Lipid-based insulin-resistance markers predict cardiovascular events in metabolic dysfunction associated steatotic liver disease.

BACKGROUND: Insulin resistance (IR) is the cornerstone of Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD), pathophysiologically being the key link between MASLD, metabolic disorders, and cardiovascular (CV) diseases. There are no prospective studies comparing the predictive values of different markers of insulin resistance (IR) in identifying the presence of MASLD and the associated risk of cardiovascular events (CVEs). METHODS: Post hoc analysis of the prospective Plinio Study, involving dysmetabolic patients evaluated for the presence of MASLD. The IR markers considered were Homeostatic Model Assessment for IR (HOMA-IR), Triglycerides-Glycemia (TyG) index, Triglycerides to High-Density Lipoprotein Cholesterol ratio (TG/HDL-C), Lipid Accumulation Product (LAP) and Visceral Adiposity Index (VAI). Receiver operative characteristic (ROC) analyses were performed to find the optimal cut-offs of each IR marker for detecting MASLD and predicting CVEs in MASLD patients. Logistic and Cox multivariable regression analyses were performed, after dichotomizing the IR markers based on the optimal cut-offs, to assess the factors independently associated with MASLD and the risk of CVEs. RESULTS: The study included 772 patients (age 55.6 ± 12.1 years, 39.4% women), of whom 82.8% had MASLD. VAI (Area Under the Curve [AUC] 0.731), TyG Index (AUC 0.723), and TG/HDL-C ratio (AUC: 0.721) predicted MASLD but was greater with HOMA-IR (AUC: 0.792) and LAP (AUC: 0.787). After a median follow-up of 48.7 (25.4-75.8) months, 53 MASLD patients experienced CVEs (1.8%/year). TyG index (AUC: 0.630), LAP (AUC: 0.626), TG/HDL-C (AUC: 0.614), and VAI (AUC: 0.590) demonstrated comparable, modest predictive values in assessing the CVEs risk in MASLD patients. CONCLUSION: In dysmetabolic patients HOMA-IR and LAP showed the best accuracy in detecting MASLD. The possible use of lipid-based IR markers in stratifying the CV risk in patients with MASLD needs further validation in larger cohorts.

The Association between Levels of Physical Activity and Lifestyle, Life Expectancy, and Quality of Life in Patients with Alzheimer's Disease.

BACKGROUND: Engaging in physical activity could help improve the quality of life in patients with Alzheimer's disease. The objective of this study was to determine the association between the levels of physical activity and lifestyle, life expectancy, and quality of life in patients with Alzheimer's disease in Iran and Italy. METHODS: A total of 165 participants from Iran and Italy were enrolled in this cross-sectional study. In Iran, 85 patients participated in the study. In Italy, we enrolled 80 patients at the Sapienza University teaching hospital, Policlinico Umberto 1 in Rome. The inclusion criteria in this study include patients over 60 years old, non-smokers, and non-users of antidepressants and hypnotics. RESULTS: The results of Tukey's post hoc test of the study conducted in Iran showed that the lifestyle of patients with moderate (p = 0.001) and low (p = 0.009) physical activity levels was significantly better than inactive patients. Life expectancy in patients with moderate physical activity levels was significantly higher than inactive patients (p = 0.011). The quality of life was significantly better in patients with moderate (p = 0.001) and low (p = 0.002) physical activity levels than inactive patients. On the other hand, the findings of Tukey's post hoc test of the study in Italy showed that the quality of life in patients with low (p = 0.001) and moderate physical activity levels (p = 0.01) was significantly higher than inactive patients. CONCLUSIONS: A low to moderate level of physical activity could be associated with an improved lifestyle, life expectancy, and quality of life in patients with Alzheimer's disease compared to inactivity.

Serum Uric Acid Levels Are Associated with the Echogenic Features of Carotid Plaque Vulnerability in Elderly Patients with Atherosclerotic Disease.

