Giancarlo Agnelli

Università degli Studi di Perugia, Terni, Umbria, Italy

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Publications (146)1032.17 Total impact

  • Article: Obesity and the Risk of Intracerebral Hemorrhage: The Multicenter Study on Cerebral Hemorrhage in Italy.
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    ABSTRACT: BACKGROUND AND PURPOSE: The effect of obesity on the risk of intracerebral hemorrhage (ICH) may depend on the pathophysiology of vessel damage. To further address this issue, we investigated and quantified the correlations between obesity and obesity-related conditions in the causal pathways leading to ICH. METHODS: A total of 777 ICH cases ≥55 years of age (287 lobar ICH and 490 deep ICH) were consecutively enrolled as part of the Multicenter Study on Cerebral Hemorrhage in Italy and compared with 2083 control subjects by a multivariate path analysis model. Separate analyses were conducted for deep and lobar ICH. RESULTS: Obesity was not independently associated with an increased risk of lobar ICH (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.58-1.01) or deep ICH (OR, 1.18; 95% CI, 0.95-1.45) when compared with control subjects. The path analysis confirmed the nonsignificant total effect of obesity on the risk of lobar ICH (OR, 0.77; 95% CI, 0.58-1.02) but demonstrated a significant indirect effect on the risk of deep ICH (OR, 1.28; 95% CI, 1.03-1.57), mostly determined by hypertension (OR, 1.07; 95% CI, 1.04-1.11) and diabetes mellitus (OR, 1.04; 95% CI, 1.01-1.07). Obesity was also associated with an increased risk of deep ICH when compared with lobar ICH (OR, 1.62; 95% CI, 1.14-2.31). CONCLUSIONS: Obesity increases the risk of deep ICH, mostly through an indirect effect on hypertension and other intermediate obesity-related comorbidities, but has no major influence on the risk of lobar ICH. This supports the hypothesis of different, vessel-specific, biological mechanisms underlying the relationship between obesity and cerebral hemorrhage.
    Stroke 04/2013; · 5.73 Impact Factor
  • Article: Venous thromboembolism after laparoscopic cholecystectomy: clinical burden and prevention.
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    ABSTRACT: BACKGROUND: The clinical benefit of prophylaxis for venous thromboembolism (VTE) in laparoscopic cholecystectomy is unclear. This study aimed to assess the clinical burden of VTE and the efficacy and safety of antithrombotic prophylaxis during laparoscopic cholecystectomy. METHODS: Data sources and study selection studies were searched in MEDLINE and Embase using the terms "cholecystectomy and venous thrombosis" and "cholecystectomy and venous thromboembolism." Studies were considered for a systematic review and a metaanalysis if they reported on the methods of antithrombotic prophylaxis and on the incidence of objectively confirmed VTE in patients who had undergone laparoscopic cholecystectomy. Overall, 15 studies of patients who had undergone laparoscopic cholecystectomy were included in the systematic review. RESULTS: The incidence of VTE was lower after laparoscopic cholecystectomy than after open cholecystectomy [odds ratio (OR), 0.47; 95 % confidence interval (CI), 0.40-0.56]. No statistically significant reduction in VTE was observed in patients receiving heparin prophylaxis after laparoscopic cholecystectomy (OR, 0.86; 95 % CI, 0.12-5.82). CONCLUSIONS: The rate of VTE after laparoscopic cholecystectomy seems to be relatively low. The clinical benefit of heparin prophylaxis for patients undergoing laparoscopic cholecystectomy remains unclear.
    Surgical Endoscopy 02/2013; · 4.01 Impact Factor
  • Article: Severity of acute intracerebral haemorrhage, elderly age and atrial fibrillation: Independent predictors of poor outcome at three months.
