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1. Anticoagulant treatment for upper extremity deep vein thrombosis: A systematic review and meta-analysis

Author

Valeriani, E., Di Nisio, M., Porceddu, E., Agostini, F., Pola, R., Spoto, S., Donadini, M. P., Ageno, W., Porfidia, A., Agostini F., Pola R. (ORCID:0000-0001-5224-2931), Porfidia A. (ORCID:0000-0003-4915-2892), Valeriani, E., Di Nisio, M., Porceddu, E., Agostini, F., Pola, R., Spoto, S., Donadini, M. P., Ageno, W., Porfidia, A., Agostini F., Pola R. (ORCID:0000-0001-5224-2931), and Porfidia A. (ORCID:0000-0003-4915-2892)

Abstract

Background: Data on anticoagulant treatment for upper extremity deep vein thrombosis (UEDVT) are largely derived from studies on usual site venous thromboembolism (VTE). Objectives: The objective of this meta-analysis was to evaluate the efficacy and safety of anticoagulant therapy for UEDVT. Patients/Methods: A systematic search of MEDLINE and EMBASE was conducted for studies including patients with UEDVT. Primary outcomes were recurrent VTE and major bleeding. Secondary outcomes included clinically-relevant non-major bleeding and all-cause mortality. Summary estimates with 95% confidence intervals (CIs) were calculated by random-effect meta-analysis. Results: A total of 1473 patients from 11 prospective and nine retrospective studies were included. Sixty percent of patients had an indwelling catheter and 56.1% had cancer. Anticoagulant treatment consisted of direct oral anticoagulants, low molecular weight heparin followed by vitamin K antagonists, and low molecular weight heparin alone in 45.1%, 35.0%, and 19.9% of patients, respectively. During a median follow-up of 13 months, recurrent VTE occurred in 3% of patients (95% CI: 2–4; 21/1334 patients), major bleeding in 3% (95% CI: 2%–5%; 29/1235 patients), clinically-relevant non-major bleeding in 4% (95% CI: 3–6; 40/1075 patients), and all-cause mortality in 9% (95% CI: 5–15; 108/1084 patients). Rates of these outcomes were not significantly different between patients with or without cancer, patients with or without an indwelling catheter, and among those receiving different anticoagulant treatments. Conclusions: In patients with UEDVT, anticoagulant treatment is associated with a low risk of recurrent VTE and a nonnegligible risk of major bleeding.

Published
2022

3. Low-Dose Rivaroxaban to Prevent Recurrences of Venous Thromboembolism in Cancer: A Real-Life Experience with a Focus on Female Patients

Author

Santini, Paolo, Mosoni, Carolina, D'Errico, Alessandro, Porceddu, E., Lupascu, Andrea, Valeriani, E., Tondi, Paolo, Pola, Roberto, Porfidia, Angelo, Santini P., Mosoni C., D'Errico A., Lupascu A., Tondi P. (ORCID:0000-0003-1654-2448), Pola R. (ORCID:0000-0001-5224-2931), Porfidia A. (ORCID:0000-0003-4915-2892), Santini, Paolo, Mosoni, Carolina, D'Errico, Alessandro, Porceddu, E., Lupascu, Andrea, Valeriani, E., Tondi, Paolo, Pola, Roberto, Porfidia, Angelo, Santini P., Mosoni C., D'Errico A., Lupascu A., Tondi P. (ORCID:0000-0003-1654-2448), Pola R. (ORCID:0000-0001-5224-2931), and Porfidia A. (ORCID:0000-0003-4915-2892)

Abstract

Background: The way in which to prevent recurrent venous thromboembolism (VTE) is an unmet clinical need in cancer patients. International guidelines only provide conditional recommendations and do not specify which anticoagulant and dose should be used. In the last 2 years, we have been using low-dose rivaroxaban to prevent VTE recurrences in cancer patients. The results of this real-life experience are presented in this study. Methods: All patients had cancer and had previously completed a cycle of at least six months of full-dose anticoagulation for the treatment of a VTE index event, before receiving a prescription of low-dose rivaroxaban (10 mg once daily) for secondary prevention of VTE. Effectiveness and safety of this therapeutic regimen were evaluated in terms of VTE recurrences, major bleedings (MB), and clinically relevant non-major bleedings (CRNMB). Results: The analysis included 106 cancer patients. Their median age was 60 years (IQR 50–69). Metastatic cancer was present in 87 patients (82.1%). Six patients (5.7%) had brain metastases. Over a median follow-up time of 333 days (IQR 156–484), the incidence of VTE recurrences was 3.8% (95%CI 1.0–9.4), with a recurrence rate of 4.0 per 100 person-years (95%CI 1.1–10.2). We observed no MB (0.0%) and three CRNMB (2.8%) (95%CI 0.6–8.1). Conclusions: Low-dose rivaroxaban is potentially effective and safe in cancer patients that require prevention of recurrent VTE. Large-scale studies are needed to confirm these findings.

Published
2023

4. Ultrasound Elastography to Assess Age of Deep Vein Thrombosis: A Systematic Review

Author

Santini, Paolo, Esposto, Giorgio, Ainora, Maria Elena, Lupascu, Andrea, Gasbarrini, Antonio, Zocco, Maria Assunta, Pola, Roberto, Santini P., Esposto G., Ainora M. E., Lupascu A., Gasbarrini A. (ORCID:0000-0002-7278-4823), Zocco M. A. (ORCID:0000-0002-0814-9542), Pola R. (ORCID:0000-0001-5224-2931), Santini, Paolo, Esposto, Giorgio, Ainora, Maria Elena, Lupascu, Andrea, Gasbarrini, Antonio, Zocco, Maria Assunta, Pola, Roberto, Santini P., Esposto G., Ainora M. E., Lupascu A., Gasbarrini A. (ORCID:0000-0002-7278-4823), Zocco M. A. (ORCID:0000-0002-0814-9542), and Pola R. (ORCID:0000-0001-5224-2931)

Abstract

Background and aims: Deep-vein thrombosis (DVT) is a widely diffused condition, and its accurate staging has major clinical and therapeutic implications. Ultrasound elastography (UE) is a rapidly evolving imaging technique that allows quantification of elastic tissue properties and could play a crucial role in determining thrombus age. The aim of this review is to find clinical evidence regarding the application of UE in the evaluation of DVT and its usefulness in differentiating thrombosis age. Methods: A literature search of clinical studies was performed to identify the ability of UE of discriminate acute, subacute, and chronic DVT. Heterogeneity and publication bias were calculated. In accordance with the study protocol, a qualitative analysis of the evidence was planned. The results were summarized with a comprehensive summary table of study characteristics and baseline characteristics of participant patients. Results: Nine studies matched the predetermined eligibility requirements for this systematic review regarding the risk of bias; the greatest criticalities were found within the domains of patient selection and index test. Based on the quality assessment, two publications were excluded from the qualitative synthesis because of the presence of significant applicability concerns. Among the seven studies that were considered eligible for qualitative synthesis, four evaluated strain elastography and three evaluated shear-wave elastography. Despite significant differences concerning study design, thrombus age definitions, and patient characteristics, nearly all studies demonstrated an increase in thrombus stiffness according to DVT age. Conclusions: UE could play a key role in routine ultrasound examination of DVT. The measurement of thrombus stiffness has a high biological plausibility and its use is supported by the finding of a correlation between the stiffness and the progression of the DVT age.

