear. We conducted a systematic review and meta-analysis of the literature to evaluate the risk of myocardial infarction (MI), ischaemic stroke (IS), atrial fibrillation (AF), and heart failure (HF) in NAFLD patients. Methods and results According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed and EMBASE, from inception to 6 March 2021, and included all studies reporting the incidence of MI, IS, AF, and HF in patients with and without NAFLD. Random-effect fmodels were used to estimate pooled odds ratio (OR), 95% confidence intervals (CI), and 95% prediction intervals (PI); subgroup analyses, meta-regressions, and sensitivity analyses were additionally performed. Among 3254 records retrieved from literature, 20 studies were included. Non-alcoholic fatty liver disease was associated with an increased risk of MI (OR: 1.66, 95% CI: 1.39–1.99, 95% PI: 0.84–3.30), IS (OR: 1.41, 95% CI: 1.29–1.55, 95% PI 1.03–1.93), AF (OR: 1.27, 95% CI: 1.18–1.37, 95% PI: 1.07–1.52), and HF (OR: 1.62, 95% CI: 1.43–1.84, 95% CI: 1.04–2.51). We identified significant subgroup differences according to geographical location, study design, NAFLD definition, and risk of bias; meta-regressions identified mean age, male sex, and study-level characteristics as potential moderators of the risk of MI and IS. Conclusions Non-alcoholic fatty liver disease was associated with increased risk of MI, IS, AF, and HF. Age, sex, and study characteristics may moderate the strength of this association. Further studies are required to evaluate specific cardiovascular prevention strategies in patients with NAFLD.

The Coronavirus Disease (COVID-19) pandemic imposed a high burden of morbidity and mortality. In COVID-19, direct lung parenchymal involvement and pulmonary microcirculation dysfunction may entail pulmonary hypertension (PH). PH and direct cardiac injury beget right ventricular dysfunction (RVD) occurrence, which has been frequently reported in COVID-19 patients; however, the prevalence of RVD and its impact on outcomes during COVID-19 are still unclear. This study aims to evaluate the prevalence of RVD and associated outcomes in patients with COVID-19, through a Systematic Review and Meta-Analysis. MEDLINE and EMBASE were systematically searched from inception to 15th July 2021. All studies reporting either the prevalence of RVD in COVID-19 patients or all-cause death according to RVD status were included. The pooled prevalence of RVD and Odds Ratio (OR) for all-cause death according to RVD status were computed and reported. Subgroup analysis and meta-regression were also performed. Among 29 studies (3813 patients) included, pooled prevalence of RVD was 20.4% (95% CI 17.1–24.3%; 95% PI 7.8–43.9%), with a high grade of heterogeneity. No significant differences were found across geographical locations, or according to the risk of bias. Severity of COVID-19 was associated with increased prevalence of RVD at meta-regression. The presence of RVD was found associated with an increased likelihood of all-cause death (OR 3.32, 95% CI 1.94–5.70). RVD was found in 1 out of 5 COVID-19 patients, and was associated with all-cause mortality. RVD may represent one crucial marker for prognostic stratification in COVID-19; further prospective and larger are needed to investigate specific management and therapeutic approach for these patients.

BACKGROUND Retinal vascular occlusion is a leading cause of sight loss. Both retinal artery occlusion (RAO) and retinal vein occlusion (RVO) have been associated with hypercoagulable states; however, the burden of thrombophilia in these patients is unclear. OBJECTIVES This study aims at estimating the prevalence of inherited and acquired thrombophilias in adults with RAO or RVO through a systematic review and meta-analysis of the literature. PATIENTS/METHODS PubMed and EMBASE were systematically searched from inception to 29 February 2020. All studies reporting prevalences of factor V Leiden (FVL) and prothrombin (F-II) G20210A mutations, methylenetetrahydrofolate reductase (MTHFR) C677T and plasminogen activator inhibitor (PAI) 4G polymorphisms, antithrombin III (AT-III), protein C (PC) and protein S (PS) activity deficiencies, hyperhomocysteinemia, and antiphospholipid (APL) antibodies in adults with RAO or RVO were included. Pooled prevalences and 95% confidence intervals (CI) were calculated. RESULTS Ninety-five studies were included; FVL and F-II mutations were found in 6% (95% CI: 5-8) and 3% (95% CI: 2-4) of individuals with RVO, respectively, whereas AT-III, PC, and PS activity deficiencies were found in

The novel coronavirus 2019 (COVID-19) is clinically characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for a high number of patients needing mechanical ventilation or intensive care units treatment and for the elevated mortality risk. A link between COVID-19 and multiorgan failure may be dependent on the fact that most COVID-19 patients are complicated by pneumonia, which is known to be associated with early changes of clotting and platelet activation and artery dysfunction; these changes may implicate in thrombotic-related events such as myocardial infarction and ischemic stroke. Recent data showed that myocardial injury compatible with coronary ischemia may be detectable in SARS-CoV-2 patients and laboratory data exploring clotting system suggest the presence of a hypercoagulation state. Thus, we performed a systematic review of COVID-19 literature reporting measures of clotting activation to assess if changes are detectable in this setting and their relationship with clinical severity. Furthermore, we discussed the biologic plausibility of the thrombotic risk in SARS-CoV-2 and the potential use of an antithrombotic treatment.

