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PURPOSE: Status epilepticus (SE) is defined by abnormally prolonged seizures that may lead to brain damage and death. Our aim was to evaluate the efficacy and tolerability (effectiveness) of intravenous brivaracetam (BRV) as a second-line treatment. METHODS: Twenty-one patients (median age 68 years ± 17.28) were prospectively recruited between June 2019 and December 2022. Patients were treated with BRV (50-200 mg) as a second-line add-on therapy for SE. We evaluated the response of SE to the administration of BRV in terms of SE termination and recurrence of epileptic seizures at 6, 12, and 24 h, also monitoring safety. The first-line therapy was represented by intravenous benzodiazepines (mainly diazepam). RESULTS: Almost a quarter of patients had generalized seizures, whereas the vast majority (76.2%) presented focal seizures. In 52.4% of patients, the underlying cause was cerebrovascular. Fourteen (66.7%) patients displayed a good early response in the subsequent 6 h. At 12 and 24 h, 8 (38%) and 11 (52.4%) patients, respectively, did not present seizures. CONCLUSION: The present study highlights the potential of BRV when used as an early add-on therapy in SE, further confirming its good safety profile.
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Anticonvulsivantes , Estado Epiléptico , Humanos , Idoso , Anticonvulsivantes/efeitos adversos , Resultado do Tratamento , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/induzido quimicamente , Convulsões/tratamento farmacológico , Pirrolidinonas/efeitos adversos , Quimioterapia CombinadaRESUMO
INTRODUCTION AND OBJECTIVES: Identification of asymptomatic hepatitis B virus (HBV) and hepatitis C virus (HCV) carriers is fundamental to reach the World Health Organization objective to eradicate viral hepatitis. The aim of this study was to evaluate the HBV and HCV prevalence among patients hospitalized for a non-liver-related disease but showing increased liver enzyme values. PATIENTS AND METHODS: All consecutive patients without history of hepatic disease but showing increased amino-transferase and/or gamma-glutamil-transpeptidase levels at admission to the Internal Medicine and Surgery divisions of the Messina University Hospital from 1st January to 31st December 2019 ("study group") were tested for HBV surface antigen (HBsAg) and anti-HCV antibody. Analogously, HBsAg and anti-HCV were tested for in all the individuals with normal liver enzyme values consecutively admitted from October 1st to December 31st, 2019 ("control group"). RESULTS: Of the 332 "study group" patients, 13 (3.9%) were anti-HCV positive versus 5/306 (1.6%) patients of the "control group" (p=0.008). HCV RNA was detected in 11/13 and in 0/5 anti-HCV patients of the "study group" and "control group", respectively (p=0.001). HBsAg was detected in 5 (1.5%) "study group" patients and in none of the "control group" (p=0.03). Prevalence of diabetes, arterial hypertension, and dyslipidaemia was comparable between the two groups, whereas 75/332 (22.3%) patients of the "study group" and 34/306 (11.1%) patients of the "control group" drank > 2 alcohol units/day (p < 0.001). CONCLUSION: Testing HBsAg and anti-HCV in subjects showing increased liver enzyme values may represent an efficacious tool to identify asymptomatic carriers of hepatitis virus infections.
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Hepatite B , Hepatite C , Hepacivirus/genética , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Anticorpos Anti-Hepatite C , Humanos , PrevalênciaRESUMO
An acute metabolic complication of diabetes mellitus, especially type 1, is diabetic ketoacidosis (DKA), which is due to an increase in blood ketone concentrations. Sodium/glucose co-transporter-2 inhibitor (SGLT2-i) drugs have been associated with the occurrence of a particular type of DKA defined as euglycemic (euDKA), characterized by glycemic levels below 300 mg/dL. A fair number of euDKA cases in SGLT2-i-treated patients have been described, especially in the last few years when there has been a significant increased use of these drugs. This form of euDKA is particularly insidious because of its latent onset, associated with unspecific symptomatology, until it evolves (progressing) to severe systemic forms. In addition, its atypical presentation can delay diagnosis and treatment. However, the risk of euDKA associated with SGLT2-i drugs remains relatively low, but it is essential to promptly diagnose and manage it to prevent its serious life-threatening complications. In this narrative review, we intended to gather current research evidence on SGLT2i-associated euDKA from randomized controlled trials and real-world evidence studies, its diagnostic criteria and precipitating factors.