Published
2023

5. Editorial: Insights in thrombosis: 2022

Author

Douxfils, J., ten Cate, H., Pola, Roberto, Pola R. (ORCID:0000-0001-5224-2931), Douxfils, J., ten Cate, H., Pola, Roberto, and Pola R. (ORCID:0000-0001-5224-2931)

Abstract

N/A

Published
2023

9. No evidence of increased rate of thrombotic recurrences in patients with history of venous thromboembolism after vaccination for COVID-19

Author

Porfidia, Angelo, Esposto, Giorgio, Manzo, Cecilia, Santini, Paolo, Pola, Roberto, Porfidia A. (ORCID:0000-0003-4915-2892), Esposto G., Manzo C. (ORCID:0000-0002-0111-8663), Santini P., Pola R. (ORCID:0000-0001-5224-2931), Porfidia, Angelo, Esposto, Giorgio, Manzo, Cecilia, Santini, Paolo, Pola, Roberto, Porfidia A. (ORCID:0000-0003-4915-2892), Esposto G., Manzo C. (ORCID:0000-0002-0111-8663), Santini P., and Pola R. (ORCID:0000-0001-5224-2931)

Abstract

N/A

Published
2022

10. Second wave of the COVID-19 pandemic: D-dimer levels are not so high anymore

Author

Porfidia, Angelo, Porceddu, E., Talerico, Rosa, Montalto, Massimo, Landi, Francesco, Pola, Roberto, Porfidia A. (ORCID:0000-0003-4915-2892), Talerico R., Montalto M. (ORCID:0000-0001-8819-3684), Landi F. (ORCID:0000-0002-3472-1389), Pola R. (ORCID:0000-0001-5224-2931), Porfidia, Angelo, Porceddu, E., Talerico, Rosa, Montalto, Massimo, Landi, Francesco, Pola, Roberto, Porfidia A. (ORCID:0000-0003-4915-2892), Talerico R., Montalto M. (ORCID:0000-0001-8819-3684), Landi F. (ORCID:0000-0002-3472-1389), and Pola R. (ORCID:0000-0001-5224-2931)

Abstract

NA

Published
2021

11. Prevalence of pulmonary embolism on hospital admission in COVID-19 patients: Is there a role for pre-test probability scores and home treatment?

Author

Porfidia, Angelo, Pola, Enrico, Pola, Roberto, Porfidia A. (ORCID:0000-0003-4915-2892), Pola E. (ORCID:0000-0001-5350-3910), Pola R. (ORCID:0000-0001-5224-2931), Porfidia, Angelo, Pola, Enrico, Pola, Roberto, Porfidia A. (ORCID:0000-0003-4915-2892), Pola E. (ORCID:0000-0001-5350-3910), and Pola R. (ORCID:0000-0001-5224-2931)

Abstract

NA

Published
2021

12. Pulmonary Embolism in COVID-19 Patients: Which Diagnostic Algorithm Should We Use?

Author

Porfidia, Angelo, Mosoni, Carolina, Talerico, Rosa, Porceddu, E, Lupascu, Andrea, Tondi, Paolo, Landi, Francesco, Pola, Roberto, Porfidia A (ORCID:0000-0003-4915-2892), Mosoni C, Talerico R, Lupascu A, Tondi P (ORCID:0000-0003-1654-2448), Landi F (ORCID:0000-0002-3472-1389), Pola R. (ORCID:0000-0001-5224-2931), Porfidia, Angelo, Mosoni, Carolina, Talerico, Rosa, Porceddu, E, Lupascu, Andrea, Tondi, Paolo, Landi, Francesco, Pola, Roberto, Porfidia A (ORCID:0000-0003-4915-2892), Mosoni C, Talerico R, Lupascu A, Tondi P (ORCID:0000-0003-1654-2448), Landi F (ORCID:0000-0002-3472-1389), and Pola R. (ORCID:0000-0001-5224-2931)

Abstract

Introduction: Although pulmonary embolism (PE) is a frequent complication of the clinical course of COVID-19, there is a lack of explicit indications regarding the best algorithm for diagnosing PE in these patients. In particular, it is not clear how to identify subjects who should undergo computed tomography pulmonary angiography (CTPA), rather than simply X-ray and/or high resolution computed tomography (HRCT) of the chest. Methods: We retrospectively analyzed COVID-19 patients who presented to the Emergency Department (ED) of our University hospital with acute respiratory failure, or that developed acute respiratory failure during hospital stay, to determine how many of them had a theoretical indication to undergo CTPA for suspected PE according to current guidelines. Next, we looked for differences between patients who underwent CTPA and those who only underwent X-ray and/or HRCT of the chest. Finally, we determined whether patients with a confirmed diagnosis of PE had specific characteristics that made them different from those with a CTPA negative for PE. Results: Out of 93 subjects with COVID-19 and acute respiratory failure, 73 (78.4%) had an indication to undergo CTPA according to the revised Geneva and Wells scores and the PERC rule-out criteria, and 54 (58%) according to the YEARS algorithm. However, in contrast with these indications, only 28 patients (30.1%) underwent CTPA. Of note, they were not clinically different from those who underwent X-ray and/or HRCT of the chest. Among the 28 subjects who underwent CTPA, there were 10 cases of PE (35.7%). They were not clinically different from those with CTPA negative for PE. Conclusions: COVID-19 patients with acute respiratory failure undergo CTPA, X-ray of the chest, or HRCT without an established criterion. Nonetheless, when CTPA is performed, the diagnosis of PE is anything but rare. Validated tools for identifying COVID-19 patients who require CTPA for suspected PE are urgently needed.

Published
2021

13. Beneficial effects of remote medical care for patients with hereditary hemorrhagic telangiectasia during the covid‐19 pandemic

Author

Gaetani, Eleonora, Agostini, Francesca, Di Martino, Luigi, Occhipinti, Deni, Passali, Giulio Cesare, Santantonio, Mariaconsiglia, Marano, G., Mazza, Marianna, Pola, Roberto, Gaetani E. (ORCID:0000-0002-7808-1491), Agostini F., Di Martino L., Occhipinti D., Passali G. C. (ORCID:0000-0002-8176-0962), Santantonio M., Mazza M., Pola R. (ORCID:0000-0001-5224-2931), Gaetani, Eleonora, Agostini, Francesca, Di Martino, Luigi, Occhipinti, Deni, Passali, Giulio Cesare, Santantonio, Mariaconsiglia, Marano, G., Mazza, Marianna, Pola, Roberto, Gaetani E. (ORCID:0000-0002-7808-1491), Agostini F., Di Martino L., Occhipinti D., Passali G. C. (ORCID:0000-0002-8176-0962), Santantonio M., Mazza M., and Pola R. (ORCID:0000-0001-5224-2931)

Abstract

Background: Hereditary hemorrhagic telangiectasia (HHT) needs high‐quality care and multidisciplinary management. During the COVID‐19 pandemic, most non‐urgent clinical activities for HHT outpatients were suspended. We conducted an analytical observational cohort study to evaluate whether medical and psychological support, provided through remote consultation during the COVID‐19 pandemic, could reduce the complications of HHT. Methods: A structured regimen of remote consultations, conducted by either video‐calls, telephone calls, or e‐mails, was provided by a multidisciplinary group of physicians to a set of patients of our HHT center. The outcomes considered were: number of emergency room visits/hospitalizations, need of blood transfusions, need of iron supplementation, worsening of epistaxis, and psychological status. Results: The study included 45 patients who received remote assistance for a total of eight months. During this period, 9 patients required emergency room visits, 6 needed blood transfusions, and 24 needed iron supplementation. This was not different from what was registered among the same 45 patients in the same period of the previous year. Remote care also resulted in better management of epistaxis and improved quality of life, with the mean epistaxis severity score and the Euro‐Quality of Life‐ Visual Analogue Scale that were significantly better at the end than at the beginning of the study. Discussion: Remote medical care might be a valid support for HHT subjects during periods of suspended outpatient surveillance, like the COVID‐19 pandemic.

