Obesity related changes in cardiac structure and function: role of blood pressure and metabolic abnormalities.

BACKGROUND: It has been reported that changes in cardiac structure and ventricular function associated with obesity have to be attributable to hemodynamic and non-hemodynamic alterations. Accordingly, the aim of this was to evaluate left ventricular hypertrophy (LVH) prevalence and its effect on left ventricular systolic and diastolic function in a cohort of obese patients. MATERIALS AND METHODS: LV internal diameter (LVID), left ventricular mass (LVM) and LVM/height2.7(LVMI), relative wall thickness (RWT), LV ejection fraction (LVEF), E/A ratio, isovolumic relaxation time, deceleration time of E velocity by echocardiography and pulsed-wave Doppler and total circulating adiponectin (ADPN) b…

Episodes of second-degree ventriculo-atrial block during ventricular tachycardia

Identification of a novel mutation in the alpha-galactosidase A gene in patients with Fabry disease.

Abstract Objectives Mutation analysis of the alpha-galactosidase A (GLA) gene is a valuable tool for the diagnosis of affected families. In our work, we analyze about one thousand samples per year from patients suspected of having Fabry disease (FD). Design and methods We carried out high resolution melting analysis (HRM) and DNA sequencing of all the exons of the GLA gene. We also assayed the alpha-galactosidase A activity in patients' blood. Results In some members of one family, we identified a new mutation in the GLA gene, c.614delC. This is a deletion of a single nucleotide, a cytosine, in exon 4 of the gene which causes a frameshift mutation. Conclusions Patients with the c.614delC mu…

Attivazione immunoinfiammatoria della fase acuta e diatesi trombofilica in soggetti con ictus ischemico acuto. Studio prospettico di confronto tra diabetici e non diabetici. ;

Prevenzione del reictus

Editorial (Thematic Issue: Anderson Fabry Disease: A Multiorgan Metabolic Disease Susceptible of Treatment)

Plasma levels of inflammatory and thrombotic/fibrinolytic markers in acute ischemic strokes: Relationship with TOAST subtype, outcome and infarct site

BACKGROUND: The aim of our study was to evaluate in patients with acute ischemic stroke the relationship between immuno-inflammatory variables, clinical outcome and infarct site. MATERIALS AND METHODS: We evaluated plasma levels of IL-1beta, TNF-alpha, IL-6 and IL-10, E-selectin, P-selectin, sICAM-1 ,sVCAM-1 vWF, TPA and PAI-1. RESULTS: Patients with cardioembolic subtype showed significantly higher median plasma levels of TNF-alpha, IL-6, IL-1beta whereas the lacunar subtype showed significantly lower median plasma levels of TNF-alpha, IL-6 and IL-1beta. CONCLUSIONS: A significant association was noted between the severity of neurological deficit at admission, the diagnostic subtype and so…

Diabete mellito ed ictus ischemico: studio caso-controllo di confronto tra soggetti diabetici e non diabetici

L'ictus ischemico

Use of QT intervals for a more accurate diagnose of syncope and evaluation of syncope severity.

Abstract BACKGROUND: This study aimed to evaluate the use of QT intervals, their diagnostic predictive value in patients with syncope and their relationship with syncope severity. METHODS: One hundred and forty nine patients with a diagnosis of syncope were admitted to Internal Medicine departments at the University of Palermo, Italy, between 2006 and 2012, and 140 control subjects hospitalised for other causes were enrolled. QT maximum, QT minimum, QTpeak, QT corrected, QT dispersion and Tpeak-to-Tend interval were compared between two groups. The paper medical records were used for scoring with San Francisco Syncope Rule (SFSR), Evaluation of Guidelines in SYncope Study (EGSYS) score and …

Effects of Physical Exercise on Inflammatory Markers of Atherosclerosis

It is well established that physically fit individuals have a reduced risk of developing CVD (cardiovascular disease) and other age-related chronic disorders. Regular exercise is an established therapeutic intervention with an enormous range of benefits. Chronic low-grade systemic inflammation may be involved in atherosclerosis, diabetes and in pathogenesis of several chronic pathological conditions; recent findings confirm that physical activity induces an increase in the systemic levels of a number of cytokines and chemokines with anti-inflammatory properties. The possibility that regular physical exercise exerts anti-inflammation activity, being the interaction between contracting muscle…

ELECTROCARDIOGRAPHIC FINDINGS IN PATIENTS WITH DEMENTIA.

Intravenous high-dose furosemide and hypertonic saline solutions for refractory heart failure and ascites.

Several studies have shown the efficacy of hypertonic saline solution infusion in conditions in which regional organ blood flow is impaired. Our group has shown that treatment of patients with diuretic-resistant heart failure with high-dose furosemide plus hypertonic saline is effective and well tolerated, improving symptoms of congestion, reducing plasma levels of markers of neurohormonal and inflammatory activation, decreasing hospital readmission rates, and reducing long-term mortality. The same regimen was shown to be better than repeated paracentesis in patients with cirrhosis and refractory ascites, yielding better control of ascites, pleural effusions, and/or leg edema without an inc…

Antivitamin K Drugs in Stroke Prevention

Among the different subtypes of ischaemic strokes, almost 20 % are of cardiac origin. Different are the causes of cardioembolic stroke, but the most common is the atrial fibrillation, a supraventricular arrhythmia. Appropriate use of antiplatelet drugs and anticoagulants after transient ischaemic attack (TIA) or ischaemic stroke depends on whether the underlying cause is cardioembolic or of presumed arterial origin. Adequate antiplatelet therapy is recommended for secondary prevention after cerebral ischaemia of presumed arterial origin, whether for patients with TIA and ischaemic stroke of cardiac origin, mainly due to atrial fibrillation. Vitamin K antagonists (VKAs) are highly effective …

INFLAMMATORY CYTOKINES IN ACUTE ISCHEMIC STROKE.

Three major cytokines, namely, tumor necrosis factor (TNF-alpha), interleukin (IL)-1, and IL-6 are produced by cultured brain cells after various stimuli such as ischemia. Neurones, astrocytes, microglia and oligodendrocytes can produce inflammatory mediators, and cytokine receptors are expressed constitutionally throughout the Central Nervous System (CNS), albeit at low levels. Cytokines are involved in virtually every facet of stroke and they have numerous pro-inflammatory and pro-coagulant effects on endothelium. TNF-alpha expression after stroke stimulates expression of tissue factor and adhesion molecules for leukocytes, release of interleukin-1 (IL-1), nitric oxide, factor VIII/von Wi…

Citokines and inflammation markers in ischemic stroke.

Non-coding RNAs and other determinants of neuroinflammation and endothelial dysfunction: regulation of gene expression in the acute phase of ischemic stroke and possible therapeutic applications

Ischemic stroke occurs under a variety of clinical conditions and has different pathogeneses, resulting in necrosis of brain parenchyma. Stroke pathogenesis is characterized by neuroinflammation and endothelial dysfunction. Some of the main processes triggered in the early stages of ischemic damage are the rapid activation of resident inflammatory cells (microglia, astrocytes and endothelial cells), inflammatory cytokines, and translocation of intercellular nuclear factors. Inflammation in stroke includes all the processes mentioned above, and it consists of either protective or detrimental effects concerning the “polarization” of these processes. This polarization comes out from the intera…

heart failure, after high dose of furosemide plus small volume saline solution (HSS) and after an acute saline loading

TVP e neoplasie: modello predittivo delle variabili associate

Valore predittivo delle variabili immunoinfiammatorie nell’ictus ischemico acuto.

Piede diabetico e morbilità cardiovascolare. Studio prospettico di controllo. ;

Inflammatory activation and endothelial dysfunction markers in patients with permanent atrial fibrillation: A cross-sectional study

In recent years a growing body of evidence supported the role of inflammation in the initiation, maintenance and outcome of atrial fibrillation (AF). Nevertheless, despite a large amount of information, whether AF or the underlying structural heart disease (SHD) is the cause of the inflammatory process is still under debate. We, therefore, sought to determine if the inflammatory process reflect an underlying disease or the arrhythmia 'per se'. We evaluated plasma levels of soluble Interleukin 2 Receptor Alpha (sIL-2Rα), TNF-α and IL-18 in 100 consecutive patients with permanent AF, (43 with a SHD and 57 without a SHD) compared to 121 age and sex-matched controls which had normal sinus rhyth…

Endothelial function and arterial stiffness indexes in subjects with acute ischemic stroke: Relationship with TOAST subtype.

Abstract Background and aims Only one study has examined endothelial function in subjects with acute ischemic stroke and no study has yet assessed arterial stiffness and reactive hyperemia peripheral arterial tonometry (RH-PAT) in ischemic stroke and its clinical subtypes. Our study aimed to evaluate arterial stiffness and endothelial dysfunction indexes in patients with acute ischemic stroke and the relationship between endothelial dysfunction indexes and arterial stiffness markers and stroke subtypes according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) Classification. Methods We enrolled 98 patients with a diagnosis of acute ischemic stroke and 105 hospitalized patients witho…

Neuroinflammatory mechanisms in ischemic stroke: Focus on cardioembolic stroke, background, and therapeutic approaches

One of the most important causes of neurological morbidity and mortality in the world is ischemic stroke. It can be a result of multiple events such as embolism with a cardiac origin, occlusion of small vessels in the brain, and atherosclerosis affecting the cerebral circulation. Increasing evidence shows the intricate function played by the immune system in the pathophysiological variations that take place after cerebral ischemic injury. Following the ischemic cerebral harm, we can observe consequent neuroinflammation that causes additional damage provoking the death of the cells; on the other hand, it also plays a beneficial role in stimulating remedial action. Immune mediators are the or…

Pathogenesis and molecular mechanisms of anderson–fabry disease and possible new molecular addressed therapeutic strategies

Anderson–Fabry disease (AFD) is a rare disease with an incidenceof approximately 1:117,000 male births. Lysosomal accumulation of globotriaosylceramide (Gb3) is the element characterizing Fabry disease due to a hereditary deficiency α-galactosidase A (GLA) enzyme. The accumulation of Gb3 causes lysosomal dysfunction that compromises cell signaling pathways. Deposition of sphingolipids occurs in the autonomic nervous system, dorsal root ganglia, kidney epithelial cells, vascular system cells, and myocardial cells, resulting in organ failure. This manuscript will review the molecular pathogenetic pathways involved in Anderson–Fabry disease and in its organ damage. Some studies reported that i…

Antiplatelet treatment in ischemic stroke treatment.

Antiplatelets represent a diverse group of agents that share the ability to reduce platelet activity through a variety of mechanisms. Antithrombotic agents are effective in the secondary prevention of ischemic strokes. Most strokes are caused by a sudden blockage of an artery in the brain (called an ischaemic stroke) that is usually due to a blood clot. Immediate treatment with antiplatelet drugs such as aspirin may prevent new clots from forming and hence improve recovery after stroke. Several studies have evaluated the role of one antiplatelet agent, aspirin, in reducing stroke severity. The International Stroke Trial (IST) of 20,000 patients with acute stroke from other countries. In thi…

In-hospital death and adverse clinical events in elderly patients according to disease clustering: the REPOSI study. Marengoni A,

OBJECTIVE: The aim of the study was to recognize clusters of diseases among hospitalized elderly and to identify groups of patients at risk of in-hospital death and adverse clinical events according to disease clustering. METHOD: This was a cross-sectional study conducted in 38 internal medicine and geriatric wards in Italy participating in the Registro Politerapie SIMI (REPOSI) study during 2008. The subjects were 1,332 inpatients aged 65 years or older. Clusters of diseases (i.e., two or more co-occurrent diseases) were identified using the odds ratios (OR) for the associations between pairs of conditions, followed by cluster analysis. Logistic regression models were used to evaluate the …

Effects of clinical and laboratory variables at admission and of in-hospital treatment with cardiovascular drugs on short term prognosis of ischemic stroke. The GIFA study.

Abstract Introduction No information exists, to our knowledge, about the possible role of cardiovascular drug administration in the acute phase of ischemic stroke and possible effects on stroke outcome. The aim of our study was to evaluate the relationship between in-hospital treatment with cardiovascular drugs in patients with acute ischemic stroke and some outcome indicators. Methods and Results 1096 subjects enrolled in the GIFA study, who had a main discharge diagnosis of ischemic stroke represent the final sample. Drugs considered for the analysis were the following: ACE-inhibitors (ACEI), angiotensin II receptor blockers (ARBs), statins, calcium-channel-blockers (CCBs), antiplatelet (…

Editorial: Genetics and gene therapy of lysosomial storage disorders

Non applicabile in quanto editoriale

Diabetic foot syndrome as a possible cardiovascular marker in diabetic patients

Diabetic foot ulcerations have been extensively reported as vascular complications of diabetes mellitus associated with a high degree of morbidity and mortality; in fact, some authors showed a higher prevalence of major, previous and new-onset, cardiovascular, and cerebrovascular events in diabetic patients with foot ulcers than in those without these complications. This is consistent with the fact that in diabetes there is a complex interplay of several variables with inflammatory metabolic disorders and their effect on the cardiovascular system that could explain previous reports of high morbidity and mortality rates in diabetic patients with amputations. Involvement of inflammatory marke…

Inflammation as a therapeutic target in acute ischemic stroke treatment.

Animal models of focal ischaemia induced by middle cerebral artery occlusion (MCAO) provide most evidence for cellular inflammatory responses in stroke. Permanent MCAO results in a modest neutrophil infiltration at 24 h after ischaemia, predominantly around arterial vessels at the margins of infarction, whereas MCAO with subsequent reperfusion is associated with substantial infiltration by neutrophils throughout the entire infarct. Several studies show that C-reactive protein (CRP), an inflammatory marker, is associated with stroke outcomes and future vascular events. Several drugs, especially hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), have been demonstrated to reduce …

Increased expression of markers of early atherosclerosis in patients with inflammatory bowel disease.

Recent studies documented an increased cardiovascular risk in patients with inflammatory bowel disease (IBD). Our study aimed at investigating the prevalence of intima-media thickness (IMT) of the carotid arteries and the arterial stiffness indices as markers of early atherosclerosis in young IBD patients.We recruited 68 consecutive IBD patients, and 38 matched healthy controls less than 45years old (median age 31.6±8.1years). Clinical and demographic features, cardiovascular risk factors, history of cardiovascular events, concomitant therapies were registered on a dedicate database. Carotid IMT was evaluated by using high resolution B-mode ultrasonography. Arterial stiffness was assessed b…

Quando la diagnosi è già fatta: anemia e lombalgia in un paziente con recente diagnosi di brucellosi acuta

Profilo di rischio per neoplasia occulta in pazienti con TVP idiopatica.

Prevalence of renal failure and use of antithrombotic prophylaxis among medical inpatients at increased risk of venous thromboembolic events.