Uric acid is a marker of inflammation and a risk factor for atherosclerosis that has been suggested to play a role in carotid plaque instability. Reduced atherosclerotic plaque echogenicity at ultrasound examination is associated with alarming histopathological features and inflammation. In this study, we investigated the relationship between serum uric acid (SUA) levels and echogenic patterns of plaque instability in elderly subjects with carotid atherosclerosis. Since uric acid metabolism largely depends on renal function, SUA levels were indexed for serum creatinine levels (SUA/SCr). We enrolled 108 patients aged 65 years or more (72.7 ± 5.9 years; 50 females and 58 males) who underwent carotid duplex ultrasound to evaluate plaque echogenicity by greyscale median (GSM). The regression analysis demonstrated a significant inverse association between the GSM and the SUA/SCr ratio (ß: -0.567; 95% CI -0.751 to -0.384 and p < 0.0001). Stepwise multivariate regression showed that the SUA/SCr ratio explained 30.3% of GSM variability (ß: -0.600; 95% CI -0.777/-0.424, p < 0.0001, and semi-partial correlation 0.303). After a mean period of 3.5 ± 0.5 years, 48 patients were reevaluated according to the same baseline study protocol. The regression analysis demonstrated a still significant inverse association between the GSM and the SUA/SCr ratio (ß: -0.462; 95% CI -0.745 to -0.178 and p = 0.002). Stepwise multivariate regression showed that the SUA/SCr ratio explained 28.0% of GSM variability (coefficient -0.584, 95% CI -0.848/-0.319, p < 0.0001, and semi-partial R2 0.280). In conclusion, this study demonstrates that SUA levels indexed for serum creatinine are associated with the echogenic features of carotid plaque vulnerability in elderly patients with atherosclerotic disease. These data could suggest an influential role for uric acid metabolism in carotid plaque biology.

COVID-19 Affects Serum Brain-Derived Neurotrophic Factor and Neurofilament Light Chain in Aged Men: Implications for Morbidity and Mortality.

BACKGROUND AND METHODS: Severe COVID-19 is known to induce neurological damage (NeuroCOVID), mostly in aged individuals, by affecting brain-derived neurotrophic factor (BDNF), matrix metalloproteinases (MMP) 2 and 9 and the neurofilament light chain (NFL) pathways. Thus, the aim of this pilot study was to investigate BDNF, MMP-2, MMP-9, and NFL in the serum of aged men affected by COVID-19 at the beginning of the hospitalization period and characterized by different outcomes, i.e., attending a hospital ward or an intensive care unit (ICU) or with a fatal outcome. As a control group, we used a novelty of the study, unexposed age-matched men. We also correlated these findings with the routine blood parameters of the recruited individuals. RESULTS: We found in COVID-19 individuals with severe or lethal outcomes disrupted serum BDNF, NFL, and MMP-2 presence and gross changes in ALT, GGT, LDH, IL-6, ferritin, and CRP. We also confirmed and extended previous data, using ROC analyses, showing that the ratio MMPs (2 and 9) versus BDNF and NFL might be a useful tool to predict a fatal COVID-19 outcome. CONCLUSIONS: Serum BDNF and NFL and/or their ratios with MMP-2 and MMP-9 could represent early predictors of NeuroCOVID in aged men.

Asymptomatic and symptomatic deep venous thrombosis in hospitalized acutely ill medical patients: risk factors and therapeutic implications.

BACKGROUND: Acutely ill medical patients experience deep venous thrombosis (DVT) during the hospitalization, however the time course of DVT is still unclear. OBJECTIVES: To evaluate risk factors in acutely ill hospitalized medical patients for proximal asymptomatic DVT (ADVT) and symptomatic DVT (SDVT) at admission and discharge. PATIENTS/METHODS: In this prospective observational study, consecutive acutely ill medical patients (hospitalized mainly for acute medical disease as infections, neoplasm, anemia, heart failure) underwent compression ultrasonography (CUS) of proximal lower limb veins within 48 h from admission and at discharge to diagnose ADVT and SDVT. Covid-19 patients, anticoagulant therapy, surgical procedures, acute SDVT, and acute pulmonary embolism, were exclusion criteria. Biographical characteristics at hospitalization, D-Dimer (assessed by ELISA)) and DD-improve score. RESULTS: Of 2,100 patients (1002 females, 998 males, age 71 ± 16 years) 58 (2.7%) had proximal ADVT at admission. Logistic regression analysis showed that age, and active cancer were independently associated with ADVT at admission. The median length of hospitalization was 10 days [interquartile range: 6-15]. During the hospital stay, 6 patients (0.3%) with a negative CUS at admission experienced DVT (2 SDVT and 4 ADVT). In the subgroup of patients (n = 1118), in whom D-dimer was measured at admission, D-Dimer and IMPROVE-DD score were associated with ADVT at admission (n = 37) and with all DVT (n = 42) at discharge. ROC curve defined an IMPROVE-DD score of 2.5 as the optimal cut-off for discriminating patients with and without thrombotic events. CONCLUSIONS: We provide evidence of early development of ADVT in unselected acutely ill medical patients suggesting the need of investigating patients by CUS immediately after hospital admission (within 48 h). Advanced age, active cancer, known thrombophilia and increased IMPROVE-DD score may identify patients at risk. The benefit of anticoagulation needs to be investigated in patients with these specific risk factors and negative CUS at admission. TRIAL REGISTRATION: NCT03157843.