Published
2021

14. Sonic Hedgehog Signaling Pathway in Endothelial Progenitor Cell Biology for Vascular Medicine

Author

Salybekov, Aa, Salybekova, Ak, Pola, R, Asahara, T, Pola R (ORCID:0000-0001-5224-2931), Salybekov, Aa, Salybekova, Ak, Pola, R, Asahara, T, and Pola R (ORCID:0000-0001-5224-2931)

Abstract

The Hedgehog (HH) signaling pathway plays an important role in embryonic and postnatal vascular development and in maintaining the homeostasis of organs. Under physiological conditions, Sonic Hedgehog (SHH), a secreted protein belonging to the HH family, regulates endothelial cell growth, promotes cell migration and stimulates the formation of new blood vessels. The present review highlights recent advances made in the field of SHH signaling in endothelial progenitor cells (EPCs). The canonical and non-canonical SHH signaling pathways in EPCs and endothelial cells (ECs) related to homeostasis, SHH signal transmission by extracellular vesicles (EVs) or exosomes containing single-strand non-coding miRNAs and impaired SHH signaling in cardiovascular diseases are discussed. As a promising therapeutic tool, the possibility of using the SHH signaling pathway for the activation of EPCs in patients suffering from cardiovascular diseases is further explored.

Published
2018

15. Incidence of deep vein thrombosis among non-ICU patients hospitalized for COVID-19 despite pharmacological thromboprophylaxis

Author

Santoliquido, Angelo, Porfidia, Angelo, Nesci, Domenico Arturo, De Matteis, Giuseppe, Marrone, Giuseppe, Porceddu, Enrica, Camma, Giulia, Giarretta, Igor, Fantoni, M., Landi, Francesco, Gasbarrini, Antonio, Pola, Roberto, D'Alfonso, Maria Elena, Lo Monaco, Maria Rita, Santoliquido A. (ORCID:0000-0003-1539-4017), Porfidia A., Nesci A. (ORCID:0000-0001-9466-1755), De Matteis G., Marrone G., Porceddu E., Camma G., Giarretta I. (ORCID:0000-0001-5380-0843), Landi F. (ORCID:0000-0002-3472-1389), Gasbarrini A. (ORCID:0000-0002-7278-4823), Pola R. (ORCID:0000-0001-5224-2931), D'Alfonso M. E., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Santoliquido, Angelo, Porfidia, Angelo, Nesci, Domenico Arturo, De Matteis, Giuseppe, Marrone, Giuseppe, Porceddu, Enrica, Camma, Giulia, Giarretta, Igor, Fantoni, M., Landi, Francesco, Gasbarrini, Antonio, Pola, Roberto, D'Alfonso, Maria Elena, Lo Monaco, Maria Rita, Santoliquido A. (ORCID:0000-0003-1539-4017), Porfidia A., Nesci A. (ORCID:0000-0001-9466-1755), De Matteis G., Marrone G., Porceddu E., Camma G., Giarretta I. (ORCID:0000-0001-5380-0843), Landi F. (ORCID:0000-0002-3472-1389), Gasbarrini A. (ORCID:0000-0002-7278-4823), Pola R. (ORCID:0000-0001-5224-2931), D'Alfonso M. E., and Lo Monaco M. R. (ORCID:0000-0002-1457-7981)

Abstract

Background: A remarkably high incidence of venous thromboembolism (VTE) has been reported among critically ill patients with COVID-19 assisted in the intensive care unit (ICU). However, VTE burden among non-ICU patients hospitalized for COVID-19 that receive guideline-recommended thromboprophylaxis is unknown. Objectives: To determine the incidence of VTE among non-ICU patients hospitalized for COVID-19 that receive pharmacological thromboprophylaxis. Methods: We performed a systematic screening for the diagnosis of deep vein thrombosis (DVT) by lower limb vein compression ultrasonography (CUS) in consecutive non-ICU patients hospitalized for COVID-19, independent of the presence of signs or symptoms of DVT. All patients were receiving pharmacological thromboprophylaxis with either enoxaparin or fondaparinux. Results: The population that we screened consisted of 84 consecutive patients, with a mean age of 67.6 ± 13.5 years and a mean Padua Prediction Score of 5.1 ± 1.6. Seventy-two patients (85.7%) had respiratory insufficiency, required oxygen supplementation, and had reduced mobility or were bedridden. In this cohort, we found 10 cases of DVT, with an incidence of 11.9% (95% confidence interval [CI] 4.98-18.82). Of these, 2 were proximal DVT (incidence rate 2.4%, 95% CI −0.87-5.67) and 8 were distal DVT (incidence rate 9.5%, 95% CI 3.23-5.77). Significant differences between subjects with and without DVT were D-dimer > 3000 µg/L (P <.05), current or previous cancer (P <.05), and need of high flow nasal oxygen therapy and/or non-invasive ventilation (P <.01). Conclusions: DVT may occur among non-ICU patients hospitalized for COVID-19, despite guideline-recommended thromboprophylaxis.

Published
2020

16. Correction to: Venous thromboembolism and heparin use in COVID-19 patients: juggling between pragmatic choices, suggestions of medical societies and the lack of guidelines (Journal of Thrombosis and Thrombolysis, (2020), 50, 1, (68-71), 10.1007/s11239-020-02125-4)

Author

Porfidia, Angelo, Pola, Roberto, Porfidia A. (ORCID:0000-0003-4915-2892), Pola R. (ORCID:0000-0001-5224-2931), Porfidia, Angelo, Pola, Roberto, Porfidia A. (ORCID:0000-0003-4915-2892), and Pola R. (ORCID:0000-0001-5224-2931)

Abstract

In the original version of the article, the article title was processed incorrectly. The correct article title is "Venous Thromboembolism and Heparin Use in COVID-19 Patients: Juggling between Pragmatic Choices, Suggestions of Medical Societies and the Lack of Guidelines". This has been corrected with this erratum and the original article has also been updated to reflect the change in article title.

Published
2020

17. Venous thromboembolism in patients with COVID-19: Systematic review and meta-analysis

Author

Porfidia, Angelo, Valeriani, E., Pola, Roberto, Porreca, E., Rutjes, A. W. S., Di Nisio, M., Porfidia A. (ORCID:0000-0003-4915-2892), Pola R. (ORCID:0000-0001-5224-2931), Porfidia, Angelo, Valeriani, E., Pola, Roberto, Porreca, E., Rutjes, A. W. S., Di Nisio, M., Porfidia A. (ORCID:0000-0003-4915-2892), and Pola R. (ORCID:0000-0001-5224-2931)

Abstract

Background: Venous thromboembolism (VTE) may complicate the course of Coronavirus Disease 2019 (COVID-19). Objectives: To evaluate the incidence of VTE in patients with COVID-19. Methods: MEDLINE, EMBASE, and PubMed were searched up to 24th June 2020 for studies that evaluated the incidence of VTE, including pulmonary embolism (PE) and/or deep vein thrombosis (DVT), in patients with COVID-19. Pooled proportions with corresponding 95% confidence intervals (CI) and prediction intervals (PI) were calculated by random-effect meta-analysis. Results: 3487 patients from 30 studies were included. Based on very low-quality evidence due to heterogeneity and risk of bias, the incidence of VTE was 26% (95% PI, 6%–66%). PE with or without DVT occurred in 12% of patients (95% PI, 2%–46%) and DVT alone in 14% (95% PI, 1%–75%). Studies using standard algorithms for clinically suspected VTE reported PE in 13% of patients (95% PI, 2%–57%) and DVT in 6% (95% PI, 0%–60%), compared to 11% (95% PI, 2%–46%) and 24% (95% PI, 2%–85%) in studies using other diagnostic strategies or patient sampling. In patients admitted to intensive care units, VTE occurred in 24% (95% PI, 5%–66%), PE in 19% (95% PI, 6%–47%), and DVT alone in 7% (95% PI, 0%–69%). Corresponding values in general wards were respectively 9% (95% PI, 0%–94%), 4% (95% PI, 0%–100%), and 7% (95% CI, 1%–49%). Conclusions: VTE represents a frequent complication in hospitalized COVID-19 patients and often occurs as PE. The threshold for clinical suspicion should be low to trigger prompt diagnostic testing.