Awareness of the influence of sex ands gender on the natural history of several diseases is increasing. Community-acquired pneumonia (CAP) is the most common acute respiratory disease, and it is associated with both morbidity and mortality across all age groups. Although a role for sex- and gender-based differences in the development and associated complications of CAP has been postulated, there is currently high uncertainty on the actual contribution of these factors in the epidemiology and clinical course of CAP. More evidence has been produced on the topic during the last decades, and sex- and gender-based differences have also been extensively studied in COVID-19 patients since the beginning of the SARS-CoV-2 pandemic. This review aims to provide an extensive outlook of the role of sex and gender in the epidemiology, pathogenesis, treatment, and outcomes of patients with CAP, and on the future research scenarios, with also a specific focus on COVID-19.

Community-acquired pneumonia (CAP) is a common lower respiratory tract infection, often complicated by cardiovascular events, including cardiac arrhythmias. New-onset atrial fibrillation (newAF) has been associated with increased mortality in CAP patients, especially in those critically ill; however, limited data on the prevalence of newAF in patients with CAP are available. We aim to estimate the pooled prevalence of newAF and its impact on adverse outcomes in patients with CAP, through a systematic review and meta-analysis. MEDLINE and EMBASE were systematically searched from inception to 27 January 2022. All studies reporting the prevalence of newAF in CAP patients were included and all-cause mortality was extracted when available. The pooled prevalence of newAF, 95% Confidence Intervals (CI), and 95% Prediction Intervals (PI) were computed. The inconsistency index (I2) was calculated to measure heterogeneity. Subgroup analyses were also performed. A protocol for this study was registered on PROSPERO (CRD42022307422). Among 7,655 records retrieved, 10 studies were included, with a total of 280,589 CAP patients. Pooled prevalence of newAF in CAP patients was 7.6% (95% CI 6.4-9.0%, 95% PI 4.3-13.1%, I2 = 95%). Subgroup analyses showed no significant differences according to geographical location or study design. Patients with newAF had a higher risk of mortality among the studies included in the systematic review. NewAF is a common complication, occurring in 7.6% of CAP patients, with prediction intervals suggesting an even higher burden. CAP patients who develop newAF during hospitalization may be at higher risk of mortality in both short- and long-term follow-up.

Aims The aim of this study is to perform a systematic review and meta-analysis on the epidemiology of cerebral microbleeds (CMBs) and the risk of intracranial haemorrhage (ICH) and ischaemic stroke (IS) in patients with atrial fibrillation (AF). Methods and results PubMed and EMBASE databases were systematically searched from inception to 6 March 2021. All studies reporting the prevalence of CMBs and incidence of ICH and IS in AF patients with and without CMBs were included. Meta-analysis was conducted using random-effect models; odds ratios (ORs), 95% confidence intervals (CIs), and prediction intervals (PIs) were calculated for each outcome. Subgroup analyses were performed according to the number and localization of CMBs. A total of 562 studies were retrieved, with 17 studies finally included in the meta-analysis. Prevalence of CMBs in AF population was estimated at 28.3% (95% CI: 23.8–33.4%). Individuals with CMBs showed a higher risk of ICH (OR: 3.04, 95% CI: 1.83–5.06, 95% PI 1.23–7.49) and IS (OR: 1.78, 95% CI: 1.26–2.49, 95% PI 1.10–2.87). Patients with ≥5 CMBs showed a higher risk of ICH. Metaregression showed how higher of prevalence of diabetes mellitus in AF cohort is associated with higher prevalence of CMBs. Conclusions Cerebral microbleeds are common in patients with AF, found in almost one out of four subjects. Cerebral microbleeds were associated with both haemorrhagic and thromboembolic events in AF patients. Moreover, the risk of ICH increased consistently with the burden of CMBs. Cerebral microbleeds may represent an important overlooked risk factor for both ICH and IS in adults with AF.