Masticatory Force in Relation with Age in Subjects with Full Permanent Dentition: A Cross-Sectional Study.

Masticatory performance is directly correlated with masticatory muscle work to grind and cut the food. Chewing efficacy is decisive to eating a variety of foods needed maintain general health status at all ages. Older people have oral problems that get worse with age. Elders have more pathologies such as periodontal diseases, caries, tooth loss and inadequate dental prostheses than younger subjects. OBJECTIVES: to investigate the correlation between masticatory bite force (MBF) and body mass index (BMI) vs. aging and sex. METHODS: This study was performed on 426 subjects (213 females plus 213 male) assigned into five different groups by age. Group "A" aged from 20 to 35 years; group "B" aged 45-59 years; group "C" aged 60-69 years; group "D" aged 70-79 years; and group "E" aged more than 79 years. RESULTS: There were not statistically significant differences in right-side MBF versus left-side MBF. The differences between sex were statistically significant with a stronger bite in males than females (p < 0.05). At the same time, younger subjects had a stronger bite than elders (p < 0.05). In group "E", more corpulent subjects (BMI > 25) had an MBF higher than less corpulent subjects (BMI < 25, p < 0.05). The analysis of mean MBF showed a statistically significant difference within all groups stratified by BMI with mean values inversely proportional with age (p < 0.001). CONCLUSION: The results in our study confirm data from many scientific papers. The importance of the present paper was to correlate data between and within a large sample with a wide range of ages. Our sample subjects had a 31%-33% decrease in MBF from group "A" to group "E" group, but they all had full permanent dentation and they preserved a valid MBF.

Update and Unmet Needs on the Use of Nonvitamin K Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fibrillation.

The landscape of stroke prevention in patients with atrial fibrillation (AF) is rapidly changing after the introduction of nonvitamin K oral anticoagulants (NOACs) that are replacing in many countries the use of vitamin K antagonists in virtue of their similar efficacy and better safety. The European Heart Rhythm Association has proposed a new classification for AF patients with valvular heart disease (VHD), which has clinical implications for the most appropriate choice of antithrombotic strategy. Furthermore, a growing body of evidence is available on the use of NOACs in patients with VHD. Beyond VHD, several other factors may help tailoring the antithrombotic therapy to the characteristics of patients. Thus, a new risk factors-based approach to improve the management of AF patients, namely Atrial fibrillation Better Care (ABC) pathway has been recently proposed. This includes "A" avoid stroke by adequate anticoagulant therapy, "B" better control of symptoms related to AF, and "C" optimal management of comorbidities focusing on modifiable cardiovascular risk factors. Another recent update regards the use of NOACs in patients undergoing myocardial revascularization, where the association of NOACs with antiplatelet offers a new safe option in the first period after the procedure. Finally, there are still some patients in whom NOACs have not been systematically studied, and the clinician has to decide whether to prescribe or not NOACs balancing the risk of bleeding and stroke. This review aims to summarize the most recent evidence to consider when choosing an anticoagulant therapy in AF patients.

Association of different oral anticoagulants use with renal function worsening in patients with atrial fibrillation: A multicentre cohort study.

