The importance of prognosis in geriatric patients attending the emergency department: a comparison between two common short geriatric assessment tools.

BACKGROUND: The use of short geriatric tools in the emergency department (ED) is increasing, but the literature is still conflicting. The aim of this study is to compare the precision and the accuracy of two short geriatric assessment tools to predict mortality in a cohort of older patients attending the ED. METHODS: A retrospective study was conducted including patients ≥ 65 years, attending the ED and transferred to a medical assessment unit from February to July 2022. Clinical Frailty Scale (CFS) and Brief Multidimensional Prognostic Index (Brief MPI) were administered. The association between Brief MPI and CFS and mortality was analysed via area under the curve (AUC) with its 95% confidence intervals (CIs), the C-statistics and a multivariate Cox's regression analysis, in the latter case reporting the data as hazard ratios (HRs) with their 95% CI. RESULTS: Among the 579 patients enrolled (mean age: 77 years), both Brief MPI and CFS showed a good accuracy in predicting mortality (AUC: 0.72; 95% CI: 0.61-0.83 for Brief MPI; 0.754; 95% CI: 0.65-0.83 for CFS). The discrimination of Brief MPI and CFS in predicting mortality was excellent, since the C-index of the Brief MPI was 0.85 and of CFS = 0.84. In the multivariate analysis, the risk for mortality was significantly increased for frailer subjects (HR 4.65; 95% CI: 1.45-15.00 for Brief MPI > 0.66; HR = 9.24; 95% CI: 1.16-76.90 for CFS > 6). CONCLUSIONS: Brief MPI and CFS showed a good accuracy/precision to predict mortality in older patients attending the ED. Considering that they are quick to perform, their introduction in ED clinical practice could be extremely helpful.

Lipid Peroxidation, Protein Oxidation, Gelatinases, and Their Inhibitors in a Group of Adults with Obesity.

The association between obesity and cardiovascular diseases has a multifactorial pathogenesis, including the synthesis of inflammatory molecules, the increase in oxidative stress and the dysregulation of the matrix metalloprotease (MMP) concentration and activity. In a group of adults with obesity, divided in 2 subgroups according to the body mass index (BMI), we examined lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS), protein oxidation, expressed as protein carbonyl groups (PCs), plasma gelatinases (MMP-2 and MMP-9), and their tissue inhibitors (TIMP-1 and TIMP-2). In the whole group, as well as in the 2 subgroups (with BMI 30-35 or BMI>35) of obese subjects, we observed an increase in TBARS, PCs, MMP-2, and MMP-9, and also TIMP-1 and TIMP-2 in comparison with the control group. A positive correlation between TBARS and PCs emerged in obese subjects and persisted after dividing obese subjects according to BMI. The correlation between MMP-2 and TIMP-2 was not statistically significant, while a significant correlation was present between MMP-9 and TIMP-1. The correlations between the markers of oxidative stress (TBARS and PCs) and those of the MMP/TIMP profile indicated a more marked influence of protein oxidation on MMPs and TIMPs in comparison with TBARS. The innovative aspect of our study was the simultaneous evaluation of oxidative stress markers and MMP/TIMP profile in adult obese subjects. We observed significant alterations and correlations that may negatively influence the clinical course of the disease.

Clostridioides difficile Infection in an Italian Tertiary Care University Hospital: A Retrospective Analysis.

Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality, mostly in frail patients. Notification is not mandatory in Italy, and data on incidence, risk of death, and recurrence are lacking. The purpose of this study was to determine CDI incidence and risk factors for mortality and recurrence. The "ICD-9 00845" code in hospital-standardized discharged forms (H-SDF) and microbiology datasets were used to retrieve CDI cases at Policlinico Hospital, Palermo between 2013 and 2022. Incidence, ward distribution, recurrence rate, mortality, and coding rate were considered. The risk of death and recurrence was predicted through multivariable analysis. There were 275 CDIs, 75% hospital-acquired, the median time between admission and diagnosis was 13 days, and the median stay was 21 days. Incidence increased from 0.3 to 5.6% (an 18.7-fold increase) throughout the decade. Only 48.1% of cases were coded in H-SDF. The rate of severe/severe-complicated cases increased 1.9 times. Fidaxomicin was used in 17.1% and 24.7% of cases overall and since 2019. Overall and attributable mortalities were 11.3% and 4.7%, respectively. Median time between diagnosis and death was 11 days, and recurrence rate was 4%. Bezlotoxumab was administered in 64% of recurrences. Multivariable analysis revealed that only hemodialysis was associated with mortality. No statistically significant association in predicting recurrence risk emerged. We advocate for CDI notification to become mandatory and recommend coding CDI diagnosis in H-SDF to aid in infection rate monitoring. Maximum attention should be paid to preventing people on hemodialysis from getting CDI.

The function of matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor (TIMP-1) in several clinical conditions: Results and analysis of our survey.

The goal of this research was to evaluate the plasma concentration of MMP-9 and its tissue inhibitor (TIMP-1) in different clinical conditions. It included several groups of subjects: 31 overweight subjects; 91 obese adults divided into two subgroups according to the BMI value (BMI 30-35 Kg/m2 and BMI > 35 Kg/m2); 90 subjects with metabolic syndrome (MS) divided into two subgroups (with and without diabetes mellitus); 100 subjects with preclinical carotid atherosclerosis (PCA) divided according to the number of cardiovascular risk factors and to the insulin resistance degree; 48 subjects with obstructive sleep apnoea syndrome (OSAS) divided according to the apnoea/hypopnea index (AHI); 27 subjects with chronic kidney disease (CKD) on conservative management; 31 subjects with CKD on regular haemodialysis treatment. We have found a significant increase of MMP-9 and TIMP-1 in overweight subjects, in obese adult and in MS subjects. In obese adults, the behaviour of these two parameters was not influenced by the degree of obesity, while in the group of MS subjects both these parameters were clearly influenced by the presence of diabetes mellitus. In subjects with PCA, we observed an increase of MMP-9 associated with a significant decrease of TIMP-1; the same trend was found by subdividing the entire group in accordance with the number of cardiovascular risk factors and with the insulin resistance degree. In subjects with OSAS, we noted an increase in MMP-9 and TIMP-1; this increase was more evident in subjects with OSAS having AHI > 30. In individuals with CKD on conservative and haemodialysis treatment we have found, at baseline, a marked increase in MMP-9 and a significant decrease of TIMP-1. In dialyzed subjects, after a standard dialysis session was noted, a significant increase in MMP-9 was associated with a further decrease in TIMP-1.

Behaviour of carbonyl groups in several clinical conditions: Analysis of our survey.

Protein carbonylation is a marker of oxidative protein damage, that is likely involved in the pathogenesis of several diseases. The aim of this study was to evaluate the protein carbonyl (PC) groups in different clinical conditions. It included different groups of subjects: 81 trained subjects; 23 subjects with mild essential hypertension; 31 middle-aged subjects with metabolic syndrome (MS); 106 subjects with MS not selected for age (subdivided into two subgroups, with and without diabetes mellitus); 91 obese adults subdivided in two subgroups (BMI 30-35 Kg/m2 and BMI > 35 kg/m2); 48 subjects with obstructive sleep apnea syndrome (OSAS) subdivided in accordance with the apnea/hypopnea index (AHI); 27 subjects with chronic kidney disease (CKD) on conservative therapy; 31 subjects with CKD on haemodialysis treatment; and 50 subjects with juvenile myocardial infarction. PC groups were reduced in trained subjects in comparison with sedentary controls, while no variation was observed in mild essential hypertension. PC groups were increased in MS subjects and in adult obese subjects. In MS subjects the PC groups were not influenced by the presence of diabetes mellitus and in adult obese subjects were not influenced by the obesity degree. In OSAS subjects only those with AHI > 30 showed an increase of PC groups. PC groups increased in CKD subjects undergoing conservative treatment and haemodialysis therapy. In dialyzed subjects, after a standard dialysis session, there was a marked increase in PC groups. In juvenile myocardial infarction PC groups were higher than in controls; there was no difference between STEMI and NSTEMI and their concentration was unaffected by the number of cardiovascular risk factors or stenosed coronary vessels.