Published
2020

18. Follow-up management of patients receiving direct oral anticoagulants

Author

Fantoni, C., Bertu, L., Galliazzo, S., Pola, Roberto, Pomero, F., Porfidia, Angelo, Porreca, E., Valeriani, E., Ageno, W., Pola R. (ORCID:0000-0001-5224-2931), Porfidia A. (ORCID:0000-0003-4915-2892), Fantoni, C., Bertu, L., Galliazzo, S., Pola, Roberto, Pomero, F., Porfidia, Angelo, Porreca, E., Valeriani, E., Ageno, W., Pola R. (ORCID:0000-0001-5224-2931), and Porfidia A. (ORCID:0000-0003-4915-2892)

Abstract

Over the last years, direct oral anticoagulants (DOACs) have radically changed and simplified the therapeutic approach and management of patients on anticoagulant therapy. For these patients, international guidelines recommend to set up a regular follow-up (every 1–6 months) to re-enforce education, to ensure adequate adherence and persistence to treatment. In real-life setting, the application of the suggested follow-up regimens and incidence rates of thrombotic and bleeding complications related to the intensity of follow-up strategies has not been described. We conducted a multicentre, retrospective study at 4 Italian Thrombosis Centres to describe follow-up strategies of patients on DOACs treatment and to assess the incidence of bleeding and thrombotic complications. We enrolled 534 patients, with median follow-up 24 months: 52.1% had < 3 visits/year (group 1), while 47.9% required ≥ 3 visits/year (group 2). Mean age and gender were similar between the 2 groups, while severe anaemia (4.4% and 1.2%, p 0.03) and creatinine clearance < 50 mL/min were more common in group 2 (26.8% and 17.8%, p 0.02). The incidence of thromboembolic events was 3.9% in group 2 and 1.1% in group 1 (p 0.03). Major bleeding rates were non-significantly higher in group 2, whereas non-major bleeding rates occurred significantly more frequently in group 2 (26.6% and 18.7%, respectively, p 0.03). A tailored follow-up program is of critical importance to correctly manage patients on DOACs. A less intense follow-up management is feasible and safe for a substantial proportion of patients, provided they are carefully identified at specialized centres.