AIMS: To investigate the decline of estimated glomerular filtration rate (eGFR) in patients with atrial fibrillation (AF) treated with vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs). METHODS: Multicentre prospective cohort study including 1667 patients with nonvalvular AF. The eGFR was assessed by the CKD-EPI formula at baseline and during follow-up. The primary endpoint of the study was the median annual decline of eGFR according to VKA (n = 743) or NOAC (n = 924) use. As secondary endpoints, we analysed the transition to eGFR <50 mL/min/1.73 m2 and the eGFR class worsening. RESULTS: Median age was 73.7 ± 9.1 years and 43.3% were women. VKA-treated patients showed an eGFR decline of -2.11 (interquartile range [IQR] -5.68/-0.62), which was -0.27 (IQR -9.00/4.54, P < 0.001 vs VKAs), -1.21 (IQR -9.98/4.02, P = 0.004 vs VKAs) and -1.32 (IQR -8.70/3.99, P = 0.003 vs VKAs) in patients on dabigatran, rivaroxaban and apixaban, respectively. Transition to eGFR <50 mL/min/1.73 m2 was lower in dabigatran- and apixaban-treated patients: odds ratio (OR) 0.492, 95% confidence interval (CI) 0.298-0.813, P = 0.006 and OR 0.449, 95% CI 0.276-0.728, P = 0.001, respectively. A lower rate of eGFR class worsening was found in all groups of NOACs compared to VKAs. No difference between full and reduced dose of NOAC was found. Subgroup analysis showed that the association between NOAC and eGFR changes was markedly reduced in diabetic patients. CONCLUSION: Patients prescribed NOACs showed a lower decline of renal function compared to those prescribed VKAs. This effect was partially lost in patients with diabetes.

PCSK9 Regulates Nox2-Mediated Platelet Activation via CD36 Receptor in Patients with Atrial Fibrillation.

BACKGROUND: High levels of proprotein convertase subtilisin/kexin 9 (PCSK9) is predictive of cardiovascular events (CVEs) in atrial fibrillation (AF). We hypothesized that PCSK9 may directly induce platelet activation (PA). METHODS: We measured platelet aggregation, recruitment, Thromboxane B2 (TxB2) formation and soluble P-selectin levels as markers of PA and soluble Nox2-derived peptide (sNox2-dp), H2O2, isoprostanes and oxidized Low-Density-Lipoprotein (oxLDL) to analyze oxidative stress (OS) in 88 patients having PCSK9 values < (n = 44) or > (n = 44) 1.2 ng/mL, balanced for age, sex and cardiovascular risk factors. Furthermore, we investigated if normal (n = 5) platelets incubated with PCSK9 (1.0-2.0 ng/mL) alone or with LDL (50 µg/mL) displayed changes of PA, OS and down-stream signaling. RESULTS: PA and OS markers were significantly higher in patients with PCSK9 levels > 1.2 ng/mL compared to those with values < 1.2 ng/mL (p < 0.001). Levels of PCSK9 significantly correlated with markers of PA and OS. Platelets incubation with PCSK9 increased PA, OS and p38, p47 and Phospholipase A2 (PLA2) phosphorylation. These changes were amplified by adding LDL and blunted by CD36 or Nox2 inhibitors. Co-immunoprecipitation analysis revealed an immune complex of PCSK9 with CD36. CONCLUSIONS: We provide the first evidence that PCSK9, at concentration found in the circulation of AF patients, directly interacts with platelets via CD36 receptor and activating Nox2: this effect is amplified in presence of LDL.

Oxidative stress and gut-derived lipopolysaccharides in children affected by paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections.

BACKGROUND: Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) identifies patients with acute onset of obsessive-compulsive and tic disorders. The objective of this study was to evaluate serum NOX2 levels, as well as 8-iso-prostaglandin F2α (8-iso-PGF2α) and lipopolysaccharide (LPS) of PANDAS patients. METHODS: In this study we wanted to compare serum levels of soluble NOX2-dp (sNOX-2-dp), iso-PGF2α and LPS in 60 consecutive subjects, including 30 children affected by PANDAS and 30 controls (CT) matched for age and gender. Serum zonulin was used as intestinal permeability assay. RESULTS: Compared with CT, PANDAS children had increased serum levels of sNOX-2-dp, 8-iso-PGF2α and LPS. Bivariate analysis showed that serum sNOX2-dp was significantly correlated with LPS (Rs = 0.359; p = 0.005), zonulin (Rs = 0.444; p < 0.001) and 8-iso-PGF2α (Rs = 0.704; p < 0.001). Serum LPS significantly correlated with zonulin (Rs = 0.610; p < 0.001), and 8-iso-PGF2α (Rs = 0.591; p = 0.001). Finally, a multiple linear regression analysis showed that serum 8-iso-PGF2α and zonulin were the only independent variables associated with sNOX2-dp (R2 = 68%). CONCLUSION: This study shows that children affected by PANDAS have high circulating levels of sNOX2-dp, isoprostanes and of LPS that could be involved in the process of neuroinflammation.

