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R Marchioli

Publications and source records attributed to R Marchioli.

At least 37 records · Page 2Linked to original sources

The risk of thrombosis in patients with lupus anticoagulants is predicted by their specific coagulation profile.

Lupus anticoagulants belong to the family of antiphospholipid antibodies. They include two phospholipid-dependent inhibitors of coagulation that may be distinguished on the basis of specific coagulation profiles generated from the comparison of the ratios of the Kaolin Clotting Time (KCT) and the dilute Russell's Viper Venom Time (dRVVT): when the ratio of the KCT exceeds that of the dRVVT, the plasma is allocated to the "KCT" coagulation profile, when the opposite occurs, the plasma is defined to belong to the "dRVVT" coagulation profile group. We prospectively followed-up a historical cohort of 100 consecutive patients with lupus anticoagulants referred to our Institution between January 1988 and October 1997 to investigate the relationship between their coagulation profile at diagnosis and the development of thrombosis during a median follow-up time of 37.5 months (range 1-115 months). Fifty-six patients were allocated to the "dRVVT" coagulation profile, whereas the other 44 displayed the "KCT" profile. Lupus anticoagulants were transient in 17 patients, without differences between the two groups. None of these patients developed clinical events before disappearance of the phospholipid-dependent inhibitors of coagulation. The 83 cases with persistent lupus anticoagulants consistently displayed the same coagulation profile they had been allocated to at entry. Fourteen patients developed 18 thromboembolic events during the follow-up, with an overall rate of thrombosis of 4.2% patients-year. Twelve of them belonged to the "dRVVT" coagulation profile, whereas the other 2 to the "KCT" profile (p = 0.03). The "dRVVT" coagulation profile gave an odds ratio of thrombosis of 5.25 (95% confidence interval [C.I]: 1.17-23.50). Ten of the 14 patients who developed thrombosis during follow-up had already experienced thrombosis: a previous thrombotic event caused an odds ratio of recurrency of 2.72 (95% C.I.: 0.85-8.73) (p = 0.09). By multivariate analysis, the "dRVVT" coagulation profile was still associated with a trend to a higher risk of thrombosis, but the difference did not reach statistical significance. Increased levels of anticardiolipin antibodies (> 40 GPL and/or MPL units) were found in all the 14 patients (p = 0.0064). The "KCT" coagulation profile was significantly associated (p = 0.005) with moderate thrombocytopenia (platelets 50-150 X 10(9)/l). Neither profile was found to represent a risk factor for the development of recurrent miscarriages, neoplastic diseases and death. In conclusion, the "dRVVT" profile appears to have predictive value with respect to the thrombotic complications suffered by patients with antiphospholipid antibodies.

Adult↗

Diet and gallstones in Italy: the cross-sectional MICOL results.

Fifteen thousand nine hundred ten men and 13,674 women (age, 30-69 years) were enrolled in an epidemiological survey of the general population, between December 1984 and April 1987. Each participant was submitted to ultrasonography (US) of the gallbladder and completed a food-frequency questionnaire, covering 38 food items. A common portion size was identified and subjects were asked how often each item was consumed. Nutrient intake was computed by multiplying the intake frequency and nutrient content per portion for each item, and then by summing the product over all foods. Each nutrient intake was adjusted for energy intake. Alcohol intake was calculated by summing the consumption of wine, beer, and liquor. Having excluded subjects aware of having gallstones (GS) or previously submitted to cholecystectomy (to avoid prothopatic bias), 787 males and 1,014 females with GS and 14,272 males and 10,836 females without GS were available for analysis. Relative risks (RR) of GS were computed by quintiles of nutrient intake. The overnight fasting period was calculated as the difference between the specified time of dinner and the time of the next meal (breakfast or lunch). A significant negative association was found between RR of GS and total energy intake for males (chi2 for trend = 8.37; P = .004), fiber intake for females (chi2 = 5.45; P = .02), and daily alcohol consumption for males (chi2 = 10.86; P = .001). A positive association was observed between RR of GS and carbohydrate (chi2 = 5.95; P = .01 for males; chi2 = 9.39; P = .002 for females) and protein intake only for males (chi2 = 10.92; P = .01). Prevalence of GS was higher among subjects who had an overnight fasting period of over 12 hours than subjects with that of less than 12 hours. (RR: 1.35; 95% CI: 1.01-1.80 for males; RR: 1.28; 95% CI: 1.03-1.60 for females). These data do not confirm that high energy intake is associated with an increased risk of GS. Factors protecting against GS comprise: low carbohydrate (males and females) and protein (males) intakes, high fiber (females) and moderate alcohol intake (males) consumption, and a shorter overnight fasting period for both sexes.