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    ABSTRACT: BACKGROUND AND PURPOSE: Prognostic risk factors of haemorrhagic stroke are not yet fully identified. This study investigated clinical factors leading to poor outcome at three months in patients with intracerebral haemorrhage (ICH) in order to better understand the role of clinical features in prognostic evaluation. SUBJECTS AND METHODS: This was a prospective cohort study on patients having ICH admitted to two Italian hospitals (the Stroke Units at "Ospedale Santa Maria della Misericordia", Perugia and "Ospedale C. Poma", Mantua) between January 1, 2006 and June 30, 2010. RESULTS: A total of 470 consecutive ICH patients (mean age 73.89±13.02years) were included and of these, 241 (51.1%) were males. At three months, 293 (62.3%) patients had poor outcome including 133 (27.6%) deaths. The resulting significant predictors of poor outcome from univariate analysis included: age, NIH Stroke Scale Score (NIHSSS) at admission, hyperglycaemia and the presence of atrial fibrillation (AF). These variables were confirmed in logistic regression analyses as being independent predictors of disability: age (OR 1.04 95% CI, 1.02-1.07, p=0.0001), AF (OR 3.18 95% CI, 1.12-9.05 p=0.03) and NIHSSS (OR 1.38 95% CI, 1.28-1.48, p=0.0001), while elderly age (OR 1.10 95% CI, 1.06-1.14, p≤0.0001) and high NIHSSS (OR 1.25 95% CI, 1.19-1.31, p≤0.0001) resulted being independent predictors of mortality. CONCLUSIONS: This study found that severity of ICH, elderly age and AF were independent predictors of poor outcome in ICH patients at three months. Thereby, this highlights the importance of understanding the roles of clinical features in ICH prognostic evaluation.
    European Journal of Internal Medicine 01/2013; · 2.00 Impact Factor
  • Article: Apixaban for Extended Treatment of Venous Thromboembolism.
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    ABSTRACT: Background Apixaban, an oral factor Xa inhibitor that can be administered in a simple, fixed-dose regimen, may be an option for the extended treatment of venous thromboembolism. Methods In this randomized, double-blind study, we compared two doses of apixaban (2.5 mg and 5 mg, twice daily) with placebo in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was clinical equipoise regarding the continuation or cessation of anticoagulation therapy. The study drugs were administered for 12 months. Results A total of 2486 patients underwent randomization, of whom 2482 were included in the intention-to-treat analyses. Symptomatic recurrent venous thromboembolism or death from venous thromboembolism occurred in 73 of the 829 patients (8.8%) who were receiving placebo, as compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P<0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. The rate of death from any cause was 1.7% in the placebo group, as compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group. Conclusions Extended anticoagulation with apixaban at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding. (Funded by Bristol-Myers Squibb and Pfizer; AMPLIFY-EXT ClinicalTrials.gov number, NCT00633893 .).
    New England Journal of Medicine 12/2012; · 53.30 Impact Factor
  • Article: Intravenous Thrombolysis for Acute Ischemic Stroke Associated to Extracranial Internal Carotid Artery Occlusion: The ICARO-2 Study.
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    ABSTRACT: Background and Purposes: In a case-control study in patients with acute ischemic stroke and extracranial internal carotid artery (eICA) occlusion, thrombolytic treatment was associated with increased mortality. The aim of this cohort study was to assess the efficacy and safety of thrombolysis in patients with eICA occlusion compared to those without eICA occlusion. Methods: Consecutive patients treated with intravenous tissue-type plasminogen activator within 4.5 h from symptom onset included in the Safe Implementation of Thrombolysis in Stroke - International Stroke Thrombolysis Registry (SITS-ISTR) in 20 Italian centres were analyzed. Acute carotid occlusion was diagnosed using ultrasound examination, angio-CT scan or angio-MRI. Since the SITS-ISTR database did not plan to report the site of vessel occlusion, each participating center provided the code of the patient with eICA occlusion. Patients were divided into 2 groups, those with and those without eICA occlusion. Main outcome measures were: death, disability (modified Rankin Scale, mRS, 3-6) and any intracranial bleeding at 3 months. Multiple logistic regression analysis was performed to reveal predictors for main outcomes. The following variables of interest were included in the analysis: presence of eICA occlusion, age, gender, diabetes mellitus, hyperlipidemia, atrial fibrillation, congestive heart failure, previous stroke, current smoking, antiplatelet treatment at stroke onset, baseline NIHSS score, baseline blood glucose, cholesterol and blood pressure, history of hypertension and stroke onset to treatment time. Results: A total of 1,761 patients without eICA occlusion and 137 with eICA occlusion were included in the study. At 3 months, 42 patients were lost to follow-up (3 with eICA occlusion). Death occurred in 30 (22.4%) patients with eICA occlusion and in 175 (10.2%) patients without (p < 0.0001). Death or disability at 3 months occurred in 91 of 134 patients with eICA occlusion (67.9%) compared with 654 of 1,722 patients without eICA occlusion (37.9%, p < 0.0001). No or minimal disability at 3 months (mRS 0-1) was reported in 25 (18.7%) patients with eICA occlusion and in 829 (48.2%) patients without (p < 0.0001). Any intracranial bleeding detected by CT or MRI at posttreatment imaging was seen in 16 (11.7%) patients with eICA occlusion and in 314 (17.8%) of those without (p = 0.09). The proportion of symptomatic intracerebral hemorrhage was 5.8% for patients with eICA occlusion and 8.0% for patients without (p = 0.16). At logistic regression analysis, eICA occlusion was associated with mortality (odds ratio, OR 5.7; 95% confidence interval, CI 2.9-11.1) and mortality or disability (OR 5.0; 95% CI 2.9-8.7) at 90 days. Conclusions: This cohort study in patients with acute ischemic stroke treated with thrombolysis showed an association between eICA occlusion and adverse outcome.