Oxidative Stress and Gut-Derived Lipopolysaccharides in Neurodegenerative Disease: Role of NOX2.

BACKGROUND: Neurodegenerative diseases (ND) as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis represent a growing cause of disability in the developed countries. The underlying physiopathology is still unclear. Several lines of evidence suggest a role for oxidative stress and NADPH oxidase 2 (NOX2) in the neuropathological pathways that lead to ND. Furthermore, recent studies hypothesized a role for gut microbiota in the neuroinflammation; in particular, lipopolysaccharide (LPS) derived from Gram-negative bacteria in the gut is believed to play a role in causing ND by increase of oxidative stress and inflammation. The aim of this study was to assess NOX2 activity as well as serum 8-iso-prostaglandin F2α (8-iso-PGF2α (8-iso-PGF2. METHODS: One hundred and twenty-eight consecutive subjects, including 64 ND patients and 64 controls (CT) matched for age and gender, were recruited. A cross-sectional study was performed to compare serum activity of soluble NOX2-dp (sNOX2-dp), blood levels of isoprostanes, serum H2O2, and LPS in these two groups. Serum zonulin was used to assess gut permeability. RESULTS: Compared with CT, ND patients had higher values of sNOX2-dp, 8-iso-PGF2α (8-iso-PGF2p < 0.001), zonulin (Rs = 0.411; p < 0.001), zonulin (Rs = 0.411; p < 0.001), zonulin (Rs = 0.411; α (8-iso-PGF2p < 0.001), zonulin (Rs = 0.411; p < 0.001), zonulin (Rs = 0.411; α (8-iso-PGF2p < 0.001), zonulin (Rs = 0.411; ß, 0.459; p < 0.001), zonulin (Rs = 0.411; α (8-iso-PGF2ß, 0.459; p < 0.001), zonulin (Rs = 0.411; R 2 = 57%). CONCLUSION: This study provides the first report attesting that patients with ND have high NOX2 activation that could be potentially implicated in the process of neuroinflammation.

Seronegative antiphospholipid syndrome: refining the value of "non-criteria" antibodies for diagnosis and clinical management.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial and venous thrombotic manifestations and/or pregnancy-related complications in patients with persistently high antiphospholipid antibodies (aPL), the most common being represented by anticardiolipin antibodies (aCL), anti-beta 2 glycoprotein-I (aß2GPI), and lupus anticoagulant (LAC). A growing number of studies have showed that, in some cases, patients may present with clinical features of APS but with temporary positive or persistently negative titers of aPL. For these patients, the definition of seronegative APS (SN-APS) has been proposed. Nevertheless, the negativity to classic aPL criteria does not imply that other antibodies may be present or involved in the onset of thrombosis. The diagnosis of SN-APS is usually made by exclusion, but its recognition is important to adopt the most appropriate anti-thrombotic strategy to reduce the rate of recurrences. This research is in continuous development as the clinical relevance of these antibodies is far from being completely clarified. The most studied antibodies are those against phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, vimentin/cardiolipin complex, and annexin A5. Moreover, the assays to measure the levels of these antibodies have not yet been standardized. In this review, we will summarize the evidence on the most studied non-criteria aPL, their potential clinical relevance, and the antithrombotic therapeutic strategies available in the setting of APS and SN-APS.

Von Willebrand and Factor VIII Portosystemic Circulation Gradient in Cirrhosis: Implications for Portal Vein Thrombosis.