Background Long-term anticoagulation in patients with atrial fibrillation (AF) imposes a careful balance between the thromboembolic and hemorrhagic risks. An association between cerebral microbleeds (CMBs) and an increased risk of intracranial hemorrhage (ICH) has already been described; however, conflicting evidence exist on the association with ischemic stroke (IS). Although CMBs are often observed in AF patients, the actual prevalence and the magnitude of the risk of adverse events in patients with CMBs is unclear. Purpose We aimed to estimate the pooled prevalence of CMBs in patients with AF through a systematic review and meta-analysis of the literature. Additionally, we evaluated the risk of ICH and IS according to the presence and burden of CMBs. Methods We perform a systematic search on PubMed and EMBASE from inception to 6th March 2021. We included all studies reporting the prevalence of CMBs, the incidence of ICH and/or IS in AF by presence of CMBs. Pooled prevalence and odds ratios (OR), along with their 95% Confidence Intervals (CI), were computed using random-effect models; we also calculated 95% Prediction Intervals (PI) for each outcome investigated. Additionally, we performed subgroup analyses according to the number and localization of CMBs. Results We retrieved 562 records from the literature search, and 17 studies were finally included. Pooled prevalence of CMBs in AF population was 28.3% (95% CI: 23.8%-33.4%; 95% PI: 12.2%-52.9%, Figure 1). Individuals with CMBs showed a higher risk of both ICH (OR: 3.04, 95% CI: 1.83–5.06) and IS (OR: 1.78, 95% CI: 1.26–2.49). Moreover, patients with more than 5 CMBs, as well as patients with both lobar and mixed CMBs, showed a higher risk of ICH. Conclusions CMBs were found in 28.3% of AF patients, with 95% PIs indicating a potentially higher prevalence. Moreover, CMBs were associated with an increased risk of both ICH and IS, with the effect potentially modulated by their number and localization. CMBs may represent an important and often overlooked risk factor for adverse outcomes in patients with AF. Funding Acknowledgement Type of funding sources: None. Prevalence of CMBs in patients with AF

Atrial fibrillation (AF) is one of the most common cardiovascular complications in patients hospitalized with community-acquired pneumonia (CAP). However, predisposing clinical factors associated with AF in CAP patients have not been fully elucidated. We enrolled 545 patients consecutively hospitalized for CAP. Data on demographic characteristics and co-morbidities were collected and all patients underwent ECG, echocardiography, and laboratory measurements. During the in-hospital stay, 9.5% of patients experienced a new episode of AF within 24 to 72 hours from admission. CAP patients who experienced AF had a higher indexed left atrial area (LAAi) and a higher proportion of concentric left ventricular hypertrophy than those not presenting AF. Univariate logistic regression analysis showed that hypertension, history of coronary heart disease, high Pneumonia Severity Index classes, history of paroxysmal AF, systolic heart failure, concentric left ventricular hypertrophy, and an enlarged LAAi were associated with a new episode of AF. A multivariable logistic analysis showed that history of paroxysmal AF (odds ratio [OR] 11.7; 95% confidence interval [CI] 5.8 to 23.7; p0.001), enlarged LAAi (OR 5.4; 95% CI 2.5 to 11.9; p0.001), and concentric left ventricular hypertrophy (OR 2.2; 95 CI 1.1 to 4.6; p = 0.034) remained independently associated with AF occurrence. In conclusion, in this large cohort of CAP patients, history of paroxysmal AF, enlarged LAAi, and concentric left ventricular hypertrophy are independent predictors of AF occurrence during the early stages of pneumonia.

INTRODUCTION: Patients with community-acquired pneumonia display enhanced levels of lipopolysaccharides (LPS) compared with controls, suggesting that low-grade endotoxemia may be implicated in vascular disturbances. It is unknown whether this occurs in patients with coronavirus 2019 (COVID-19) and its impact on thrombotic complications. METHODS: We measured serum levels of zonulin, a marker of gut permeability, LPS, and D-dimer in 81 patients with COVID-19 and 81 healthy subjects; the occurrence of thrombotic events in COVID-19 during the intrahospital stay was registered. RESULTS: Serum LPS and zonulin were higher in patients with COVID-19 than in control subjects and, in COVID-19, significantly correlated (R = 0.513; P < 0.001). Among the 81 patients with COVID-19, 11 (14%) experienced thrombotic events in the arterial (n = 5) and venous circulation (n = 6) during a median follow-up of 18 days (interquartile range 11-27 days). A logistic regression analysis showed that LPS (P = 0.024) and D-dimer (P = 0.041) independently predicted thrombotic events. DISCUSSION: The study reports that low-grade endotoxemia is detectable in patients with COVID-19 and is associated with thrombotic events. The coexistence of low-grade endotoxemia with enhanced levels of zonulin may suggest enhanced gut permeability as an underlying mechanism.