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BACKGROUND: Fever is one of the most frequent symptoms highlighted during medical assistance. Due to this great impact, our study has the purpose of analyzing the demographic and laboratory characteristics of patients hospitalized in our center and identifying predictive markers to make the differential diagnosis between infectious and non-infectious fever. METHODS: Our population included 220 children, collected from January 2017 to August 2022, hospitalized for continuous fever (4 days or more in duration with at least one temperature peak ≥37.5 °C) and excluded cases of discharge against medical advice and/or transfer to other operating units. Demographic (mean age at the time of admission, frequency of hospitalization, and mean days of hospitalization), laboratory, and instrumental variables were analyzed in order to find correlation with fever etiology. RESULTS: Older age at the time of hospitalization, family history of periodic fever, fever lasting more than 8 days, and longer hospitalization are strongly associated with non-infectious fever, together with anemia, high platelet count, high CRP and ferritin, and hyponatremia at the time of admission. Paracetamol is the preferred antipyretic treatment. Echocardiogram has shown anomalies in patients with infectious fever, while ECG anomalies were detected in non-infectious fever. CONCLUSIONS: Our data underline the importance of predictive markers, such as clinical and laboratory parameters, to differentiate infectious from non-infectious fevers, but further studies are necessary.
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BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a highly frequent condition in patients with type 2 diabetes (T2D), but the identification of subjects at higher risk of developing the more severe forms remains elusive in clinical practice. The aim of this study was to evaluate the occurrence and severity of liver fibrosis and its predictive factors in T2D outpatients without a known history of chronic liver disease by using recommended non-invasive methods. METHODS: Consecutive T2D outpatients underwent a set of measurements of clinical and laboratory parameters, FIB-4 score (Fibrosis-4 index), and liver stiffness with controlled attenuation-parameter (CAP) performed by transient elastography (FibroScan) after excluding previous causes of liver disease. RESULTS: Among the 205 T2D outpatients enrolled in the study (median age: 64 years, diabetes duration: 11 years, HbA1c: 7.4%, and BMI: 29.6 kg/m2), 54% had high ALT and/or AST levels, 15.6% had liver stiffness value > 10.1 kPa (severe fibrosis), 55.1% had CAP values > 290 dB/m (severe steatosis), and FIB-4 score was >2 in 11.2% of subjects (>2.67 in 15 subjects). Moreover, 49 (23.9%) T2D patients had clinically meaningful liver harm, with either a FIB-4 score > 2 and/or FibroScan > 10.1 kPa. At regression analysis, BMI, HbA1c, creatinine, and triglycerides values were independent predictors of liver fibrosis. CONCLUSIONS: Liver fibrosis is a frequent finding in T2D outpatients without a known history of liver disease, especially in those with obesity, hypertriglyceridemia, worse glycemic control, and high creatinine levels.
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BACKGROUND: Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic and disabling diseases that affect patient health-related quality of life (HRQoL). IBD patients are frequently exposed to high levels of stress and psychological distress. Biological drugs have been proven to reduce inflammation, hospitalization, and most of the complications that characterize IBDs; their potential contribution to patients' HRQoL remains to be explored. AIM: To evaluate and compare any change in the HRQoL and markers of inflammation in IBD patients undergoing biological drugs (infliximab or vedolizumab). MATERIAL AND METHODS: A prospective observational study was conducted on a cohort of IBD patients, aged >18 years, who were prescribed with infliximab or vedolizumab. Demographic and disease-related data at baseline were collected. Standard hematological and clinical biochemistry parameters, including C-reactive protein (CRP), white blood cells count (WBC), erythrocytes sedimentation rate (ESR), and α1 and α2 globulins were measured after a 12-h fast at baseline (T0), after 6 weeks (T1), and at 14 weeks (T2) of biological treatment. Steroid use, disease activity as measured by the Harvey-Bradshaw index (HBI) and partial Mayo score (pMS) for the CD and UC, respectively, were also recorded at each timepoint. The Short Form 36 Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT-F), and Work Productivity and Activity Impairment-General Health Questionnaire (WPAI:GH) were administered to each patient at baseline, T1, and T2 to address the study aims. RESULTS: Fifty eligible consecutive patients (52% with CD and 48% with UC) were included in the study. Twenty-two patients received infliximab and twenty-eight received vedolizumab. We noted a significant reduction in the CRP, WBC, α1, and α2 globulins from T0 to T2 (p = 0.046, p = 0.002, p = 0.008, and p = 0.002, respectively). Participants showed a significant decrease in steroid administration during the observation period. A significant reduction in the HBI of CD patients at all three timepoints and a similarly significant decrease in the pMS of UC patients from baseline to T1 were recorded. Statistically significant changes were observed in all questionnaires during follow-up as well as an overall improvement in the HRQoL. The interdependence analysis carried out between the biomarkers and the scores of the individual subscales showed a significant correlation between the variation (Δ) of the CRP, Hb, MCH, and MCV with physical and emotional dimensions of the SF-36 and FACIT-F tools; work productivity loss expressed by some of the WPAI:GH items negatively correlated with the ΔWBC and positively with the ΔMCV, ΔMCH, and Δ α1 globulins. A sub-analysis according to the type of treatment showed that patients receiving infliximab experienced a more pronounced improvement in their HRQoL (according to both SF-36 and FACIT-F) compared with patients receiving vedolizumab. CONCLUSIONS: Both infliximab and vedolizumab played an important role in contributing to the improvement of the HRQoL in IBD patients by also reducing inflammation and, consequently, steroid use in patients with an active disease. HRQoL, being one of the treatment goals, should also be assessed when taking charge of IBD patients to assess their clinical response and remission. The specific correlation between the biomarkers of inflammation and life's spheres, as well as their possible role as clinical markers of HRQoL, should be further investigated.
