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.

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.

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.

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.

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.

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.

The Metabolic Syndrome Predicts Longitudinal Changes in Clock Drawing Test Performance in Older Nondemented Hypertensive Individuals.

OBJECTIVES: The present study evaluated the metabolic syndrome (MetS) as independent predictor of 1-year longitudinal changes in cognitive function. METHODS: 104 stroke- and dementia-free older hypertensive subjects were studied. MetS was defined by NCEP ATP-III criteria. Cognitive function was assessed by the Clock Drawing Test (CDT); 1-year changes in cognitive function were expressed as annual changes in CDT performance. Brain magnetic resonance imaging studies (1.5T) were performed. RESULTS: Participants with MetS exhibited greater cognitive decline than those without (-1.78 ± 1.47 versus -0.74 ± 1.44 CDT points, t = 3.348, df = 102, p < 0.001). MetS predicted cognitive decline (ß = -0.327, t = -3.059, df = 96, p = 0.003) independently of its components, age, baseline cognition, neuroimaging findings, blood pressure levels, and duration of hypertension. With the exception of systolic blood pressure, none of the individual components of MetS explained 1-year changes in CDT performance. CONCLUSIONS: MetS as an entity predicted accelerated 1-year decline in cognitive function, assessed by CDT, in a sample of older hypertensive subjects.

The Mozart Effect: A quantitative EEG study.

The aim of this study is to investigate the influence of Mozart's music on brain activity through spectral analysis of the EEG in young healthy adults (Adults), in healthy elderly (Elderly) and in elderly with Mild Cognitive Impairment (MCI). EEG recording was performed at basal rest conditions and after listening to Mozart's K448 or "Fur Elise" Beethoven's sonatas. After listening to Mozart, an increase of alpha band and median frequency index of background alpha rhythm activity (a pattern of brain wave activity linked to memory, cognition and open mind to problem solving) was observed both in Adults and in Elderly. No changes were observed in MCI. After listening to Beethoven, no changes in EEG activity were detected. This results may be representative of the fact that said Mozart's music is able to "activate" neuronal cortical circuits related to attentive and cognitive functions.

Executive dysfunction assessed by Clock-Drawing Test in older non-demented subjects with metabolic syndrome is not mediated by white matter lesions.

AIMS: Metabolic syndrome (MetS) has been associated with greater occurrence of white matter hyperintensities (WMH). It remains uncertain whether MetS as a construct is associated with poorer cognitive performances. This study explores whether MetS is associated with poorer performances in global and domain-specific cognitive tests in older non-demented subjects independently of its individual components, WMH severity and other variables. METHODS: MetS was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III definition. Brain magnetic resonance studies (1.5T) were performed. Deep and periventricular WMH were graded using the Fazekas scale. Subjects underwent the Mini-Mental State Examination, the Babcock Short Story Recall test and the Clock-Drawing Test (CDT). RESULTS: Eighty community-dwellers aged 67-91 years were studied. Subjects with MetS (n = 35) had more severe WMH, and poorer performances on the CDT (P = 0.003) and the Babcock Short Story Recall test (P = 0.027). After multiple adjustment, MetS was inversely associated with CDT scores (B = -1.285; 95% confidence interval = -1.996--0.575; P = 0.001) but not with episodic memory. Results were not affected by WMH severity. Interestingly, none of the individual components of MetS predicted poorer cognitive performances. CONCLUSIONS: Impairment in executive functions assessed by CDT may represent an early and specific sign of cognitive decline in older individuals with MetS. Future longitudinal studies are needed to better establish the predictive role of MetS on dementia and to demonstrate the possibility of dementia prevention by targeting MetS.

[Physical and psychological stress in a group of Italian caregivers: a new medical emergency? A pilot study]. / Stress psicofisici in un gruppo di operatori sanitari italiani; nuova emergenza medica? Uno studio pilota.

INTRODUCTION: this study aimed to evaluate physical and psychological stress in a group of italian caregivers. METHODS: 20 subjects were enrolled in the study and divided into 2 groups: 10 healthy controls and 10 caregivers. Every subject underwent an cognitive, clinical and instrumental assessment. RESULTS: the statistical analysis showed an increased presence of pathological alterations in caregivers group such as decreased ejection fraction, cognitive impairment and depressed mood. CONCLUSIONS: the study shows the figure of a elderly caregiver, predominantly women, who spend many hours in patient care. The caregiver-type takes about four drugs a day and is not involved in screening programs offered by the health service for his age group. Results a high risk of social isolation, emotional fragility and an increased risk of cardiovascular events and cognitive impairment.

Olfactory deficit and hippocampal volume loss for early diagnosis of Alzheimer disease: a pilot study.