An in‐depth characterization of the incidence, morphology, and onset of COVID‐19‐vaccines cutaneous adverse reactions is currently lacking. The existing literature on COVID‐19 vaccination‐related cutaneous adverse reactions largely focused on messenger RNA vaccines and mainly included type 1 hypersensitivity reactions, such as urticaria and angioedema. Other cutaneous manifestations are still poorly characterized and have been classified as delayed hypersensitivity rash. Our prospective observational study on a sample of 2740 subjects who underwent the COVID‐19 vaccination aimed at defining the prevalence of cutaneous adverse reactions and at identifying their timing of onset and their correlation with the administered dose. Vaccine‐related cutaneous adverse reactions occurred in 50 subjects. Patients were asked to complete a questionnaire on the type of COVID‐19 vaccine received, the time of onset of cutaneous reactions, and the dates of administration. Out of 2740 individuals who received the COVID‐19 vaccination, 50 were diagnosed with cutaneous adverse reactions to vaccine, after the first dose in 28 patients, after the second in 20, and after both in two. We reported localized injection site erythema in 12 patients and generalized cutaneous reactions in 38 patients. Our study shows that cutaneous adverse reactions to COVID‐19 vaccination are not common and most often occur after the first dose, recurring infrequently after the second dose. These reactions are usually easily manageable and, even in severe generalized cases, oral antihistamines and corticosteroids were sufficient for resolution. Therefore, except for immediate hypersensitivity reactions, cutaneous adverse reactions do not represent a contraindication to the completion of the vaccination cycle.

Background and Purpose: Patients with community acquired pneumonia (CAP) may suffer from myocardial injury, which is associated with increased risk of major adverse cardiovascular events (MACE). Corticosteroids are often prescribed to CAP patients, but the relationship between their use, myocardial injury and outcomes in these patients is unknown. Experimental Approach: 541 CAP patients were recruited (334 males; mean age: 71.9±16.2 years). High-sensitivity troponin T (hs-cTnT) was measured at admission, during the hospital stay and at discharge. MACE occurrence was registered during a long-term follow-up. Key Results: Overall, 318 patients (59%) showed hs-cTnT elevation > 99th percentile (>0.014 µg/L). Patients with hs-cTnT elevation were older, more likely to be former smokers, and with a higher prevalence of cardiovascular comorbidities. In a median follow-up of 22.7 months, a multivariable Cox proportional hazard regression analysis showed age, heart failure and the increasing quintiles of hs-cTnT (HR: 2.16; 95% CI: 1.82-2.58; p 0.014 µg/L at admission, 102 patients (31%) were on corticosteroids and showed lower intra-hospital hs-cTnT increase compared to untreated ones (p=0.003). Among patients with hs-cTnT >0.014 µg/L, corticosteroid-treated patients showed a lower incidence of MACE than untreated ones [29% (27/99) vs. 43% (92/213); p value =0.042]; no effect of corticosteroids on MACE was observed in CAP patients with normal troponin. Conclusion and Implications: The study provides evidence that corticosteroid use is associated with lower increase of hs-cTnT and incidence of MACE in CAP patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be complicated by myocardial injury but at-risk patients as well as mechanism of disease are unclear. We gathered data regarding troponin levels in the so far reported SARS-CoV-2 patients and found a large variability in terms of troponin levels, patients with more severe disease, as those treated by ICU, presenting with higher percentage of troponin elevation. However, lack of prospective studies hampers adequate analysis of risk factors of myocardial damage. Previous study demonstrated that Nox2 is up-regulated in pneumonia and closely associated with troponin elevation suggesting Nox2 activation as mechanism eliciting myocardial damage; data in SARS-CoV-2 are still lacking. We hypothesize that SARS-Cov-2 may induce myocardial injury via Nox2-related ROS production and that analysis and eventually targeting Nox2 may be a novel approach to manage SARS-CoV-2.

Background. Previous reports suggest that community-acquired pneumonia (CAP) is associated with an enhanced risk of cardiovascular complications. However, a contemporary and comprehensive characterization of this association is lacking. Methods. In this multicenter study, 1182 patients hospitalized for CAP were prospectively followed for up to 30 days after their hospitalization for this infection. Study endpoints included myocardial infarction, new or worsening heart failure, atrial fibrillation, stroke, deep venous thrombosis, cardiovascular death, and total mortality. Results. Three hundred eighty (32.2%) patients experienced intrahospital cardiovascular events (CVEs) including 281 (23.8%) with heart failure, 109 (9.2%) with atrial fibrillation, 89 (8%) with myocardial infarction, 11 (0.9%) with ischemic stroke, and 1 (0.1%) with deep venous thrombosis; 28 patients (2.4%) died for cardiovascular causes. Multivariable Cox regression analysis showed that intrahospital Pneumonia Severity Index (PSI) class (hazard ratio [HR], 2.45, P = .027; HR, 4.23, P < .001; HR, 5.96, P < .001, for classes III, IV, and V vs II, respectively), age (HR, 1.02, P = .001), and preexisting heart failure (HR, 1.85, P < .001) independently predicted CVEs. One hundred three (8.7%) patients died by day 30 postadmission. Thirty-day mortality was significantly higher in patients who developed CVEs compared with those who did not (17.6% vs 4.5%, P < .001). Multivariable Cox regression analysis showed that intrahospital CVEs (HR, 5.49, P < .001) independently predicted 30-day mortality (after adjustment for age, PSI score, and preexisting comorbid conditions). Conclusions. CVEs, mainly those confined to the heart, complicate the course of almost one-third of patients hospitalized for CAP. More importantly, the occurrence of CVEs is associated with a 5-fold increase in CAP-associated 30-day mortality.