Abstract Background Evidence-based guidelines recommend the use of antithrombotic prophylaxis in medical patients at risk of venous thromboembolism (VTE). Low molecular weight heparins (LMWHs) are usually preferred to unfractionated heparin. However, when prophylactic doses of LMWH are administered, patients with renal failure (RF) are exposed to the risk of excessive accumulation, and thus to an increased risk of bleeding. We aimed to assess the prevalence of RF among medical inpatients at increased risk of VTE and the use and dosage of antithrombotic prophylaxis in these patients. Methods In a cross sectional study carried out at three different hospitals, information on all medical inpat…

A precise stroke classification for evaluation of ischemic stroke subtypes and their relation with diabetes: is TOAST the best?

To The Editor: Regarding the study by Turin et al1 performed to estimate the secular time trends in incidence using a population-based stroke registry in Japan, we discuss some issues of potential interest. First, have the authors classified stroke subtypes according TOAST classification or Oxfordshire classification? No mention has been made in the text concerning the classification methodology of ischemic stroke. It is conceivable that applying the TOAST classification2 of ischemic stroke (a classification with clinical, pathophysiological, anatomic, and instrumental basis that is easily applicable and widely validated) could provide a more precise selection of patients with lacunar strok…

Mediterranean Diet in patients with acute ischemic stroke: Relationships between Mediterranean Diet score, diagnostic subtype, and stroke severity index

Abstract Background Adherence to a Mediterranean Diet appears to reduce the risk of cardiovascular disease, cancer, Alzheimer's disease, and Parkinson's disease, as well as the risk of death due to cardiovascular disease. No study has addressed the association between diagnostic subtype of stroke and its severity and adherence to a Mediterranean Diet in subjects with acute ischemic stroke. Aim To evaluate the association between Mediterranean Diet adherence, TOAST subtype, and stroke severity by means of a retrospective study. Methods The type of acute ischemic stroke was classified according to the TOAST criteria. All patients admitted to our ward with acute ischemic stroke completed a 137…

Scompenso Cardiaco da disfunzione sistolica

HLA and KIR Interaction in Patients with Ischemic Stroke

Background: T-cells expressing the KIR2DS2 activating receptor were found to be prevalent in the coronary culprit atherosclerotic plaque in patients with acute coronary syndromes (ACS), suggesting a possible cytolytic activity against the endothelium of the plaque, leading to plaque rupture and in turn to superimposed thrombosis and sudden occlusion of the artery. To explore if a similar pathogenetic mechanism occurs in acute ischemic stroke, we analyzed the possible association between the genetic KIR and HLA repertoire and the susceptibility to ischemic stroke. Methods: Fourteen patients with ischemic stroke and ten controls with atherosclerotic disease without ischemic stroke matched for…

A curious case of pancytopenia and fever in a patient with Erdheim–Chester disease

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Diabetic and non-diabetic subjects with ischemic stroke: Differences, subtype distribution and outcome

Abstract Background and aim Diabetes mellitus increases the risk of stroke, and pathophysiological changes of diabetic cerebral vessels may differ in comparison with non-diabetic ones; nonetheless, the clinical and prognostic profile of stroke in diabetic patients is not yet fully understood. On this basis, the aim of our study was to evaluate cerebrovascular risk factor prevalence in diabetic stroke patients in comparison with non-diabetics, to analyze whether diabetics have a different prevalence of stroke subtypes as classified by the TOAST classification, and determine whether diabetics and non-diabetics have a different prognosis. Methods and results We enrolled 102 diabetics and 204 n…

Insufficienza renale acuta da necrosi tubulare acuta iatrogena

Serum pentraxin 3 as a clinical biomarker of branch atheromatous disease: a marker of brain ischaemia or an atherotrombosis marker?

Arterial stiffness in symptomatic smokers with normal lung function

Chronic obstructive pulmonary disease (COPD) is associated with cardiovascular morbidity and mortality. Arterial stiffness and endothelial dysfunction index are validated surrogate cardiovascular markers and are increased in subjects with COPD. We tested whether increased arterial stiffness and endothelial dysfunction occur in symptomatic smokers with no evidence of bronchial obstruction. Clinical and lung functional assessments were conducted in smoker subjects with chronic respiratory symptoms and in COPD patients. Pulse wave velocity (PWV), aortic augmentation index (AIx) and reactive hyperaemia index (RHI) were measured to estimate the cardiovascular risk. 48 smokers (male n=37, female …

Sodium thiosulfate not always resolves calciphylaxis: an ambiguous response

Calciphylaxis is a severe “vascular ossification–calcification,” associated with a very high mortality rate that involvesarterial wall, venular wall, and nerves resulting in ischemia and necrosis of skin, subcutaneous fat, visceral organs,and skeletal muscles. Sodium thiosulfate has recently been used as a novel treatment option for calciphylaxisbecause of its dual role as an antioxidant and a chelator. Multiple case reports demonstrated that such therapy hasresulted in pain relief and healing of skin ulceration. We report a case of calciphylaxis of large severity that had anambiguous response to sodium thiosulfate treatment (improvement of symptomatology and skin lesions, improve-ment of b…

Arterial stiffness and ischemic stroke in subjects with and without metabolic syndrome.

We conducted a study to evaluate arterial stiffness markers in subjects with acute ischemic stroke and metabolic syndrome and in relation to TOAST subtype of stroke. We enrolled 130 patients with acute ischemic stroke and metabolic syndrome, 127 patients with acute ischemic stroke without metabolic syndrome and 120 control subjects without acute stroke. Applanation tonometry to record pulse wave velocity (PWV). Stroke patients with metabolic syndrome, compared control subjects without stroke showed higher PWV. In subjects with ischemic stroke and metabolic syndrome, PWV was more significantly and positively correlated with body mass index, systolic blood pressure, hypertension, diabetes, gl…

Immunoinflammatory and thrombotic/ fybrinolytic markers as a diagnostic panel of acute ischemic stroke

Robustness of PET Radiomics Features: Impact of Co-Registration with MRI

Radiomics holds great promise in the field of cancer management. However, the clinical application of radiomics has been hampered by uncertainty about the robustness of the features extracted from the images. Previous studies have reported that radiomics features are sensitive to changes in voxel size resampling and interpolation, image perturbation, or slice thickness. This study aims to observe the variability of positron emission tomography (PET) radiomics features under the impact of co-registration with magnetic resonance imaging (MRI) using the difference percentage coefficient, and the Spearman’s correlation coefficient for three groups of images: (i) original PET, (ii) PET after co-…

Ketogenic diet, physical activity, and hypertension—a narrative review

Several studies link cardiovascular diseases (CVD) with unhealthy lifestyles (unhealthy dietary habits, alcohol consumption, smoking, and low levels of physical activity). Therefore, the strong need for CVD prevention may be pursued through an improved control of CVD risk factors (impaired lipid and glycemic profiles, high blood pressure, and obesity), which is achievable through an overall intervention aimed to favor a healthy lifestyle. Focusing on diet, different recommendations emphasize the need to increase or avoid consumption of entire classes of food, with only partly known and only partly foreseeable consequences on the overall level of health. In recent years, the ketogenic diet (…

Familial hypobetalipoproteinemia due to apolipoprotein B R463W mutation causes intestinal fat accumulation and low postprandial lipemia

Abstract Objective Familial hypobetalipoproteinemia (FHBL) is characterized by inherited low plasma levels of apolipoprotein B (apoB)-containing lipoproteins. In this paper we investigated whether the already described APOB R463W missense mutation, a FHBL mutation able to impair the activity of microsomal triglyceride transfer protein (MTP), may cause intestinal fat accumulation and reduced postprandial lipemia. Methods Four out of five probands harboring APOB R463W mutation were compared with six healthy controls and six patients with celiac disease (CD). An oral fat load supplemented with retinyl palmitate (RP) was administered and a gastro-duodenal endoscopy with biopsy was performed. Re…

Patients' Acceptability of Different Fentanyl Products for Breakthrough Cancer Pain

OTFC (6) 1.7 (0.5) 1.5 (0.5) 2.0 (0.6) 1.5 (0.8) 1.5 (0.5) 33.1 (43.5) FBT (19) 2.0 (0.6) 2.0 (0.7) 1.8 (0.7) 1.8 (0.8) 1.9 (0.7) 15.9 (7.3) SLF (37) 2.1 (0.5) 2.2 (0.4) 1.8 (0.4) 2.0 (0.6) 2.1 (0.5) 16.7 (12.5) INFS (7) 2.1 (0.4) 2.1 (0.4) 2.0 (0.6) 2.0 (0.8) 2.0 (0.8) 15.7 (13.7) PFEN (11) 2.4 (0.5) 2.2 (0.4) 1.8 (0.4) 1.9 (0.7) 2.1 (0.5) 15.0 (13.7) P 0.120 0.043* 0.870 0.595 0.178 0.015x *,x Oral transmucosal fentanyl was significantly considered to be more problematic.

Clinical Trial: High-dose furosemide plus small-volume hypertonic saline solutions vs. repeated paracentesis as treatment of refractory ascites.

Summary Background  In patients with cirrhosis, ascites is defined as refractory when it cannot be mobilized or recurs early in standard diuretic therapy. Aim  To compare the safety and efficacy of intravenous high-dose furosemide + hypertonic saline solutions (HSS) with repeated paracentesis in patients with cirrhosis and refractory ascites. Patients and methods  Eighty-four subjects (59/25 M/F) with cirrhosis, mostly of viral aetiology, admitted for refractory ascites, were randomly assigned to receive furosemide (250–1000 mg/bid i.v.) plus HSS (150 mL H2O with NaCl 1.4–4.6% or 239–187 mEq/L) (60 patients, Group A) or to repeated paracentesis and a standard diuretic schedule (24 patients,…

A second-degree atrioventricular block with double escape rhythm secondary to paroxysmal vagal hypertonia.

Arterial stiffness indexes and serum cytokine levels in seronegative spondyloarthritis: relationships between stiffness markers and metabolic and immunoinflammatory variables

Objective: The aim of this study was to investigate the relationship between immunoinflammatory markers and indexes of arterial stiffness in patients with seronegative spondyloarthritis (SpA).Method: We enrolled consecutive patients with inflammatory seronegative SpA referred to a rheumatology outpatient clinic. Control subjects were patients admitted in the same period for any cause other than chronic inflammatory disease or acute cardiovascular and cerebrovascular events. Carotid-femoral pulse wave velocity (PWV) was measured and the aortic pressure waveform was used to calculate the augmentation index (Aix). We also evaluated plasma levels of C-reactive protein (CRP), interleukin (IL)-1β…

Predictors of outcome in acute ischemic cerebrovascular syndromes: The GIFA study

Abstract Background Today it may be more useful to use the term acute ischemic cerebrovascular syndrome (AICS) to define a spectrum of disease ranging from TIA to stroke and that share a similar underlying pathophysiology: cerebral ischemia . The aim of this study is to evaluate the prognostic importance of some demographic, laboratory and clinical variables on the outcome in hospitalized patients with a discharge diagnosis suggestive of acute ischemic cerebral syndrome (AICS). Methods 17,377 Subjects were enrolled in the GIFA study, a multicenter survey of hospitalized older patients. 1878 Subjects with a main discharge diagnosis suggestive of acute ischemic cerebrovascular syndrome (AICS)…

Biomarkers in Anderson–Fabry Disease

Fabry disease is a rare lysosomal storage disorder caused by a deficiency of α-galactosidase A, resulting in multisystemic involvement. Lyso-Gb3 (globotriaosylsphingosine), the deacylated form of Gb3, is currently measured in plasma as a biomarker of classic Fabry disease. Intensive research of biomarkers has been conducted over the years, in order to detect novel markers that may potentially be used in clinical practice as a screening tool, in the context of the diagnostic process and as an indicator of response to treatment. An interesting field of application of such biomarkers is the management of female heterozygotes who present difficulty in predictable clinical progression. This revi…

Lipoproteins in atherosclerosis process

Background:Dyslipidaemias is a recognized risk factor for atherosclerosis, however, new evidence brought to light by trials investigating therapies to enhance HDLcholesterol have suggested an increased atherosclerotic risk when HDL-C is high.Results:Several studies highlight the central role in atherosclerotic disease of dysfunctional lipoproteins; oxidised LDL-cholesterol is an important feature, according to “oxidation hypothesis”, of atherosclerotic lesion, however, there is today a growing interest for dysfunctional HDL-cholesterol. The target of our paper is to review the functions of modified and dysfunctional lipoproteins in atherogenesis.Conclusion:Taking into account the central ro…

Cardiovascular risk profile and morbidity in subjects affected by type 2 diabetes with and without diabetic foot. ;

Genetics and Gene Therapy of Anderson-Fabry Disease.

Fabry's disease is a genetic disorder of X-linked inheritance caused by mutations in the alpha galactosidase A gene resulting in deficiency of this lysosomal enzyme. The progressive accumulation of glycosphingolipids, caused by the inadequate enzymatic activity, is responsible of organ dysfunction and thus of clinical manifestations. In the presence of a high clinical suspicion, a careful physical examination and specific laboratory tests are required, finally diagnosis of Fabry's disease is confirmed by the demonstration of absence or reduced alpha-galactosidase A enzyme activity in hemizygous men and gene typing in heterozygous females; in fact the performance of enzymatic activity assay …

Stroke subtypes and their possible implication in stroke prevention drug strategies

Thrombotic strokes can affect large or small arteries in the brain. Drugs to prevent atherosclerosis complication such as thrombotic strokes, should be drugs able to prevent the accumulation of intravascular fat, reduce vascular proliferation, decrease blood pressure levels with the resulting shear stress, reduce platelet aggregation, and possibly partially or totally reverse carotid plaques. Any of the commonly used antihypertensive drugs lower the incidence of stroke, with larger reductions in BP resulting in larger reductions in risk. Experimental and clinical data suggest that reducing the activity of the renin-angiotensin aldosterone system (RAAS) may have beneficial effects beyond the…

La claudicatio intermittens

Molecular Mechanisms of Inflammasome in Ischemic Stroke Pathogenesis.

Ischemic stroke (also called cerebral ischemia) is one of the leading causes of death and severe disability worldwide. NLR inflammasomes play a crucial role in sensing cell damage in response to a harmful stimuli and modulating the inflammatory response, promoting the release of pro-inflammatory cytokines such as IL-18 and IL-1β following ischemic injury. Therefore, a neuroprotective effect is achieved by inhibiting the expression, assembly, and secretion of inflammasomes, thus limiting the extent of brain detriment and neurological sequelae. This review aims to illustrate the molecular characteristics, expression levels, and assembly of NLRP3 (nucleotide-binding oligomerization domain-like…

Inter-familial and intra-familial phenotypic variability in three Sicilian families with Anderson-Fabry disease.