    Cerebrovascular Diseases 12/2012; 34(5-6):430-435. · 2.72 Impact Factor
  • Article: Clinical features and short term outcomes of patients with acute pulmonary embolism. The Italian Pulmonary Embolism Registry (IPER).
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    ABSTRACT: BACKGROUND: Registries are essential to obtain information on the whole spectrum of patients with pulmonary embolism (PE). The aim of the Italian Pulmonary Embolism Registry (IPER) is to report on demographics, clinical features, management, and outcomes of patients diagnosed with PE in everyday clinical practice. METHODS: Patients with confirmed acute PE were enrolled in a web-based registry, in Cardiology, Emergency or Internal Medicine Departments in 47 hospitals in Italy. RESULTS: Overall, 1716 patients were included, mean age 70±15years, (14% of the patients were <50 and 43% >75year old); 57% of female gender and 11.7% hemodynamically unstable at presentation/diagnosis. D-dimer was performed in 1358 patients (80%). Computerized tomographic pulmonary angiogram (CT) was used for diagnosis in the majority of the patients (82.1%), followed by perfusion lung scan (8.6%). Thrombolytic agents were used in 185 (10.8%) patients, percutaneous thrombectomy in 14 (0.8%) and surgery in 2 (0.1%). One hundred sixteen patients died while in-hospital (6.7%), 68 (3.9%) due to PE. Death or clinical deterioration occurred in 138 patients (8.0%). All-cause mortality was 31.8% in hemodynamically unstable patients and 3.4% in hemodynamically stable patients; the corresponding PE-related deaths were 23.3% and 1.4% respectively. Age >75 (HR 1.50, 95% CI 1.01-2.25), immobilization >3days before diagnosis of PE (HR 2.54, 95% CI 1.72-3.77) and hemodynamic impairment (HR 6.38, 95% CI 4.26-9.57) were independent predictors for in-hospital death. CONCLUSIONS: Patients with PE have a considerable risk of death during the hospital stay, PE being the most common cause of early mortality.
    Thrombosis Research 08/2012; · 2.44 Impact Factor
  • Article: Perioperative stroke risk in nonvascular surgery.