The role of oxidative stress, an imbalance between reactive oxygen species production (ROS) and antioxidants, has been described in several patho-physiological conditions, including cardiovascular, neurological diseases and cancer, thus impacting on individuals’ lifelong health. Diet, environmental pollution, and physical activity can play a significant role in the oxidative balance of an organism. Even if physical training has proved to be able to counteract the negative effects caused by free radicals and to provide many health benefits, it is also known that intensive physical activity induces oxidative stress, inflammation, and free radical-mediated muscle damage. Indeed, variations in type, intensity, and duration of exercise training can activate different patterns of oxidant–antioxidant balance leading to different responses in terms of molecular and cellular damage. The aim of the present review is to discuss (1) the role of oxidative status in athletes in relation to exercise training practice, (2) the implications for muscle damage, (3) the long-term effect for neurodegenerative disease manifestations, (4) the role of antioxidant supplementations in preventing oxidative damages.

While the inflammatory response to severe pneumonia is paramount in limiting and resolving the infection, excessive inflammation can lead to deleterious effects. We theorized that patients with severe community-acquired pneumonia (CAP) who were treated with macrolides and aspirin would receive benefit beyond that of conventional antibiotic therapy. An observational study was conducted with patients with severe CAP. All patients were admitted to 5 teaching hospitals (in Italy, the United States, Japan, and China), and data were gathered from their electronic medical records. Severe pneumonia was defined according to Infectious Diseases Society of America/American Thoracic Society criteria. Patients were divided into 4 groups, i.e., (i) the aspirin-only group (ASG), (ii) the macrolide-only group (MG), (iii) the aspirin plus macrolide group (ASMG), or (iv) the neither aspirin nor macrolide group (NASMG). Survival rates for the 4 groups were evaluated after adjustment for confounders and after weighting by propensity score. A total of 1,295 patients were included in the analysis. There were 237 patients (18.3%) in the ASG, 294 (22.7%) in the MG, 148 (11.4%) in the ASMG, and 616 (47.6%) in the NASMG. The mortality rate at 30 days was 15.5% in the ASMG, compared to 28.2% in the NASMG, 23.8% in the MG, and 21.1% in the ASG. After propensity score analysis, receipt of aspirin plus macrolide (hazard ratio, 0.71 [95% confidence interval, 0.58 to 0.88]; P = 0.002) was associated with a higher 30-day survival rate. This is a hypothesis-generating study in which data suggest that the combination of aspirin plus a macrolide improves 30-day survival rates for patients with severe CAP. Further randomized studies will need to be undertaken to confirm this phenomenon.

Adults hospitalized for community-acquired pneumonia (CAP) have an increased risk of myocardial infarction. Corticosteroid treatment lowers CAP morbidity and mortality, but it is not known whether it influences in-hospital myocardial infarction.The aim of the present study was to investigate the potential interplay between corticosteroid treatment and in-hospital myocardial infarction in adults with CAP.We retrospectively analyzed adults with CAP referred to the University Hospital Policlinico Umberto I (Rome, Italy), consecutively recruited, and prospectively followed until discharge. The primary outcome was the occurrence of myocardial infarction during hospitalization. We used propensity score-adjusted Cox models to examine the association between corticosteroid use and myocardial infarction.Seven hundred fifty-eight patients (493 males, 265 females; mean ± standard deviation age, 71.7 ± 14.4 yr) were included in the study. Of these, 241 (32%) were treated with systemic corticosteroids (methylprednisolone, betamethasone, or prednisone). During follow-up, 62 (8.2%) had a myocardial infarction during their hospitalization (incidence, 0.72 per 100 person-days; 95% confidence interval [CI], 0.55 to 0.92). Those treated with corticosteroids had a lower incidence of myocardial infarction (0.42 per 100 person-days) than those not treated with corticosteroids (0.89 per 100 person-days; absolute rate difference, -0.48 per 100 person-days; 95% CI, -0.85 to -0.10). In a propensity score-adjusted Cox model, corticosteroid use was associated with a lower incidence of myocardial infarction (hazard ratio, 0.46; 95% CI, 0.24 to 0.88; P = 0.02).We found that in-hospital corticosteroid treatment was associated with a lower incidence of myocardial infarction in adults hospitalized with CAP.