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BACKGROUND: Endocan is a soluble dermatan sulfate proteoglycan (50 kDa) secreted by endothelial cells and expressed by dermal, coronary, pulmonary and adipose tissue microvasculature. It plays an important role in the pathogenesis of vascular disorders, inflammatory state, endothelium dysfunction and neoangiogenesis. Aims of the study were to compare fasting serum endocan levels between children with obesity and healthy controls and to investigate the relationships between endocan, body mass index (BMI) and other indices of cardiometabolic risk. METHODS: This single-center, observational, retrospective study included 19 pediatric patients with obesity aged 11.94 ± 0.52 years and 19 lean matched controls. Each patient underwent clinical and auxological examination and laboratory investigations including routine organs function tests and lipid profile. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Fasting endocan serum levels were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared to healthy subjects, serum endocan levels were found to be significantly upraised in children with obesity. Endocan resulted significantly correlated with insulin levels (rho 0.47; p = 0.04); in addition, an association with HOMA-IR values with a trend toward the statistical significance (rho 0.43; p = 0.07) was found. No significant correlation with fasting blood glucose values and lipid serum levels was demonstrated. Although not statistically significant, a correlation between endocan and the presence and grading of liver steatosis on ultrasound (rho 0.51; p = 0.08 and rho 0.51; p = 0.08, respectively) was found. CONCLUSIONS: These findings confirm the association between endothelial damage and insulin resistance in children with obesity. Endocan could be used as a biomarker of early endothelial dysfunction in children with obesity and could be a valid predictor of future cardiovascular risk in adulthood.
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Doenças Cardiovasculares , Resistência à Insulina , Humanos , Criança , Doenças Cardiovasculares/diagnóstico , Células Endoteliais , Estudos Retrospectivos , Fatores de Risco , Biomarcadores , Fatores de Risco de Doenças Cardíacas , LipídeosRESUMO
Chronic inflammation represents the cornerstone of the raised cardiovascular (CV) risk in patients with inflammatory rheumatic diseases (IRD), including vasculitis. Standardized mortality ratios in these patients are higher as compared to the general population, and the excess of premature mortality is due to early atherosclerotic events. Thus, IRD patients need appropriate CV risk assessment and management according to this CV disease (CVD) burden. Adequate control of CV risk is still lacking in usual care, but early diagnosis of silent and subclinical CVD is crucial to improve the long-term prognosis of these patients. Increased arterial stiffness may provide a pathophysiological link between inflammation and increased cardiovascular risk. Several noninvasive methods are now available to estimate artery stiffness in the clinical setting, including pulse wave velocity assessment. The independent predictive value of arterial stiffness for cardiovascular events has been demonstrated in general as well as in selected populations, and reference values adjusted for age and blood pressure have been suggested. Thus, arterial stiffness is an interesting biomarker for cardiovascular risk stratification. This systematic review summarizes the additional value that PWV measurement can provide in the setting of vasculitis, with a focus in the different clinical stages and CV risk prevention. This systematic review is registered with registration number: Prospero CRD42021259603.