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    ABSTRACT: Background: Perioperative stroke is an ischemic or hemorrhagic cerebrovascular accident that can arise intraoperatively or from 3 to 30 days after surgery. This relatively rare complication deserves attention because of its high mortality and serious disability, the latter of which can lead to prolonged hospital stay as well as disswcharge to long-term care facilities. The aim of this article was to review the literature on perioperative stroke in general surgery, excluding carotid and cardiac surgeries because these have already been thoroughly investigated in previous papers. Methods: A search strategy was designed to identify all relevant studies on perioperative stroke in the English language. This search was restricted to papers published up to December 5, 2011. Studies were initially identified from the Medline/PubMed database, EMBASE and the Cochrane Database using the search terms 'surgery', 'perioperative stroke', 'risk factors', 'anticoagulation treatment' and 'antiplatelet treatment'. Results: The incidence of perioperative stroke among patients who undergo nonvascular surgery is reported to be about 0.08-0.7%. This depends on the type and complexity of the surgical procedure along with patient risk factors. The reported perioperative mortality is 18-26%. One of the main issues is the management of patients taking anticoagulant or antiplatelet drugs, as the risk of bleeding has to be counterbalanced with the risk of arterial thrombosis due to discontinuation. Additionally, the presence of symptomatic carotid stenosis should be taken into account in the risk evaluation. Conclusions: To date, current guidelines are incomplete regarding the management of patients with vascular disease undergoing nonvascular surgery. It is recommended to stop oral anticoagulation approximately 5 days before major surgery to adequately allow the INR to normalize, and at the same time subcutaneous low-molecular-weight heparin or intravenous unfractionated heparin should be started. Regarding new anticoagulants, dabigatran does not need to be withheld for minor procedures. Currently, there are no clear recommendations on the use of rivaroxaban and apixaban. Data concerning the management of patients undergoing antiplatelet therapy are lacking. To date, neurologists discourage the perioperative withdrawal of aspirin (acetylsalicylic acid, ASA) especially in patients in secondary prevention. The 'Antiplatelet Agents in the Perioperative Management of Patients Trial' is ongoing to assess the safety and determine the optimal use of ASA in the perioperative management of patients undergoing general and abdominal surgery. In the meantime an individualized, accurate, multidisciplinary (surgical, neurological, cardiological and anesthesiological) risk/benefit assessment remains the best basis for treatment decision.
    Cerebrovascular Diseases 08/2012; 34(3):175-81. · 2.72 Impact Factor
  • Article: Lung ultrasound in the diagnosis of stroke-associated pneumonia.
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    ABSTRACT: Pneumonia is a common complication in stroke patients; it is associated with an adverse outcome, prolonged hospital stay and increased health costs. The aim of this study was to assess the ability of lung ultrasound to rule in or rule out pneumonia in patients with stroke. Patients with ischemic or hemorrhagic stroke were included in the study if they had a clinical suspicion of pneumonia. Lung ultrasound imaging and chest X-ray studies were performed within 24 h from the onset of symptoms of pneumonia; the sonographer and radiologists were unaware of the chest X-ray study and ultrasound imaging results, respectively. In case of discordant results, lung computed tomography (CT) was performed if a definitive diagnosis was required to optimize clinical management. Seventy patients were included in the study. Among 24 patients with unilaterally positive chest X-ray studies, the ultrasound imaging was unilaterally positive in 19 cases (79.2 %), bilaterally positive in 3 cases (12.5 %) and negative in 2 cases (8.3 %). Among 44 patients with negative chest X-ray studies, ultrasound imaging was unilaterally positive in 17 cases (38.6 %), bilaterally positive in 2 cases (4.6 %), negative in 19 cases (43.2 %) and non-conclusive in 6 cases (13.6 %). A lung CT scan was performed in 9 of the 21 discordant cases, and it always confirmed the ultrasound imaging results. Ultrasound imaging and chest X-ray studies were concordant in 42 out of 63 cases, 66.7 % (Pearson χ(2) = 11.97, p = 0.001). In conclusions, this study shows the utility of LUS imaging to rule in or rule out pneumonia in patients with stroke. We believe that lung ultrasound imaging can help clinicians in the diagnosis of stroke-associated pneumonia.
    Internal and Emergency Medicine 07/2012; · 2.06 Impact Factor
  • Article: Aspirin for preventing the recurrence of venous thromboembolism – WARFASA trial
    New England Journal of Medicine (NEJM). 05/2012;
  • Article: Aspirin for preventing the recurrence of venous thromboembolism.
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    ABSTRACT: About 20% of patients with unprovoked venous thromboembolism have a recurrence within 2 years after the withdrawal of oral anticoagulant therapy. Extending anticoagulation prevents recurrences but is associated with increased bleeding. The benefit of aspirin for the prevention of recurrent venous thromboembolism is unknown. In this multicenter, investigator-initiated, double-blind study, patients with first-ever unprovoked venous thromboembolism who had completed 6 to 18 months of oral anticoagulant treatment were randomly assigned to aspirin, 100 mg daily, or placebo for 2 years, with the option of extending the study treatment. The primary efficacy outcome was recurrence of venous thromboembolism, and major bleeding was the primary safety outcome. Venous thromboembolism recurred in 28 of the 205 patients who received aspirin and in 43 of the 197 patients who received placebo (6.6% vs. 11.2% per year; hazard ratio, 0.58; 95% confidence interval [CI], 0.36 to 0.93) (median study period, 24.6 months). During a median treatment period of 23.9 months, 23 patients taking aspirin and 39 taking placebo had a recurrence (5.9% vs. 11.0% per year; hazard ratio, 0.55; 95% CI, 0.33 to 0.92). One patient in each treatment group had a major bleeding episode. Adverse events were similar in the two groups. Aspirin reduced the risk of recurrence when given to patients with unprovoked venous thromboembolism who had discontinued anticoagulant treatment, with no apparent increase in the risk of major bleeding. (Funded by the University of Perugia and others; WARFASA ClinicalTrials.gov number, NCT00222677.).
