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3. Plasma levels of extracellular vesicles and the risk of post-operative pulmonary embolism in patients with primary brain tumors: a prospective study

Author

Passamonti, S, Artoni, A, Carrabba, G, Merati, G, Abbattista, M, Capecchi, M, Castellani, M, Marenghi, C, Trombetta, E, Giammattei, L, Caroli, M, Bucciarelli, P, Scalambrino, E, Peyvandi, F, Martinelli, I, Passamonti S. M., Artoni A., Carrabba G., Merati G., Abbattista M., Capecchi M., Castellani M., Marenghi C., Trombetta E., Giammattei L., Caroli M., Bucciarelli P., Scalambrino E., Peyvandi F., Martinelli I., Passamonti, S, Artoni, A, Carrabba, G, Merati, G, Abbattista, M, Capecchi, M, Castellani, M, Marenghi, C, Trombetta, E, Giammattei, L, Caroli, M, Bucciarelli, P, Scalambrino, E, Peyvandi, F, Martinelli, I, Passamonti S. M., Artoni A., Carrabba G., Merati G., Abbattista M., Capecchi M., Castellani M., Marenghi C., Trombetta E., Giammattei L., Caroli M., Bucciarelli P., Scalambrino E., Peyvandi F., and Martinelli I.

Abstract

Primary brain tumors are associated with an increased risk of pulmonary embolism (PE), particularly in the early post-operative period. The pathophysiological mechanisms of PE are poorly understood. This study aims to describe prospectively extracellular vesicles (EVs) levels and investigate whether or not their variations allow to identify patients at increased risk of post-operative PE. Consecutive meningioma or glioma patients candidate to tumor resection were included in the study if a pulmonary perfusion scan (Q-scan) performed before surgery ruled out PE. EVs derived from platelets (CD41+) or endothelial cells (CD144+), tissue factor-bearing EVs (CD142+) and their procoagulant subtype (annexin V+) were analyzed by flow cytometry before surgery (T0), within 24 h (T1), two (T2) and seven days (T7) after surgery. Q-scan was repeated at T2. Ninety-three patients with meningioma, 59 with glioma and 76 healthy controls were included in the study. CD142+ and annexin V+/CD142+ EVs were increased at T0 in meningioma and glioma patients compared to healthy controls. Twenty-nine meningioma (32%) and 16 glioma patients (27%) developed PE at T2. EVs levels were similar in meningioma patients with or without PE, whereas annexin V+ and annexin V+/CD142+ EVs were significantly higher at T1 and T2 in glioma patients with PE than in those without. Procoagulant EVs, particularly annexin V+/CD142+, increase after surgery and are more prevalent in glioma patients who developed PE after surgery than in those who did not.

Published
2021

14. Rationale and design of two prospective, multicenter, observational studies on reproductive outcome in women with recurrent failures after spontaneous or assisted conception: OTTILIA and FIRST registries

Author

Villani, M., Baldini, D., Totaro, P., Larciprete, G., Kovac, M., Carone, D., Passamonti, S. M., Permunian, E. T., Bartolotti, T., Lojacono, A., Cacciola, R., Pinto, G. L., Bucherini, E., De Stefano, Valerio, Lodigiani, C., Lavopa, C., Cho, Y. S., Pizzicaroli, C., Colaizzo, D., Grandone, E., De Stefano V. (ORCID:0000-0002-5178-5827), Villani, M., Baldini, D., Totaro, P., Larciprete, G., Kovac, M., Carone, D., Passamonti, S. M., Permunian, E. T., Bartolotti, T., Lojacono, A., Cacciola, R., Pinto, G. L., Bucherini, E., De Stefano, Valerio, Lodigiani, C., Lavopa, C., Cho, Y. S., Pizzicaroli, C., Colaizzo, D., Grandone, E., and De Stefano V. (ORCID:0000-0002-5178-5827)