Community-acquired pneumonia (CAP) is complicated by cardiovascular events as myocardial infarction and stroke but the underlying mechanism is still unclear. We hypothesized that endothelial dysfunction may be implicated and that endotoxemia may have a role.Fifty patients with CAP and 50 controls were enrolled. At admission and at discharge, flow-mediated dilation (FMD), serum levels of endotoxins and oxidative stress, as assessed by serum levels of nitrite/nitrate (NOx) and isoprostanes, were studied.At admission, a significant difference between patients with CAP and controls was observed for FMD (2.1±0.3 vs 4.0±0.3%, p0.001), serum endotoxins (157.8±7.6 vs 33.1±4.8pg/ml), serum isoprostanes (341±14 vs 286±10 pM, p=0.009) and NOx (24.3±1.1 vs 29.7±2.2μM). Simple linear correlation analysis showed that serum endotoxins significantly correlated with Pneumonia Severity Index score (Rs=0.386, p=0.006). Compared to baseline, at discharge CAP patients showed a significant increase of FMD and NOx (from 2.1±0.3 to 4.6±0.4%, p0.001 and from 24.3±1.1 to 31.1±1.5μM, p0.001, respectively) and a significant decrease of serum endotoxins and isoprostanes (from 157.8±7.6 to 55.5±2.3pg/ml, p0.001, and from 341±14 to 312±14 pM, p0.001, respectively). Conversely, no changes for FMD, NOx, serum endotoxins and isoprostanes were observed in controls between baseline and discharge. Changes of FMD significantly correlated with changes of serum endotoxins (Rs=-0.315; p=0.001).The study provides the first evidence that CAP is characterized by impaired FMD with a mechanism potentially involving endotoxin production and oxidative stress.

Background and objective Community-acquired pneumonia (CAP) is associated with an increased risk of arterial and venous thrombosis but the underlying pathophysiological mechanisms are still unclear. We investigated if, in patients with CAP, a pro-thrombotic state does exist and its relationship with serum levels of endotoxins. Methods A total of 104 consecutive patients with CAP were prospectively recruited and followed up until discharge. At admission and at discharge, serum endotoxins, systemic markers of clotting activation and zonulin, a marker of gut permeability, were analysed. Hospitalized patients matched for gender, age and comorbidities but without infections were used as control. Results At admission, CAP patients showed higher plasma levels of F1 +2, a marker of thrombin generation (P = 0.023), and lower levels of protein C (PC; P

Community-acquired pneumonia (CAP) is often complicated by elevation of cardiac troponin, a marker of myocardial injury that can be isolated or associated with myocardial infarction (MI). A retrospective study showed that corticosteroid treatment lowers the incidence of MI during the hospital stay. No data exist so far on the effect of corticosteroids on myocardial injury in CAP patients. The primary objective of the study is to evaluate if methylprednisolone is able to reduce myocardial injury, as assessed by serum high-sensitivity cardiac T Troponin (hs-cTnT), in a cohort of patients hospitalized for CAP. Secondary aims are to evaluate the potential effect of methylprednisolone on cardiovascular events during hospitalization, at 30 days from hospital admission and during 2 years’ follow-up. The trial will also examine whether the potential protective effects of methylprednisolone might be due to platelet activation down-regulation. Double-blind randomized placebo-controlled trial. One hundred twenty-two eligible patients will be randomized to a week treatment with iv methylprednisolone (20 mg b.i.d) or placebo from hospital admission. Serum hs-cTnT will be measured at admission and every day until up 3 days from admission. ECG will be monitored every day until discharge. After discharge, all patients will be followed-up 2 years. This is the first clinical trial aimed at examining whether methylprednisolone treatment may reduce myocardial injury. The results of this trial may constitute the basis for conducting a larger multicenter trial aimed to evaluate the effect of corticosteroid on cardiovascular events in this setting.

Management of patients presenting to the Emergency Department with chest pain is continuously evolving. In the setting of acute coronary syndrome, the availability of high-sensitivity cardiac troponin assays (hs-cTn) has allowed for the development of algorithms aimed at rapidly assessing the risk of an ongoing myocardial infarction. However, concerns were raised about the massive application of such a simplified approach to heterogeneous real-world populations. As a result, there is a potential risk of underdiagnosis in several clusters of patients, including women, for whom a lower threshold for hs-cTn was suggested to be more appropriate. Implementation in clinical practice of sex-tailored cut-off values for hs-cTn represents a hot topic due to the need to reduce inequality and improve diagnostic performance in females. The aim of this review is to summarize current evidence on sex-specific cut-off values of hs-cTn and their application and usefulness in clinical practice. We also offer an extensive overview of thresholds reported in literature and of the mechanisms underlying such differences among sexes, suggesting possible explanations about debated issues.