    New England Journal of Medicine 05/2012; 366(21):1959-67. · 53.30 Impact Factor
  • Article: MULTIDETECTOR COMPUTED TOMOGRAPHY FOR ACUTE PULMONARY EMBOLISM: EMBOLIC BURDEN AND CLINICAL OUTCOME.
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    ABSTRACT: Background In patients with acute pulmonary embolism (PE) the correlation between the embolic burden assessed at multidetector computed tomography (MDCT) and clinical outcome remains unclear. Patients with symptomatic acute PE diagnosed by MDCT were included in a multicenter study aimed at assessing the prognostic role of the embolic burden evaluated at MDCT.Methods Embolic burden was assessed as i) localization of the emboli: central (saddle or at least one main pulmonary artery), lobar or distal (segmental or sub-segmental arteries) and ii) the obstruction index (OI) by the scoring system of Qanadli. The primary outcome was 30-day all-cause-death and/or clinical deterioration. Predictors of all-cause-death and/or clinical deterioration were identified by Cox regression statistics.ResultsOverall 579 patients were included in the study; 60 (10.4%) died or had clinical deterioration at 30 days. Central localization of emboli was not associated with all-cause-death and/or clinical deterioration (hazard ratio [HR] 2.42; 95% CI 0.77-7.59, p=0.13). However, in the 516 hemodynamically stable patients, central localization of emboli (HR 8.3, 95% CI 1.0-67, p=0.047) was an independent predictor of all-cause-death and/or clinical deterioration while distal emboli were inversely associated with these outcome events (HR 0.12, 95% CI 0.015-0.97, p=0.047). No correlation was found between OI (evaluated in 448 patients) and all-cause-death and/or clinical deterioration in the overall study population and in hemodynamically stable patients.Conclusions In hemodynamically stable patients with acute PE, central emboli are associated with an increased risk for all-cause-death and/or clinical deterioration; this risk is low in patients with segmental or subsegmental PE.
    Chest 05/2012; · 5.25 Impact Factor
  • Article: Long-term death and recurrence in patients with acute venous thromboembolism: the MASTER registry.
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    ABSTRACT: The long-term clinical outcome of VTE has been essentially assessed in cohorts of selected patients. The aim of this multicenter registry was to prospectively assess the long-term clinical outcome in a cohort of unselected patients with objectively confirmed acute VTE. Death and VTE recurrence at 24 months were the main study outcomes. Univariate and multivariate survival analyses were performed according to the Kaplan-Meyer and Cox proportional hazard model, respectively. 2119 patients with acute VTE were included in the registry: 1541 (72.7%) with deep vein thrombosis, 206 (9.7%) with pulmonary embolism and 372 (17.6%) with both. Information about death was available in 2021 patients (95.4%) and about recurrence in 1988 patients (93.8%). 167 patients (4.55% patient-year) died during follow-up. After adjusting for age, cancer (Hazard ratio [HR]: 7.2; 95%CI 4.8-10.8), long-term heparin treatment (HR: 2.5; 95%CI 1.8-3.5), in-hospital management of VTE (HR: 2.0; 95%CI 1.3-3.0), and ileo-caval thrombosis (HR: 1.7; 95%CI 1.2-2.4) were found to be independent predictors of death. 124 (3.63% patient-year) patients had a VTE recurrence during follow-up. In-hospital management of VTE (HR: 1.8; 95%CI 1.2-2.9), male gender (HR: 1.7; 95%CI 1.2-2.4) were independent risk factors for recurrent VTE. Cancer (HR: 1.6; 95%CI 1.0-2.8) showed a trend for increased risk of VTE recurrence (p=0.056). The reported rate of major bleeding was 2.5%. In a large cohort of unselected VTE patients, cancer, ileo-caval thrombosis, long-term heparin treatment and in-hospital management were associated with increased mortality during long-term follow-up. In-hospital management, male gender were associated with an increased risk of VTE recurrence.