// Antonino Tuttolomondo 1 , Irene Simonetta 1 , Giovanni Duro 2 , Rosaria Pecoraro 1 , Salvatore Miceli 1 , Paolo Colomba 2 , Carmela Zizzo 2 , Antonia Nucera 3, 4 , Mario Daidone 1 , Tiziana Di Chiara 1 , Rosario Scaglione 1 , Vittoriano Della Corte 1 , Francesca Corpora 1 , Danai Vogiatzis 1 and Antonio Pinto 1 1 U.O.C di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), University of Palermo, Palermo, Italy 2 CNR-IBIM: Institute of Biomedicine and Molecular Immunology “A. Monroy” Palermo, Palermo, Italy 3 Stroke Unit, Neurology, Saint Andrea Hospital, La Spezia, Italy 4 Department of Clinical Neurological Sciences, Western Univer…

Electrocardiographic Diagnosis of Atrial Tachycardia: Classification, P-Wave Morphology, and Differential Diagnosis with Other Supraventricular Tachycardias

Atrial tachycardia is defined as a regular atrial activation from atrial areas with centrifugal spread, caused by enhanced automaticity, triggered activity or microreentry. New ECG classification differentiates between focal and macroreentrant atrial tachycardia. Macroreentrant atrial tachycardias include typical atrial flutter and other well characterized macroreentrant circuits in right and left atrium. Typical atrial flutter has been described as counterclockwise reentry within right atrial and it presents a characteristic ECG “sawtooth” pattern on the inferior leads. The foci responsible for focal atrial tachycardia do not occur randomly throughout the atria but tend to cluster at chara…

β-amyloid wall deposit of temporal artery in subjects with spontaneous intracerebral haemorrhage.

// Antonino Tuttolomondo 1 , Rosario Maugeri 4 , Elisabetta Orlando 2 , Giulio Giannone 2 , Francesco Ciccia 3 , Aroldo Rizzo 5 , Domenico Di Raimondo 1 , Francesca Graziano 4 , Rosaria Pecoraro 1 , Carlo Maida 1 , Irene Simonetta 1 , Anna Cirrincione 1 , Francesca Portelli 2 , Francesca Corpora 1 , Domenico Gerardo Iacopino 4 and Antonio Pinto 1 1 Internal Medicine and Stroke Care Ward, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy 2 Human Pathology Section, Human Pathology Section, Department of Health Sciences, University of Palermo, Palermo, Italy 3 Rheumathology Ward, Dipartimento Biomedico di Medicina Interna e Specialistica, Univers…

Oxidative stress biomarkers in Fabry disease: is there a room for them?

Abstract Background Fabry disease (FD) is an X-linked lysosomal storage disorder, caused by deficient activity of the alpha-galactosidase A enzyme leading to progressive and multisystemic accumulation of globotriaosylceramide. Recent data point toward oxidative stress signalling which could play an important role in both pathophysiology and disease progression. Methods We have examined oxidative stress biomarkers [Advanced Oxidation Protein Products (AOPP), Ferric Reducing Antioxidant Power (FRAP), thiolic groups] in blood samples from 60 patients and 77 healthy controls. Results AOPP levels were higher in patients than in controls (p < 0.00001) and patients presented decreased levels of…

New Therapeutic Targets in Clinical Medicine (Editorial)

Early high-dosage atorvastatin treatment improved serum immune-inflammatory markers and functional outcome in acute ischemic strokes classified as large artery atherosclerotic stroke: A randomized trial

Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the…

Impaired circadian heart rate variability in Parkinson’s disease: a time-domain analysis in ambulatory setting

Abstract Background Heart rate variability (HRV) decreases in Parkinson’s disease (PD) and it can be considered a marker for cardiovascular dysautonomia. The purpose of this pilot study is to evaluate long-term time-domain analysis of HRV of PD patients and compare the results with those of matched healthy individuals. Methods Idiopathic PD patients without comorbidity impairing HRV, and age-matched healthy individuals were recruited in a pilot study. A long-term time domain analysis of HRV using 24-h ambulatory ECG was performed. Results Overall, 18 PD patients fulfilling inclusion criteria completed the evaluation (mean age was 55.6 ± 8.8, disease duration: 5.0 ± 4.7). Mean SCOPA-AUT scor…

Cell immunity in Coronary Artery Disease (CAD)

Numerous researches have detected immune cellular elements in coronary lesions of atherosclerotic origin in human and animal models, and these cells are suspected of contributing to plaque instability. Patients affected by acute coronary syndrome present high levels of pro-inflammatory molecules, as shown in numerous studies. This finding implies similarity between CAD and well-known immune-mediated inflammatory diseases. Due to incongruent findings, this “infection hypothesis” cannot be rejected, thus further research is needed to better understand the relationship between pathogen-induced chronic inflammatory response, with its pathogenic mechanisms, and the atherosclerotic process. Sever…

Neurological complications of Anderson-Fabry disease

Characteristic clinical manifestations of AFD such as acroparesthesias, angiokeratoma, corneal opacity, hypo/ and anhidrosis, gastrointestinal symptoms, renal and cardiac dysfunctions can occur in male and female patients, although heterozygous females with AFD usually seems to be less severely affected. The most prominent CNS manifestations consist of cerebrovascular events such as transient ischaemic attacks (TIAs) and (recurrent) strokes . For the most part, CNS complications in AFD have been attributed to cerebral vasculopathy, including anatomical abnormalities. The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both …

Successful salvage therapy of intravenous cyclophosphamide for refractory polymyositis in an elderly patient: a case report.

Dermatomyositis and polymyositis may affect children and adults and are now widely recognized as major causes of disability which, thanks to the introduction of immunosuppressive drugs, is often treatable, at least to some extent. Few data exist regarding polymyositis in elderly patients. We describe a case of refractory life-threatening polymyositis in an elderly patient, successfully treated with intravenous cyclophosphamide

C-reactive protein and efficacy of antiplatelet therapy in (intracranial) atherosclerosis

C-reactive protein (CRP) and other inflammatory biomarkers can indicate both the severity and extent of atherosclerosis, reflecting the inflammatory nature of the disease process.1 Atherogenesis begins with an inflammatory response to vascular injury with cells and mediators initiating the healing response and later inducing growth of atherosclerotic plaques. Inflammation then increases plaque instability, promoting rupture, fissuring, or erosion—the pathogenetic milieu of thrombosis in atherothrombotic ischemic strokes.

Inflammation and Aortic Stiffness: An Individual Participant Data Meta‐Analysis in Patients With Inflammatory Bowel Disease

Background The recent finding that aortic pulse wave velocity ( aPWV ) is increased in patients with inflammatory bowel disease may explain why the cardiovascular risk is increased despite the low prevalence of traditional cardiovascular risk factors. We aimed to test whether inflammation is associated with aortic stiffening in this setting after adjustment for major confounders and to perform subgroup analyses. Methods and Results A systematic literature search for aPWV in inflammatory bowel disease was performed using PubMed, Scopus, Web of Science, and Google Scholar databases (last accessed May 7, 2017). Inclusion criterion was peer‐reviewed publications on clinical studies reporting o…

Metabolic and Vascular Effect of the Mediterranean Diet

Several studies indicated how dietary patterns that were obtained from nutritional cluster analysis can predict disease risk or mortality. Low-grade chronic inflammation represents a background pathogenetic mechanism linking metabolic risk factors to increased risk of chronic degenerative diseases. A Mediterranean diet (MeDi) style has been reported as associated with a lower degree of inflammation biomarkers and with a protective role on cardiovascular and cerebrovascular events. There is heterogeneity in defining the MedDiet, and it can, owing to its complexity, be considered as an exposome with thousands of nutrients and phytochemicals. Recently, it has been reported a novel positive ass…

Diabetic Foot Syndrome as a Possible Cardiovascular Marker in Diabetic Patients

Diabetic foot ulcerations have been extensively reported as vascular complications of diabetes mellitus associated with a high degree of morbidity and mortality; in fact, some authors showed a higher prevalence of major, previous and new-onset, cardiovascular, and cerebrovascular events in diabetic patients with foot ulcers than in those without these complications. This is consistent with the fact that in diabetes there is a complex interplay of several variables with inflammatory metabolic disorders and their effect on the cardiovascular system that could explain previous reports of high morbidity and mortality rates in diabetic patients with amputations. Involvement of inflammatory marke…

KIR2DL3 and the KIR ligand groups HLA-A-Bw4 and HLA-C2 predict the outcome of hepatitis B virus infection.

Killer immunoglobulin-like receptors (KIRs) regulate the activation of Natural Killer cells through their interaction with human leukocyte antigens (HLA). KIR and HLA loci are highly polymorphic and certain HLA-KIR combinations have been found to protect against viral infections. In this study we analyzed whether the KIR/HLA repertoire may influence the course of hepatitis B virus (HBV) infection. Fifty-seven subjects with chronic hepatitis B (CHB), 44 subjects with resolved HBV infection, and 60 healthy uninfected controls (HC) were genotyped for KIR and their HLA ligands. The frequency of the HLA-A-Bw4 ligand group was higher in CHB (58%) than subjects with resolved infection (23%) (crude…

Obstructive Sleep Apnea Is Associated with Liver Damage and Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease

Background/Aims We assessed whether obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with severity of liver fibrosis and carotid atherosclerosis in patients with biopsy-proven NAFLD and low prevalence of morbid obesity. Secondary aim was to explore the association of OSA and hypoxemia with NASH and severity of liver pathological changes. Methods Consecutive patients (n = 126) with chronically elevated ALT and NAFLD underwent STOP-BANG questionnaire to estimate OSA risk and ultrasonographic carotid assessment. In patients accepting to perform cardiorespiratory polygraphy (PG, n = 50), OSA was defined as an apnea/hypopnea index ≥5. A carotid atherosclerotic plaque was defi…

Cytokines, Selectins and Adhesion Molecules Plasma Levels in Acute Ischaemic Stroke: Relationship with Stroke Subtype, Ischaemic Lesion Site and Clinical Outcome

Assessment of heart rate variability (HRV) in subjects with type 2 diabetes mellitus with and without diabetic foot: correlations with endothelial dysfunction indices and markers of adipo-inflammatory dysfunction

Abstract Background Some studies have suggested that patients with diabetes and foot complications have worse cardiovascular and cerebrovascular risk profiles, higher degrees of endothelial dysfunction and arterial stiffness and a higher inflammatory background than patients with diabetes without diabetic foot complications. Patients with diabetes mellitus have an alteration in the sympathovagal balance as assessed by means of heart rate variability (HRV) analysis, which is also related to the presence of endothelial dysfunction. Other studies suggest a possible role of inflammation coexisting with the alteration in the sympathovagal balance in favor of the atherosclerotic process in a mixe…

Ischemic Stroke Pathogenesis: Genetics, Epigenetics and Inflammation

Autonomic dysfunction in a group of lower extremities arterial disease outpatients.

Background: The understanding of the specific role of sympathetic neural control and dysregulation in lower extremities arterial disease (LEAD) is still very limited. Aim of our study was to investigate the autonomic profile in LEAD patients and to evaluate if the eventual autonomic alterations were more severe in patients with advanced disease. Methods: We enrolled all consecutive outpatients with LEAD referred to our Departments between July 2012 and September 2014. They were compared to a group of matched outpatients without LEAD. All patients underwent Holter ECG monitoring. Time-domain analysis of heart rate variability (HRV) was evaluated. Results: Compared to controls, patients with …

Positional brain ischemia with MCA occlusion successfully treated with extra-intracranial bypass.

408 Positional cerebral ischemia (PCI) is an extremely rare condition in which dramatic central nervous system deficits are triggered by standing in patients with severe stenosis or occlusion of the major brain-supplying blood vessels [1] . Because PCI is generally associated with orthostatic hypotension [2, 3] , a hemodynamic mechanism has been proposed [4] . However, PCI has been reported even in patients without orthostatic hypotension [1] . The treatment is medical, but surgery can be considered in refractory cases (endarterectomy for carotid artery stenosis or either highor low-flow extra-intracranial bypass – for carotid occlusion) [3] . We report a case of PCI associated with middle …

Endothelial function and pathogenesis of endothelial dysfunction

Background: The crucial role of endothelium is due to the ability of endothelial cells to receive and concurrently respond to humoral and hemodynamic stimuli. The mechanisms that mediate these reactions are: the production of endothelium-derived factors and metabolizing enzymes; the expression of binding proteins and adhesive molecules; and the consequential shape changes. In fact, a wide range of anti-atherosclerotic action substances is produced by the endothelial cells with the objective of maintaining the balance between vasoconstriction and vasodilation, and inhibit or stimulate the proliferation and migration of smooth muscle cells, thrombogenesis and fibrinolysis. Smoke, age, hyperch…

L'ictus emorragico

Novel alpha-galactosidase A mutation in a female with recurrent strokes.

Abstract Anderson–Fabry disease (AFD) is an X-linked inborn error of glycosphingolipid catabolism resulting from the deficient activity of the lysosomal exoglycohydrolase, a-galactosidase A. The complete genomic and cDNA sequences of the human alpha-galactosidase A gene have been determined and to date, several disease-causing alpha-galactosidase A mutations have been identified, including missense mutations, small deletions/insertions, splice mutations, and large gene rearrangements We report a case of a 56-year-old woman with recurrent cryptogenic strokes. Ophthalmological examination revealed whorled opacities of the cornea (cornea verticillata) and dilated tortuous conjunctival vessels.…

HLA and killer cell immunoglobulin-like receptors influence the natural course of CMV infection.

Background. Natural killer (NK) cells provide a major defense against cytomegalovirus (CMV) infection through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulinlike receptors (KIRs), and human leukocyte antigens (HLA) class I molecules. This study assessed whether the KIR and HLA repertoire may influence the risk of developing symptomatic or asymptomatic disease after primary CMV infection in the immunocompetent host. Methods. Sixty immunocompetent patients with primary symptomatic CMV infection were genotyped for KIR and their HLA ligands, along with 60 subjects with a previous asymptomatic infection as controls. Results. The frequency…

Cerebrovascular risk factors and clinical classification of strokes

Cerebrovascular risk represents a progressive and evolving concept owing to the particular distribution of risk factors in patients with ischemic stroke and in light of the newest stroke subtype classifications that account for pathophysiological, instrumental, and clinical criteria. Age represents the strongest nonmodifiable risk factor associated with ischemic stroke, while hypertension constitutes the most important modifiable cerebrovascular risk factor, confirmed by a host of epidemiological data and by more recent intervention trials of primary (HOT, Syst-Eur, LIFE) and secondary (PROGRESS) prevention of stroke in hypertensive patients. To be sure, a curious relationship exists betwee…

IgG4 Related Syndrome: Another Multiorgan Disease in the Interest Field of Internal Medicine.