Erythrocyte deformability and nitric oxide metabolites in athletes before and after a cardiopulmonary test.

OBJECTIVE: To evaluate erythrocyte deformability, nitric oxide metabolites, and their modifications induced by exercise in athletes who practised different sports. DESIGN: This evaluation was effected before and after cardiopulmonary test, using a cycloergometer. SETTING: The study was performed in the Department of Internal Medicine, Cardiovascular and Renal Diseases of the University of Palermo. PARTICIPANTS: We enrolled 62 male athletes who practised endurance (n = 23), mixed (n = 20), and power (n = 19) sports and 20 sedentary male subjects as controls. ASSESSMENT OF RISK FACTORS: No subject had diabetes or hypertension or dyslipidemia. Five control subjects and 14 athletes were smokers. MAIN OUTCOME MEASURES: Erythrocyte deformability was examined as elongation index (EI) using a diffractometer. The nitric oxide metabolites (nitrite + nitrate = NOx) were evaluated employing the Griess reagent. RESULTS: In the whole group, an increase in EI and NOx was present. Subdividing the whole group into 3 subgroups, we noted an increase in EI and NOx only in endurance and mixed athletes. The EI before and after the cardiopulmonary test significantly decreased in the whole group and in power athletes but not in endurance and mixed athletes. Before and after the test, NOx did not significantly change in the whole group and in the 3 subgroups. CONCLUSIONS: In athletes who practised endurance and mixed sports, we observed an increase of NOx level and an increase of erythrocyte deformability. The latter did not change after an exercise test in the same subgroups, whereas it decreased in power athletes.

Lipid peroxidation and total antioxidant status in juvenile myocardial infarction.

In a group of young subjects with acute myocardial infarction (AMI) (97 men and 8 women; mean age 39.6+/-5.5 years) we examined the thiobarbituric acid - reactive substances and the total antioxidant status at the initial stage and after 12 months. The same parameters were examined in a group of 55 control subjects. Our results show that, while in control subjects there was a negative correlation (p<0.001) between these two parameters, no correlation was found in juvenile myocardial infarction at the initial stage as well as after 12 months.

Relationship between elastase and total antioxidant status in young subjects with recent myocardial infarction.

In a group of young subjects with acute myocardial infarction (AMI) (68 men and 7 women; mean age 39.6+/-5.7 years) we examined the plasma concentration of elastase, the thiobarbituric acid-reactive substances (TBARS) and the total antioxidant status (TAS) at the initial stage of AMI. In this group we found an increase of elastase (p<0.001) and TBARS (p<0.001) and a decrease of TAS (p<0.001). A statistical correlation was observed in the whole group of AMI patients between plasma elastase and TAS (p<0.01) and this correlation was more statistically significant in patients with more risk factors and not in those with more involved vessels.

Analysis of the Blood Viscosity Behavior in the Sicilian Study on Juvenile Myocardial Infarction.