Abstract

Background: Spontaneous pregnancy loss and implantation failure after assisted reproductive technologies (ART) are very common occurrences. Although 50-60% of all cases remains unexplained, various predisposing factors, including thrombophilias, have been identified. Thus, the potential benefit of a prophylaxis with low-molecular-weight heparins in improving outcomes has been often investigated over the years. However, the majority of studies are observational and results from randomized clinical trials (RCTs) are inconclusive, probably due to heterogeneity and limited sample size. To cover these unmet needs and to have further data mainly based on the real-life clinical management, we designed these multicenter registries. Methods: OTTILIA (Observational sTudy on antiThrombotic prevention in thrombophILIA and pregnancy loss) and FIRST (recurrent Failures in assIsted Reproductive Techniques) registries are two prospective, multicenter, observational studies to evaluate pregnancy or ART outcomes in consecutive women with previous reproductive failures after spontaneous or assisted conception, respectively. All enrolled women are observed from their first visit after positive pregnancy test (OTTILIA) or before commencing a new ART cycle (FIRST) until the end of pregnancy or ART procedure (negative pregnancy test/end of pregnancy, if successful cycle), respectively. Data are collected by means of questionnaires and recorded in a central database. Follow-up investigations are performed during hospital stay, routine clinical follow-up visits or telephone interviews. Primary outcome is live birth rate in the OTTILIA register and clinical pregnancy rate in the FIRST. Discussion: Although RCTs are the 'gold standard' for evaluating treatment outcomes, we believe that our registries represent a valid alternative in improving knowledge on mechanisms involved in reproductive failures and supporting future clinical decisions. Trial registration: NCT 02385461, retrospectively re

Published
2019

15. The effect of recanalization on long-term neurological outcome after cerebral venous thrombosis

Author

Rezoagli, E, Martinelli, I, Poli, D, Scoditti, U, Passamonti, S, Bucciarelli, P, Ageno, W, Dentali, F, Rezoagli E., Martinelli I., Poli D., Scoditti U., Passamonti S. M., Bucciarelli P., Ageno W., Dentali F., Rezoagli, E, Martinelli, I, Poli, D, Scoditti, U, Passamonti, S, Bucciarelli, P, Ageno, W, Dentali, F, Rezoagli E., Martinelli I., Poli D., Scoditti U., Passamonti S. M., Bucciarelli P., Ageno W., and Dentali F.

Abstract

Essentials The role of cerebral venous thrombosis (CVT) recanalization on neurologic outcome is still debated. We studied a large cohort of 508 CVT patients with 419 patient years of radiological follow-up. Recanalization rate is high during the first months after CVT and neurologic outcome is favorable. High recanalization grade of CVT independently predicts good neurological outcome. Summary: Background Studies with limited sample size and with discordant results described the recanalization time-course of cerebral venous thrombosis (CVT). The neurological outcome after a first episode of CVT is good, but the role of recanalization on neurological dependence is still debated. Objectives The aim of the study is to assess the recanalization rate after cerebral venous thrombosis (CVT) and its prognostic role in long-term neurological outcome. Patients/Methods In a retrospective observational multicenter cohort study, patients with an acute first episode of CVT with at least one available imaging test during follow-up were enrolled. Patency status of the vessels was categorized as complete, partial or not recanalized. Neurological outcome was defined using the modified Rankin scale (mRS) as good (mRS = 0–1) or poor (mRS = 2–6). Results Five-hundred and eight patients (median [IQR] age, 39 [28.5–49] years; 26% male) were included. Complete or partial recanalization was not differently represented in patients undergoing scans at different periods of time (from 28-day to 3 month-period up to a 1–3 year-period). mRS at the time of follow-up imaging was available in 483 patients; 92.8% of them had a mRS of 0-1. CVT recanalization (odds ratio [OR], 2.56; 95% confidence interval [CI], 1.59–4.13) was positively associated, whereas cancer (OR, 0.29; 95% CI, 0.09–0.88), and personal history of venous thromboembolism (VTE) (OR, 0.36; 95% CI, 0.14–0.92) were negatively associated as independent predictors of favorable (mRS = 0–1) outcome at follow-up. Conclusions Most patients wi