BACKGROUND: IgG4-related disease is a rare, clinical and pathologic disease entity of unknown etiology. Its main features are increased serum concentrations of IgG4 > 1,35 g/l, lymphocyte and IgG4+plasma-cell infiltration within tissues, fibrosis or sclerosis. The classical presentation of IgG4-RSD is pancreatitis which is combined with the involvement of biliary ducts in 74 percent of patients. Extrapancreatic manifestations include: abdominal or mediastinal lymphadenopathy; the involvement of salivary glands and lacrimal glands, kidneys, lung, retroperitoneum. Since IgG4-related disease is a multiorgan lymphoproliferative syndrome, it requires a careful differential diagnosis from othe…

Editorial: Ischemic Stroke Prevention

PREVALENCE OF ARTERIAL HYPERTENSION AND CHARACTERISTICS OF NOCTURNAL BLOOD PRESSURE PROFILE OF ASTHMA PATIENTS ACCORDING TO THERAPY AND SEVERITY OF THE DISEASE: THE BADA STUDY

Background: several studies report an increased risk for asthmatic subjects to develop arterial hypertension and the relationship between these two diseases, frequently co-existing, still has some unclear aspects. Methods: The BADA (blood pressure levels, clinical features and markers of subclinical cardiovascular damage of asthma patients) study is aimed to evaluate the prevalence of the cardiovascular comorbidities of asthma and their impact on the clinical outcome. The main exclusion criteria were the presence of other respiratory diseases, current smoking, any contraindication to ambulatory blood pressure monitoring (ABPM). Results: The overall percentage of asthmatics having also hyper…

Cardiac involvement in patients with cirrhosis: a focus on clinical features and diagnosis

Cirrhotic heart has been traditionally considered protected from cardiovascular disease, even if a large amount of literature has recently shown that patients affected by chronic liver disease are exposed to cardiovascular events, as well. Since the first recognition of cardiac involvement in cirrhosis, all published studies explain that decompensated cirrhotic patients suffer from haemodynamic changes, currently known as hyperdynamic syndrome, which finally lead to cirrhotic cardiomyopathy. This is defined by the presence of a subclinical systolic dysfunction unmasked under stress conditions, impaired diastolic function and electrophysiological abnormalities, in the absence of any known ca…

Predictors of outcome in acute ischemic cerebrovascular syndromes:

The Role of Immunosenescence in Cerebral Small Vessel Disease: A Review.

Cerebral small vessel disease (CSVD) is one of the most important causes of vascular dementia. Immunosenescence and inflammatory response, with the involvement of the cerebrovascular system, constitute the basis of this disease. Immunosenescence identifies a condition of deterioration of the immune organs and consequent dysregulation of the immune response caused by cellular senescence, which exposes older adults to a greater vulnerability. A low-grade chronic inflammation status also accompanies it without overt infections, an “inflammaging” condition. The correlation between immunosenescence and inflammaging is fundamental in understanding the pathogenesis of age-related CSVD (ArCSVD). Th…

Single nucleotide polymorphisms (SNPs) of pro-inflammatory/anti-inflammatory and thrombotic/fibrinolytic genes in patients with acute ischemic stroke in relation to TOAST subtype.

Abstract Background The genetic basis of complex diseases like ischemic stroke probably consists of several predisposing risk factors, such as genes involved in inflammation and thrombotic pathways. On this basis the aim of our study was to evaluate the role of SNPs (single nucleotide polymorphisms) of some pro-inflammatory/anti-inflammatory and coagulation/fibrinolytic genes in patients with acute ischemic stroke. Methods The study population consisted of 144 consecutive Caucasian adult patients who were hospitalized in the Internal Medicine Department at the University of Palermo between November 2006 and January 2008, and who met inclusion criteria. The cases were patients admitted with …

Immunoinflammatory activation during the acute phase of lacunar and non-lacunar ischemic stroke: Association with time of onset and diabetic state

Several studies have stressed the involvement of inflammation in the pathophysiology of acute brain ischemia, but the role of immunoinflammatory activation in diabetic stroke patients has not yet been fully evaluated. The aim of our study was to evaluate immunoinflammatory activation of acute phase of stroke in relation to time of symptoms onset, diabetic state and diagnostic subtype. We enrolled 60 patients (32 diabetics; 28 non- diabetics) with acute ischemic stroke and 123 subjects without acute ischemic stroke, and measured levels of IL-1β, TNF-α, IL-6, IL-10, E-selectin, P-selectin, sICAM-1, sVCAM-1, VWF, 24–72 h and 7–10 days after stroke onset; TPA, PAI-1 plasma levels at 24–72h. Ou…

Epicardial Fat, Cardiac Geometry and Cardiac Function in Patients with Nonalcoholic Fatty Liver Disease: Association with the Severity of Liver Disease

Background & Aims Non-alcoholic fatty liver disease (NAFLD) has been associated with increased cardiovascular risk, including coronary artery disease and cardiac dysfunction. In addition, recent evidence highlighted the possible role of epicardial fat as a new cardiometabolic risk factor. We tested the correlation between epicardial fat, alterations in cardiac geometry and function, and severity of liver damage, in patients with biopsy-proven NAFLD. Methods The anthropometric, biochemical and metabolic features were recorded in 147 consecutive biopsy-proven NAFLD cases (Kleiner score). Epicardial fat thickness was measured by echocardiography. Results Epicardial fat was higher in patients w…

Metabolic memory in diabetic foot syndrome (dfs): epigenetic changes of the expression of micro-rnas and single nucleotide polymorphisms (snps) frequency in a cohort of diabetic patients with and without foot ulceration and correlation with indices of endothelial and adipo-inflammatory dysfunction

Background: Diabetic foot is a significant cause of morbidity in diabetic patients, with a rate that is approximatelytwice that of patients without foot ulcers. “Metabolic memory” represents the epigenetic changes induced by chronic hyperglycaemia, despite the correction of the glucose levels themselves. These epigenetic modifications appear to perpetuate the damage caused by persistently elevated glucose levels even in their absence, acting at various levels, mostly affecting the molecular processes of diabetic ulcer healing. Methods: The aim of our cross-sectional study was to analyse a cohort of patients with diabetes with and without lower limb ulcers. We examined the effects of epigene…

Corrigendum to “Arterial stiffness indexes in acute ischemic stroke: Relationship with stroke subtype” [Atherosclerosis 211 (2010) 187–194]

Metabolic and anti-inflammatory effects of a home-based programme of aerobic physical exercise

Summary Aims Regular exercise demonstrated the ability to provide enormous benefits to many diseases, atherosclerotic-based, degenerative and neoplastic, but also to grant anti-inflammatory actions, assessed by various authors in different populations. Despite of these clear benefits, many patients are unable to attain long-term results through chronic physical activity for different causes. On this basis, the aim of our study was to assess the metabolic and anti-inflammatory effects of a home-based programme of fast walking in patients affected by metabolic syndrome (MS). Materials and methods We enrolled 176 subjects with MS as stated by ATP III criteria. Patients were invited to walk for…

Peripheral Frequency of CD4+ CD28- Cells in Acute Ischemic Stroke: Relationship With Stroke Subtype and Severity Markers.

CD4+ CD28− T cells also called CD28 null cells have been reported as increased in the clinical setting of acute coronary syndrome. Only 2 studies previously analyzed peripheral frequency of CD28 null cells in subjects with acute ischemic stroke but, to our knowledge, peripheral frequency of CD28 null cells in each TOAST subtype of ischemic stroke has never been evaluated. We hypothesized that CD4+ cells and, in particular, the CD28 null cell subset could show a different degree of peripheral percentage in subjects with acute ischemic stroke in relation to clinical subtype and severity of ischemic stroke. The aim of our study was to analyze peripheral frequency of CD28 null cells in subjects…

Descrizione del quarto caso di aceruloplasminemia familiare diagnosticato in Italia.

Arterial stiffness, endothelial and cognitive function in subjects with type 2 diabetes in accordance with absence or presence of diabetic foot syndrome

BACKGROUND: Endothelial dysfunction is an early marker of cardiovascular disease so endothelial and arterial stiffness indexes are good indicators of vascular health. We aimed to assess whether the presence of diabetic foot is associated with arterial stiffness and endothelial function impairment. METHODS: We studied 50 subjects with type 2 diabetes mellitus and diabetic foot syndrome (DFS) compared to 50 diabetic subjects without diabetic foot, and 53 patients without diabetes mellitus, by means of the mini mental state examination (MMSE) administered to evaluate cognitive performance. Carotid-femoral pulse wave velocity (PWV) and augmentation index (Aix) were also evaluated by Applanation…

A family with various symptomatology suggestive of Anderson-Fabry disease and a genetic polymorphism of alpha galactosidase A gene.

Background: Anderson/Fabry disease expresses a wide range of clinical variability in patients that it is possible to explain referring to a genetic variability with numerous mutations described in the literature (more than 600). Methods: We report some clinical cases of some members of a Sicilian family to express phenotypical variability of this disease in subjects with the same genetic mutation. Results: The first case was a 59-year-old female. Brain MRI revealed right frontal periventricular white matter of likely vascular-degenerative origin. The proband's alpha galactosidase A activity was 3.7. nmol/mL/h. Molecular genetics revealed a polymorphism: - 10 C. >. T; IVS 2-76_80del5; IVS…

Relationship between Diabetes and Ischemic Stroke: Analysis of Diabetes- Related Risk Factors for Stroke and of Specific Patterns of Stroke Associated with Diabetes Mellitus

Diabetes and ischemic stroke are common diseases that frequently occurring together. Among patients with diabetes mellitus several factors contribute in varying degrees to the overall cerebrovascular risk including hyperglycemia, vascular risk factors such as hypertension and dyslipidemia and also genetic, demographic, and lifestyle factors and several studies have shown that people with diabetes have approximately twice the risk of ischemic stroke compared with those without diabetes. The association between ischemic stroke and diabetes is bidirectional and it is not limited to acute ischemic stroke since diabetes may contribute to a more insidious brain damage represented by lacunar infar…

Effects of ACE-Inhibitors and Angiotensin Receptor Blockers on Inflammation

The role of inflammation in cardiovascular disease and in hypertensive disease above all, is complex. Several studies confirm that activation of renin-angiotensin-aldosterone system (RAAS), through increase in the production of angiotensin II (Ang II), is closely related to local vascular inflammation. Over the BP lowering effects of anti-hypertensive treatments, several ancillary effects for every class may be found, distinguishing the various drugs from one another. Given the pro-inflammatory effects of Ang II and aldosterone, agents that interfere with the components of RAAS, such as ACE inhibitors, Angiotensin Receptor Blockers (ARBs), and mineralocorticoid receptor antagonists (spirono…

Fetuin-A and CD40L plasma levels in acute ischemic stroke: differences in relation to TOAST subtype and correlation with clinical and laboratory variables

Abstract Introduction Accumulating evidence suggests that inflammation plays an important role in the acute phase of ischemic stroke. CD40 L is a well recognized atherosclerotic inflammatory marker, whereas recent evidence suggests a pro-inflammatory role of Fetuin-A. To analyze the role of an inflammatory marker such as CD40 L and of a candidate pro-inflammatory marker such as Fetuin-A in acute stroke we evaluated their serum levels in subjects with acute ischemic stroke and their possible association with other laboratory and clinical variables. Materials and methods We enrolled 107 consecutive patients with a diagnosis of acute ischemic stroke admitted to the Internal Medicine Department…

Ischemic stroke subtypes and the implications for stroke management

Internal Medicine & Cardioangiology Ward, Dipartimento Biomedico di Medicina Interna & Specialistica, University of Palermo, Italy *Author for correspondence: Tel.: +39 091 6552197; bruno.tuttolomondo@unipa.it

Endothelial function, adipokine serum levels and white matter hyperintesities in subjects with diabetic foot syndrome.

Abstract Context No study has analyzed the prevalence of white matter hyperintensities (WMHs) in subjects with diabetic foot syndrome (DFS) and their relationship to adipokine serum levels and indexes of endothelial and cognitive performance. Objective To evaluate omentin and vaspin serum levels and the prevalence of WMHs in subjects with DFS and to analyze their relationship with other endothelial, arterial stiffness, and cognitive functions. Design Case-control study enrolling 40 subjects with DFS, 40 diabetic subjects without foot complications, 40 controls with foot lesions without diabetes, and 40 patients without diabetes mellitus. Main Outcome Measures Pulse wave velocity (PWV), augm…

Appropriateness of requests for human serum albumin at the University Hospital of Palermo, Italy: a prospective study

Abstract OBJECTIVE: First, to assess the appropriateness of requests for albumin using current guidelines; second, to evaluate physicians' compliance with this protocol. DESIGN: Descriptive, prospective study. SETTING: 'Paolo Giaccone' University Hospital in Palermo (Italy). PARTICIPANTS: The six departments with the highest orders for albumin. INTERVENTION: An experimental, pharmacist-driven process for daily orders of albumin was activated over a period of 1 month. Pharmacy personnel handed out order forms on six different wards. Physicians were required to select one of a number of intended uses listed on the form. MAIN OUTCOME MEASURES: Data on albumin and serum protein levels; number o…

Validity criteria for the diagnosis of fatty liver by M probe-based controlled attenuation parameter.

Background & Aims Controlled attenuation parameter (CAP) can be performed together with liver stiffness measurement (LSM) by transient elastography (TE) and is often used to diagnose fatty liver. We aimed to define the validity criteria of CAP. Methods CAP was measured by the M probe prior to liver biopsy in 754 consecutive patients with different liver diseases at three centers in Europe and Hong Kong (derivation cohort, n = 340; validation cohort, n = 414; 101 chronic hepatitis B, 154 chronic hepatitis C, 349 non-alcoholic fatty liver disease, 37 autoimmune hepatitis, 49 cholestatic liver disease, 64 others; 277 F3-4; age 52 ± 14; body mass index 27.2 ± 5.3 kg/m2). The primary outco…

Intravenous high dose furosemide plus small volume of hypertonic saline solution (HSS) versus seriated paracentesis in treatment of refractory ascites: a pilot study

Citokines, Selectins and adhesion molecules plasma levels in acute ischemic stroke: relationship with stroke, subtype, ischemic lesion site and clinical outcome

Relationship between HRV measurements and demographic and clinical variables in a population of patients with atrial fibrillation.

Little is known about the role of HRV in atrial fibrillation (AF) patients. Aim of our study was to assess the relationship between HRV measurements and demographic and clinical variables in a population of 274 AF patients. We selected all consecutive patients with persistent/permanent AF among whom had performed a Holter ECG in our Department from April 2010 to April 2015. Time-domain analysis of HRV was evaluated. Demographic and clinical variables were collected for each patient. At multivariable logistic regression, a higher pNN50 was associated with ACE inhibitors/ARBs (p = 0.016) and a lower pNN50 with obesity (p = 0.037) and higher heart rate (HR) (p < 0.0005). A higher RMSSD w…

Relationship between adherence to the Mediterranean Diet, intracerebral hemorrhage, and its location

INTRODUCTION: Although some authors evaluated the relationship between adherence to the Mediterranean Diet (MeDi) and both ischemic and hemorrhagic stroke, hemorrhagic stroke alone is not yet examined. AIMS: We conducted a retrospective study to evaluate the relationship between adherence to MeDi and intracerebral hemorrhage (ICH) and different locations of ICH (ganglionic/internal capsule, brainstem/cerebellum, or lobar). METHODS: We analyzed charts and collected data of all consecutive patients with ICH admitted to our Internal Medicine Ward from 2005 to 2014. A scale indicating the degree of adherence to the traditional MeDi Score was constructed. RESULTS: When compared with 100 subjects…

Corpus callosum involvement: a useful clue for differentiating Fabry Disease from Multiple Sclerosis.