OBJECTIVES: Portal vein thrombosis seems to be dependent on local hypercoagulation and venous stasis; data regarding endothelial damage are lacking. METHODS: von Willebrad factor, a marker of endothelial damage/perturbation, factor VIII, and lipopolysaccharides (LPS) were studied in the portal and systemic circulation of 20 cirrhotic patients undergoing transjugular intrahepatic portosystemic procedure. RESULTS: von Willebrad factor, factor VIII, and LPS were higher in the portal compared with systemic circulation, with a significant correlation between LPS and the other 2 variables. DISCUSSION: Endothelial damage and hypercoagulation coexist in the portal tree of patients with cirrhosis, and both could contribute to portal vein thrombosis. LPS may be a potential trigger of endothelial damage.

Multiparametric ultrasound in the evaluation of kidney disease in elderly.

After the age of 30 years, GFR progressively declines at an average rate of 8 mL/min/1.73 m/decade. A problem of advanced age is that the evaluation of renal function on the basis of indicators valid in young adults, such as creatininemia, is unreliable. In fact, many patients with chronic renal failure may have serum creatinine levels within the normal range even if they have a significant reduction in renal function. Ultrasound has become a routine method of investigation in renal disease: kidney size and parenchymal echogenicity are considered markers of renal function, so US is useful in assessing the presence and degree of renal failure. CEUS is useful in the evaluation of kidney disease in the elderly: the increased hemodynamic resistance of renal microvessels reduces perfusion in the renal cortex, so fewer microbubbles enter the renal cortex. EcoColor and EcoDoppler are also useful in the evaluation of senile alterations: here, the distribution of color-signals, as compared to that in the young adult population, appears more attenuated, limited to intersegmental and interlobar districts. Among the ecoDoppler parameters, the resistance index can be considered a marker of renal damage progression, with attention needing to paid to possible concomitant confounding factors. Ultrasonography, color-Doppler and CEUS are a non-invasive and convenient modality for managing kidney disease; their integration with anamnestic, objective and laboratory data permits fast and reliable clinical, diagnostic, and therapeutic classification. It also allows early therapeutic intervention and, ultimately, improvements in patient management.

Lysosomal acid lipase activity and liver fibrosis in the clinical continuum of non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Recent evidence showed a reduced activity of the lysosomal acid lipase (LAL) in patients with non-alcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC). However, the relationship between LAL activity and liver fibrosis has never been investigated. METHODS: Cross-sectional study including 575 outpatients referred for the management of cardio-metabolic and liver disease. The absence of liver fibrosis was defined by a FIB-4 < 1.30 and NAFLD fibrosis score (NFS) <-1.455. LAL activity was measured with dried blood spot technique. RESULTS: Overall, 515 patients had a diagnosis of NAFLD (454 NAFL and 61 biopsy-proven NASH) and 60 of CC. The value of LAL activity progressively decreased from healthy subjects to NAFL/NASH patients to CC (P < .001). LAL activity was reduced by 10% in patients with NAFL, by 20% in NASH and by 50% in CC. The prevalence of CC decreased across the tertiles of LAL activity: 22.2% in the lowest, 4.6% in the intermediate and 0.5% in the highest tertile. In NAFLD patients, 69.9% had a FIB4 < 1.30, and 43.1% a NFS <-1.455. Multivariate logistic regression analysis showed that Log (LAL activity) was associated with FIB-4 < 1.30 (Odds ratio [OR] 2.19 95% confidence interval [CI] 1.33-3.62, P = .002) and NFS < -1.455 (OR 2.43, 95% CI 1.51-3.91, P < .001) after adjustment for confounding factors. CONCLUSIONS: We found a progressive reduction of LAL activity according to liver disease severity. LAL activity was inversely associated with markers of liver fibrosis in patients with NAFLD.

Interaction between serum endotoxemia and proprotein convertase subtilisin/kexin 9 (PCSK9) in patients with atrial fibrillation: A post-hoc analysis from the ATHERO-AF cohort.