    Thrombosis Research 05/2012; 130(3):369-73. · 2.44 Impact Factor
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    Article: Long-term outcomes of patients with cerebral vein thrombosis: a multicenter study.
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    ABSTRACT: Little information is available on the long-term clinical outcome of cerebral vein thrombosis (CVT). In an international, retrospective cohort study, we assessed the long-term rates of mortality, residual disability and recurrent venous thromboembolism (VTE) in a cohort of patients with a first CVT episode. Seven hundred and six patients (73.7% females) with CVT were included. Patients were followed for a total of 3171 patient-years. Median follow-up was 40 months (range 6, 297 months). At the end of follow-up, 20 patients had died (2.8%). The outcome was generally good: 89.1% of patients had a complete recovery (modified Rankin Score [mRS] 0-1) and 3.8% had a partial recovery and were independent (mRS 2). Eighty-four per cent of patients were treated with oral anticoagulants and the mean treatment duration was 12 months. CVT recurred in 31 patients (4.4%), and 46 patients (6.5%) had a VTE in a different site, for an overall incidence of recurrence of 23.6 events per 1000 patient-years (95% confidence Interval [CI] 17.8, 28.7) and of 35.1 events/1000 patient-years (95% CI, 27.7, 44.4) after anticoagulant therapy withdrawal. A previous VTE was the only significant predictor of recurrence at multivariate analysis (hazard ratio [HR] 2.70; 95% CI 1.25, 5.83). The long-term risk of mortality and recurrent VTE appears to be low in patients who survived the acute phase of CVT. A previous VTE history independently predicts recurrent events.
    Journal of Thrombosis and Haemostasis 05/2012; 10(7):1297-302. · 5.73 Impact Factor
  • Article: A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the Protecht score.
    Internal and Emergency Medicine 05/2012; 7(3):291-2. · 2.06 Impact Factor
  • Article: Predictive value of admission blood glucose level on short-term mortality in acute cerebral ischemia.
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    ABSTRACT: Admission hyperglycemia increases the risk of death in patients with acute stroke. However, the most appropriate cut-off of glucose level indicating an increased risk of short-term mortality remains unknown. We aimed at establishing the optimum cut-offs of several variables (including admission blood glucose levels) predicting case-fatality (72hours, 7days) and unfavorable outcome [modified Rankin Scale (mRS) score 5-6 at 7 days] in consecutive first-ever acute ischemic stroke. Receiver operating characteristic (ROC) curves were constructed. Eight hundred eleven consecutive patients were included [median age of 77 (69-83) years; 418 (52%) male; 239 (30%) diabetics; median admission National Institutes of Health Stroke Scale (NIHSS) 7 (4-12), 32 (4%) dead within 72hours; 64 (8%) dead within day 7; 155 (19%) with unfavorable outcome]. Median admission glucose levels were 113 (97-155)mg/dL. Diabetics had significantly higher median glucose levels than non-diabetics [163 (133-214) vs. 107 (92-123) mg/dL, p<0.001]. According to ROC analysis, the only significant predictive value of glycemia was ≥143mg/dL for 72-hour fatality (sensitivity 88% and specificity 70%) especially in non-diabetics (sensitivity 88% and sensitivity 62%). This cut-off point was an independent predictor for 72-hour fatality (overall: OR=4.0, CI=1.6-9.9, p=0.003; non-diabetics: OR=4.9, CI=1.7-14.5, p=0.004). The cut-offs of fasting total cholesterol levels and admission leukocytes had poor predictive values for each outcome, while those of admission NIHSS had good discrimination in predicting short-term outcome measures. Admission hyperglycemia (≥143mg/dL) is a strong and an independent predictor for 72-hour fatality, especially in patients with no prior history of diabetes mellitus.
    Journal of diabetes and its complications 04/2012; 26(2):70-6. · 2.11 Impact Factor
  • Article: Oral rivaroxaban for the treatment of symptomatic pulmonary embolism.