PURPOSE: Multiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS. METHODS: In this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms. RESULTS: WMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the…

Immune-inflammatory markers and arterial stiffness indexes in subjects with acute ischemic stroke.

Abstract No study has yet evaluated the relationship between arterial stiffness indexes and immuno-inflammatory pathway in patients with an acute cardiovascular or cerebrovascular event. The aim of our study was to evaluate in patients with acute ischemic stroke the relationship between immune-inflammatory markers and arterial stiffness indexes. Methods 107 subjects with acute ischemic stroke and 107 controls without stroke. We evaluated plasma levels of C-reactive protein (CRP), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10), E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1…

Antiplatelets in stroke prevention

Stroke is the second cause of death worldwide and one of the leading cause of disability. Due to the high rate of recurrence, in high risk-patients (eg patients affected by atherosclerotic vascular disease), long-term antiplatelet therapy reduces the risk of vascular events such as non-fatal myocardial infarction, non-fatal stroke, or vascular death. The percentage of reduction of the events can be estimated in approximately 25%. These data justify the directions that are given to us by the current guidelines for prevention of secondary stroke, which recommend the broad use of antiplatelet therapy both for the secondary prevention of stroke in patients with a history of non-cardioembolic st…

A re-entry tachycardia triggered by the spontaneous interruption of an atrial tachycardia.

The common atrioventricular nodal re-entry tachycardia is the most common form of paroxysmal supraventricular tachycardia. It starts frequently with a supraventricular ectopic beat that, on finding the fast pathway in refractory period, travels in the slow pathway as to appear as a prolongation of the PR interval on the ECG. In this study, we show a singular case of a common atrioventricular nodal re-entry tachycardia triggered by the spontaneous interruption of an atrial tachycardia.

Residual vein thrombosis for assessing duration of anticoagulation after unprovoked deep vein thrombosis of the lower limbs: the extended DACUS study.

Abstract The safest duration of anticoagulation after idiopathic deep vein thrombosis (DVT) is unknown. We conducted a prospective study to assess the optimal duration of vitamin K antagonist (VKA) therapy considering the risk of recurrence of thrombosis according to residual vein thrombosis (RVT). Patients with a first unprovoked DVT were evaluated for the presence of RVT after 3 months of VKA administration; those without RVT suspended VKA, while those with RVT continued oral anticoagulation for up to 2 years. Recurrent thrombosis and/or bleeding events were recorded during treatment (RVT group) and 1 year after VKA withdrawal (both groups). Among 409 patients evaluated for unprovoked DVT…

Vascular health in subjects with rheumatoid arthritis: assessment of endothelial function indices and serum biomarkers of vascular damage

Background The cardiovascular risk (CVD) in patients with rheumatoid arthritis (RA) is 1.5–2 times higher than that in individuals of the same age and sex. Aims To analyse the degree of endothelial dysfunction, the atherogenic immunoinflammatory serum background and the relationships among some vascular indices, cardiovascular comorbidities, and cognitive performance in subjects with RA. Patients and methods All consecutive patients with a rheumatoid arthritis diagnosis admitted to the Rheumatology Ward of “Policlinico Paolo Giaccone” Hospital of Palermo were enrolled from July 2019 to September 2020. We evaluated our patients’ cognitive functions by administering the Mini-Mental State Exam…

The Role of the Coagulation System in Peripheral Arterial Disease: Interactions with the Arterial Wall and Its Vascular Microenvironment and Implications for Rational Therapies

Peripheral artery disease (PAD) is a clinical manifestation of atherosclerotic disease with a large-scale impact on the economy and global health. Despite the role played by platelets in the process of atherogenesis being well recognized, evidence has been increasing on the contribution of the coagulation system to the atherosclerosis formation and PAD development, with important repercussions for the therapeutic approach. Histopathological analysis and some clinical studies conducted on atherosclerotic plaques testify to the existence of different types of plaques. Likely, the role of coagulation in each specific type of plaque can be an important determinant in the histopathological compo…

Variazione dei livelli sierici di peptidi natriuretici e citochine dopo terapia con alte dosi di furosemide e soluzioni saline ipertoniche (SSI) e dopo carico salino in soggetti con disfunzione ventricolare sinistra e/o scompenso cardiaco congestizio

Molecular Biology of Atherosclerotic Ischemic Strokes

Among the causes of global death and disability, ischemic stroke (also known as cerebral ischemia) plays a pivotal role, by determining the highest number of worldwide mortality, behind cardiomyopathies, affecting 30 million people. The etiopathogenetic burden of a cerebrovascular accident could be brain ischemia (~80%) or intracranial hemorrhage (~20%). The most common site when ischemia occurs is the one is perfused by middle cerebral arteries. Worse prognosis and disablement consequent to brain damage occur in elderly patients or affected by neurological impairment, hypertension, dyslipidemia, and diabetes. Since, in the coming years, estimates predict an exponential increase of people w…

Treatment of Lysosomal Storage Disorders (LSDs)

Successful “Salvage” Therapy of Intravenous Cyclophosphamide for Refractory Polymyositis in an Elderly Patient: Case Report

Dermatomyositis and polymyositis may affect children and adults and are now widely recognized as major causes of disability which, thanks to the introduction of immunosuppressive drugs, is often treatable, at least to some extent. Few data exist regarding polymyositis in elderly patients. We describe a case of refractory life-threatening polymyositis in an elderly patient, successfully treated with intravenous cyclophosphamide.

Ruolo dell'interazione NK/KIR nella storia naturale delle infezioni virali

Immunological mechanisms involved in the genesis of the immune response against viral infections take into account the activation of both innate adaptative response. Innate immune defenses trigger a rapid local response, which is often sufficient to control viral infection, and promotes the subsequent activation of specific immune defenses. Natural killer (NK) cells that constitute a subpopulation of lymphocyte-related cells are a key factor of innate immune response and play a role in defense against viral infections by killing infected cells or by producing cytokines and interacting with adaptative immune system's cells. Killer immunoglobulin-like receptors (KIRs) regulate the activation …

Terapia antiaggregante ed arteriopatia obliterante cronica degli arti inferiori

Echocardiographic Evaluation of the Cardiac Chambers in Asthmatic Patients: The BADA (Blood Pressure Levels, Clinical Features and Markers of Subclinical Cardiovascular Damage of Asthma Patients) Study-ECO

The &ldquo;Blood pressure levels, clinical features and markers of subclinical cardiovascular Damage of Asthma patients&rdquo; (BADA) study is aimed at defining the cardiovascular risk profile and the markers of subclinical and clinical vascular and cardiac damage in asthmatic patients. Very few studies have assessed asthmatic patients without concomitant heart disease through a transthoracic echocardiogram. The goal of the present study is to investigate the prevalence of morphology and/or function changes in the cardiac chambers of a sample of 86 patients with chronic asthma, referred to the dedicated outpatient unit of the Division of Respiratory Diseases of the AOUP &ldquo;P. Giaccone&r…

Inflammation, Endothelial Dysfunction and Arterial Stiffness as Therapeutic Targets in Cardiovascular Medicine

In the last decades, many factors thought to be associated with the atherosclerotic process and cardiovascular events have been studied, and some of these have been shown to correlate with clinical outcome, such as arterial stiffness, endothelial dysfunction and immunoinflammatory markers. Arterial stiffness is an important surrogate marker that describes the capability of an artery to expand and contract in response to pressure changes. It can be assessed with different techniques, such as the evaluation of PWV and AIx. It is related to central systolic pressure and it is an independent predictor of cardiovascular morbidity and mortality in hypertensive patients, type 2 diabetes, end-stage…

Association between diabetes and stroke subtype on survival and functional outcome 3 months after stroke: data from the European BIOMED Stroke Project.

Bowel resection reduces aortic pulse wave velocity in patients with ulcerative colitis. A longitudinal study.

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Ischemic stroke in patients with diabetic foot

Arterial stiffness indexes in acute ischemic stroke: Relationship with stroke subtype

INTRODUCTION: No study has evaluated both arterial stiffness indexes (PWV and Aix) in patients with an acute cerebrovascular event. The aim of our study was to evaluate arterial stiffness indexes in subjects with acute ischemic stroke and to evaluate the relationship between these indexes and other clinical and laboratory variables. MATERIALS AND METHODS: We enrolled all consecutive patients with a diagnosis of acute ischemic stroke admitted to the Internal Medicine Department at the University of Palermo between November 2006 and January 2009, and hospitalized control patients without a diagnosis of acute ischemic stroke. The type of acute ischemic stroke was classified according to the TO…

Monocyte Distribution Width (MDW) as a biomarker of sepsis: An evidenced-based laboratory medicine approach.

Monocyte Distribution Width (MDW) is a new generation cell blood count parameter providing a measure of monocyte anisocytosis. In the last decades, it has emerged as a reliable biomarker of sepsis in the acute setting, especially emergency department, and intensive care unit. MDW has several advantages over commonly used sepsis biomarkers, including low-cost, ease and speed of measurement. The clinical usefulness of MDW has been established in several studies and some clinical laboratory medicines have already implemented it in their routine. In this article, we describe the analytical and clinical features of MDW to guide its appropriate use in clinical practice by integrating the research…

ADIPONECTIN, RESISTIN AND IL-6 PLASMA LEVELS IN SUBJECTS WITH DIABETIC FOOT AND POSSIBLE CORRELATION WITH CLINICAL VARIABLES AND CARDIOVASCULAR CO-MORBIDITY

Abstract Introduction It is very suggestive that diabetic foot is characterized by a pronounced inflammatory reaction and the pathogenic significance of this inflammation has received little attention. On this basis the aim of our study was to evaluate plasma levels of adiponectin, resistin and IL-6 in subjects with diabetic foot in comparison with subjects without foot complications. Materials and methods We recruited 34 subjects with type 2 diabetes mellitus and foot ulceration hospitalized for every condition related to diabetic disease, but not for new vascular events (group A). As controls we recruited 37 patients with type 2 diabetes mellitus without foot ulceration (group B) hospital…

New frontiers in anticoagulation: non vitamin-K oral anticoagulants in stroke prevention

ABSTRACTIntroduction: Non vitamin-K oral anticoagulants (NOACs) are direct and specific inhibitors of the coagulation factors IIa (dabigatran) and Xa (apixaban, rivaroxaban, edoxaban) which share many pharmacokinetic properties. However, indications are lacking regarding the use of NOACs during thrombolysis, surgery and bleeding events.Areas covered: In this paper, the authors retrospectively analyzed the relevant literature on the NOACs using the PubMed and Google Scholar databases.Expert commentary: Although warfarin is effective in cardioembolic stroke prevention, easier handling and more favorable risk-benefit profile often render NOACs a more preferable therapy choice for neurologists.…

Inflammation and Inflammatory Cell Recruitment in Acute Cerebrovascular Diseases

Inflammation seems to play a major role in the pathogenesis of ischemic stroke as well as in other forms of brain damage. Ischemic brain injury induces a strong inflammatory response that begins in the microcirculation and involves several cell types and molecules, leading to neuronal death. The immune system is actively involved in the pathogenesis of acute brain damage through a set of events that include leukocyte and monocyte infiltration into the brain, activation of resident cells, including microglia, astrocytes and endothelial cells, and the elevated production of several inflammatory molecules, such as cytokines, that together play a complex role in the pathophysiology of ischemic …

When sepsis affects the heart: A case report and literature review

A 59-year-old nursing home patient with Down syndrome was brought to the internal medicine department of our hospital due to fever, cough without expectorate, and dyspnea. A thoracic computed tomography revealed the presence of bilateral basal parenchymal opacities. Her condition deteriorated after admission and troponin reached a peak serum concentration of 16.9 ng/mL. The patient was in cardiogenic shock. In addition to fluid resuscitation, vaso-active amine infusion was administered to achieve hemodynamic stabilization. The differential diagnosis investigated possible pulmonary embolism, myocardial infarction, and myocarditis. Furthermore, a second transthoracic echocardiogram suggested …

Plasma derived protein C in severe sepsis: report of two cases

Severe sepsis is defined as sepsis-associated organ dysfunction, (arterial hypoxemia, acute oliguria, coagulation abnormalities, thrombocytopenia, hyperbilirubinemia), hypoperfusion (hyperlactatemia) and arterial hypotension (mean arterial pressure \70 mmHg, or a systolic blood pressure decrease[40 mmHg) [3, 4]. Septic shock [3, 4] is defined as acute circulatory failure induced by sepsis with hypotension despite adequate fluid resuscitation. A dysfunction of the protein C (PC) pathway is always present in severe sepsis and contributes to the development of coagulopathy and necrosis [12, 13]. This decrease is caused by consumption of protein C during systemic activation of blood coagulation…

Immuno-inflammatory predictors of stroke at follow-up in patients with chronic non-valvular atrial fibrillation (NVAF).