Cholelithiasis↗

BEAM chemotherapy and autologous haemopoietic progenitor cell transplantation as front-line therapy for high-risk patients with diffuse large cell lymphoma.

In two consecutive and unselected cohorts of diffuse large cell lymphoma (DLCL) patients with advanced stage disease (IIB or bulk or more) and aged < 60 years, we compared a standard (MACOP-B for 12 weeks, 60 patients) versus a high-dose chemotherapy programme (8 weeks of MACOP-B plus one or two cycles of intensification with mitoxanthrone, dexamethasone, high-dose Ara-C, and finally BEAM chemotherapy with autologous haemopoietic progenitor cell transplantation, 61 patients). 41 patients (68%) in the standard group and 51 (84%) in the high-dose chemotherapy group, achieved a complete remission (CR) or an uncertain complete remission (CRu) (P = 0.0491). With a median follow-up time of 28 months for the high-dose group and 63.5 months for the standard group, the actuarial estimate of event-free survival (EFS) at 2 years demonstrates a significant benefit (70% v 50%, P = 0.03) for patients treated with the intensive regimen. The analysis of subgroups of patients showed that only high-risk patients (two or three risk factors) benefitted from the high-dose chemotherapy programme. Nevertheless, the overall survival does not show a significant difference between the two treatment modalities. The treatment-related morbidity was similar and the mortality rate was 8% in the standard (MACOP-B) group and 3% in the high-dose chemotherapy programme. In conclusion, our results show that high-dose chemotherapy and autologous stem cell transplantation is a safe procedure which should be considered for the front-line treatment of non-Hodgkin lymphoma patients with poor prognostic features.

Adult↗

Long-term haematological reconstitution following BEAM and autologous transplantation of circulating progenitor cells in non-Hodgkin's lymphoma.

We report on long-term haematological recovery and clinical outcome after high-dose chemotherapy supported by circulating progenitor cells (CPC) transplantation in non-Hodgkin's lymphoma (NHL) patients, and analyse the role of variables which might influence engraftment. 63 consecutive NHL patients were enrolled in this study. Two groups of patients were considered for analysis: the first 34 patients had untreated diffuse large cell lymphoma with unfavourable prognostic factors. A second group of 29 patients underwent transplantation for resistant or relapsing NHL with low, intermediate and high grade histology. All patients received the BEAM conditioning regimen. As already reported in many studies, all patients showed a rapid haematological reconstitution. 43 patients (68%) achieved long-term complete trilineage engraftment within a median of 107 d from CPC transplantation. The neutrophil count was the first parameter reaching complete normalization, and haemoglobin was the last. Failure to meet the trilineage levels was due to lack of platelet recovery and was more frequent in patients transplanted in the setting of salvage protocols. By Kaplan-Meier analysis, the probability of a full reconstitution was 80% in patients to whom transplant was offered as part of a front-line therapy and 50% when transplant was given in the salvage programmes. Multivariate analysis showed that sustained long-term haematological reconstitution was significantly related to younger age, the time taken to achieve short-term reconstitution, and bone marrow involvement.

Adolescent↗

European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP): a randomized trial.