Published
2020

19. Assessment of neurological manifestations in hospitalized patients with COVID-19

Author

Luigetti, Marco, Iorio, Raffaele, Bentivoglio, Anna Rita, Tricoli, Luca, Riso, Vittorio, Marotta, Jessica, Piano, Carla, Primiano, Guido Alessandro, Zileri Del Verme, L., Lo Monaco, Maria Rita, Calabresi, Paolo, Abbate, V., Acampora, N., Addolorato, G., Agostini, F., Ainora, M. E., Akacha, K., Amato, E., Andreani, F., Andriollo, G., Annetta, Maria Giuseppina, Annicchiarico, B. E., Antonelli, Massimo, Antonucci, G., Anzellotti, G. M., Armuzzi, A., Baldi, F., Barattucci, I., Barillaro, C., Barone, F., Bellantone, R. D. A., Bellieni, A., Bello, G., Benicchi, A., Benvenuto, F., Berardini, L., Berloco, F., Bernabei, R., Bianchi, A., Biasucci, D. G., Biasucci, L. M., Bibbo, S., Bini, A., Bisanti, A., Biscetti, F., Bocci, M. G., Bonadia, N., Bongiovanni, F., Borghetti, A., Bosco, G., Bosello, Silvia Laura, Bove, V., Bramato, G., Brandi, V., Bruni, T., Bruno, C., Bruno, D., Bungaro, M. C., Buonomo, A., Burzo, L., Calabrese, A., Calvello, M. R., Cambieri, A., Cambise, C., Camma, G., Candelli, M., Canistro, G., Cantanale, A., Capalbo, G., Capaldi, L., Capone, E., Capristo, E., Carbone, L., Cardone, S., Carelli, S., Carfi, A., Carnicelli, A., Caruso, C., Casciaro, F. A., Catalano, L., Cauda, R., Cecchini, A. L., Cerrito, L., Cesarano, M., Chiarito, A., Cianci, Rossella, Cicchinelli, S., Ciccullo, A., Cicetti, M., Ciciarello, F., Cingolani, A., Cipriani, M. C., Consalvo, M. L., Coppola, G., Corbo, G. M., Corsello, A., Costante, F., Costanzi, M., Covino, M., Crupi, D., Cutuli, S. L., D'Addio, S., D'Alessandro, A., D'Alfonso, M. E., D'Angelo, E., D'Aversa, F., Damiano, F., De Berardinis, G. M., De Cunzo, T., De Gaetano, D. K., De Luca, G., De Matteis, G., De Pascale, G., De Santis, P., De Siena, M., De Vito, F., Del Gatto, V., Del Giacomo, P., Del Zompo, F., Dell'Anna, A. M., Della, P. D., Di Gialleonardo, L., Di Giambenedetto, S., Di Luca, R., Di Maurizio, L., Di Muro, M., Dusina, A., Eleuteri, D., Esperide, A., Fachechi, D., Faliero, D., Falsiroli, C., Fantoni, M., Fedele, A., Feliciani, D., Ferrante, C., Ferrone, G., Festa, R., Fiore, M. C., Flex, A., Forte, E., Franceschi, Francesco, Francesconi, A., Franza, L., Funaro, B., Fuorlo, M., Fusco, D., Gabrielli, M., Gaetani, E., Galletta, C., Gallo, A., Gambassi, G., Garcovich, M., Gasbarrini, A., Gasparrini, I., Gelli, S., Giampietro, A., Gigante, L., Giuliano, G., Giupponi, B., Gremese, E., Grieco, Domenico Luca, Guerrera, M., Guglielmi, V., Guidone, C., Gulli, A., Iaconelli, A., Iafrati, A., Ianiro, Gianluca, Iaquinta, A., Impagnatiello, M., Inchingolo, R., Intini, E., Iorio, R., Izzi, I. M., Jovanovic, T., Kadhim, C., La Macchia, R., La Milia, D. I., Landi, F., Landi, G., Landi, R., Landolfi, R., Leo, M., Leone, P. M., Levantesi, L., Liguori, A., Liperoti, R., Lizzio, M. M., Lo Monaco Maria, R., Locantore, P., Lombardi, F., Lombardi, G., Lopetuso, L., Loria, V., Losito, A. R., Lucia, M. B. P., Macagno, F., Macerola, N., Maggi, G., Maiuro, G., Mancarella, F., Mangiola, F., Manno, A., Marchesini, D., Maresca, G. M., Marrone, G., Martis, I., Martone, A. M., Marzetti, Emanuele, Mattana, C., Matteo, M. V., Maviglia, R., Mazzarella, A., Memoli, C., Miele, Luca, Migneco, A., Mignini, I., Milani, A., Milardi, D., Montalto, M., Montemurro, G., Monti, F., Montini, Luca, Morena, T. C., Morra, V., Morretta, C., Moschese, D., Murace, C. A., Murdolo, M., Murri, Rita, Napoli, M., Nardella, E., Natalello, G., Natalini, D., Navarra, S. M., Nesci, A., Nicoletti, A., Nicoletti, R., Nicoletti, T. F., Nicolo, R., Nicolotti, N., Nista, E. C., Nuzzo, E., Oggiano, M., Ojetti, V., Pagano, F. C., Paiano, G., Pais, C., Pallavicini, F., Palombo, A., Paolillo, F., Papa, Alfredo, Papanice, D., Papparella, L. G., Paratore, M., Parrinello, G., Pasciuto, G., Pasculli, P., Pecorini, G., Perniola, S., Pero, E., Petricca, L., Petrucci, M., Picarelli, C., Piccioni, A., Piccolo, A., Piervincenzi, E., Pignataro, G., Pignataro, R., Pintaudi, G., Pisapia, L., Pizzoferrato, M., Pizzolante, F., Pola, R., Policola, C., Pompili, M., Pontecorvi, F., Pontecorvi, V., Ponziani, F., Popolla, V., Porceddu, E., Porfidia, A., Porro, L. M., Potenza, A., Pozzana, F., Privitera, G., Pugliese, D., Pulcini, G., Racco, S., Raffaelli, F., Ramunno, V., Rapaccini, G. L., Richeldi, Luca, Rinninella, Emanuele, Rocchi, S., Romano, B., Romano, S., Rosa, F., Rossi, L., Rossi, R., Rossini, E., Rota, E., Rovedi, F., Rubino, C., Rumi, G., Russo, A., Sabia, L., Salerno, A., Salini, S., Salvatore, L., Samori, D., Sandroni, Claudio, Sanguinetti, M., Santarelli, L., Santini, P., Santolamazza, D., Santoliquido, A., Santopaolo, F., Santoro, M. C., Sardeo, F., Sarnari, C., Saviano, A., Saviano, L., Scaldaferri, Franco, Scarascia, R., Schepis, T., Schiavello, F., Scoppettuolo, G., Sedda, D., Sessa, F., Sestito, L., Settanni, C., Siciliano, M., Siciliano, V., Sicuranza, R., Simeoni, B., Simonetti, J., Smargiassi, A., Soave, P. M., Sonnino, C., Staiti, D., Stella, C., Stella, L., Stival, E., Taddei, E., Talerico, R., Tamburello, E., Tamburrini, E., Tanzarella, E. S., Tarascio, E., Tarli, C., Tersali, A., Tilli, P., Timpano, J., Torelli, E., Torrini, F., Tosato, M., Tosoni, A., Tricoli, L., Tritto, M., Tumbarello, M., Tummolo, A. M., Vallecoccia, M. S., Valletta, F., Varone, F., Vassalli, F., Ventura, G., Verardi, L., Vetrone, L., Vetrugno, G., Visconti, E., Visconti, F., Viviani, A., Zaccaria, R., Zaccone, C., Zelano, L., Zileri Dal Verme, L., Zuccala, G., Luigetti M. (ORCID:0000-0001-7539-505X), Iorio R. (ORCID:0000-0002-6270-0956), Bentivoglio A. R. (ORCID:0000-0002-9663-095X), Tricoli L., Riso V., Marotta J., Piano C., Primiano G., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Calabresi P. (ORCID:0000-0003-0326-5509), Annetta M. G. (ORCID:0000-0001-7574-1311), Antonelli M. (ORCID:0000-0003-3007-1670), Bosello S. (ORCID:0000-0002-4837-447X), Cianci R. (ORCID:0000-0001-5378-8442), Franceschi F. (ORCID:0000-0001-6266-445X), Grieco D. L. (ORCID:0000-0002-4557-6308), Ianiro G. (ORCID:0000-0002-8318-0515), Marzetti E. (ORCID:0000-0001-9567-6983), Miele L. (ORCID:0000-0003-3464-0068), Montini L. (ORCID:0000-0003-4602-5134), Murri R. (ORCID:0000-0003-4263-7854), Papa A. (ORCID:0000-0002-4186-7298), Richeldi L. (ORCID:0000-0001-8594-1448), Rinninella E. (ORCID:0000-0002-9165-2367), Sandroni C. (ORCID:0000-0002-8878-2611), Scaldaferri F. (ORCID:0000-0001-8334-7541), Luigetti, Marco, Iorio, Raffaele, Bentivoglio, Anna Rita, Tricoli, Luca, Riso, Vittorio, Marotta, Jessica, Piano, Carla, Primiano, Guido Alessandro, Zileri Del Verme, L., Lo Monaco, Maria Rita, Calabresi, Paolo, Abbate, V., Acampora, N., Addolorato, G., Agostini, F., Ainora, M. E., Akacha, K., Amato, E., Andreani, F., Andriollo, G., Annetta, Maria Giuseppina, Annicchiarico, B. E., Antonelli, Massimo, Antonucci, G., Anzellotti, G. M., Armuzzi, A., Baldi, F., Barattucci, I., Barillaro, C., Barone, F., Bellantone, R. D. A., Bellieni, A., Bello, G., Benicchi, A., Benvenuto, F., Berardini, L., Berloco, F., Bernabei, R., Bianchi, A., Biasucci, D. G., Biasucci, L. M., Bibbo, S., Bini, A., Bisanti, A., Biscetti, F., Bocci, M. G., Bonadia, N., Bongiovanni, F., Borghetti, A., Bosco, G., Bosello, Silvia Laura, Bove, V., Bramato, G., Brandi, V., Bruni, T., Bruno, C., Bruno, D., Bungaro, M. C., Buonomo, A., Burzo, L., Calabrese, A., Calvello, M. R., Cambieri, A., Cambise, C., Camma, G., Candelli, M., Canistro, G., Cantanale, A., Capalbo, G., Capaldi, L., Capone, E., Capristo, E., Carbone, L., Cardone, S., Carelli, S., Carfi, A., Carnicelli, A., Caruso, C., Casciaro, F. A., Catalano, L., Cauda, R., Cecchini, A. L., Cerrito, L., Cesarano, M., Chiarito, A., Cianci, Rossella, Cicchinelli, S., Ciccullo, A., Cicetti, M., Ciciarello, F., Cingolani, A., Cipriani, M. C., Consalvo, M. L., Coppola, G., Corbo, G. M., Corsello, A., Costante, F., Costanzi, M., Covino, M., Crupi, D., Cutuli, S. L., D'Addio, S., D'Alessandro, A., D'Alfonso, M. E., D'Angelo, E., D'Aversa, F., Damiano, F., De Berardinis, G. M., De Cunzo, T., De Gaetano, D. K., De Luca, G., De Matteis, G., De Pascale, G., De Santis, P., De Siena, M., De Vito, F., Del Gatto, V., Del Giacomo, P., Del Zompo, F., Dell'Anna, A. M., Della, P. D., Di Gialleonardo, L., Di Giambenedetto, S., Di Luca, R., Di Maurizio, L., Di Muro, M., Dusina, A., Eleuteri, D., Esperide, A., Fachechi, D., Faliero, D., Falsiroli, C., Fantoni, M., Fedele, A., Feliciani, D., Ferrante, C., Ferrone, G., Festa, R., Fiore, M. C., Flex, A., Forte, E., Franceschi, Francesco, Francesconi, A., Franza, L., Funaro, B., Fuorlo, M., Fusco, D., Gabrielli, M., Gaetani, E., Galletta, C., Gallo, A., Gambassi, G., Garcovich, M., Gasbarrini, A., Gasparrini, I., Gelli, S., Giampietro, A., Gigante, L., Giuliano, G., Giupponi, B., Gremese, E., Grieco, Domenico Luca, Guerrera, M., Guglielmi, V., Guidone, C., Gulli, A., Iaconelli, A., Iafrati, A., Ianiro, Gianluca, Iaquinta, A., Impagnatiello, M., Inchingolo, R., Intini, E., Iorio, R., Izzi, I. M., Jovanovic, T., Kadhim, C., La Macchia, R., La Milia, D. I., Landi, F., Landi, G., Landi, R., Landolfi, R., Leo, M., Leone, P. M., Levantesi, L., Liguori, A., Liperoti, R., Lizzio, M. M., Lo Monaco Maria, R., Locantore, P., Lombardi, F., Lombardi, G., Lopetuso, L., Loria, V., Losito, A. R., Lucia, M. B. P., Macagno, F., Macerola, N., Maggi, G., Maiuro, G., Mancarella, F., Mangiola, F., Manno, A., Marchesini, D., Maresca, G. M., Marrone, G., Martis, I., Martone, A. M., Marzetti, Emanuele, Mattana, C., Matteo, M. V., Maviglia, R., Mazzarella, A., Memoli, C., Miele, Luca, Migneco, A., Mignini, I., Milani, A., Milardi, D., Montalto, M., Montemurro, G., Monti, F., Montini, Luca, Morena, T. C., Morra, V., Morretta, C., Moschese, D., Murace, C. A., Murdolo, M., Murri, Rita, Napoli, M., Nardella, E., Natalello, G., Natalini, D., Navarra, S. M., Nesci, A., Nicoletti, A., Nicoletti, R., Nicoletti, T. F., Nicolo, R., Nicolotti, N., Nista, E. C., Nuzzo, E., Oggiano, M., Ojetti, V., Pagano, F. C., Paiano, G., Pais, C., Pallavicini, F., Palombo, A., Paolillo, F., Papa, Alfredo, Papanice, D., Papparella, L. G., Paratore, M., Parrinello, G., Pasciuto, G., Pasculli, P., Pecorini, G., Perniola, S., Pero, E., Petricca, L., Petrucci, M., Picarelli, C., Piccioni, A., Piccolo, A., Piervincenzi, E., Pignataro, G., Pignataro, R., Pintaudi, G., Pisapia, L., Pizzoferrato, M., Pizzolante, F., Pola, R., Policola, C., Pompili, M., Pontecorvi, F., Pontecorvi, V., Ponziani, F., Popolla, V., Porceddu, E., Porfidia, A., Porro, L. M., Potenza, A., Pozzana, F., Privitera, G., Pugliese, D., Pulcini, G., Racco, S., Raffaelli, F., Ramunno, V., Rapaccini, G. L., Richeldi, Luca, Rinninella, Emanuele, Rocchi, S., Romano, B., Romano, S., Rosa, F., Rossi, L., Rossi, R., Rossini, E., Rota, E., Rovedi, F., Rubino, C., Rumi, G., Russo, A., Sabia, L., Salerno, A., Salini, S., Salvatore, L., Samori, D., Sandroni, Claudio, Sanguinetti, M., Santarelli, L., Santini, P., Santolamazza, D., Santoliquido, A., Santopaolo, F., Santoro, M. C., Sardeo, F., Sarnari, C., Saviano, A., Saviano, L., Scaldaferri, Franco, Scarascia, R., Schepis, T., Schiavello, F., Scoppettuolo, G., Sedda, D., Sessa, F., Sestito, L., Settanni, C., Siciliano, M., Siciliano, V., Sicuranza, R., Simeoni, B., Simonetti, J., Smargiassi, A., Soave, P. M., Sonnino, C., Staiti, D., Stella, C., Stella, L., Stival, E., Taddei, E., Talerico, R., Tamburello, E., Tamburrini, E., Tanzarella, E. S., Tarascio, E., Tarli, C., Tersali, A., Tilli, P., Timpano, J., Torelli, E., Torrini, F., Tosato, M., Tosoni, A., Tricoli, L., Tritto, M., Tumbarello, M., Tummolo, A. M., Vallecoccia, M. S., Valletta, F., Varone, F., Vassalli, F., Ventura, G., Verardi, L., Vetrone, L., Vetrugno, G., Visconti, E., Visconti, F., Viviani, A., Zaccaria, R., Zaccone, C., Zelano, L., Zileri Dal Verme, L., Zuccala, G., Luigetti M. (ORCID:0000-0001-7539-505X), Iorio R. (ORCID:0000-0002-6270-0956), Bentivoglio A. R. (ORCID:0000-0002-9663-095X), Tricoli L., Riso V., Marotta J., Piano C., Primiano G., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Calabresi P. (ORCID:0000-0003-0326-5509), Annetta M. G. (ORCID:0000-0001-7574-1311), Antonelli M. (ORCID:0000-0003-3007-1670), Bosello S. (ORCID:0000-0002-4837-447X), Cianci R. (ORCID:0000-0001-5378-8442), Franceschi F. (ORCID:0000-0001-6266-445X), Grieco D. L. (ORCID:0000-0002-4557-6308), Ianiro G. (ORCID:0000-0002-8318-0515), Marzetti E. (ORCID:0000-0001-9567-6983), Miele L. (ORCID:0000-0003-3464-0068), Montini L. (ORCID:0000-0003-4602-5134), Murri R. (ORCID:0000-0003-4263-7854), Papa A. (ORCID:0000-0002-4186-7298), Richeldi L. (ORCID:0000-0001-8594-1448), Rinninella E. (ORCID:0000-0002-9165-2367), Sandroni C. (ORCID:0000-0002-8878-2611), and Scaldaferri F. (ORCID:0000-0001-8334-7541)