BACKGROUND AND AIMS: Lipopolysaccharides (LPS) is emerging as a novel risk factor for cardiovascular events (CVEs). Furthermore, in vitro evidence suggested that LPS may elicit proprotein convertase subtilisin/kexin 9 (PCSK9) expression, but their relationship in vivo has not been investigated. METHODS: We conducted a post-hoc analysis of a prospective, single centre cohort study of 907 patients with non-valvular atrial fibrillation (AF). At baseline, PCSK9, LPS and NADPH oxidase (sNox2-dp) were measured. PCSK9 and LPS were correlated with the incidence of CVEs. RESULTS: Median PCSK9 and LPS were 1200 [900-1970] and 49.9 [15.0-108.2] pg/ml, respectively. LPS and PCSK9 were significantly correlated (rS 0.378, p < 0.001). Logistic regression analysis showed that LPS was associated with PCSK9 above the median (odds ratio [OR] 1.727 95% confidence interval [CI] 1.147-2.600 p = 0.009). Other factors associated with PCSK9 above the median were sNox2-dp (OR 1.759 C.I. 95% 1.167-2.650, p = 0.007), use of antiplatelet drugs (OR 0.437 95%CI 0.219-0.871 p = 0.017) and high adherence to Mediterranean diet (OR 0.737 95%CI 0.643-0.845 p = 0.001). Olive oil (OR 0.376 95%CI 0.185-0.763, p = 0.001) and wine (OR 0.460 95%CI 0.289-0.733 p = 0.007) were negatively associated with PCSK9. Patients with concomitant high PCSK9 and LPS (LPS ≥88 pg/ml and PCSK9 ≥1570 pg/ml) had an increased risk of CVEs compared to those with low levels (LPS <24.3 pg/ml and PCSK9 <1000 pg/ml, Log-Rank test, p = 0.022). CONCLUSIONS: This study demonstrated, for the first time in vivo, that circulating levels of PCSK9 and LPS are associated with a mechanism possibly involving NADPH oxidase activation. Patients with concomitant increase of PCSK9 and LPS showed a higher risk of CVEs.

Impairment between Oxidant and Antioxidant Systems: Short- and Long-term Implications for Athletes' Health.

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.

Multiparametric MRI Versus Multiparametric US in the Detection of Prostate Cancer.

BACKGROUND/AIM: The aim of the study was to compare the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI), multiparametric ultrasound (mpUS) and US/MRI fusion imaging techniques in the detection of prostate cancer. PATIENTS AND METHODS: A total of 82 patients with persistently high prostate specific antigen (PSA) levels after medical therapy were prospectively evaluated. All patients underwent digital rectal examination, mpMRI, mpUS and prostate biopsy. RESULTS: Histological outcome was positive for prostate cancer (PCa) in 46/82 patients (56.1%). MpMRI detected 54/82 lesions; histological analysis confirmed PCa in 44 lesions (sensitivity 91.3% and specificity 66.7%). Ratio estimation with semiquantitative elastography, between lesions and the peripheral portion showed a higher sensitivity and specificity compared to strain ration (SR) evaluation between lesions and adenomas (sensitivity 84.8% vs. 78.3%; specificity 66.6% vs. 61.1%). Quantitative analysis of contrast-enhanced ultrasound (CEUS) showed 40.0% sensitivity and 97.2% specificity. A total of 54 lesions detected by mpMRI and MRI/TRUS fusion targeted biopsy had a high number of positive samples (81.5%). CONCLUSION: mpMRI is more accurate than mpUS which still remains a valuable technique used after MRI for prostate fusion-guided biopsy.

Virulence of MRSA USA300 is enhanced by sub-inhibitory concentration of two different classes of antibiotics.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 is responsible of many kinds of infections of skin and soft-tissue. Antibiotic resistance, biofilm formation and the ability to adhere and invade are virulence factors that contribute to MRSA pathogenesis. In some cases, decreased bioavailability of antibiotics in systemic circulation could result; in these conditions sub-therapeutic levels of the antibiotics may be established, exposing bacteria to sub-inhibitory concentrations. On the basis of several published scientific data it is fair to assume that all these events could induce an increase of bacterial virulence. In the present study, we investigated this process by measuring the effects of low doses of two different classes of antibiotics on some virulence features of MRSA USA300 isolate, like the ability to adhere and invade eukaryotic cells. Results obtained strongly support the importance of the respect of a correct dosage of antibiotic in therapy to escape the insurgence of more virulent phenotypes.