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    ABSTRACT: A fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism. In a randomized, open-label, event-driven, noninferiority trial involving 4832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis, we compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding. Rivaroxaban was noninferior to standard therapy (noninferiority margin, 2.0; P=0.003) for the primary efficacy outcome, with 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%) (hazard ratio, 1.12; 95% confidence interval [CI], 0.75 to 1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard-therapy group (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P=0.23). Major bleeding was observed in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P=0.003). Rates of other adverse events were similar in the two groups. A fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit-risk profile. (Funded by Bayer HealthCare and Janssen Pharmaceuticals; EINSTEIN-PE ClinicalTrials.gov number, NCT00439777.).
    New England Journal of Medicine 04/2012; 366(14):1287-97. · 53.30 Impact Factor
  • Article: New and old anticoagulants in cancer.
    Melina Verso, Giancarlo Agnelli
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    ABSTRACT: Venous thromboembolism (VTE) is frequently encountered in patients with cancer. Cancer patients have an increased risk of VTE during the entire course of their disease, but this risk is particularly high during the first months after cancer diagnosis and during the advanced stage of disease. VTE is a relevant cause of morbidity and mortality in patients with cancer and has a significant impact on their quality of life. Since 50 years, heparin and vitamin K antagonists are the mainstay anticoagulants for the prevention and treatment of VTE. At present, the treatment of VTE in patients with cancer does not differ from that of other medical patients. However, patients with cancer still have unmet clinical needs with the currently available antithrombotic agents. These patients are known to be at two- to four-fold risk for both VTE recurrence and anticoagulant-related bleeding, despite adequate anticoagulation, in comparison to non cancer patients Several new antithrombotic drugs targeting activated factor X or activated thrombin have been developed in the last decades for treatment of VTE. Some of them seems to have a potential therapeutic value for VTE treatment in patients with cancer, but no randomized studies have been specifically conducted in cancer patients. Until data with these novel agents in the specific oncology setting will be available, their efficacy and safety for both prevention and treatment of VTE in cancer patients remains to be defined.
    Thrombosis Research 04/2012; 129 Suppl 1:S101-5. · 2.44 Impact Factor
  • Article: Old and new oral anticoagulants for venous thromboembolism and atrial fibrillation: a review of the literature.
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    ABSTRACT: Heparin, fondaparinux and vitamin K antagonists (VKAs) are effective for the prevention and treatment of venous thromboembolism. VKAs reduce by almost 60% the rate of cardioembolic complications in patients with atrial fibrillation. The risk for bleeding and the inconvenience for laboratory monitoring, dose adjustment and drug or food interactions are the main limits for VKAs while parenteral administration is the main limit for heparin and fondaparinux. New oral anticoagulants with more predictable anticoagulant response and no need for laboratory monitoring have been shown to be effective for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in patients with atrial fibrillation. The pharmacokinetic and pharmacodynamic profile of the new agents differ for mechanisms of action - mainly anti Xa and one antithrombin agent- bioavailability, half life, renal or live clearance. Drug interactions have been described with the new agents and inhibitors or inducers of P-gp or CYP3A4. Overall, in the prevention of venous thromboembolism after major elective orthopaedic surgery dabigatran was shown to be non-inferior, rivaroxaban and apixaban to be superior to enoxaparin. Both, rivaroxaban and dabigatran were shown to be non-inferior to low-molecular weight heparin and VKAs for the treatment of venous thromboembolism. Dabigatran 150mg twice daily reduced the incidence of both ischemic and hemorrhagic stroke in patients with atrial fibrillation respect to warfarin. In these patients rivaroxaban and apixaban reduced the incidence of hemorrhagic stroke with a similar incidence of ischemic stroke. No bleeding concern emerged with the new anticoagulant agents in this indication.
    Thrombosis Research 03/2012; 129(3):392-400. · 2.44 Impact Factor
  • Article: Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer.