Considering the role of hemorheology in coronary circulation, we studied blood viscosity in patients with juvenile myocardial infarction. We examined whole blood viscosity at high shear rate using the cone-on-plate viscosimeter Wells-Brookfield ½ LVT and at low shear rate employing a viscometer Contraves LS30 in 120 patients (aged <46 years) with myocardial infarction, at the initial stage and subsequently 3 and 12 months after. At the initial stage, patients had an increased whole blood viscosity in comparison to normal controls. This hemorheological profile was not influenced by the cardiovascular risk factors, nor by the extent of coronary lesions, even if some differences were evident between patients with ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). The blood viscosity pattern at the initial stage did not influence recurring ischemic events or the onset of heart failure during an 18 months' follow-up. The neutrophil to lymphocyte ratio did not affect the blood viscosity pattern. We reevaluated 83 patients 3 months after and 70 patients 12 months after the acute coronary syndrome, and we found that the hemorheological parameters were still altered in comparison to normal controls at both times. We observed an impairment of the hemorheological pattern in young patients with myocardial infarction, partially influenced by the infarction type (STEMI and NSTEMI) and persisting in the long term.

Evaluation of oxidative status in coronary heart disease at baseline and during exercise test.

Oxidative stress has probably a role in coronary heart disease (CHD), but studies focused on the behaviour of oxidative status in patients with stable CHD have obtained controversial results. On the other hand, an increased release of leukocyte elastase is considered a marker of CHD. Exercise can induce oxidative stress and leukocyte activation, so the aim of this study was to evaluate oxidative status and plasma elastase level in a group of subjects with stable coronary heart disease (CHD), at baseline and during an exercise test. We enrolled 15 patients with previous acute myocardial infarction, all treated with statins and platelet antiaggregating agents. As parameters of oxidative status we determined the thiobarbituric acid reactive substances and total antioxidant status (TAS). The exercise test was performed according to the Bruce protocol. At baseline, elastase level was higher in CHD subjects than in normal controls and during the exercise test it increased in both groups in comparison with basal values. Regarding oxidative status, only TAS was slightly lower in CHD subjects than in normal controls. In both groups, during exercise test, no parameter of oxidative status was significantly different compared to basal values. In conclusion, CHD patients showed, at rest, an abnormal neutrophil activation and a lower antioxidant status. The exercise test further activated neutrophils but did not influence oxidative status. The absence of a marked oxidative stress in our patients may be partly due to the pharmacological treatment, which apparently did not influence the abnormal leukocyte activation.

Clinical conditions responsible for hyperviscosity and skin ulcers complications.

In this brief review, we have examined some clinical conditions that result to be associated to an altered hemorheological profile and at times accompanied by skin ulcers. This skin condition may be observed in patients with the following condtions, such as primary polycythemic hyperviscosity (polycythemia, thrombocytemia) treated with hydroxyurea, primary plasma hyperviscosity (multiple myeloma, cryoglobulinemia, cryofibrinogenemia, dysfibrinogenemia, and connective tissue diseases), primary sclerocythemic hyperviscosity (hereditary spherocytosis, thalassemia, and sickle cell disease). In addition, it may be present in patients with secondary hyperviscosity conditions such as diabetes mellitus, arterial hypertension, critical limb ischemia and chronic venous insufficiency.

Polymorphonuclear leukocyte membrane fluidity and cytosolic Ca2+ concentration in subjects with vascular atherosclerotic disease subdivided according to its extent.

An abnormal activation state of polymorphonuclear leukocytes (PMN) plays a key role in organ injury induced by vascular atherosclerotic disease (VAD) and diabetes mellitus (DM). PMN membrane fluidity and cytosolic Ca2+ content can be considered markers of PMN activation. In this research we evaluated the PMN membrane fluidity and cytosolic Ca2+ content in VAD subjects with and without type 2 DM and examined the association between these parameters and the mono- or polyvascular localization. We enrolled 155 VAD subjects, including 92 non-diabetic (group A: mean age 63.6 +/- 9.2 years) and 63 diabetic patients (group B: mean age 65.4 +/- 7.8 years). Among group A 63 patients had monovascular and 29 polyvascular disease; among group B 30 patients had monovascular and 22 polyvascular disease. In each patient we evaluated the PMN membrane fluidity labelling the cells with the fluorescent probe 1,4-(trimethylamino)-phenyl-4-phenylhexatriene (TMA-DPH) and the PMN cytosolic Ca2+ content marking the cells with the fluorescent probe Fura 2-AM. PMN membrane fluidity did not discriminate normal subjects from diabetic and non-diabetic VAD subjects, while cytosolic Ca2+ content was increased in both groups. PMN membrane fluidity did not distinguish normal subjects from mono- or polyvascular VAD patients with and without type 2 DM. PMN cytosolic Ca2+ content was increased especially in monovascular VAD patients; both mono- and polyvascular VAD subjects with DM had a PMN cytosolic Ca2+ content higher than normals. Our results show the presence of an increased PMN cytosolic Ca2+ content in diabetic and non-diabetic VAD subjects but no association was observed between this increase and the mono- or polyvascular localization.

