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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.

Platelet activation seems to be implicated in the cardiovascular events occurring in patients with community-acquired pneumonia (CAP) but the underlying mechanism is still unclear. Aim of the study was to assess the mechanism involved in platelet activation in CAP patients.Two-hundred-seventy-eight consecutive patients hospitalized for CAP were recruited and followed-up until discharge. Hospitalized patients matched for sex, age and comorbidities but without acute infectious diseases were used as controls.At hospital admission patients disclosed enhanced plasma levels of sP-selectin, a maker of in-vivo platelet activation, serum sNOX2-dp, a marker of NADPH-oxidase activation, serum Lipopolysaccharide (LPS) and serum zonulin, a marker of gut permeability, compared to controls (p 0.001). Baseline sP-selectin was independently associated to serum LPS, sNOX2-sp and Pneumonia Severity Index score (p 0.001). Plasma sP-selectin, serum sNOX2-dp, LPS and zonulin coincidentally decreased at hospital discharge (p 0.001). An in vitro study showed that LPS, at concentration similar to that found in CAP patients, induced sP-selectin release by agonist-activated platelets, a phenomenon that was counteract by treating cells with gp91ds-tat, a specific inhibitor of NOX2.CAP patients display enhanced platelet activation, which is related to LPS-mediated NOX2 activation. Enhanced gut permeability seems be implicated in enhancing circulating levels of LPS.

Community-acquired pneumonia (CAP) is complicated by cardiac events in the early phase of the disease. Aim of this study was to assess if these intrahospital cardiac complications may account for overall mortality and cardiovascular events occurring during a long-term follow-up. Three hundred one consecutive patients admitted to the University-Hospital, Policlinico Umberto I, with community-acquired pneumonia were prospectively recruited and followed up for a median of 17.4 months. Primary end point was the occurrence of death for any cause, and secondary end point was the occurrence of cardiovascular events (cardiovascular death, nonfatal myocardial infarction [MI], and stroke). During the intrahospital stay, 55 patients (18%) experienced a cardiac complication. Of these, 32 had an MI (29 non-ST-elevation MI and 3 ST-elevation MI) and 30 had a new episode of atrial fibrillation (7 nonmutually exclusive events). During the follow-up, 89 patients died (51% of patients with an intrahospital cardiac complication and 26% of patients without, p0.001) and 73 experienced a cardiovascular event (47% of patients with and 19% of patients without an intrahospital cardiac complication, p0.001). A Cox regression analysis showed that intrahospital cardiac complications, age, and Pneumonia Severity Index were significantly associated with overall mortality, whereas intrahospital cardiac complications, age, hypertension, and diabetes were significantly associated with cardiovascular events during the follow-up. In conclusion, this prospective study shows that intrahospital cardiac complications in the early phase of pneumonia are associated with an enhanced risk of death and cardiovascular events during long-term follow-up.

Increased oxidative stress may contribute to cancer anorexia, which could be ameliorated by antioxidant supplementation. methylcholanthrene (MCA) sarcoma-bearing Fisher rats were studied. After tumour inoculation, rats were randomly assigned to standard diet (CTR group, n = 6), or to an antioxidant-enriched diet (AOX group, n = 8). Eight more rats (STD-AOX group) switched from standard to antioxidant diet when anorexia developed. At the end of the study, food intake (FI, g/d), body weight and tumour weight (g) were recorded, and plasma samples were obtained. On day 16, anorexia has appeared only in CTR and STD-AOX animals. At the end of the study, FI in AOX animals was still higher than in the other groups (p = 0.08). No differences in body and tumour weights were observed among groups. However, hydrogen peroxide and interleukin-1β levels were significantly reduced only in AOX rats. Data obtained suggest that early antioxidant supplementation improves cancer anorexia, ameliorates oxidative stress and reduces inflammation.