Published
2018

19. Clinical course of isolated distal deep vein thrombosis in patients with active cancer: a multicenter cohort study

Author

Serena M. Passamonti, Stefano Barco, Giovanni Barillari, Michelangelo Sartori, Federica Bagna, Daniela Mastroiacovo, S. Pegoraro, Walter Ageno, Raffaella Benedetti, Francesco Dentali, Corrado Lodigiani, Nicola Mumoli, Mariasanta Napolitano, M. Di Nisio, M. N. D. Di Minno, Fulvio Pomero, Dentali, F, Pegoraro, S, Barco, S, DI MINNO, Matteo, Mastroiacovo, D, Pomero, F, Lodigiani, C, Bagna, F, Sartori, M, Barillari, G, Mumoli, N, Napolitano, M, Passamonti, S. M, Benedetti, R, Ageno, W, Di Nisio, M., Dentali, F., Pegoraro, S., Barco, S., di Minno, M., Mastroiacovo, D., Pomero, F., Lodigiani, C., Bagna, F., Sartori, M., Barillari, G., Mumoli, N., Napolitano, M., Passamonti, S., Benedetti, R., and Ageno, W.

Subjects
Male, medicine.medical_specialty, distal deep vein thrombosis, mortality, neoplasm, observational study, venous thromboembolism, Hematology, Time Factors, Deep vein, Hemorrhage, 030204 cardiovascular system & hematology, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Risk Factors, Neoplasms, Internal medicine, medicine, Humans, 030212 general & internal medicine, Aged, Proportional Hazards Models, Retrospective Studies, Venous Thrombosis, business.industry, Incidence, Clinical course, Anticoagulants, Cancer, distal deep vein thrombosi, Venous Thromboembolism, Heparin, Middle Aged, medicine.disease, Thrombosis, Surgery, Treatment Outcome, medicine.anatomical_structure, Italy, Female, Pulmonary Embolism, business, Venous thromboembolism, Distal deep vein thrombosis, Mortality, Neoplasm, Observational study, medicine.drug, Cohort study
Abstract

Essentials Isolated distal deep vein thrombosis (IDDVT) is frequently associated with cancer. No study has specifically evaluated the long-term clinical course of cancer-associated IDDVT. Patients with cancer-associated IDDVT are at very high risk of symptomatic recurrence and death. We observed low rates of major bleeding during anticoagulation. SummaryBackground Although isolated distal deep vein thrombosis (IDDVT) is frequently associated with cancer, no study has specifically evaluated the long-term clinical course of IDDVT in this setting. Aim To provide data on the rate of recurrent venous thromboembolism (VTE), major bleeding events and death in IDDVT patients with active cancer. Patients and Methods Consecutive patients with active cancer and an objective IDDVT diagnosis (January 2011 to September 2014) were included from our files. We collected information on baseline characteristics, IDDVT location and extension, VTE risk factors, and type and duration of anticoagulant treatment. Results A total of 308 patients (mean age 66.2 [standard deviation (SD), 13.2 years]; 57.1% female) with symptomatic IDDVT and a solid (n = 261) or hematologic (n = 47) cancer were included at 13 centers. Cancer was metastatic in 148 (48.1%) patients. All but three (99.0%) patients received anticoagulant therapy, which consisted of low-molecular-weight heparin in 288 (93.5%) patients. Vitamin K antagonists were used for the long-term treatment in 46 (14.9%) patients, whereas all others continued the initial parenteral agent for a mean treatment duration of 4.2 months (SD, 4.6 months). During a total follow-up of 355.8 patient-years (mean, 13.9 months), there were 47 recurrent objectively diagnosed VTEs for an incidence rate of 13.2 events per 100 patient-years. During anticoagulant treatment, the annual incidence of major bleeding was 2.0 per 100 patient-years. Conclusions Cancer patients with IDDVT have a high risk of VTE recurrence. Additional studies are warranted to investigate the optimal intensity and duration of anticoagulant treatment for these patients.