Persistence of the altered polymorphonuclear leukocyte rheological and metabolic variables after 12 months in juvenile myocardial infarction.

Acute myocardial infarction (AMI) is associated with an elevated polymorphonuclear leukocyte (PMN) count and a PMN rheological impairment. In this study we evaluated two major rheological aspects (membrane fluidity and cytosolic Ca2+ concentration) in a group of young adults with AMI. We enrolled 41 AMI patients (39 men and 2 women; mean age 41.0 +/- 4.0 years), who were examined 5-10 days after AMI (T1) and 12 months later (T2). The membrane fluidity was obtained labelling granulocytes with the fluorescent probe 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) and considering the degree of fluorescence polarization, inversely correlated to the membrane lipid fluidity. The cytosolic Ca2+ content was obtained marking PMN cells with the fluorescent probe Fura-2AM and considering the ratio between the Fura 2-Ca2+ complex and the unchelated Fura 2 fluorescence intensity. Both parameters were evaluated at baseline and after in vitro activation with 4-phorbol 12-myristate 13-acetate (PMA) at the concentration of 4.5 muM, prolonged for 5 and 15 minutes. At T1 the PMN membrane fluidity and cytosolic Ca2+ content in AMI patients were respectively decreased and increased in comparison with control group. At T2 the membrane fluidity was not any more different from control subjects, but there was also a further increase in cytosolic Ca2+ content. In vitro, PMN activation caused no significant variation of these parameters in the control group, while in AMI patients membrane fluidity significantly decreased and cytosolic Ca2+ content increased not only during the initial stage, but also after 12 months. The long-term functional alteration of PMN cells observed in young adults with AMI confirms the role of these cells in the inflammatory response following AMI. In the light of these data, the use of molecules able to modulate granulocyte activity, such as calcium channel blockers or pentoxifylline, should be reconsidered in myocardial infarction, together with the usual pharmacological treatment.

Gelatinases and their tissue inhibitors in a group of subjects with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is associated with an elevated risk of cardiovascular events and stroke. Matrix metalloproteinases (MMPs) are endopeptidases involved in extracellular matrix degradation and then in the development and progression of cardiovascular diseases. Our aim was to evaluate plasma levels of gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) in a group of subjects with OSAS. We enrolled 48 subjects (36 men and 12 women; mean age 49.7 ± 14.68 yrs) with OSAS diagnosed with a 1-night cardiorespiratory study and then we subdivided these subjects into two subgroups according to the apnea/hypopnea index (AHI): Low (L = 21 subjects with AHI <30) and High (H = 27 subjects with AHI >30). We measured plasma concentration of the gelatinases and their inhibitors using ELISA kits. We observed a significant increase in plasma concentration of MMP-9, MMP-2, TIMP-1 and TIMP-2 in the entire group of OSAS subjects and in the two subgroups, with higher levels in the H in comparison with the L subgroup. In the whole group of OSAS subjects we also noted a significant decrease in MMP-9/TIMP-1 ratio in comparison with normal controls. Only MMP-9 was significantly correlated with the severity of the disease, expressed as AHI, with the oxygen desaturation index and also with the mean oxygen saturation. MMPs pattern is altered in OSAS and significantly influenced by the severity of the disease; it probably contributes to the vascular remodeling that leads to the atherosclerotic disease and cardiovascular complications.