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    ABSTRACT: Patients receiving chemotherapy for cancer are at increased risk for venous thromboembolism. Limited data support the clinical benefit of antithrombotic prophylaxis. In this double-blind, multicenter trial, we evaluated the efficacy and safety of the ultra-low-molecular-weight heparin semuloparin for prevention of venous thromboembolism in patients receiving chemotherapy for cancer. Patients with metastatic or locally advanced solid tumors who were beginning to receive a course of chemotherapy were randomly assigned to receive subcutaneous semuloparin, 20 mg once daily, or placebo until there was a change of chemotherapy regimen. The primary efficacy outcome was the composite of any symptomatic deep-vein thrombosis, any nonfatal pulmonary embolism, and death related to venous thromboembolism. Clinically relevant bleeding (major and nonmajor) was the main safety outcome. The median treatment duration was 3.5 months. Venous thromboembolism occurred in 20 of 1608 patients (1.2%) receiving semuloparin, as compared with 55 of 1604 (3.4%) receiving placebo (hazard ratio, 0.36; 95% confidence interval [CI], 0.21 to 0.60; P<0.001), with consistent efficacy among subgroups defined according to the origin and stage of cancer and the baseline risk of venous thromboembolism. The incidence of clinically relevant bleeding was 2.8% and 2.0% in the semuloparin and placebo groups, respectively (hazard ratio, 1.40; 95% CI, 0.89 to 2.21). Major bleeding occurred in 19 of 1589 patients (1.2%) receiving semuloparin and 18 of 1583 (1.1%) receiving placebo (hazard ratio, 1.05; 95% CI, 0.55 to 1.99). Incidences of all other adverse events were similar in the two study groups. Semuloparin reduces the incidence of thromboembolic events in patients receiving chemotherapy for cancer, with no apparent increase in major bleeding. (Funded by Sanofi; ClinicalTrials.gov number, NCT00694382.).
    New England Journal of Medicine 02/2012; 366(7):601-9. · 53.30 Impact Factor
  • Article: 96 hours ECG monitoring for patients with ischemic cryptogenic stroke or transient ischaemic attack.
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    ABSTRACT: Atrial fibrillation (AF) is intermittent in 30% of patients with cardioembolic stroke and, therefore, might not be seen in a single standard ECG recording. The aim of this study was to evaluate if prolonged ECG monitoring (96 h) finds episodes of intermittent AF beyond the 24 h ECG monitoring in patients with cryptogenic stroke or transient ischemic attack (TIA). We prospectively evaluated consecutive patients affected by cryptogenic stroke or TIA who had sinus rhythm on a 12-lead ECG on admission, and during ECG monitoring performed in the acute phase (for at least 24 h). Patients had continuous 96 h Holter ECG monitoring within 30 days from stroke onset. 114 patients were included in the study (mean age 63.1 ± 15.1, 59 males). AF was found in 29 patients (24.3%). In 20 patients, AF was found in the first 24 h of recording, and in nine patients after 24 h. In addition, several other dysrhythmias such as supraventricular ectopic activity (33), ventricular tachycardia (10), sinus pause (4) and sinus-atrial block (1) were found. In patients with cryptogenic stroke or TIA, 96 h ECG monitoring detected a high rate of AF. One-third of AF was seen beyond 24 h of ECG monitoring.
    Internal and Emergency Medicine 01/2012; · 2.06 Impact Factor

Institutions

  • 1981–2013
    • Università degli Studi di Perugia
      • Department of Internal Medicine
      Terni, Umbria, Italy
  • 2012
    • Azienda Ospedaliera San Carlo Borromeo Milano
      Milano, Lombardy, Italy
  • 2009–2011
    • Azienda Ospedaliera Santa Maria della Misericordia
      Udine, Friuli Venezia Giulia, Italy
    • University of Padua
      • Department of Cardiac, Thoracic and Vascular Sciences
      Padova, Veneto, Italy
  • 2008–2011
    • Università degli Studi dell'Insubria
      Varese, Lombardy, Italy
    • Azienda Unita Sanitaria Locale di Piacenza
      Piacenza, Emilia-Romagna, Italy
    • Universita degli studi di Ferrara
      • Department of Morphology, Surgery and Experimental Medicine
      Ferrara, Emilia-Romagna, Italy
    • Instytut Gruzlicy i Chorób Pluc w Warszawie
      Warsaw, Masovian Voivodeship, Poland
  • 2007
    • Ospedale Santa Maria della Misericordia, Rovigo
      Rovigo, Veneto, Italy
    • Università degli Studi di Torino
      Torino, Piedmont, Italy
  • 2006
    • Université Paris Descartes
      Paris, Ile-de-France, France
    • Azienda Ospedaliero Universitaria Careggi
      Firenzuola, Tuscany, Italy
  • 2005–2006
    • Thrombosis Research Institute
      London, ENG, United Kingdom