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Background: Circulating CD34+ progenitor cells (CD34+CPCs) are characterized by pronounced tissue regeneration activity. Dyslipidemic subjects seemed to have reduced CD34+CPCs, and statin therapy appeared to restore their levels. We aimed to evaluate the effects of PCSK9 inhibitors (PCSK9-i) on CD34+CPCs and pulse wave velocity (PWV) in a cohort of heterozygous familial hypercholesterolemia (HeFH) subjects. Methods: We determined CD34+ cell count and its change after PCSK9-i in 30 selected HeFH subjects and 30 healthy controls. Lipid profile and PWV were evaluated at baseline (T0), 6 months after intensive lipid lowering strategy (statin plus ezetimibe, T1), and after 6 months of optimized therapy with PCSK9-i (T2); CD34+ cell count was reported at T1 and T2. Results: At T1, the median value of CD34+ cells was not significantly different between HeFH subjects and controls, and the same result was obtained at T2. PWV was significantly reduced at T1 (ΔPWV − 14.8%, p < 0.001 vs. T0) and T2 (ΔPWV − 10.96%, p < 0.001 vs. T1). Dividing HeFH subjects into two groups of high- and low-CD34+ cell count, CD34+CPCs appeared to be polarized with a significant difference between the two groups (1.2 (0.46) vs. 4.74 (1.92), p < 0.001), also with respect to controls (both p < 0.001). This polarization was no longer observed at T2, and neither with respect to controls. ΔCD34+ was +67.4% in the low-CD34+ group and −39.24% in the high-CD34+ group (p < 0.001). Lastly, we found a significant correlation between ΔCD34+ cell number and ΔPWV in HeFH subjects (rho = −0.365, p < 0.05), particularly in the low-CD34+ group (rho = −0.681, p < 0.001). Conclusion: PCSK9-i exhibited favorable effects on CD34 + CPCs as was on PWV values in a cohort of FH subjects. Our preliminary findings suggest a possible positive role of this novel lipid-lowering strategy on vascular homeostasis.
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Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a key regulator of low-density lipoprotein (LDL) metabolism involved in the degradation of the low-density lipoprotein receptor (LDLR) through complex mechanisms. The PCSK9 plasma levels change according to lipid lowering therapy (LLT). Few data exist regarding the role of PCSK9 in vascular damage. We aimed to evaluate the impact of PCSK9 plasma levels on pulse wave velocity (PWV) and the effect of PCSK9 inhibitors (PCSK9-i) on circulating PCSK9 and PWV in a cohort of heterozygous familial hypercholesterolemia (HeFH) subjects. In a previous step, HeFH patients were enrolled and LLT was prescribed according to guidelines. Biochemical analyses and PWV assessment were performed at baseline (T0), after 6 months of high-efficacy statin plus ezetimibe (T1) and after 6 months of PCSK9-i (T2). The PCSK9 levels were evaluated in 26 selected HeFH subjects at the three time points and 26 healthy subjects served as controls for the reference value for PCSK9 plasma levels. The PWV values decreased at each time point in HeFH subjects after LLT starting (8.61 ± 2.4 m/s, −8.7%; p < 0.001 vs. baseline at T1, and 7.9 ± 2.1 m/s, −9.3%; p < 0.001 vs. both T1 and baseline) and it was correlated to PCSK9 (r = 0.411, p = 0.03). The PCSK9 levels increased on statin/EZE therapy (+42.8% at T1) while it decreased after PCSK9-i was started (−34.4% at T2). We noted a significant relationship between PCSK9 levels and PWV changes at T1 and T2. In conclusion, PCSK9 levels were associated with baseline PWV values in HeFH subjects; moreover, we found that PCSK9 level variations seemed to be correlated with PWV changes on LLT. A longer observation time and wider sample size are needed to assess the potential role of PCSK9 plasma levels on the vascular function and remodelling, and to clarify the effects of PCSK9-i in these pathways.
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Aterosclerose , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipoproteinemia Tipo II , Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Lipoproteínas LDL , Inibidores de PCSK9/uso terapêutico , Pró-Proteína Convertase 9/sangue , Análise de Onda de PulsoRESUMO
Familial combined hyperlipidemia (FCH) is a very common inherited lipid disorder, characterized by a high risk of developing cardiovascular (CV) disease and metabolic complications, including insulin resistance (IR) and type 2 diabetes mellitus (T2DM). The prevalence of non-alcoholic fatty liver disease (NAFLD) is increased in FCH patients, especially in those with IR or T2DM. However, it is unknown how precociously metabolic and cardiovascular complications appear in FCH patients. We aimed to evaluate the prevalence of NAFLD and to assess CV risk in newly diagnosed insulin-sensitive FCH patients. From a database including 16,504 patients, 110 insulin-sensitive FCH patients were selected by general practitioners and referred to the Lipid Center. Lipid profile, fasting plasma glucose and insulin were determined by standard methods. Based on the results of the hospital screening, 96 patients were finally included (mean age 52.2 ± 9.8 years; 44 males, 52 females). All participants underwent carotid ultrasound to assess carotid intima media thickness (cIMT), presence or absence of plaque, and pulse wave velocity (PWV). Liver steatosis was assessed by both hepatic steatosis index (HSI) and abdomen ultrasound (US). Liver fibrosis was non-invasively assessed by transient elastography (TE) and by fibrosis 4 score (FIB-4) index. Carotid