Polymorphonuclear leukocyte integrins in chronic renal failure.

Patients with chronic renal failure (CRF), in comparison with general population, show a higher cardiovascular mortality, not fully explained by the "traditional" risk factors. Among the new factors that have been hypothesized, leukocytes might play an important role. In a group of patients with mild CRF we determined, at baseline and after in vitro activation with 4-phorbol-12-myristate-13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP), the polymorphonuclear leukocytes (PMN) beta2-integrin pattern (CD11a, CD11b, CD11c and CD18) by using indirect immunofluorescence with a flow cytometer. At baseline we observed an increase in the phenotypical expression of CD11b, CD11c and CD18 in CRF patients. In normal subjects, after activation with both agents, we noted an increase of all adhesion molecules, while in CRF patients we found an increase in the expression of CD11b, CD11c and CD18 but not of CD11a. The altered behaviour of the PMN integrin pattern in mild CRF patients, likely reflecting a state of PMN activation, might have a pathophysiological significance, considering the high incidence of cardiovascular events in CRF.

Plasma markers of platelet and polymorphonuclear leukocyte activation in young adults with acute myocardial infarction.

Our goal was to evaluate some plasma markers of platelet and polymorphonuclear leukocyte (PMN) activation in a group of young adults with acute myocardial infarction (AMI) at the initial stage and after three months. We enrolled 49 AMI subjects aged<45 years and examined plasmatic levels of platelet factor 4 (PF4), beta-thromboglobulin (beta-TG), elastase and myeloperoxidase (MPO) using ELISA methods. PF4 and beta-TG were increased, compared to control subjects, both at the initial stage and after 3 months. In control subjects and in AMI patients, at both times of observation, there was a significant and positive correlation between the two platelet parameters, while no correlation was present between each parameter and platelet count. In AMI patients there was an increase in elastase levels in comparison with the control group; this increase was evident at the initial stage and after 3 months. There was no difference in MPO levels between control subjects and AMI patients. In control subjects and in AMI patients there was a significant and positive correlation between elastase and MPO level, whereas no relationship was found between each marker and PMN count. Our data show that in young AMI patients the discharge treatment including antiplatelet drugs did not modify platelet activation and suggest the association of molecules able to inhibit PMN activation to the conventional therapy of these AMI patients.

Lipid peroxidation and nitric oxide metabolites in a group of subjects with obstructive sleep apnea syndrome.

It is known that in OSAS the plasma lipid peroxidation has an opposite behavior in comparison with nitric oxide metabolites. In the re-examination of our survey of OSAS subjects we calculated the ratio between thiobarbituric acid reactive substances (TBARS) and nitric oxide metabolites (NOx) in relation to OSAS severity. The study has regarded 48 OSAS subjects subdivided in two subgroups according to the apnea/hypopnea index - AHI- (Low = 21 subjects with AHI <30 and High = 27 subjects with AHI >30). From the obtained data it is evident that the TBARS/NOx ratio is significantly higher in the H subgroup compared to L subgroup as well as this ratio is reduced in L subgroup in comparison with the whole group of OSAS subjects. In the entire group of OSAS subjects the TBARS/NOx ratio results positively correlated with AHI and ODI and inversely correlated with mSO2.

Nitric oxide metabolites and erythrocyte deformability in a group of subjects with obstructive sleep apnea syndrome.