Accumulating evidence suggests that inflammation plays an important role in the acute phase of ischemic stroke. CD40 L is a well recognized atherosclerotic inflammatory marker, whereas recent evidence suggests a pro-inflammatory role of Fetuin-A. To analyze the role of an inflammatory marker such as CD40 L and of a candidate pro-inflammatory marker such as Fetuin-A in acute stroke we evaluated their serum levels in subjects with acute ischemic stroke and their possible association with other laboratory and clinical variables. MATERIALS AND METHODS: We enrolled 107 consecutive patients with a diagnosis of acute ischemic stroke admitted to the Internal Medicine Department at the University of…

Key lncRNAs involved in ischemic strokes

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Endothelial Dysfunction and Chronic Inflammation: The Cornerstones of Vascular Alterations in Age-Related Diseases

Vascular diseases of the elderly are a topic of enormous interest in clinical practice, as they have great epidemiological significance and lead to ever-increasing healthcare expenditures. The mechanisms underlying these pathologies have been increasingly characterized over the years. It has emerged that endothelial dysfunction and chronic inflammation play a diriment role among the most relevant pathophysiological mechanisms. As one can easily imagine, various processes occur during aging, and several pathways undergo irreversible alterations that can promote the decline and aberrations that trigger the diseases above. Endothelial dysfunction and aging of circulating and resident cells are…

A New Preclinical Decision Support System Based on PET Radiomics: A Preliminary Study on the Evaluation of an Innovative 64Cu-Labeled Chelator in Mouse Models

The 64Cu-labeled chelator was analyzed in vivo by positron emission tomography (PET) imaging to evaluate its biodistribution in a murine model at different acquisition times. For this purpose, nine 6-week-old female Balb/C nude strain mice underwent micro-PET imaging at three different time points after 64Cu-labeled chelator injection. Specifically, the mice were divided into group 1 (acquisition 1 h after [64Cu] chelator administration, n = 3 mice), group 2 (acquisition 4 h after [64Cu]chelator administration, n = 3 mice), and group 3 (acquisition 24 h after [64Cu] chelator administration, n = 3 mice). Successively, all PET studies were segmented by means of registration with a standard te…

Longitudinal Strain Analysis and Correlation with TIMI Frame Count in Patients with Ischemia with No Obstructive Coronary Artery (INOCA) and Microvascular Angina (MVA)

Background: The aim of the study is to evaluate the subclinical alterations of cardiac mechanics detected using speckle-tracking echocardiography and compare these data with the coronary angiography indices used during coronary angiography in a population of patients diagnosed with ischemia with no obstructive coronary artery (INOCA) and microvascular angina (MVA). Methods: The study included 85 patients admitted to our center between November 2019 and January 2022 who were diagnosed with INOCA compared with a control group of 70 healthy patients. A collection of anamnestic data and a complete cardiovascular physical examination, and echocardiogram at rest with longitudinal strain were perf…

4. Inflammation, Endothelial Dysfunction and Arterial Stiffness as Therapeutic Targets in Cardiovascular Medicine.

In the last decades, many factors thought to be associated with the atherosclerotic process and cardiovascular events have been studied, and some of these have been shown to correlate with clinical outcome, such as arterial stiffness, endothelial dysfunction and immunoinflammatory markers. Arterial stiffness is an important surrogate marker that describes the capability of an artery to expand and contract in response to pressure changes. It can be assessed with different techniques, such as the evaluation of PWV and AIx. It is related to central systolic pressure and it is an independent predictor of cardiovascular morbidity and mortality in hypertensive patients, type 2 diabetes, end-stage…

Protective and causative killer Ig-like receptor (KIR) and metalloproteinase genetic patterns associated with Herpes simplex virus 1 (HSV-1) encephalitis occurrence

Abstract Background The cerebral innate immune system has a critical role in control processes of viral replication in the brain after primary infactivo and immunologic disregulation and inflammation has been reported as a primary determinant of pathogenesis and prognosis of subsequent HSV-1 related encephalitis (HSE). Interaction linking LTR3-activated DCs is also represented by the killer Ig-like receptor (KIR) + pathways on NK cells. Only a few studies analyzed the role of of MMP-9 activity regulating genetic polymorphism on clinical outcome of viral infections. Susceptibility to symptomatic encephalitis depends on SNC viral invasion and BBB disruption. We hypothesize that certain KIR ge…

Systematic review and meta-analysis of cardiovascular risk in rheumatological disease: Symptomatic and non-symptomatic events in rheumatoid arthritis and systemic lupus erythematosus

Abstract Although each autoimmune disease is associated with specific tissue or organ damage, rheumatic diseases share a pro-inflammatory pattern that might increase cardiovascular risk. Retrospective and prospective studies on patients affected by systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) highlighted the concept of “accelerated atherosclerosis”. Therefore, the purpose of this systematic review and meta-analysis is the assessment of symptomatic or asymptomatic cardiovascular events among patients with rheumatic diseases as RA and SLE. The literature research obtained all manuscripts published in the English language between 2015 and 2019 for a total of 2355 manuscript…

Approccio terapeutico alla claudicatio intermittens e all'ischemia critica.

Immune-inflammatory and metabolic effects of high dose furosemide plus hypertonic saline solution (HSS) treatment in cirrhotic subjects with refractory ascites

Introduction Patients with chronic liver diseases are usually thin as a result of hypermetabolism and malnutrition expressed by reduced levels of leptin and impairment of other adyponectins such as visfatin. Aims We evaluated the metabolic and inflammatory effects of intravenous high-dose furosemide plus hypertonic saline solutions (HSS) compared with repeated paracentesis and a standard oral diuretic schedule, in patients with cirrhosis and refractory ascites. Methods 59 consecutive cirrhotic patients with refractory ascites unresponsive to outpatient treatment. Enrolled subjects were randomized to treatment with intravenous infusion of furosemide (125-250mg⁄bid) plus small volumes of HSS …

The supraventricular tachycardias: Proposal of a diagnostic algorithm for the narrow complex tachycardias

AbstractThe narrow complex tachycardias (NCTs) are defined by the presence in a 12-lead electrocardiogram (ECG) of a QRS complex duration less than 120ms and a heart rate greater than 100 beats per minute; those are typically of supraventricular origin, although rarely narrow complex ventricular tachycardias have been reported in the literature.As some studies document, to diagnose correctly the NCTs is an arduous exercise because sometimes those have similar presentation on the ECG. In this paper, we have reviewed the physiopathological, clinical, and ECG findings of all known supraventricular tachycardias and, in order to reduce the possible diagnostic errors on the ECG, we have proposed …

Immuno-inflammatory activation in acute cardio-embolic strokes in comparison with other subtypes of ischaemic stroke

Few studies have examined the relationship between inflammatory biomarker blood levels, cardioembolic stroke subtype and neurological deficit. So the aim of our study is to evaluate plasma levels of immuno-inflammatory variables in patients with cardio-embolic acute ischaemic stroke compared to other diagnostic subtypes and to evaluate the relationship between immuno-inflammatory variables, acute neurological deficit and brain infarct volume. One hundred twenty patients with acute ischaemic stroke and 123 controls without a diagnosis of acute ischaemic stroke were evaluated. The type of acute ischaemic stroke was classified according to the TOAST classification. We evaluated plasma levels o…

HLA and killer cell immunoglobulin-like receptor (KIRs) genotyping in patients with acute ischemic stroke

Abstract Introduction In humans, a major component of natural killer (NK) and T cell target recognition depends on the surveillance of human leukocyte antigen (HLA) class I molecules by killer immunoglobulin-like receptors (KIRs). Aims To implement the knowledge about the immunological genetic background of acute ischemic stroke susceptibility in relation to the frequency of the KIR genes and HLA alleles. Methods Subjects with acute ischemic stroke and subjects without stroke were genotyped for the presence of KIR genes and of the three major KIR ligand groups, HLA-C1, HLA-C2, and HLA-Bw4, both HLA-B and HLA-A loci. Results Between November 2013 and February 2016, consecutive patients with …

Inflammation in Ischemic Stroke Subtypes

Determining the cause of stroke does influence choices for management. categorization of subtypes of ischemic stroke has had considerable study, but definitions are hard to formulate and their application for diagnosis in an individual patient is often problematic. Cerebral ischemia initiates a complex cascade of events at genomic, molecular, and cellular levels, and inflammation is important in this cascade. In 1993 for For the Trial of Org 10172 in Acute Stroke Treatment (TOAST), Adams et al] conducted a placebo-controlled, randomized, blinded study of the low-molecular-weight heparinoid given to patients within 24 hours after stroke and developed a system for diagnosis of subtype of isch…

L’ischemia critica

Valutazione mediante monitoraggio ambulatoriale della pressione arteriosa (ABPM) dell’effetto di un programma di attività fisica centrata sul “fast walking” sui livelli pressori in soggetti ipertesi. ; .

Hyperhomocysteinemia in patients with cognitive impairment

Cognitive impairment is common in elderly people and represents clinical feature of neurodegenerative diseases. Not all of patients with Mild Cognitive Impairment (MCI) finally develop dementia and it is interesting to investigate the role of possible markers for early diagnosis. Hyperhomocysteinemia is associated to several pathologies including cognitive impairment; aim of this study is to evaluate the correlation between cognitive performance assessment and homocysteine plasma levels. Total 74 patients and 75 healthy controls were enrolled and MCI were defined by a MMSE score lower than 26 after adjustment for years of schooling. Homocysteine plasma levels were determined. Homocysteine l…

Decreasing incidence of lacunar vs other types of cerebral infarction in a Japanese population

Cytokines, adhesion molecules and Selectins plasma levels and laboratory parameters in patients with different subtypes of ischemic stroke.

New insights about the putative role of myokines in the context of cardiac rehabilitation and secondary cardiovascular prevention.

Exercise training prevents the onset and the development of many chronic diseases, acting as an effective tool both for primary and for secondary prevention. Various mechanisms that may be the effectors of these beneficial effects have been proposed during the past decades: some of these are well recognized, others less. Muscular myokines, released during and after muscular contraction, have been proposed as key mediators of the systemic effects of the exercise. Nevertheless the availability of an impressive amount of evidence regarding the systemic effects of muscle-derived factors, few studies have examined key issues: (I) if skeletal muscle cells themselves are the main source of cytokin…

The Presence of White Matter Lesions Is Associated With the Fibrosis Severity of Nonalcoholic Fatty Liver Disease

Abstract We tested whether nonalcoholic fatty liver disease (NAFLD) and/or its histological severity are associated with vascular white matter lesions (WML) in patients with biopsy-proven NAFLD and in non-NAFLD controls. Data were recorded in 79 consecutive biopsy-proven NAFLD, and in 82 controls with normal ALT and no history of chronic liver diseases, without ultrasonographic evidence of steatosis and liver stiffness value  45 years (OR 3.09, 95% CI: 1.06–9.06, P = 0.03; and OR 11.1, 95% CI: 1.14–108.7, P = 0.03), and F2–F4 fibrosis (OR 3.36, 95% CI: 1.29–8.73, P = 0.01; and OR 5.34, 95% CI: 1.40–20.3, P = 0.01) were independently associated with WML (mostly of mild grade) by multivariate…

Immune-inflammatory markers and arterial stiffness indexes in subjects with acute ischemic stroke with and without metabolic syndrome.

Objective: The aim of our study was to evaluate the associations between arterial stiffness indexes and immune-inflammatory markers in subjects with acute ischemic stroke with and without metabolic syndrome. Materials/Methods: We enrolled 130 patients with acute ischemic stroke and metabolic syndrome, 127 patients with acute ischemic stroke without metabolic syndrome and 120 control subjects without acute stroke. Applanation tonometry was used to record the augmentation index (Aix) and pulse wave velocity (PWV). We also evaluated plasma levels of C-reactive protein (CRP), Interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6) and Interleukin-10 (IL-10), E-selec…

Effects of transcranial random noise stimulation combined with Graded Repetitive Arm Supplementary Program (GRASP) on motor rehabilitation of the upper limb in sub-acute ischemic stroke patients: a randomized pilot study.

We evaluated the combined use of transcranial random noise stimulation (tRNS) with the Graded Repetitive Arm Supplementary Program (GRASP) in sub-acute ischemic stroke patients suffering from arm impairment. Eighteen ischemic stroke patients with upper limb disability were randomly assigned to either the GRASP + tRNS or GRASP + Sham stimulation group. Fugl-Meyer Assessment-Upper extremity (FMA-UE) was performed to evaluate upper limb impairment before treatment (T0), after the last stimulation (T1) and after 30 days (T2). At T1 and T2, beneficial effects in the tRNS group correlated with better FMA-UE score than sham stimulation group (p &lt; 0.001) and these results did not correlate to st…

Studies of selective TNF inhibitors in the treatment of brain injury from stroke and trauma: a review of the evidence to date

Antonino Tuttolomondo, Rosaria Pecoraro, Antonio Pinto Biomedical Department of Internal and Specialistic Medicine, University of Palermo, Palermo, Italy Abstract: The brain is very actively involved in immune-inflammatory processes, and the response to several trigger factors such as trauma, hemorrhage, or ischemia causes the release of active inflammatory substances such as cytokines, which are the basis of second-level damage. During brain ischemia and after brain trauma, the intrinsic inflammatory mechanisms of the brain, as well as those of the blood, are mediated by leukocytes that communicate with each other through cytokines. A neuroinflammatory cascade has been reported to be activ…

Immunoinflammatory activation of the acute phase as a possibile marker of acute ischemic stroke. is .

A particular bigeminy during atrial tachycardia.

The ECG shows clearly visible P waves only in lead V1 (Fig. 1). Regular PP intervals and an isoelectric baseline are present between the P waves, so the diagnosis is atrial tachycardia [1]. During the ECG recording, lead V1 shows 12 P waves but some of these are not visible because they are concealed by the QRS complex (Fig. 2). In lead V1, the beats following the long RR intervals are conducted by the first and the seventh P wave and the premature QRS complexes are conducted by the third and the ninth P wave because the fourth and the tenth P wave are too close to the following QRS complex to conduct the impulse. Consequently, the atrial tachycardia presents an alternating 2:1 and 4:1 cond…

Effects of intravenous furosemide plus small-volume hypertonic saline solutions on markers of heart failure.

Aims: We sought to compare the effects of furosemide + hypertonic saline solution (HSS) treatment in patients with acute decompensated heart failure in comparison with furosemide alone and the response in a compensated state after an acute saline load with regard to serum levels of heart failure biomarkers. Methods and results: We enrolled 141 patients with acute decompensated heart failure with reduced ejection fraction admitted to our Internal Medicine ward from March 2017 to November 2019. A total of 73 patients were randomized to treatment with i.v. high-dose furosemide plus HSS, whereas 68 patients were randomized to i.v. high-dose furosemide alone. Patients treated with furosemide plu…

Drug-related falls and thraumatic brain injury in very old patients: antithrombotic drugs as new potential culpruit factors

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The "Neurocentric" Approach to Essential Hypertension: How Reliable is the Paradigm of Hyperkinetic Hypertension? A Focus on the Sympathetic Nervous System Dysregulation in Essential Hypertensive Patients with Elevated Resting Heart Rate.