Thrombotic complications characterize the clinical course of polycythemia vera (PV) and represent the main cause of morbidity and mortality. However, uncertainty still exists as to the benefit/risk ratio of aspirin prophylaxis in this setting. In vivo platelet biosynthesis of thromboxane A2 is enhanced and can be suppressed by low-dose aspirin in PV, thus providing a rationale for assessing the efficacy and safety of a low-dose aspirin regimen in these patients. The Gruppo Italiano Studio Policitemia Vera has recently performed a pilot study on 112 patients randomized to receive aspirin, 40 mg daily, or placebo and followed for 16 +/- 6 months (mean +/- SD). This study showed that low-dose aspirin is well tolerated in PV patients, and that a large-scale efficacy trial is feasible in this setting. In this article we report the protocol of the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) study, which is a randomized trial designed to assess the risk/benefit ratio of low-dose aspirin in PV. To estimate the size and the follow-up duration required for the ECLAP trial, a retrospective analysis of the clinical epidemiology of a large PV population has recently been completed by the Gruppo Italiano Studio Policitemia Vera. On this basis, approximately 3500 patients will be enrolled in the ECLAP study with a follow-up of 3 to 4 years. The uncertainty principle will be used as the main eligibility criterion: Polycythemic patients of any age, having no clear indication for or contraindication to aspirin treatment, will be randomized in a double-blind fashion to receive oral aspirin (100 mg daily) or placebo. According to current therapeutic recommendations, the basic treatment of randomized patients should be aimed at maintaining the hematocrit value < or = 45% in subjects aged < or = 50, and hematocrit < 45% as well as platelet count < 400 x 10(9)/L in patients aged > 50. Randomization will be stratified by participating center. The study is funded by the European Union BIOMED 2 program.

Aspirin↗

Mechanisms of bleeding and thrombosis in myeloproliferative disorders.

Arterial and venous thromboses and microcirculatory disturbances such as erythromelalgia and neurologic and visual symptoms are the thrombotic manifestations occurring in Polycythaemia Vera and Essential Thrombocythaemia. The increased in vivo thromboxane A2 generation existing in these patients and the selective sensitivity of erythromelalgia to aspirin suggest that platelet PGG/H synthase products may be involved in transducing the increased thrombotic risk. The relationship between Thromboxane A2 production and thrombotic accidents will be investigated by the European Collaboration on Low-Dose Aspirin in Polycythaemia Vera (ECLAP) which will test the efficacy of low-dose aspirin by a randomised clinical trial. The haemorrhagic diathesis of polycythaemic and thrombocythaemic subjects is generally mild and spontaneous bleeding usually manifests in patients with very high platelet count. Its mechanism may be related to quantitative as well as to qualitative platelet changes. Possible mechanisms linking the high grade thrombocytosis to bleeding are consumption of von Willebrand factor and clot fragility due to a mechanical effect of the high platelet count or to inhibition of fibrin polymerization by platelet Glycoprotein Ib.

Blood Platelets↗

Meta-analysis, clinical trials, and transferability of research results into practice. The case of cholesterol-lowering interventions in the secondary prevention of coronary heart disease.

OBJECTIVE: To evaluate, in the comprehensive scenario of "evidence-based" medicine, the transferability of the results of published randomized clinical trials and meta-analyses on cholesterol-lowering interventions to clinical practice. METHOD: Overview of randomized clinical trials on cholesterol-lowering interventions in the secondary prevention of coronary heart disease. RESULTS: The present overview on secondary prevention of coronary heart disease included 34 trials with cholesterol-lowering interventions in 24968 individuals. There was a 12.5% mortality in the group that was allocated active intervention and a 17.2% mortality in the control group (risk reduction, 13%; 95% confidence interval, -19% to -6%). Coronary and cardiovascular odds of deaths were significantly reduced. No clear association was found between noncoronary mortality and cholesterol-lowering interventions. Baseline total cholesterol levels had no clear influence on total mortality. Intermediate (10%-20%) and high ( > 20%) total cholesterol reductions were associated with similar reductions in the odds of death (-23% and -30%, respectively). No conclusion could be reached for patients who were less represented in the studies (ie, women and elderly persons). Patients with more complicated baseline clinical conditions (eg, congestive heart failure) had little nonsignificant benefit from cholesterol-lowering interventions. CONCLUSIONS: The effect of cholesterol-lowering interventions at least in the secondary prevention of coronary heart disease can be considered as established, but the transferability of such results to real-life patients remains the critical, unanswered question.

Anticholesteremic Agents↗