Our aim was to evaluate nitric oxide metabolites (nitrite and nitrate), expressed as NOx, and erythrocyte deformability, expressed as elongation index, in a group of subjects with obstructive sleep apnea syndrome (OSAS). We enrolled 48 subjects (36 men and 12 women; mean age 50.3±14.68 yrs) with OSAS diagnosed after a 1-night cardiorespiratory sleep study. OSAS severity was assessed evaluating the apnea/hypopnea index (AHI) and subjects were subdivided in two subgroups: Low (L=AHI<30) and High (H=AHI>30). NOx was examined converting nitrate into nitrite with a nitrate reductase and then assessing nitrite with spectrophotometry after the addition of Griess reagent. The elongation index was obtained using the diffractometer Rheodyn SSD of Myrenne at shear stresses of 30 and 60 Pa and it was expressed as elongation index (EI). We found no difference in NOx among the entire group of OSAS subjects and normal controls, while we observed a NOx decrease in the H subgroup in comparison with L subgroup, but not in comparison with normal controls. We noted a significant decrease in EI at each shear stress in the entire group and also in the two subgroups in comparison with controls. The decrease in NO bioavailability and in erythrocyte deformability might contribute to explain the increased cardiovascular risk in OSAS subjects.

Polymorphonuclear leukocyte integrin profile in vascular atherosclerotic disease.

Leukocyte-endothelial interactions could have a pathogenic role in atherogenesis. Adhesion molecules expressed by endothelial cells, such as intercellular adhesion molecule 1 (ICAM-1), interact with leukocyte integrins mediating the firm adhesion of leukocytes to endothelium which is followed by their transendothelial migration. The aim of our research was to evaluate polymorphonuclear leukocyte (PMN) integrin expression, at baseline and after activation, in a group of subjects with chronic vascular atherosclerotic disease (VAD). In 27 subjects with VAD we examined, at baseline and after in vitro activation with 4-phorbol 12-myristate 13-acetate (PMA), the PMN integrin pattern (CD11a, CD11b, CD11c, CD18) using indirect immunofluorescence and a flow cytometer. At baseline VAD subjects showed an increase of CD11a and CD18 and a decrease of Cd11b and Cd11c as compared to normal subjects. After activation, in normal subjects, we found an increase in the expression of all integrins, while in VAD subjects we observed an increase of CD11b and Cd11c and a decrease of Cd11a and CD18. In VAD subjects, at baseline, the upregulation of Cd11a and CD18 may reflect PMN in vivo activation; after in vitro activation, the decrease of CD11a may be related to the lack of cytoplasmic deposits of this molecule, while CD18 might be internalized. The integrin behaviour pattern in chronic VAD deserves further investigation, considering that integrins are potential targets of therapeutical strategies, with the aim of preventing the atherosclerotic plaque progression and acute ischaemic events.

Residual vein thrombosis and onset of post-thrombotic syndrome: influence of the 4G/5G polymorphism of plasminogen activator inhibitor-1 gene.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is the most important inhibitor of plasminogen activator. The functional 4G/5G polymorphism of the gene coding for PAI-1 may affect PAI-1 plasmatic activity, influencing the imbalance between coagulation and fibrinolysis cascades. In this prospective cohort analytic study, we investigated the role of this single nucleotide polymorphism in the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome. PATIENTS/METHODS: In a group of 168 patients with post-surgical deep vein thrombosis of the legs, we analyzed the 4G/5G polymorphism in the promoter of PAI-1 gene and plasmatic PAI-1 activity. Enrolled patients were divided in two groups: patients with 4G/5G polymorphism and increased PAI-1 activity (n=85) and patients without 4G/5G polymorphism and normal PAI-1 activity (n=83). All patients were treated according to current protocols and re-examined after 3, 12 and 36 months in order to evaluate the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome. RESULTS: We found a significantly increased PAI activity in carrier of the 4G allele, who experienced much more frequently a persistence of thrombosis after 3, 12 and 36 months and/or the development of post-thrombosis syndrome, in spite of the anticoagulant treatment. CONCLUSIONS: These data not only confirm the role played by PAI-1 activity and by the 4G/5G SNP of the PAI-1 gene, but also suggest that current therapeutic protocols, recommending the administration of low weight molecular heparin and oral anticoagulant for the treatment of deep vein thrombosis, could be non sufficient for patients genetically predisposed to a less efficient clot lysis.