Summary Background & aims In hospitalized patients, lack of appetite, i.e., disease-associated anorexia, is the main factor determining insufficient food intake and weight loss, which in turn increase morbidity and mortality. Controversies exist on which tool should be preferred when diagnosing anorexia. Aim of the study was to evaluate in hospitalized medical patients, the performance of 4 different tools [i.e., self-assessment of appetite, FAACT-ESPEN score, visual analog scale (VAS), and the Anorexia Questionnaire (AQ)] in assessing disease-associated anorexia and predicting nutritional and clinical variables. Materials and methods Hospitalized patients consecutively admitted to the Internal Medicine ward at our institution were considered. After informed consent was obtained, patients were asked to self-assess their appetite vs the previous month. The VAS, the FAACT-ESPEN score and the Anorexia Questionnaire were also submitted. Food intake immediately following the interview was recorded. Nutritional (i.e., body weight, height), functional (i.e., handgrip strength) and clinical variables (i.e., length of stay) were registered upon admission and before discharge. Results We studied 105 patients (74M:31F; 66.2 ± 16.3 yrs). The prevalence of anorexia as assessed by patients' self assessment, FAACT-ESPEN score, and the Anorexia Questionnaire was 23%, 10% and 48%, respectively. VAS did not show any correlation with food intake. Anorexic patients as identified by the self assessment of appetite showed reduced food intake and weaker handgrip strength than non-anorexic. The FAACT-ESPEN score correlated with body weight, food intake and handgrip strength, but was not related with length of stay. Anorexic patients as identified by the Anorexia Questionnaire showed reduced food intake, lower body weight, weaker handgrip strength and longer hospital stay than non-anorexic patients. Discussion The prevalence of anorexia significantly varies according to the diagnostic tool used. Except for VAS, all the tested tools identify patients with impaired nutritional and functional variables. However, only the Anorexia Questionnaire identifies patients with longer hospital stay. Our results suggest that in clinical practice, modification of appetite reflects different underlying mechanisms whose impacts on clinical outcome measures may differ. Therefore, an ideal anorexia assessment tool does not appear to exist, but it should be chosen according to the outcome measures to be assessed (i.e., Anorexia Questionnaire to predict length of stay).

BackgroundTroponins may be elevated in patients with pneumonia, but associations with myocardial infarction (MI) and with platelet activation are still undefined.ObjectivesThe aim of this study was to investigate the relationship between troponin elevation and in vivo markers of platelet activation in the early phase of hospitalization of patients affected by community-acquired pneumonia.MethodsA total of 278 consecutive patients hospitalized for community-acquired pneumonia, who were followed up until discharge, were included. At admission, platelet activation markers such as plasma soluble P-selectin, soluble CD40 ligand, and serum thromboxane B2 (TxB2) were measured. Serum high-sensitivity cardiac troponin T levels and electrocardiograms were obtained every 12 and 24 h, respectively.ResultsAmong 144 patients with elevated high-sensitivity cardiac troponin T, 31 had signs of MI and 113 did not. Baseline plasma levels of soluble P-selectin and soluble CD40 ligand and serum TxB2 were significantly higher in patients who developed signs of MI. Logistic regression analysis showed plasma soluble CD40 ligand (p < 0.001) and soluble P-selectin (p < 0.001), serum TxB2 (p = 0.030), mean platelet volume (p = 0.037), Pneumonia Severity Index score (p = 0.030), and ejection fraction (p = 0.001) to be independent predictors of MI. There were no significant differences in MI rate between the 123 patients (45%) taking aspirin (100 mg/day) and those who were not aspirin treated (12% vs. 10%; p = 0.649). Aspirin-treated patients with MIs had higher serum TxB2 compared with those without MIs (p = 0.005).ConclusionsMI is an early complication of pneumonia and is associated with in vivo platelet activation and serum TxB2 overproduction; aspirin 100 mg/day seems insufficient to inhibit thromboxane biosynthesis. (MACCE in Hospitalized Patients With Community-acquired Pneumonia; NCT01773863)