Background: Platelet activation and oxidative stress seem to play a key role in coronary thrombus formation and are associated with thrombus burden in ST-elevation myocardial infarction (STEMI). However, the interplay between oxidative stress and platelet activation has not been fully elucidated. Materials and Methods: For 32 patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) and 10 patients with stable angina (SA) and oxidative stress, as assessed by NADPH isoform 2 activity (soluble Nox2-derived peptide, sNox2-dp), levels of oxidized low-density lipoproteins (oxLDLs) and platelet activation markers such as soluble CD40 Ligand (sCD40L) and soluble P-selectin (sP-selectin) were measured in the retrieved material (coronary thrombi plus blood waste) of STEMI patients and in intracoronary blood of SA patients, respectively, and in peripheral blood samples of both groups. Results: In aspirated thrombi and blood waste of STEMI patients we found higher serum levels of sNox2-dp, oxLDLs, sCD40L, and sP-selectin, as compared to the intracoronary blood samples of SA patients. Moreover, in thrombi and blood waste of STEMI patients, a direct correlation between markers of oxidative stress and of platelet activation was found. Also, in STEMI patients a progressive increase of oxidative stress and platelet activation markers was observed according to the thrombus score burden. STEMI patients showed higher peripheral blood Nox2 activity and oxLDL levels as compared to SA patients. Conclusion: This study shows a close relationship between oxidative stress and platelet activation in the intracoronary blood waste and aspirated thrombi of STEMI patients, suggesting a role of oxidative stress in promoting thrombus formation and growth.

Background: Gut microbiota seems to be implicated in the athero-thrombotic process. Its relationship with coronary thrombosis has never been investigated. Methods: Serum levels of bacterial lipopolysaccharides (LPS) against Escherichia Coli (EC) and EC DNA amplification by polymerase chain reaction, plasma sP-selectin, a marker of platelet activation, and zonulin, a marker of gut permeability, were measured in patients with ST-elevation myocardial infarction (STEMI) (n=50) or stable coronary disease (SA) (n=50) and controls (n=50). Serum LPS and sP-selectin were also measured in coronary thrombi and coronary blood of patients with STEMI and stable coronary disease, respectively. Immuno-histochemical analysis was performed in coronary thrombi of 12 STEMI patients. Finally, in vitro study was undertaken to evaluate if LPS stimulate leucocyte-platelet interaction. Results: Compared to controls, patients with SA and STEMI had higher systemic levels of LPS (p Conclusion: Bacterial LPS is detected in coronary thrombi of STEMI patients and may be implicated in the thrombotic process via leucocyte-mediated platelet activation.

Background: Previous reports suggest that patients hospitalized for community-acquired pneumonia (CAP) have an enhanced risk of myocardial infarction (MI). Glucocorticoids have been proposed for the treatment of CAP. Although a recent meta-analysis showed that glucocorticoids can reduce morbidity and mortality in severe CAP, their role in the treatment of pneumonia remains unclear. Experiments in vitro and in vivo demonstrated that glucocorticoids inhibit platelet aggregation and platelet-related arterial thrombosis. Since enhanced platelet activation seems to play a role in the occurrence of MI in CAP patients, aim of the study was to assess the impact of glucocorticoids on MI occurrence in a cohort of patients hospitalized for CAP. Methods and Results: Consecutive patients admitted to the University-Hospital Policlinico Umberto I (Rome, Italy) with CAP were recruited and prospectively followed-up until discharge. The primary outcome of the study was the occurrence of an MI during hospitalization. Seven-hundred fifty-eight patients (493 males, 265 females; age: 71.7 ± 14.4 years) were included in the study: 241 (32%) were treated with systemic glucocorticoids (methylprednisolone, betamethasone or prednisone) during in-hospital follow-up, whereas 517 patients were not treated with systemic glucocorticoids. During the follow-up, 62 patients (8.2%) had an MI. Compared to the nonglucocorticoid group, patients treated with glucocorticoids showed a lower incidence of MI (9.5% vs. 5.4%; p=0.011). A Cox regression analysis showed that age, a history of coronary heart disease, and a major degree of respiratory impairment (pO2 Conclusion: This study shows that in-hospital glucocorticoids treatment is associated with a lower incidence of MI within hospital-stay in a large cohort of patients with pneumonia.

To investigate the association between adherence to the Mediterranean Diet (Med-Diet), cardiometabolic disorders and polypharmacy.Cross-sectional study.Geriatrics outpatient clinic, Policlinico Umberto I, Sapienza University of Rome.508 patients (219 male, 289 female) aged 50 to 89 who were evaluated for cardiovascular and metabolic disorders.Patients underwent a comprehensive medical assessment including medical history and the use of medications. Adherence to Med-Diet was assessed using the validated Med-Diet 14-item questionnaire; for the analysis, patients were divided in high (≥8) and medium-low (8) adherence. Polypharmacy was defined as taking ≥5 medications.476 patients completed the study. Mean age was 70.4 years; 58% female. Median Med-Diet score was 8 (interquartile range, 6-9). Patients with medium-low adherence had higher body mass index (p=0.029) and higher prevalence of arterial hypertension (p0.001), previous coronary (p=0.002) and cerebrovascular events (p=0.011), diabetes, (p0.001) and dyslipidemia (p=0.001) compared to those at high adherence. Med-Diet score decreased with the number of cardiometabolic disorders (p0.001). The prevalence of polypharmacy was 39%. Consumption of olive oil (p=0.005), vegetables, (p0.001), wine (p=0.017), legumes (p=0.028), fish (p=0.046) and nuts (p=0.045) were all inversely associated with the overall number of medications. In a multivariable regression model, medium-low adherence to Med-Diet was independently associated to polypharmacy (O.R.:1.859; 95% CI 1.142 to 3.025; p=0.013), after adjusting for possible confounding factors.Med-Diet was inversely associated with cardiometabolic disorders and with polypharmacy, suggesting that improved Med-Diet adherence might potentially delay the onset of age-related health deterioration and reduce the need of multiple medications.