Published
2017
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20. Residual vein obstruction in patients diagnosed with acute isolated distal deep vein thrombosis associated with active cancer

Author

M. N. D. Di Minno, S. Pegoraro, F. Bagna, Serena M. Passamonti, Nicola Mumoli, Stefano Barco, Giovanni Barillari, Walter Ageno, Corrado Lodigiani, Mariasanta Napolitano, Daniela Mastroiacovo, Francesco Dentali, M. Di Nisio, Raffaella Benedetti, Fulvio Pomero, Michelangelo Sartori, Dentali, F., Barco, S., Pegoraro, S., Di Minno, M. N. D., Mastroiacovo, D., Pomero, F., Lodigiani, C., Bagna, F., Sartori, M., Barillari, G., Mumoli, N., Napolitano, M., Passamonti, S. M., Benedetti, R., Ageno, W., Di Nisio, M., Dentali F., Barco S., Pegoraro S., Di Minno M.N.D., Mastroiacovo D., Pomero F., Lodigiani C., Bagna F., Sartori M., Barillari G., Mumoli N., Napolitano M., Passamonti S.M., Benedetti R., Ageno W., and Di Nisio M.

Subjects
Adult, Male, medicine.medical_specialty, medicine.drug_class, Deep vein, 030204 cardiovascular system & hematology, Compression ultrasound, Distal deep vein thrombosis, Recurrence, Residual vein obstruction, Venous thromboembolism, Hematology, Cardiology and Cardiovascular Medicine, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Neoplasms, medicine, Humans, In patient, Distal deep vein thrombosi, Aged, Ultrasonography, Venous Thrombosis, business.industry, Risk Factor, Anticoagulant, Cancer, Anticoagulants, Venous Thromboembolism, Middle Aged, medicine.disease, Thrombosis, Surgery, Discontinuation, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Acute Disease, Neoplasm, Female, business, Human, Cohort study
Abstract

After acute proximal deep vein thrombosis (DVT) the thrombotic mass decreases, especially during the first months of anticoagulation. The persistence of residual vein obstruction (RVO) may predict future recurrence in patients with cancer-associated DVT. We aimed to evaluate the proportion of patients with RVO after an episode of cancer associated isolated distal DVT (IDDVT), to identify variables associated with RVO, and to provide initial evidence of its association with recurrent VTE. We performed a post-hoc analysis of a multicenter cohort study of patients with isolated cancer-associated acute IDDVT. We included patients who underwent a control ultrasonography at the end of the anticoagulant treatment between day 30 and day 365 after index IDDVT, given that no recurrent VTE had already occurred on anticoagulant treatment. A total of 153 patients had ultrasonographic follow-up after a median of 92 days from index IDDVT: 45.8% had RVO and 54.2% exhibited complete recanalization. Female sex, Body Mass Index > 30Kg/m2 and involvement of axial calf veins showed the strongest association with RVO. The risk of recurrence was twofold higher in patients with (versus without) RVO. RVO persisted in approximately half of patients with an episode of cancer-associated IDDVT at anticoagulant discontinuation. Patients with RVO appeared to be at a higher risk for recurrent events.

Published
2018

21. Pretransplant Single Antigen Bead-Detected HLA Antibodies in Kidney Transplant Long-term Outcome: A Single-Center Cohort Experience.

Author

Passamonti SM, Cannavò A, Espadas de Arias A, Innocente A, Ramondetta M, Regalia A, Messa P, Ferraresso M, and Cardillo M

Subjects
Adult, Cohort Studies, Female, Graft Rejection immunology, Humans, Isoantibodies analysis, Male, Middle Aged, Proportional Hazards Models, Retrospective Studies, Graft Survival immunology, HLA Antigens immunology, Histocompatibility Testing methods, Isoantibodies immunology, Kidney Transplantation methods
Abstract