plaque was found in 44 out of 96 (45.8%) patients, liver steatosis was found in 68 out of 96 (70.8%) and in 41 out of 96 (42.7%) patients by US examination and HSI, respectively. Overall, 72 subjects (75%) were diagnosed with steatosis by either ultrasound or HSI, while 24 (25%) had steatosis excluded (steatosis excluded by both US and HSI). Patients with liver steatosis had a significantly higher body mass index (BMI) compared to those without (p < 0.05). Steatosis correlated with fasting insulin (p < 0.05), liver stiffness (p < 0.05), BMI (p < 0.001), and inversely with high-density lipoprotein cholesterol (p < 0.05). Fibrosis assessed by TE was significantly associated with BMI (p < 0.001) and cIMT (p < 0.05); fibrosis assessed by FIB-4 was significantly associated with sex (p < 0.05), cIMT (p < 0.05), and atherosclerotic plaque (p < 0.05). The presence of any grade of liver fibrosis was significantly associated with atherosclerotic plaque in the multivariable model, independent of alcohol habit, sex, HSI score, and liver stiffness by TE (OR 6.863, p < 0.001). In our cohort of newly diagnosed, untreated, insulin-sensitive FCH patients we found a high prevalence of liver steatosis. Indeed, the risk of atherosclerotic plaque was significantly increased in patients with liver fibrosis, suggesting a possible connection between liver disease and CV damage in dyslipidemic patients beyond the insulin resistance hypothesis.
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OBJECTIVE: The aim of this study was to evaluate the outcomes of through-the-scope (TTS) large diameter self-expanding metal stent (SEMS) placement for palliation of malignant colorectal obstruction. MATERIAL AND METHODS: Between January 2005 and December 2009, all patients who underwent endoscopic SEMS placement for palliation of malignant colorectal obstruction were prospectively enrolled. RESULTS: Thirty-nine patients (17M and 22F; mean age 75.9 ± 10.6 years, range 50-91) were enrolled. The most frequent location was the sigmoid colon (13 cases). The causes of obstruction were colorectal malignancy in 32 patients and extracolonic malignancy in 7. Technical success was achieved in 36/39 patients (92.3%) and clinical success in 35/39 patients (89.7%). Technical failure was related to female sex (p = 0.04) and the extracolonic etiology of the stricture (p < 0.001). There were three early complications: two procedure-related perforations successfully managed conservatively and one hemorrhage treated with APC. Early complications were related to the location of strictures at the recto-sigmoid junction (p < 0.001). Late complications occurred in 10 patients: 8 of these patients experienced occlusive symptoms (attributable to tumor ingrowth in 5 cases and stool impaction in 3 cases); the remaining 2 were one case of tumor ingrowth with sub-occlusive symptoms and hemorrhage, and one case of distal migration. There was no procedure-related mortality and all complications were managed without surgical intervention. SEMS patency duration was 236 ± 128 days (range 31-497) and mean survival of the patients was 259 ± 121 days (range, 32-511). CONCLUSIONS: In our experience, TTS large-diameter SEMS placement is a safe and effective treatment for palliation of malignant colorectal obstruction.
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Doenças do Colo/terapia , Endoscopia Gastrointestinal , Obstrução Intestinal/terapia , Neoplasias/complicações , Cuidados Paliativos , Stents , Idoso , Idoso de 80 Anos ou mais , Doenças do Colo/etiologia , Endoscopia Gastrointestinal/efeitos adversos , Feminino , Humanos , Obstrução Intestinal/etiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Stents/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Systemic sclerosis (SSc) is characterized by early vasculopathy and fibrosis in the skin, lungs, and other tissues. Vascular manifestations of SSc include Raynaud's phenomenon, digital ulcers, and pulmonary artery hypertension (PAH). PAH is the second most common cause of mortality in SSc. Circulating CD34+ cells associated with cardiovascular health status in several conditions, including chronic immune-inflammatory disease. CD34+ cell numbers have been found inconstantly reduced in SSc. Endocan, a proteoglycan expressed by endothelial cells, was recently suggested as a marker of vascular stress. We tested the relationships among CD34+ cells, endocan, inflammatory markers, vitamin D levels, and clinical parameters in SSc patients with PAH. METHODS: Standard echocardiography was performed. Vitamin D levels, CD34+ cells, inflammatory markers, endocan plasma levels were determined in 36 female SSc patients (24 diffuse/12 limited) and 36 matched controls (HC). RESULTS: We found no difference in CD34+ and vitamin D levels in SSc as compared to controls; ESR, CRP, fibrinogen, endocan, sPAP were higher in SSc with respect to controls. We found a correlation between endocan and: CD34+ cells (r: -0.540, p = 0.002), pulmonary arterial pressure (sPAP) (r: 0.565, p < 0.001), tricuspid annular plane excursion (TAPSE) (r: -0.311, p < 0.01), and E/A ratio (r: -0.487, p < 0.001), but not with ejection fraction (r: -0.057, p = 0.785) in SSc. CD34+ cells correlate with fibrinogen (r: -0.619, p < 0.001), sPAP (r: -0.404, p = 0.011), E/A (r: 0.470, p < 0.005 in SSc. CONCLUSION: CD34+ cell number was significantly correlated with endocan levels and with sPAP in SSc; endocan and CD34+ progenitor cells might be suggested as a potential marker of disease status.