BACKGROUND: The aim of this pilot study was to verify the role of olfactory test and volumetric magnetic resonance imaging measure of hippocampus to predict conversion from mild cognitive impairment to Alzheimer disease (AD). MATERIALS AND METHODS: Eighteen patients with amnesic mild cognitive impairment, broadly defined, were followed at 12 months. Hypothesized baseline predictors for follow-up conversion to AD were olfactory deficit and hippocampal volumes loss. RESULTS: In the 1-year follow-up, 5 patients converted to AD. The 2 clinical predictors olfactory test and hippocampal volume loss showed the same sensitivity of 92.3% but the olfactory test showed a higher specificity than the hippocampal volume loss (75% vs. 60%). CONCLUSIONS: Our findings suggest the potential utility of olfactory test and hippocampal volume loss for early detection of AD.

Depressive symptoms in older people with metabolic syndrome: is there a relationship with inflammation?

OBJECTIVE: To investigate if there is a higher prevalence of depressive symptoms in older people with metabolic syndrome (MetS) compared with those without and whether dedpressive symptoms are independently associated to MetS and its single components and to the inflammatory markers. METHODS: Physical parameters, standard blood analytes, high sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) were assessed. Fifteen-item Geriatric Depression Scale and mini mental state examination (MMSE) were administered. RESULTS: One hundred thirty-three subjects were enrolled. MetS patients (57) exhibited higher prevalence of depressive symptoms (p < 0.0001), worse cognitive function (p < 0.0001), and higher levels of ESR and hsCRP were higher (p < 0.0001). The univariate analysis showed a linear strong correlation of depressive symptoms (p < 0.0001) with the MMSE score (r = -0.422), body mass index (r = 0.414), MetS (r = 0.582), number of MetS components (r = 0.663), fasting blood glucose (r = 0.565), ESR (r = 0.565), hsCRP (r = 0.745), central obesity (r = 0.269; p = 0.002), and high-density lipoprotein cholesterol (r = -0.241; p = 0.005). However, the multivariate analysis showed that only age (B = -0.093; p = 0.032), MetS (B = 1.446; p = 0.025), fasting blood glucose (B = 0.039; p = 0.005), and hsCRP (B = 7.649; p < 0.0001) were independently associated with depressive symptoms. CONCLUSIONS: MetS and inflammation are independently associated with depressive symptoms in older people. Inflammation may explain cognitive decline too. Further investigations are needed to better understand the direction of these associations and to determine whether these can be reversible.

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.

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.

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.

[Predictors of liver fibrosis in patients with non-alcoholic fatty liver disease. The role of metabolic syndrome, insulin-resistance and inflammation]. / Predittori di fibrosi epatica in pazienti con steatosi epatica non-alcolica. Il ruolo della sindrome metabolica, dell'insulino-resistenza e dell'infiammazione.

INTRODUCTION: NAFLD (non-alcoholic fatty liver disease) reaches an high prevalence in the general population, and it is closely related to metabolic syndrome (MetS). The entity of metabolic abnormalities and the chronic inflammation seem to play a main role in the development of liver fibrosis. The aim of our study is to determine whether subjects with NAFLD and MetS have higher liver fibrosis degree when compared with NAFLD subjects without MetS, and to investigate the relations between fibrosis, MetS and its single components and inflammation. MATERIALS AND METHODS: We considered 24 patients with NAFLD. Those who had viral- and alcohol- related liver disease were excluded. MetS was diagnosed according to NCEP ATP III criteria; inflammatory status was determined through C-reactive protein (PCR) assay. The peripheral insulin-resistance was assessed by calculating HOMA ir. Liver fibrosis was measured by transient elastography (Fibroscan®). RESULTS: Subjects with MetS had higher HOMA ir, PCR and Fibroscan® score (log value: 0.92±0.24 KPa vs 0.73±0.2 KPa; p=0.047). The linear correlation analysis showed that Fibroscan® score was related to MetS, number of MetS components, waist circumference, HOMA ir and PCR. However the multivariate regression analysis showed that only HOMA ir (B=0.077; 95%CI: -0.002- 0.157; p=0.05) and PCR (B=0.152; 95% CI: 0.006 - 0.299; p=0.006) were independent predictors of higher Fibroscan® score. CONCLUSION: MetS is associated to higher liver fibrosis degree in subjects with NAFLD. The insulin-resistance and inflammation seem to be the main determinants.

[Vascular depression in the elderly. Does inflammation play a role?]. / La depressione vascolare nell'anziano. Quale ruolo per l'infiammazione?

Vascular depression in the elderly. Does inflammation play a role?Depression is the most common comorbidity in the elderly, and it is a major determinant of disability. The late-onset depression in highly associated to cardiovascular disease. Depressive symptoms may follow vascular brain damage, especially when mood regulating areas are affected. However depression is strongly associated to vascular disease even when there is no manifest brain damage. Recently great attention has been given to chronic inflammation, both related to depression and vascular disease. Both experimental and clinical evidence shows that a rise in the concentrations of proinflammatory cytokines and glucocorticoids in depressed patients is associated with defect in serotonergic function. Chronic inflammation may underlie many forms of depression associated with vascular disease and metabolic syndrome. The importance of the inflammation hypothesis of depression lies is that psychotropic drugs may have central anti-inflammatory action, and that new generation of central anti-inflammatory drugs may be useful in depression treatment.

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.

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.