Single-antigen bead (SAB) platform permits the identification of antibodies not detectable by complement-dependent lymphocytotoxicity test, but their clinical significance is not completely understood. The aim of this study was to evaluate whether the presence of pretransplant SAB-detected antibodies is associated with the development of allograft failure. This is a single-center cohort study with 10-year follow-up in which 573 kidney recipients with negative pretransplant complement-dependent lymphocytotoxicity crossmatch who received transplants at the Kidney Transplant Center of Policlinico, Milan, from deceased donors between 1996 and 2005 were evaluated. Pretransplant plasma samples were retrospectively analyzed by SAB assay. Survival analyses were performed to assess the risk of allograft failures by SAB-detected antibodies. Pretransplant antibodies were found in 160 (28.0%) recipients, of whom 42 subsequently developed an allograft failure for a survival rate of 70.9% (95% confidence interval [CI), 63.5-78.4). Among those without antibodies, 58 (14.0%) returned to dialysis with a survival rate of 84.7% (95% CI, 81.0-88.4). In Cox regression analyses, patients with SAB-positivity had 2-fold higher risk of allograft failure than those who were SAB-negative (hazard ratio, 2.07; 95% CI, 1.39-2.79). Results did not change after adjustment for putative confounders. In conclusion, in this single-center cohort, 10-year allograft survival rate was significantly influenced by the presence of SAB-detected antibodies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Published
2019
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22. Lung Allocation Score System: First Italian Experience.

Author

Palleschi A, Benazzi E, Rossi CF, Torelli R, Passamonti SM, Pellegrini C, Lucianetti A, Tarsia P, Meloni F, Parigi P, and Nosotti M

Subjects
Adult, Female, Humans, Italy, Male, Middle Aged, Retrospective Studies, Transplants supply & distribution, United States, Health Care Rationing methods, Lung Transplantation, Waiting Lists mortality
Abstract

Background: Lung transplantation is an established therapeutic option for patients with end-stage pulmonary disease. In May 2005, the lung allocation score (LAS) was introduced in the United States to maximize the benefit to the recipient population and reduce waiting list mortality. The LAS has been applied in a region of Italy since March 2016 on a provisional basis. The aims of the study were describing waiting list characteristics and short-term outcomes after lung transplantation before and after LAS introduction., Methods: All the patients who received transplants between January 1, 2011, and March 15, 2017, were included in our retrospective study. The study population was divided into 2 cohorts (historical cohort and post-LAS cohort) and a comparison among the main perioperative data was performed., Results: The historical cohort consisted of 415 patients on the waiting list with 91 deaths and 199 lung transplants; the post-LAS cohort consisted of 134 patients with 10 deaths on the waiting list and 51 transplants. Median waiting time and mortality on the list decreased from 223 to 106 days (P = .03) and from 11.2% to 7.5% (P > .05), respectively. The transplantation rate increased from 25% to 38% (P = .001) and the probability to receive a transplant in the first year in the post-LAS era increased significantly (P = .004)., Conclusions: The results of the introduction of the LAS system in our region are encouraging and have not shown any adverse short-term effects. The regional coordination decided to prolong the experimental application of LAS in order to accumulate more data and to evaluate medium-term outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Published
2019
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23. The effect of recanalization on long-term neurological outcome after cerebral venous thrombosis.

Author

Rezoagli E, Martinelli I, Poli D, Scoditti U, Passamonti SM, Bucciarelli P, Ageno W, and Dentali F

Subjects
Adult, Cerebral Angiography methods, Cerebrovascular Circulation, Computed Tomography Angiography methods, Disability Evaluation, Female, Humans, Intracranial Thrombosis diagnostic imaging, Intracranial Thrombosis physiopathology, Magnetic Resonance Angiography methods, Male, Middle Aged, Phlebography methods, Recovery of Function, Retrospective Studies, Time Factors, Treatment Outcome, Vascular Patency, Venous Thrombosis diagnostic imaging, Venous Thrombosis physiopathology, Intracranial Thrombosis surgery, Neurosurgical Procedures adverse effects, Venous Thrombosis surgery
Abstract