BACKGROUND: Clinic resting heart rate (RHR), is one of the cardiovascular parameters more easily measurable. In the general population RHR has been associated with total and cardiovascular mortality and higher rate of vascular events. OBJECTIVE: The case of essential hypertension is in some ways peculiar: in the past decades has often been attributed to hypertensive subjects higher values of RHR than healthy controls as a result of the effects of the different factors leading to the development of essential hypertension itself, first of all the presence of an increased tone of the sympathetic nervous system Methods: Several excellent articles debated the issue of autonomic dysfunction in es…

Changes in natriuretic peptide and cytokine plasma levels in patients with heart failure, after treatment with high dose of furosemide plus hypertonic saline solution (HSS) and after a saline loading

BACKGROUND AND AIMS: Neurohormonal activation and inflammation characterizes heart failure, relates to outcome, and is a therapeutic target. The aim of this study was to evaluate the effects of high-dose furosemide plus small-volume hypertonic saline solutions (HSS) on natriuretic peptides and immuno-inflammatory marker levels and to analyze, after treatment, the response to acute saline loading. METHODS AND RESULTS: 120 patients with heart failure treated with high-dose furosemide+HSS (Furosemide/HSS group) were matched with: 30 subjects with heart failure treated with high-dose furosemide (furosemide group), 30 controls with asymptomatic left-ventricular dysfunction (ALVD) (asymptomatic g…

Effects of clinical and laboratory variables and of pretreatment with cardiovascular drugs in acute ischaemic stroke: A retrospective chart review from the GIFA study

Background: Few studies have examined the role of cardiovascular drugs on acute ischaemic stroke prognosis. Aims: To evaluate the relationship between a favourable outcome in patients with acute ischaemic stroke and specific demographic, clinical and laboratory variables and cardiovascular drug pretreatment. Methods: The 1096 patients enrolled in the GIFA study (who had a main discharge diagnosis of ischaemic stroke) represent the final patient sample used in this analysis. Drugs considered in the analysis included angiotensin converting enzyme (ACE)-inhibitors, angiotensin II receptor blockers, statins, calcium channel blockers, anti-platelet drugs, vitamin K antagonists and heparins. The …

Reactive hyperemia index (RHI) and cognitive performance indexes are associated with histologic markers of liver disease in subjects with non-alcoholic fatty liver disease (NAFLD): a case control study

BACKGROUND: No study evaluated vascular health markers in subjects with non-alcoholic fatty liver disease (NAFLD) through a combined analysis of reactive hyperemia peripheral arterial tonometry (RH-PAT) and arterial stiffness indexes. AIM OF THE STUDY: We aimed to assess whether NAFLD and its histological severity are associated with impairment of arterial stiffness and RH-PAT indexes in a mixed cohort of patients with biopsy-proven NAFLD. MATERIALS AND METHODS: The Kleiner classification was used to grade NAFLD grade. Pulse wave velocity (PWV) and augmentation index (Aix) were used as markers of arterial stiffness, whereas endothelial function was assessed using reactive hyperemia index (R…

Cardiac Remodeling According to the Nocturnal Fall of Blood Pressure in Hypertensive Subjects: The Whole Assessment of Cardiac Abnormalities in Non-Dipper Subjects with Arterial Hypertension (Wacanda) Study

Objective: Several epidemiological studies suggest that the preservation of the physiological circadian rhythm of blood pressure or its disruption affects the extent of the organ damage developed by the patient. If we classify the circadian rhythm of blood pressure into four nocturnal profiles, significant differences emerge in terms of organ damage burden and prognosis: reverse dippers have the worst prognosis while dippers and mild dippers fall into an intermediate risk range. The risk profile of extreme dippers is still debated, and the available data are very conflicting and inconclusive. Starting from this gap of knowledge, we aimed to evaluate, retrospectively, in a cohort of hyperten…

Diabetic foot syndrome: Immune-inflammatory features as possible cardiovascular markers in diabetes

Diabetic foot ulcerations have been extensively reported as vascular complications of diabetes mellitus associated with a high degree of morbidity and mortality. Diabetic foot syndrome (DFS), as defined by the World Health Organization, is an "ulceration of the foot (distally from the ankle and including the ankle) associated with neuropathy and different grades of ischemia and infection". Pathogenic events able to cause diabetic foot ulcers are multifactorial. Among the commonest causes of this pathogenic pathway it's possible to consider peripheral neuropathy, foot deformity, abnormal foot pressures, abnormal joint mobility, trauma, peripheral artery disease. Several studies reported how …

Effect of Atrial Capture Beats on the Subsequent Cycle During Slow Common Atrioventricular Nodal Reentry Tachycardia

ELECTROCARDIOGRAPHIC FINDINGS IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS.

Management of Blood Pressure and Heart Rate in Patients with Acute Stroke

BACKGROUND: Stroke represent one of the most devastating of all neurological diseases, affecting about 15 million people per year and is an important cause of morbidity and mortality worldwide and currently the leading cause of adult disability in developed countries. Blood pressure and heart rate may undergo several modifications in patients with both ischemic and hemorrhagic stroke in fact raised blood pressure levels may lead to cerebral edema, hematoma expansion or hemorrhagic transformation and in contrast low blood pressure can lead to increased cerebral infarction or perihematomal ischemia. In addition, ECG abnormalities and cardiac arrhythmias, especially atrial fibrillation, are re…

Dexcription of the fourth case of Aceruloplasminemia found in Italy.

Prospective study of type 1 and type 2 diabetes and risk of stroke subtypes: the Nurses' Health Study: response to Janghorbani et al

QT Indexes in Cirrhotic Patients: Relationship with Clinical Variables and Potential Diagnostic Predictive Value.

Background and Aims A wide spectrum of cardiovascular changes characterizes cirrhosis, ranging from subclinical alterations to hyperkinetic syndrome. We looked for ECG markers of ventricular repolarization in a population of patients with cirrhosis in comparison to patients without cirrhosis and we investigated the relationship between these and other clinical and laboratory variables. Methods In 149 patients with cirrhosis and 152 controls, we measured QT maximum interval (QTmax), QT corrected interval (QTc), QT minimum interval (QTmin), QT dispersion (QTdisp), QT peak and T peak-to-end (TpTe). Results In subjects with cirrhosis, in comparison with controls, we observed a higher mean QTmax…

Non-Coding RNA Networks as Potential Novel Biomarker and Therapeutic Target for Sepsis and Sepsis-Related Multi-Organ Failure.

According to “Sepsis-3” consensus, sepsis is a life-threatening clinical syndrome caused by a dysregulated inflammatory host response to infection. A rapid identification of sepsis is mandatory, as the extent of the organ damage triggered by both the pathogen itself and the host’s immune response could abruptly evolve to multiple organ failure and ultimately lead to the death of the patient. The most commonly used therapeutic strategy is to provide hemodynamic and global support to the patient and to rapidly initiate broad-spectrum empiric antibiotic therapy. To date, there is no gold standard diagnostic test that can ascertain the diagnosis of sepsis. Therefore, once sepsis is suspected, t…

Role of Regular Physical Activity in Neuroprotection against Acute Ischemia

One of the major obstacles that prevents an effective therapeutic intervention against ischemic stroke is the lack of neuroprotective agents able to reduce neuronal damage; this results in frequent evolution towards a long-term disability with limited alternatives available to aid in recovery. Nevertheless, various treatment options have shown clinical efficacy. Neurotrophins such as brain-derived neurotrophic factor (BDNF), widely produced throughout the brain, but also in distant tissues such as the muscle, have demonstrated regenerative properties with the potential to restore damaged neural tissue. Neurotrophins play a significant role in both protection and recovery of function followi…

A case of infective colitis due to Yersinia enterocolitica complicated by microliver abscesses mimicking multiple liver occult metastases: a case report

Abstract Background We report an unusual case of infective colitis by Yersinia enterocolitica complicated by microliver abscesses mimicking multiple liver metastases in a 79 yr old female without any risk factors for bacteriaemia by this pathogen. Case presentation The patient was admitted to the Internal Medicine with Stroke Care ward of University Policlinico “P. Giaccone” in Palermo because of the appearance of diarrhoea. After the antimicrobial treatment for infective colitis, the clinicians observed a persistently increased white blood cells (WBC) count and multiple hepatic lesions; after having excluded any neoplastic disease and inflammatory bowel disease (IBD), blood cultures positi…

Recurrent venous thromboembolism complicated by heparin-induced thrombocytopenia as a first manifestation of an occult cancer: a case report.

Heparin-Induced Trombocytopenia (HIT) is a serious and potentially fatal complication of patients on heparins. Its management is difficult and it can be more complicated in patients with cancer because of the hemorrhagic risk carried out by direct inhibitor of thrombin, the currently approved drug for HIT. At present, it is not clear whether cancer patients also have an increased risk of HIT. We describe the case of a patient with occult cancer at the moment of the index venous thrombosis, who developed Deep Vein Thrombosis (DVT) and concomitant HIT with thrombotic complications (recurrent contralateral venous thrombosis). The management of HIT was efficaciously based on the combined use o…

Heart rate variability in sick sinus syndrome: does it have a diagnostic role?

BACKGROUND: Hypothesis of our study was that the irregular rhythm of sick sinus syndrome (SSS) was characterized by an augmented HRV. Objective was to assess whether SSS patients had a typical HRV profile. METHODS: We screened all 1947 consecutive Holter ECGs performed in our Units of Vascular Medicine and Internal Medicine and Cardioangiology at the University of Palermo (Italy) from April 2010 to September 2014. Among these, we selected 30 patients with ECG criteria of SSS. They were compared to 30 patients without SSS matched for age, sex and comorbidities. RESULTS: The SSS group had a lower mean heart rate (HR) (P=0.003), and a longer mean NN max-min longer (P&lt;0.0005) compared to con…

Neurotrophic and neuroprotective effects of muscle contraction

Background: Physical activity has been shown to be associated with reduced risk of coronary heart disease but the same effect seems to be produced in neurological diseases. Objective: In this review, we focused on the interplay between physical activity and some neurological conditions (Stroke, dementia, epilepsy, headache, Parkinson’ s disease, amyotrophic lateral sclerosis, multiple sclerosis, insomnia, depression and anxiety) with the aim of describing the potential role of physical activity in the prevention of such diseases and the physiological mechanisms involved in these processes. Results: Despite a growing body of evidence which reveals that physical activity is able to reduce the…

HLA and killer cell immunoglobulin-like receptor (KIRs) genotyping in patients with acute viral encephalitis

// Antonino Tuttolomondo 1 , Claudia Colomba 2 , Danilo Di Bona 6 , Alessandra Casuccio 4 , Domenico Di Raimondo 1 , Giuseppe Clemente 1 , Valentina Arnao 5 , Rosaria Pecoraro 1 , Paolo Ragonese 5 , Anna Aiello 3 , Giulia Accardi 3 , Rosario Maugeri 5 , Carlo Maida 1 , Irene Simonetta 1 , Vittoriano Della Corte 1 , Domenico Gerardo Iacopino 5 , Calogero Caruso 3 , Antonio Cascio 2 and Antonio Pinto 1 on behalf of KIRIIND (KIR Infectious and Inflammatory Diseases) Collaborative Group 1 U.O.C di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), Universita degli Studi di Palermo, Palermo, Italy 2 U.O.C di Malattie Infettive, Dipartiment…

Interferon lambda 4 rs368234815 TT&gt;δG variant is associated with liver damage in patients with nonalcoholic fatty liver disease

Background and Aims: The IFNL3/4 locus influencing innate immunity regulation has been associated with the severity of hepatitis and fibrosis progression during chronic hepatitis C infection, while contrasting results were reported in NAFLD. In this study, we examined whether rs12979860 and the linked causal rs368234815 variant encoding for the alternative IFNL4 protein variant are associated with liver fibrosis and damage in a large multicenter cohort of patients at risk of NASH. To clarify the mechanism, we also evaluated the impact on interferon-stimulated gene (ISG) hepatic expression in a subset of patients. Methods: We considered 946 consecutive Italian individuals at risk of NASH wit…

Developing drug strategies for the neuroprotective treatment of acute ischemic stroke

Developing new treatment strategies for acute ischemic stroke in the last twenty years has offered some important successes, but also several failures. Most trials of neuroprotective therapies have been uniformly negative to date. Recent research has reported how excitatory amino acids act as the major excitatory neurotransmitters in the cerebral cortex and hippocampus. Furthermore, other therapeutic targets such as free radical scavenger strategies and the anti-inflammatory neuroprotective strategy have been evaluated with conflicting data in animal models and human subjects with acute ischemic stroke. Whereas promising combinations of neuroprotection and neurorecovery, such as citicoline,…

Association between diabetes and stroke subtype on survival and functional outcome 3 months after stroke: data from the European BIOMED Stroke Project.

To the Editor: Regarding the study by Megherbi et al1 performed to evaluate stroke features, prognosis, and functional outcome in patients with diabetes compared with patients without diabetes, we would like to discuss some issues of potential interest: First, the authors analyzed diabetic patients classified in accordance with WHO diagnostic criteria for diabetes used in 1993 (fasting plasma glucose >140 mg/dL), so it is probably an underestimation of the number of diabetic subjects in the 4537 consecutive patients with ischemic stroke enrolled. Perhaps if they could have classified diabetic patients in accordance with American Diabetes Association (1997)2 criteria (fasting plasma glucose …

Angiotensin-converting enzyme gene deletion polymorphism determines an increase in frequency of migraine attacks in patients suffering from migraine without aura.

Many authors have reported an association between the angiotensin-converting enzyme (ACE)-D allele and coronary heart disease and other cardiovascular diseases. The mechanism underlying the positive associations between the ACE-D alleles and diseases are not yet clear. Previous reports showed an association between migraine without aura and ACE-D allele polymorphism. The study is aimed to evaluate if the DD genotype could also be associated with the frequency and duration of migraine without aura. In 302 patients suffering from migraine without aura (at least for 1 year), with no history of cardiovascular diseases and major risk factors for ischemic events, the genotypes of the ACE gene, pl…

Immunoinflammatory activation of the acute phase as a possibile marker of acute ischemic stroke.

MicroRNA and receptor mediated signaling pathways as potential therapeutic targets in heart failure.

Cardiac remodelling is a complex pathogenetic pathway involving genome expression, molecular, cellular, and interstitial changes that cause changes in size, shape and function of the heart after cardiac injury. Areas covered: We will review recent advances in understanding the role of several receptor-mediated signaling pathways and micro-RNAs, in addition to their potential as candidate target pathways in the pathogenesis of heart failure. The myocyte is the main target cell involved in the remodelling process via ischemia, cell necrosis and apoptosis (by means of various receptor pathways), and other mechanisms mediated by micro-RNAs. We will analyze the role of some receptor mediated sig…

The presence of White Matter Lesions is not associated with Non-alcoholic Fatty Liver Disease but with its histological severity

Endothelial Dysfunction and Inflammation in Ischemic Stroke Pathogenesis

: Stroke is a heterogeneous disease, and within the broad category of brain ischemia and its subtypes vary dramatically in its etiology. : The endothelium can regulate the vascular homeostasis by modulating processes of vascular dilation and constriction by producing and secreting cytokines and chemical mediators, and inflammation represents one of the most important factors that contribute to alteration in vessel structure and function by dysregulation of this fine balance. : Endothelial dysfunction means a basic determinant of the vascular damage, which can be identified in all different clinical subtypes of stroke, and, recently, it has been recognized as an interesting determinant of c…

Anderson-Fabry Disease: A Multiorgan Disease

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A . FD causes glycolipids, such as globotriaosylceramide (Gb3), to accumulate in the vascular endothelium of several organs (fig.2), including the skin, kidneys, nervous system, and heart, thereby triggering inflammation and fibrosis . These processes generally result in organ dysfunction, which is usually the first clinical evidence of FD. Patients with classic FD have various symptoms, eg, acroparesthesias, hypohidrosis, angiokeratomas, corneal opacities, cerebrovascular lesions, cardiac disorders, andrenal dysfunction.However, evolving knowledge about the natural course o…

CLINICAL COURSE OF NIMESULIDE-INDUCED LIVER INJURY

Epigenomics in acute cerebrovascular diseases.