Abstract

Background and purpose: The objective of this study was to assess the neurological manifestations in a series of consecutive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients, comparing their frequency with a population hospitalized in the same period for flu/respiratory symptoms, finally not related to SARS-CoV-2. Methods: Patients with flu/respiratory symptoms admitted to Fondazione Policlinico Gemelli hospital from 14 March 2020 to 20 April 2020 were retrospectively enrolled. The frequency of neurological manifestations of patients with SARS-CoV-2 infection was compared with a control group. Results: In all, 213 patients were found to be positive for SARS-CoV-2, after reverse transcriptase polymerase chain reaction on nasal or throat swabs, whilst 218 patients were found to be negative and were used as a control group. Regarding central nervous system manifestations, in SARS-CoV-2-positive patients a higher frequency of headache, hyposmia and encephalopathy always related to systemic conditions (fever or hypoxia) was observed. Furthermore, muscular involvement was more frequent in SARS-CoV-2 infection. Conclusions: Patients with COVID-19 commonly have neurological manifestations but only hyposmia and muscle involvement seem more frequent compared with other flu diseases.

Published
2020

20. Venous thromboembolism in COVID-19 patients

Author

Porfidia, Angelo, Pola, Roberto, Porfidia A. (ORCID:0000-0003-4915-2892), Pola R. (ORCID:0000-0001-5224-2931), Porfidia, Angelo, Pola, Roberto, Porfidia A. (ORCID:0000-0003-4915-2892), and Pola R. (ORCID:0000-0001-5224-2931)

Abstract

We read with interest the study published by Tang and coll.1 in a recent issue of the Journal of Thrombosis and Haemostasis. In this retrospective analysis, conducted at the Tongji Hospital of Wuhan, China, it is reported that heparin treatment reduces mortality in subjects affected by severe COVID-19 who have “sepsis-induced coagulopathy”. The definition of severe COVID-19 was the presence of at least one of following: respiratory rate ≥30 breaths /min; arterial oxygen saturation ≤93% at rest; PaO2/FiO2 ≤300 mmHg. The Authors of this study also reported that, among subjects not treated with heparin, mortality raised according with D-dimer levels. Of note, patients that received heparin in this study were mostly treated with enoxaparin, at the thromboprophylactic dose of 40-60 mg/day, for at least 7 days.