Essentials The role of cerebral venous thrombosis (CVT) recanalization on neurologic outcome is still debated. We studied a large cohort of 508 CVT patients with 419 patient years of radiological follow-up. Recanalization rate is high during the first months after CVT and neurologic outcome is favorable. High recanalization grade of CVT independently predicts good neurological outcome., Summary: Background Studies with limited sample size and with discordant results described the recanalization time-course of cerebral venous thrombosis (CVT). The neurological outcome after a first episode of CVT is good, but the role of recanalization on neurological dependence is still debated. Objectives The aim of the study is to assess the recanalization rate after cerebral venous thrombosis (CVT) and its prognostic role in long-term neurological outcome. Patients/Methods In a retrospective observational multicenter cohort study, patients with an acute first episode of CVT with at least one available imaging test during follow-up were enrolled. Patency status of the vessels was categorized as complete, partial or not recanalized. Neurological outcome was defined using the modified Rankin scale (mRS) as good (mRS = 0-1) or poor (mRS = 2-6). Results Five-hundred and eight patients (median [IQR] age, 39 [28.5-49] years; 26% male) were included. Complete or partial recanalization was not differently represented in patients undergoing scans at different periods of time (from 28-day to 3 month-period up to a 1-3 year-period). mRS at the time of follow-up imaging was available in 483 patients; 92.8% of them had a mRS of 0-1. CVT recanalization (odds ratio [OR], 2.56; 95% confidence interval [CI], 1.59-4.13) was positively associated, whereas cancer (OR, 0.29; 95% CI, 0.09-0.88), and personal history of venous thromboembolism (VTE) (OR, 0.36; 95% CI, 0.14-0.92) were negatively associated as independent predictors of favorable (mRS = 0-1) outcome at follow-up. Conclusions Most patients with a first CVT had complete or partial recanalization at follow-up. Recanalization was independently associated with a favorable neurological outcome., (© 2018 International Society on Thrombosis and Haemostasis.)

Published
2018
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24. Pregnancy outcome after a first episode of cerebral vein thrombosis.

Author

Martinelli I, Passamonti SM, Maino A, Abbattista M, Bucciarelli P, Somigliana E, Artoni A, Gianniello F, and Peyvandi F

Subjects
Adolescent, Adult, Case-Control Studies, Cerebral Veins pathology, Cohort Studies, Female, Heparin therapeutic use, Humans, Intracranial Thrombosis epidemiology, Male, Obstetrics, Pregnancy, Pregnancy Complications, Hematologic drug therapy, Pregnancy Outcome, Recurrence, Thrombophilia blood, Venous Thrombosis prevention & control, Young Adult, Anticoagulants therapeutic use, Heparin, Low-Molecular-Weight therapeutic use, Thrombophilia complications, Venous Thrombosis drug therapy
Abstract

Essentials Little is known about recurrences and pregnancy outcome after cerebral vein thrombosis (CVT). We studied a cohort of pregnant women with CVT. Women with CVT appear at increased risk of late obstetrical complications despite prophylaxis. Risks of recurrent thrombosis and bleeding in women on heparin prophylaxis while pregnant are low., Summary: Background The risk of recurrent thrombosis and bleeding episodes in women with previous cerebral vein thrombosis (CVT) on antithrombotic prophylaxis with low-molecular-weight heparin (LMWH) during pregnancy is not established and little information is available on pregnancy outcome. Objectives The aims of this study were to evaluate the risk of obstetrical complications, recurrent venous thrombosis and bleeding in a cohort of pregnant women on LMWH after a first episode of CVT. In addition, to estimate the relative risk of obstetrical complications, patients were compared with healthy women without thrombosis and with at least one pregnancy in their life. Patients We studied a cohort of 52 patients and 204 healthy women. Results The risk of developing late obstetrical complications was 24% (95% CI, 18-38%), leading to a relative risk of 6.09 (95% CI, 2.46-15.05). The risk of miscarriage was not increased. The higher risk of late obstetrical complications in patients appeared unrelated to a previous history of obstetrical complications, to the carriership of thrombophilia abnormalities, or to the presence of co-morbidities. The incidence of termination observed in patients with thrombophilia was double that observed in those without. No recurrent thrombosis or bleeding episodes were observed. Conclusions Women with previous CVT on LMWH prophylaxis during pregnancy have a low risk of developing recurrent thrombosis or bleeding episodes, but seem to have an increased risk of late obstetrical complications., (© 2016 International Society on Thrombosis and Haemostasis.)

Published
2016
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