Does sympathetic overactivation feature all hypertensives? Differences of sympathovagal balance according to night/day blood pressure ratio in patients with essential hypertension

When evaluating the 'night/day BP ratio', both hypertensives and normotensives can be arbitrarily classified into four groups: extreme dippers (ratio ⩽0.8), dippers (0.8<ratio ⩽0.9), mild dippers (0.9<ratio⩽1.0) and reverse dippers (ratio ⩾1.0). Reverse and mild dipper hypertensives have poorer prognoses compared with the physiological dipper profile, but the prognostic relevance of the extreme dipper profile remains uncertain. The evaluation of heart rate variability (HRV), obtained by 24-h Holter ECG monitoring, is the most frequently used noninvasive form of assessment of the activity of the autonomic nervous system. Reverse and mild dipper hypertensives have reduced HRV, indicating an o…

Aceruloplasminemia: a case report

Hereditary aceruloplasminemia is a rare autosomal recessive disease, firstly identified by Miyajima et al. in Japan in 1987 [1]. The disease is caused by the absence of an a2glycoprotein, the ceruloplasmin (Cp), a copper-containing ferroxidase, mainly synthesized in hepatocytes and widely expressed, including the central nervous system, which catalyses the oxidation of ferrous to ferric iron, a change required for release of iron to plasma transferrin [2]. It is hypothesized that in reticuloendothelial (RE) cells and hepatocytes Cp cooperates to export iron with the iron exporter protein ferroportin 1 (FPN1) [3]. As a consequence, Cp deficiency results in iron deposition in the liver, pancr…

Intravenous high dose furosemide plus small volume of hypertonic saline solution (HSS) versus seriated paracentesis in treatment of refractory ascites.

Editorial (Thematic Issue: New Therapeutic Targets in Clinical Medicine).

Atherosclerosis as an inflammatory disease.

In many ways, atherosclerosis is a chronic inflammatory disorder and this issue is confirmed by recent investigations of that have focused on inflammation, providing new insight into mechanisms of disease. Several recent studies have addressed the role of chemokines in leukocyte accumulation in atherosclerosis, extending our knowledge and understanding of the complex and cell type-specific functions of chemokines in atherosclerosis. Activated T-lymphocytes within the atherosclerotic vessel wall express the CD40 ligand surface molecule, known to play a major role in several immunological pathways. In addition to activated T-lymphocytes, functional CD40 and CD40L are coexpressed by human vasc…

Pathogenetic Mechanisms of Hypertension-Brain-Induced Complications: Focus on Molecular Mediators.

There is growing evidence that hypertension is the most important vascular risk factor for the development and progression of cardiovascular and cerebrovascular diseases. The brain is an early target of hypertension-induced organ damage and may manifest as stroke, subclinical cerebrovascular abnormalities and cognitive decline. The pathophysiological mechanisms of these harmful effects remain to be completely clarified. Hypertension is well known to alter the structure and function of cerebral blood vessels not only through its haemodynamics effects but also for its relationships with endothelial dysfunction, oxidative stress and inflammation. In the last several years, new possible mechani…

Una presentazione clinica atipica di appendicite acuta in un giovane con malposizione intestinale

Stroke as a target in medicinal chemistry and drug discovery.

Treatment of Anderson-Fabry Disease

Fabry disease is an X-linked disorder of glycosphingolipid metabolism that results in progressive accumulation of neutral glycosphingolipids, predominantly globotriaosylsphingosine (Gb3) in lysosomes, as well as other cellular compartments of several tissues, causing multi-organ manifestations (acroparesthesias, hypohidrosis, angiokeratomas, signs and symptoms of cardiac, renal, cerebrovascular involvement). Pathogenic mutations lead to a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA). In the presence of high clinical suspicion, a careful physical examination and specific laboratory tests are required. Finally, the diagnosis of Fabry’s disease is confirmed by the demonstrat…

Anderson‐Fabry Disease: A Rare Cause of Levodopa‐Responsive Early‐Onset Parkinsonism

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Cardiovascular risk profile and morbidity in subjects affected by type 2 diabetes mellitus with and without diabetic foot

Diabetic foot syndrome (DFS) is the most frequent cause of hospitalization of diabetic patients and one of the most economically demanding complications of diabetes. People with diabetes have been shown to have higher mortality than people without diabetes. On this basis, the aim of our study was to evaluate the possible role of diabetic foot as a cardiovascular risk marker in patients with type 2 diabetes mellitus. We enrolled 102 consecutive patients with type 2 diabetes mellitus with diabetic foot and 123 patients with type 2 diabetes mellitus without limb lesions to compare the prevalence of main cardiovascular risk factors, subclinical cardiovascular disease, previous cardiovascular mo…

An atypical clinical presentation of acute appendicitis in a young man with midgut malrotation

Abstract Midgut malrotation occurs as a result of failure in normal intestinal rotation and fixation during early pregnancy. Pathological conditions reported in the literature involving midgut malrotation predominantly relate to infants and children. In adults malrotation is often revealed as an incidental finding on computed tomography (CT), or the associated altered anatomy can be the cause of atypical clinical symptoms of relatively common intestinal disorders. An unusual presentation of acute appendicitis, with fever and recurrent pain in left iliac fossa is reported. Underlying intestinal malrotation delayed the correct clinical diagnosis of acute appendicitis. It was not until a CT sc…

Immuno-inflammatory and thrombotic/fibrinolytic variables associated with acute ischemic stroke diagnosis.

Abstract Introduction Accumulating evidence suggests that inflammation plays an important role in the development of acute cerebrovascular disease. The aim of this study is to evaluate the predictive value of a series of candidate serum immuno-inflammatory and thrombotic/fibrinolitic molecules towards diagnosis of acute ischemic stroke. Materials and methods We enrolled 120 consecutive patients with a diagnosis of acute ischemic stroke and 123 consecutive hospitalized control patients without a diagnosis of acute ischemic stroke. We evaluated plasma levels of IL-1β, TNF-β, IL-6 and IL-10, E-selectin, P-selectin, sICAM-1 and sVCAM-1 as markers of immuno-inflammatory activation, vWF plasma le…

A case control study between diabetic and non-diabetic subjects with ischemic stroke

Immunoinflammatory activation of the acute phase of ischemic stroke in relation to time of symptom onset, diabetic state and diagnostic subtype.

“The importance of being external”: review of the literature of the rare phenomenon of common carotid occlusion with bulb reverse-crossed stenosis and external collaterals activation. Is still correct speaking about carotid steal?

Common carotid artery occlusion (CCAO) is a rare phenomenon associated with the development of neurological symptoms. In CCAO, diversion of blood flow from the external carotid artery (ECA) to the internal carotid artery (ICA) via the carotid bulb (CB) may occur. This pathway activation has been called "carotid steal". Starting from a particular case we describe the ECD finding of a complete occlusion of CCA with patency of ICA and ECA. In case of occlusion of CCA, inversion of the ECA flow may occur, towards the ICA, and it can be damped by a significant stenosis crossed in retrograde direction that may concur to maintain the pressure balance between the two circulations. Usually, this par…

Immunoinflammatory activation of the acute phase of ischemic stroke in relation to time of symptoms onset, diabetic state and diagnostic subtype.

Immunoinflammatory and thrombotic/ fibrinolytic markers as a diagnostic panel of caute ischemic stroke

redictors of outcome in acute ischemic cerebrovascular syndromes: The GIFA Study

Livelli sierici di citochine infiammatorie, selectine e molecole di adesione nella fase acuta dell’ictus lacunare e non lacunare: relazione con il tempo di comparsa dei sintomi e con il diabete.

Un caso complesso di tromboembolismo venoso. ;

Mediterranean Diet Adherence and Congestive Heart Failure: Relationship With Clinical Severity and Ischemic Pathogenesis

Abstract Objectives To our knowledge, no study has addressed the relationship between adherence to a Mediterranean diet style and severity of heart failure. The aim of this retrospective study was to evaluate the relationship between adherence to the Mediterranean diet assessed using the calculation of Mediterranean diet score and congestive heart failure (CHF), its severity, and pathogenesis. Methods We analyzed charts and collected data of all consecutive patients with a diagnosis of CHF at admission to our Internal Medicine Ward from 2008 to 2014. Results We analyzed 209 patients with CHF and 200 controls. Patients with CHF showed a significantly lower mean MeDi score than controls. At r…

Old and New Drugs for Treatment of Advanced Heart Failure.

Background: Advanced heart failure (HF) is a progressive disease with high mortality and limited medical therapeutic options. Long-term mechanical circulatory support and heart transplantation remain goldstandard treatments for these patients; however, access to these therapies is limited by the advanced age and multiple comorbidities of affected patients, as well as by the limited number of organs available. Methods: Traditional and new drugs available for the treatment of advanced HF have been researched. Results: To date, the cornerstone for the treatment of patients with advanced HF remains water restriction, intravenous loop diuretic therapy and inotropic support. However, many patien…

Chronic hyponatremia in a patient with renal salt wasting and without cerebral disease: relationship between RSW, risk of fractures and cognitive impairment

Renal salt wasting syndrome (RSW) is defined as a renal loss of sodium leading to hyponatremia and a decrease in extracellular fluid volume (ECV). Differentiation of this disorder from the syndrome of inappropriate antidiuretic hormone secretion (SIADH), a common cause of hyponatremia, can be difficult because both can present with hyponatremia and concentrated urine with natriuresis. Our clinical case about a 78-year-old woman with a recent fracture of the right femur not only confirms that this syndrome can occur in patients without intracranial pathologies (CT documented), but depicts how the hyponatremia caused by RSW can show a chronic, oscillating course. This is an interesting point …

Effects of Mediterranean Diet Combined with CrossFit Training on Trained Adults’ Performance and Body Composition

CrossFit is a high-intensity training discipline increasingly practiced in recent years. Specific nutritional approaches are usually recommended to maximize performance and improve body composition in high-intensity training regimens; notwithstanding, to date there are no targeted nutritional recommendations for CrossFit athletes. The Mediterranean Diet (MD) is a diet approach with a well-designed proportion of macronutrients, using only available/seasonal food of the Mediterranean area, whose health benefits are well demonstrated. No studies have evaluated this dietary strategy among CrossFit athletes and practitioners; for this reason, we tested the effects of 8 weeks of MD on CrossFit at…

Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus in refractory congestive heart failure: long-term effects.

Background Diuretics have been accepted as first-line treatment in refractory congestive heart failure (CHF), but a lack of response to them is a frequent event. A randomized, single-blind study was performed to evaluate the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) infusion in the treatment of refractory New York Heart Association (NYHA) class IV CHF and a normosodic diet during follow-up. Materials and Methods One hundred seven patients (39 women and 68 men, age range 65-90 years) with refractory CHF (NYHA class IV) of different etiologies, who were unresponsive to high oral doses of furosemide, angiotensin-converting enzyme inhib…

Diabetes and Ischemic Stroke: An Old and New Relationship an Overview of the Close Interaction between These Diseases

Diabetes mellitus is a comprehensive expression to identify a condition of chronic hyperglycemia whose causes derive from different metabolic disorders characterized by altered insulin secretion or faulty insulin effect on its targets or often both mechanisms. Diabetes and atherosclerosis are, from the point of view of cardio- and cerebrovascular risk, two complementary diseases. Beyond shared aspects such as inflammation and oxidative stress, there are multiple molecular mechanisms by which they feed off each other: chronic hyperglycemia and advanced glycosylation end-products (AGE) promote ‘accelerated atherosclerosis’ through the induction of endothelial damage and cellular dysfunction. …

Fattori predittivi della prognosi nelle sindromi cerebrovascolari acute: lo studio GIFA

Efficacy of dulaglutide on vascular health indexes in subjects with type 2 diabetes: a randomized trial

Abstract Background Recent cardiovascular outcome trials have shown significant reductions in major cardiovascular (CV) events with glucagon-like peptide (GLP)-1 receptor agonists. Additionally, adjunctive surrogates for cardiovascular risk validated by some studies include arterial stiffness and endothelial function indexes. To date, no randomized trial has addressed the possible effects of antidiabetic interventional drugs such as GLP1 agonists on endothelial and arterial stiffness indexes as surrogate markers of vascular damage. Aims We aimed to evaluate metabolic efficacy and surrogate vascular efficacy endpoints of once-weekly dulaglutide (1.5 mg) plus traditional antidiabetic treatmen…

Twenty-Four Hour Ambulatory Blood Pressure Monitoring to Evaluate Effects on Blood Pressure of Physical Activity in Hypertensive Patients

OBJECTIVE: Elevated blood pressure is an important risk factor for cardiovascular disease and stroke. Several studies have demonstrated that physical exercise reduces blood pressure levels in hypertensive subjects and improves control of several well-known risk factors for atherosclerosis such as diabetes mellitus, blood lipid profile and obesity. Our group attempted to evaluate if an exercise program based on periodic controlled fast walking sessions would reduce blood pressure levels in hypertensive subjects. DESIGN: We enrolled hypertensive subjects not suffering from obesity (Body Mass Index <30) already under pharmacological therapy; in these subjects we performed a six-week program of…

Hepatitis C Virus Eradication by Direct Antiviral Agents Improves Carotid Atherosclerosis in patients with Severe Liver Fibrosis.

Abstract BACKGROUND AND AIM: Recent studies suggest an association between HCV infection and cardiovascular damage, including carotid atherosclerosis, with a possible effect of HCV clearance on cardiovascular outcomes. We aimed to examine whether HCV eradication by direct antiviral agents (DAA) improves carotid atherosclerosis in HCV-infected patients with advanced fibrosis/compensated cirrhosis. MATERIALS AND METHODS: One hundred eighty-two consecutive HCV patients with advanced fibrosis or compensated cirrhosis were evaluated by virological, anthropometric and metabolic measurements. All patients underwent DAA-based antiviral therapy according to AISF/EASL guidelines. Intima-media thickne…

Distribution of KIR Genes and Their HLA Ligands in Different Viral Infectious Diseases: Frequency Study in Sicilian Population

Natural killer (NK) cells play a role in defence against viral infections by killing infected cells or by producing cytokines and interacting with adaptive immune cells. Killer immunoglobulin-like receptors (KIRs) regulate the activation of NK cells through their interaction with human leucocyte antigens (HLA). Ninety-six Sicilian patients positive to Human Immunodeficiency Virus-1 (HIV) and ninety-two Sicilian patients positive to SARS-CoV-2 were genotyped for KIRs and their HLA ligands. We also included fifty-six Sicilian patients with chronic hepatitis B (CHB) already recruited in our previous study. The aim of this study was to compare the distribution of KIR–HLA genes/groups of these t…

Are the Myokines the Mediators of Physical Activity-Induced Health Benefits?

BACKGROUND: The concept of the muscle as a secretory organ, developed during the last decades, partially answers to the issue of how the crosstalk between skeletal muscle and distant tissues happens. The beneficial effects of exercise transcend the simple improved skeletal muscle functionality: systemic responses to exercise have been observed in distal organs like heart, kidney, brain and liver. Increasing data have accumulated regarding the synthesis, the kinetics of release and the biological roles of muscular cytokines, now called myokines. The most recent techniques have meaningfully improved the identification of the muscle cell secretome, but several issues regarding the extent of se…

P1030 : The presence of white matter lesions is not associated with non-alcoholic fatty liver disease but with its histological severity

Commentary: Anderson‐Fabry Disease: A Rare Cause of Levodopa‐Responsive Early Onset Parkinsonism

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L’ictus lacunare

Immunoinflammatory predictors of stroke in patients with chronic non valvular atrial fibrillation (NVAF).