Published
2020

21. Risk of intracranial bleeding in patients with primary brain cancer receiving therapeutic anticoagulation for venous thromboembolism: A meta-analysis

Author

Porfidia, Angelo, Giordano, Marzia, Sturiale, Carmelo Lucio, D'Arrigo, Sonia, Donadini, M. P., Olivi, Alessandro, Ageno, W., Pola, Roberto, Porfidia A. (ORCID:0000-0003-4915-2892), Giordano M., Sturiale C. L. (ORCID:0000-0002-4080-2492), D'Arrigo S. (ORCID:0000-0001-6740-3195), Olivi A. (ORCID:0000-0002-4489-7564), Pola R. (ORCID:0000-0001-5224-2931), Porfidia, Angelo, Giordano, Marzia, Sturiale, Carmelo Lucio, D'Arrigo, Sonia, Donadini, M. P., Olivi, Alessandro, Ageno, W., Pola, Roberto, Porfidia A. (ORCID:0000-0003-4915-2892), Giordano M., Sturiale C. L. (ORCID:0000-0002-4080-2492), D'Arrigo S. (ORCID:0000-0001-6740-3195), Olivi A. (ORCID:0000-0002-4489-7564), and Pola R. (ORCID:0000-0001-5224-2931)

Abstract

Introduction: Venous thromboembolism (VTE) is common in glioma patients. Also, spontaneous intracerebral hemorrhage (ICH) is frequently observed in subjects with primary brain tumors. Thus, the management of anticoagulant therapy for VTE is challenging and controversial in these patients. We performed a meta-analysis to clarify the risk of ICH in glioma patients treated with anticoagulant therapy for VTE compared to glioma patients without VTE. Materials and Methods: A systematic search of the literature was conducted using PubMed, Scopus, and EMBASE databases between January 1980 and January 2019 without language restrictions. Summary statistics for ICH were obtained by calculating the odds ratio (OR) using a random effects model, and heterogeneity across studies was estimated by the I2 statistic. The Newcastle–Ottawa Scale was used to evaluate the quality of studies. Results: A total of 368 studies were initially identified. Of these, 346 were excluded after title review. The remaining 22 studies were reviewed in detail. According to the PICO criteria, 15 studies were excluded. Finally, 7 studies were included in the meta-analysis. The OR for ICH in glioma patients receiving therapeutic anticoagulation for VTE versus those who did not receive anticoagulation was 3.66 (95% confidence interval [CI], 1.84–7.29; I2 = 31%). Conclusions: This meta-analysis demonstrates that anticoagulation for VTE increases the risk of ICH in subjects with malignant brain tumors. Future studies are warranted to fully understand the best medical treatment of VTE in glioma patients.

Published
2020

22. Upper extremity deep vein thrombosis treated with direct oral anticoagulants: a multi-center real world experience

Author

Porfidia, Angelo, Agostini, Fabiana, Giarretta, Igor, Tonello, D., Pastori, D., Pignatelli, P., Santoliquido, Angelo, Sartori, M., Lessiani, G., Visona, A., Donadini, M. P., Pola, Roberto, Porfidia A. (ORCID:0000-0003-4915-2892), Agostini F., Giarretta I. (ORCID:0000-0001-5380-0843), Santoliquido A. (ORCID:0000-0003-1539-4017), Pola R. (ORCID:0000-0001-5224-2931), Porfidia, Angelo, Agostini, Fabiana, Giarretta, Igor, Tonello, D., Pastori, D., Pignatelli, P., Santoliquido, Angelo, Sartori, M., Lessiani, G., Visona, A., Donadini, M. P., Pola, Roberto, Porfidia A. (ORCID:0000-0003-4915-2892), Agostini F., Giarretta I. (ORCID:0000-0001-5380-0843), Santoliquido A. (ORCID:0000-0003-1539-4017), and Pola R. (ORCID:0000-0001-5224-2931)

Abstract

Upper-extremity deep vein thrombosis (UEDVT) accounts for about 5–10% of all cases of deep vein thrombosis (DVT). It is often associated with cancer and/or presence of a central venous catheter (CVC), but it may also occur in the absence of these favoring conditions. The safety and efficacy of using direct oral anticoagulants (DOACs) in subjects with UEDVT has not been systematically evaluated and the only data available in the literature derive from anecdotal evidence, analysis of registries, and small single-centre studies. In addition, a specific analysis of UEDVT not associated with cancer and/or CVC has never been made. In this study, we specifically focused on patients with no cancer and without a CVC who were diagnosed with a first episode of UEDVT and were treated with a DOAC. We studied 61 patients, treated in six Italian centres between January 2014 and December 2018. Treatment lasted at least 3 months in all patients. In terms of efficacy, no recurrence of thrombosis or pulmonary embolism were recorded, while Doppler ultrasonography, performed after at least three months of treatment, documented in all cases either partial or complete recanalization of obstructed veins. In terms of safety, no cases of major bleedings were recorded. This is the only series available in the literature of patients treated with DOACs for UEDVT not associated with cancer and/or CVC. This small multicenter real world experience supports the concept that DOACs might be safe and effective for treating UEDTV. Further studies are required to better understand the role of DOACs in these patients.

Published
2020

23. The hedgehog signaling pathway in ischemic tissues

Author

Giarretta, Igor, Gaetani, Eleonora, Bigossi, M., Tondi, Paolo, Asahara, T., Pola, Roberto, Giarretta I. (ORCID:0000-0001-5380-0843), Gaetani E. (ORCID:0000-0002-7808-1491), Tondi P. (ORCID:0000-0003-1654-2448), Pola R. (ORCID:0000-0001-5224-2931), Giarretta, Igor, Gaetani, Eleonora, Bigossi, M., Tondi, Paolo, Asahara, T., Pola, Roberto, Giarretta I. (ORCID:0000-0001-5380-0843), Gaetani E. (ORCID:0000-0002-7808-1491), Tondi P. (ORCID:0000-0003-1654-2448), and Pola R. (ORCID:0000-0001-5224-2931)

Abstract

Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in the ischemic condition is also presented.

Published
2019

24. Differences in Clinical Presentation, Rate of Pulmonary Embolism, and Risk Factors Among Patients With Deep Vein Thrombosis in Unusual Sites.