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miR profile could be associated to CV risk, and also to prognosis/outcome in response to therapeutic approach. We aimed to evaluate if anti-hypertensive drugs enalapril, losartan or olmesartan have effects on monocyte miR profile in essential hypertensives without target organ involvement. For this purpose, 82 hypertensives and 49 controls were included; we evaluated SBP/DBP, lipid profile, glucose, CRP, fibrinogen, arterial stiffness indices (PWV; AIx), and cIMT at baseline (T0) and after 24 weeks of treatment (T1). Subjects with LDL-C ≥ 160 mg/dL, TG ≥ 200 mg/dL, BMI ≥ 30, and other additional CV risk factors were excluded. Patients who were prescribed to receive once-a-day enalapril 20 mg, losartan 100 mg or olmesartan 20 mg were eligible for the study. At T1, we found a significant improvement of SBP (-18.5%), DBP (-18%), HDL-C and LDL-C (+3% and -5.42%), glucose (-2.15%), BMI (-3.23%), fibrinogen (-11%), CRP (-17.5%,), AIx (-49.1%) PWV (-32.2%), and monocyte miR expression (miR-221: -28.4%; miR-222: -36%; miR-145: +41.7%) with respect to baseline. miR profile was compared to control subjects at baseline and at T1. We found some little difference in the behaviour of the three treatments on some variables: olmesartan was the most effective in reducing fibrinogen, DBP, CRP, and AIx (-13.1%, -19.3%, -21.4%, and -56.8%, respectively). Enalapril was the drug more significantly increasing the expression of miR-145. In conclusion, enalapril, losartan and olmesartan are effective in improving mechanical and humoral factors associated to AS and atherogenesis. These drugs appear to be able to modify miRs 221/222 and miR-145 expression in drug-naïve hypertensives, making it closer to that of control subjects; additionally, this provides a good blood pressure compensation, contributing to slow the progression of vascular damage.
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BACKGROUND: It is unknown how much precociously the cigarette smoking (CS) may compromise the integrity of the cardiovascular (CV) system. Myocardial function can be routinely assessed by conventional echocardiography, but abnormalities are only detected when somewhat a remodelling has already occurred. These limitations could be overcome by strain imaging. METHODS: We evaluated whether young smokers with normal left ventricular (LV) geometry, wall motion and ejection fraction may present abnormalities in myocardial deformation, both at rest and during physical effort. We selected 50 young smokers with no additional CV risk factors, and 60 non-smokers to undergo a standardized exercise-test. Consistently, we evaluated the CV adaptation to exercise by both conventional echocardiography and speckle-tracking analysis (2D-STE). RESULTS: We found no difference between smokers and controls regarding baseline characteristics; as expected, smokers presented with lower HDL-cholesterol (p < 0.005), and higher fibrinogen, C-reactive protein (CRP), and interleukin-6 (p < 0.001). Conventional echocardiography parameters were not different between groups, while we detected a different behaviour of global longitudinal strain (GLS), global circumferential strain (GCS) and twist by 2D-STE during exercise-test. Indeed, GLS, GCS and twist behaved differently during exercise test in smokers with respect to controls. We found an association between CS, inflammation and LV mechanics changes uncovered by physical effort, and regression analysis confirmed that the intensity of the exposure to cigarette smoking, together with the inflammatory status (CRP, fibrinogen and Il-6) plasma levels, drive this impairment. CONCLUSIONS: We confirm strain imaging (2D-STE) as a very useful tool to identify early changes in cardiac mechanics, as adaptation to exercise; our findings may reflect a very precocious functional abnormality in active smokers, likely long before structural damage occurs.