Oxidative stress plays an important role in chronic respiratory diseases where the use of non-invasive ventilation seems to reduce the oxidative damage. Data on acute respiratory failure are still lacking. The aim of the study is to investigate the interplay between oxidative stress and acute respiratory failure, and the role of non-invasive ventilation in this setting. We enrolled 60 patients suffering from acute respiratory failure (PaO2/FiO2 ratio

Background and objectives: Retinal vein occlusion (RVO), one of the most relevant causes of vision loss, still represents an open issue in ophthalmology and vascular medicine. Its epidemiology and management approach have not been clearly characterized yet, with several grey zones requiring investigation. Significance of RVO on cardiovascular prognosis is also unclear. “High focused Evaluation of Atherosclerotic risk profile in Retinal Thrombosis: Vascular events Incidence, Sex involvement and Interventional outcomes assessed by Ophthalmologists and internists Network” (HEART VISION) is a longitudinal, prospective, multi-center study which aims at determining the epidemiology, potentially modifiable risk factors and the determinants of RVO in an Italian-based cohort. Methods: Enrollment of all the eligible patients presenting to recruiting centers (i.e. ophthalmology emergency room and thrombosis centers) with suspect of RVO. At baseline, all patients will undergo an opthalmologic evaluation and further investigations about cardiovascular co-morbidities and risk factors. Recruited patients will be followed for a 2-year period. Outcome measures: Data about adverse cardiovascular events and eye-related outcomes will be recorded. Discussion: HEART VISION will present data on prevalence and will inform on the prognosis of RVO in an Italian-based cohort. Characterization and prospective evaluation of these patients will be useful in developing novel strategies for management of RVO and their cardiovascular-related risk factors. Ethics and dissemination: This study protocol (n. 1.0, 01.07.2014) was approved by the Sapienza-University of Rome, Ethics Board (Protocol No. 1076/14). This study will be performed in accordance with the Declaration of Helsinki. Dissemination plans include presentations at scientific conferences and publication in scientific journals. Trial registration: ClinicalTrials.gov Identifier: NCT02257333 on October 6, 2014.

Objectives Extra virgin olive oil (EVOO) supplementation is associated with a significant reduction in cardiovascular disease but the underlying mechanism is still unclear. Methods In platelets that were taken from healthy subjects (n = 5), agonist-induced hydrogen peroxide (H 2 O 2 ) production and NADPH oxidase 2 (NOX2) activation in the presence of or without catalase, which catabolizes H 2 O 2 , were investigated. Platelet H 2 O 2 production, NOX2 activation, EVOO vitamin E, and total polyphenols as well as EVOO's ability to scavenge H 2 O 2 were also measured. Results Platelet NOX2 activation and H 2 O 2 production were significantly inhibited in catalase-treated platelets and platelets that were incubated with five different EVOOs. The EVOO content of vitamin E was 53 to 223 mg/kg and total polyphenols 145 to 392 mg/L Gallic acid equivalent. EVOOs quenched in vitro H 2 O 2 by 39 to 62%, which is an effect that is significantly correlated with vitamin E and total polyphenol concentrations ( R = 0.688; P R = 0.541; P Conclusions This in vitro study provides the first evidence that EVOO downregulates platelet H 2 O 2 and in turn NOX2 activity via H 2 O 2 scavenging.

Background Time in therapeutic range (TTR) reflects the quality of anticoagulation and is inversely correlated with ischemic stroke in atrial fibrillation (AF) patients. Few data on the relationship between TTR and myocardial infarction (MI) are available. We investigated the association between TTR and Major Adverse Cardiovascular Events (MACE) in a cohort of anticoagulated AF patients. Methods We calculated TTR for 627 AF patients on vitamin K antagonists, who were followed for a median of 30.8months (1755patients/year). The primary outcome was a combined endpoint of MACE including fatal/nonfatal MI and cardiovascular death. Results Mean age was 73.3 (±8.2) years, and 40.2% were women. During follow-up, we recorded 67 events: 19 stroke/TIA (1.1%/year) and 48 MACE (2.9%/year): 24 MI and 24 cardiovascular deaths. The cohort was categorized according to tertiles of TTR values: TTR 13–58%, 59–74%, and 75–100%. There was a significant increased rate of MACE across tertiles of TTR (Log-Rank test: p Conclusion TTR was an independent predictor of MACE in our cohort of AF patients. Our findings suggest that a good anticoagulation control is necessary to reduce not only the risk of stroke but also that of MACE.