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Teste de Esforço , Ventrículos do Coração/fisiopatologia , Fumar/efeitos adversos , Disfunção Ventricular Esquerda/fisiopatologia , Adolescente , Adulto , Estudos de Casos e Controles , Ecocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Fumar/fisiopatologia , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Adulto JovemRESUMO
AIM: To measure plasma D-dimer levels in cirrhotic patients with and without ascites, assessing the effect of ascites resolution in D-dimer concentration. METHODS: Seventy consecutive cirrhotic patients (M = 44, F = 26, mean age 65 years, SD +/- 13), observed from October 2005 to March 2006 were enrolled. Circulating D-dimer levels were measured using a latex-enhanced, immunoturbidimetric test. In patients with ascites (n = 42) the test was repeated after ascites resolution. RESULTS: Ascites was present in 42 patients (group A) and absent in 28 (group B). Group A patients had more advanced liver disease. Hepatocellular carcinoma (HCC) was diagnosed in 14 patients and was more frequent in group B. Above normal range D-dimers were found in 45/70 patients. High D-dimers were more frequent in group A than in group B (P = 0.001). High D-dimers were associated with presence of HCC (P = 0.048) only in group B. After ascites resolution, obtained in all patients, mean D-dimer values decreased in those 34 patients with high basal levels (P = 0.007), returning to normal in 17. CONCLUSION: In patients with liver cirrhosis, ascites and HCC are the main factors associated with increased fibrinolytic activity.
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Ascite/sangue , Carcinoma Hepatocelular/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Cirrose Hepática/sangue , Neoplasias Hepáticas/sangue , Idoso , Idoso de 80 Anos ou mais , Ascite/etiologia , Ascite/terapia , Carcinoma Hepatocelular/etiologia , Dieta Hipossódica , Progressão da Doença , Diuréticos/uso terapêutico , Feminino , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , ParacenteseRESUMO
Circulating progenitor cells (CPCs) represent a pool of cells capable of differentiating into mature cells of different organs and systems, promoting tissue maintenance and repair. Among CPCs, CD34+cells (CD34+CPCs) seem to predict outcome in CV disease, also in elderly people. A decline in CD34+CPCs was reported with advancing age. Moreover, aging is associated with a state of chronic inflammation, influencing life expectancy. Our purpose was to investigate a 10-year predictive ability of CD34+CPCs, inflammatory marker levels, classic CV risk factors (CVRFs), and Framingham Risk Score (FRS) in a population of healthy, self-sufficient octogenarians. We found that baseline CD34+CPCs was strongly associated with mortality, showing a significant difference in CD34+CPC numbers between deceased and living patients. Moreover, by dividing our patients into tertiles based on age reached, this difference was more remarkable the higher the age reached. Regressive analyses suggested that the chances of reaching an older age depend on higher CD34+CPCs at baseline and are not significantly affected by inflammatory markers levels, FRS, CVFRs, or HDL-C levels. We found that higher CD34+CPCs predict longer life also in the oldest old, providing additional insights on the predictive role of CD34+CPCs in subjects aged 80 years or more.
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Antígenos CD34/sangue , Longevidade , Células-Tronco/metabolismo , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Contagem de Leucócitos , Masculino , Células-Tronco/citologiaRESUMO
CD34+ circulating progenitor cells (CD34+CPCs) are a population of multipotent cells which can delay the development of atherosclerosis and cardiovascular disease (CVD) in conditions of increased CV risk. MicroRNAs (miRs) 221 and 222 modulate different genes regulating angiogenesis and inflammation; moreover, miR221/22 have beenshown to participate in differentiation and proliferation of CD34+CPCs, inhibiting cell migration and homing. miR221/222 in CD34+CPCs from hypertensive subjects are also increased and associated with CD34+cell number and reactive oxygen species (ROS). We evaluated CD34+CPC number, intracellular miR221/222 and ROS levels, arterial stiffness (AS)and echocardiography indices at baseline (T0).Then, after a six-month treatment with olmesartan, 20 mg/day (T1), in 57 hypertensive patients with left ventricular hypertrophy (LVH) and with no additional risk factor for CVD, and in 29 healthy controls (baseline),fibrinogen, C-reactive protein (CRP), glucose and lipid profiles were also evaluated.At T1, blood pressure values, CRP and fibrinogen levels, ROS and miR221/222 were significantly decreased (all p <0.001), as were AS indices and LV mass index (p<0.001), while cell number was increased (p<0.001). Olmesartan is effective in reducing miR and ROS levels in CD34+CPCs from hypertensive subjects, as well as in increasing CD34+CPC number, providing multilevel CV protection, in addition to its expected pharmacological effects.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/sangue , Imidazóis/uso terapêutico , MicroRNAs/sangue , Células-Tronco/patologia , Tetrazóis/uso terapêutico , Adulto , Antígenos CD34/sangue , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/genética , Masculino , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND AND AIMS: Young cigarette smokers may already present with early signs of vascular inflammation and damage; biglycan (BGN) has been shown to play a critical role in the initiation and progression of vascular lesions, also in young smokers. We investigated whether after smoke cessation, monocyte BGN expression is reduced; moreover, we evaluated any improvement of pro-atherogenic profile and arterial stiffness (AS), and their relationship with BGN in abstinent smokers. METHODS: Two-hundred-fifty-one young people who had decided to quit smoking were enrolled; of these, 71 had completed the 12-month observation period maintaining smoking abstinence. At enrollment and 12 months later, we evaluated anthropometrics, laboratory profile, carotid-femoral pulse wave velocity (cf-PWV), carotid intima-media thickness (cIMT), BGN expression. RESULTS: After 12-month smoke abstinence, we found a significant decrease in inflammatory markers (Hs-CRP: -23.3%; fibrinogen: -11.8%; IL-6: -9.2%), and increased HDL-C levels (+9.3%); blood pressure values were also slightly reduced. cf-PWV (-8.9%) appeared to be improved; cIMT remained unchanged. BGN expression appeared to be reduced (-42.8% relative reduction). BGN reduction appeared to be associated with fibrinogen reduction, and smoking burden. Reduced cf-PWV appeared to be dependent on change in fibrinogen, SBP, IL-6, and BGN by multiple regression analysis. CONCLUSIONS: After the first year of smoke abstinence, the levels of IL-6, CRP, fibrinogen, HDL-C, and BGN expression, as well cf-PWV, are significantly improved as compared to baseline. This is the first evidence that removing exposure to a well-known cardiovascular risk factor, such as cigarette smoking, leads to significant reduction of BGN expression.
Assuntos
Aterosclerose/sangue , Biglicano/sangue , Endotélio Vascular/fisiopatologia , Inflamação/sangue , Abandono do Hábito de Fumar , Prevenção do Hábito de Fumar , Adolescente , Adulto , Fatores Etários , Aterosclerose/diagnóstico , Aterosclerose/etiologia , Aterosclerose/fisiopatologia , Biomarcadores/sangue , Pressão Sanguínea , HDL-Colesterol/sangue , Regulação para Baixo , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Humanos , Inflamação/diagnóstico , Inflamação/etiologia , Inflamação/fisiopatologia , Mediadores da Inflamação/sangue , Masculino , Análise de Onda de Pulso , Recuperação de Função Fisiológica , Fatores de Risco , Fumar/efeitos adversos , Fumar/sangue , Fatores de Tempo , Adulto JovemRESUMO
AIM: The utility of serum alpha-fetoprotein (alpha-FP) in the detection of hepatocellular carcinoma (HCC) is questionable. Very high circulating levels of nociceptin/orphanin FQ (N/OFQ), a ligand for a novel opioid receptor, have recently been reported in HCC. The aim of this study was to assess the role of plasma N/OFQ in the diagnosis of HCC arising in patients with liver cirrhosis. METHODS: Plasma N/OFQ levels were measured by ELISA in 58 patients (28 HCC and 30 liver cirrhosis) and in 25 healthy controls. The values were correlated with clinical and laboratory features including alpha-FP. Spearman index, biserial correlation coefficient, non parametric combination (NPC) test and discriminant stepwise analysis were used for statistical evaluation of data. RESULTS: The upper normal limit of nociceptin was 122 pg/mL. Plasma levels above this cut-off were found in 21.4% of patients with HCC, in 23.3% of those with cirrhosis and in 8% of healthy subjects. alpha-FP serum levels > 200 ng/mL were found in 46.4% of the patients with HCC and in none of those with cirrhosis. No correlation was found between N/OFQ levels and any of the clinical and laboratory features, including alpha-FP. By NPC test, HCC and cirrhotic patients were different with regard to alpha-FP (P = 0.000) but not in terms of nociceptin (P = 0.595). By point biserial correlation, HCC presence was positively correlated with alpha-FP (rpb = 0.52, P = 0.000) but not with N/OFQ (rpb = 0.16, P = 0.157). In a discriminant analysis, alpha-FP was significant in the Wilks test (Y = -0.709 + 0.03 alpha-FP) and properly classified 81% of all patients and 61% of HCC. N/OFQ had lower sensitivity, specificity and predictive values than alpha-FP. CONCLUSION: Nociceptin is increased in patients with chronic liver disease, independently of the presence of HCC, although the underlying mechanism has yet to be clarified. We conclude it is not a useful marker for HCC.