Author

Porfidia, Angelo, Porceddu, Enrica, Feliciani, Daniela, Giordano, Marzia, Agostini, Fabiana, Ciocci, G, Cammà, G, Giarretta, Igor, Gaetani, Eleonora, Tondi, Paolo, Pola, Roberto, Porfidia A (ORCID:0000-0003-4915-2892), Porceddu E, Feliciani D, Giordano M, Agostini F, Giarretta I (ORCID:0000-0001-5380-0843), Gaetani E (ORCID:0000-0002-7808-1491), Tondi P (ORCID:0000-0003-1654-2448), Pola R. (ORCID:0000-0001-5224-2931), Porfidia, Angelo, Porceddu, Enrica, Feliciani, Daniela, Giordano, Marzia, Agostini, Fabiana, Ciocci, G, Cammà, G, Giarretta, Igor, Gaetani, Eleonora, Tondi, Paolo, Pola, Roberto, Porfidia A (ORCID:0000-0003-4915-2892), Porceddu E, Feliciani D, Giordano M, Agostini F, Giarretta I (ORCID:0000-0001-5380-0843), Gaetani E (ORCID:0000-0002-7808-1491), Tondi P (ORCID:0000-0003-1654-2448), and Pola R. (ORCID:0000-0001-5224-2931)

Abstract

Unusual site deep vein thrombosis (USDVT) is an uncommon form of venous thromboembolism with heterogeneous signs and symptoms, unknown rate of pulmonary embolism (PE), and poorly defined risk factors. We conducted a retrospective analysis of 107 consecutive cases of USDVTs, discharged from our University Hospital over a period of 2 years. Patients were classified based on the site of thrombosis and distinguished between patients with cerebral vein thrombosis, jugular vein thrombosis, thrombosis of the deep veins of the upper extremities, and abdominal vein thrombosis. We found statistically significant differences between groups in terms of age (P < .0001) and gender distribution (P < .05). We also found that the rate of symptomatic patients was significantly different between groups (P < .0001). Another interesting finding was the significant difference between groups in terms of rate of PE (P < .01). Finally, we found statistically significant differences between groups in terms of risk factors for thrombosis, in particular cancer (P < .01). Unprovoked cases were differently distributed among groups (P < .0001). This study highlights differences between patients with USDVT, which depend on the site of thrombosis, and provides data which might be useful in clinical practice.

Published
2019

25. Antithrombotic therapy and intracranial bleeding in subjects with sporadic brain arteriovenous malformations: preliminary results from a retrospective study.

Author

Sturiale, Carmelo Lucio, Pignotti, Fabrizio, Giordano, Marzia, Porfidia, Angelo, Albanese, Alessio, Giarretta, Igor, Puca, Alfredo, Gaetani, Eleonora, D'Arrigo, Sonia, Truma, A, Olivi, Alessandro, Pola, Roberto, Sturiale CL (ORCID:0000-0002-4080-2492), Pignotti F, Porfidia A (ORCID:0000-0003-4915-2892), Albanese A (ORCID:0000-0001-8783-2974), Giarretta I (ORCID:0000-0001-5380-0843), Puca A (ORCID:0000-0001-6096-1776), Gaetani E (ORCID:0000-0002-7808-1491), D'Arrigo S (ORCID:0000-0001-6740-3195), Olivi A (ORCID:0000-0002-4489-7564), Pola R (ORCID:0000-0001-5224-2931), Sturiale, Carmelo Lucio, Pignotti, Fabrizio, Giordano, Marzia, Porfidia, Angelo, Albanese, Alessio, Giarretta, Igor, Puca, Alfredo, Gaetani, Eleonora, D'Arrigo, Sonia, Truma, A, Olivi, Alessandro, Pola, Roberto, Sturiale CL (ORCID:0000-0002-4080-2492), Pignotti F, Porfidia A (ORCID:0000-0003-4915-2892), Albanese A (ORCID:0000-0001-8783-2974), Giarretta I (ORCID:0000-0001-5380-0843), Puca A (ORCID:0000-0001-6096-1776), Gaetani E (ORCID:0000-0002-7808-1491), D'Arrigo S (ORCID:0000-0001-6740-3195), Olivi A (ORCID:0000-0002-4489-7564), and Pola R (ORCID:0000-0001-5224-2931)

Abstract

Whether antithrombotic treatment is safe and/or affects the risk of intracranial bleeding in subjects with sporadic brain arteriovenous malformations (AVMs) is unknown. We conducted a retrospective analysis on the use of antithrombotics among patients affected by brain AVMs in follow-up at our institution. Attention was paid to the type of antithrombotic drug (either antiplatelets or anticoagulants), current or past use, dosage, and duration of treatment. Several clinical and angioarchitectural features of brain AVMs were also taken into consideration. The association between the use of antithrombotics and haemorrhagic onset was analyzed. A total of 77 patients were included in this study. Among them, ten patients were taking antithrombotic drugs at the time of AVM diagnosis. The rate of haemorrhagic onset was not significantly different between subjects who were and were not taking antithrombotic drugs (40 vs 55.2%, p = ns). Among the many clinical and angioarchitectural features analyzed, the only parameter that showed a statistically significant association with haemorrhagic onset was the size of the nidus. Patients who took antithrombotic treatments after being diagnosed with a brain AVM did not show an increased rate of intracranial haemorrhage over time considering a mean follow-up 4 years. In our study, antithrombotic treatment was not associated with increased intracranial bleeding among subjects with brain AVMs. In the presence of a strong clinical indication, antiplatelet and anticoagulant medications should not be denied a priori to patients with brain AVMs. Studies on larger populations are necessary to confirm these data.

Published
2018

26. Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease.

Author

Giarretta, Igor, Gatto, Ilaria, Marcantoni, Margherita, Lupi, G, Tonello, D, Gaetani, Eleonora, Pitocco, Dario, Iezzi, Roberto, Truma, A, Porfidia, Angelo, Visonà, A, Tondi, Paolo, Pola, Roberto, Giarretta I (ORCID:0000-0001-5380-0843), Gatto I, Marcantoni M, Gaetani E (ORCID:0000-0002-7808-1491), Pitocco D (ORCID:0000-0002-6220-686X), Iezzi R (ORCID:0000-0002-2791-481X), Porfidia A (ORCID:0000-0003-4915-2892), Tondi P (ORCID:0000-0003-1654-2448), Pola R. (ORCID:0000-0001-5224-2931), Giarretta, Igor, Gatto, Ilaria, Marcantoni, Margherita, Lupi, G, Tonello, D, Gaetani, Eleonora, Pitocco, Dario, Iezzi, Roberto, Truma, A, Porfidia, Angelo, Visonà, A, Tondi, Paolo, Pola, Roberto, Giarretta I (ORCID:0000-0001-5380-0843), Gatto I, Marcantoni M, Gaetani E (ORCID:0000-0002-7808-1491), Pitocco D (ORCID:0000-0002-6220-686X), Iezzi R (ORCID:0000-0002-2791-481X), Porfidia A (ORCID:0000-0003-4915-2892), Tondi P (ORCID:0000-0003-1654-2448), and Pola R. (ORCID:0000-0001-5224-2931)

Abstract

Sonic hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh + MPs) have shown the ability to contribute to reparative neovascularization after ischemic injury in mice. The goal of this study was to test the hypothesis that, in humans with peripheral artery disease (PAD), there is increased number of circulating Shh + MPs. This was done by assessing the number of Shh + MPs in plasma of patients with PAD and control subjects without PAD. We found significantly higher number of Shh + MPs in plasma of subjects with PAD, compared to controls, while the global number of MPs—produced either by endothelial cells, platelets, leukocytes, and erythrocytes—was not different between PAD patients and controls. We also found a significant association between the number of Shh + MPs and the number of collateral vessels in the ischemic limbs of PAD patients. Interestingly, the concentration of Shh protein unbound to MPs—which was measured in MP-depleted plasma—was not different between subjects with PAD and the controls, indicating that, in the setting of PAD, the call for Shh recapitulation does not lead to secretion of protein into the blood but to binding of the protein to the membrane of MPs. These findings provide novel information on Shh signaling during ischemia in humans, with potentially important biological and clinical implications.

Published
2018

27. Genome-wide association study of sporadic brain arteriovenous malformations

Author

Weinsheimer, S., Bendjilali, N., Nelson, J., Guo, D.E., Zaroff, J.G., Sidney, S., McCulloch, C.E., Salman, R. Al-Shahi, Berg, J.N., Koeleman, B.P.C., Simon, M., Bostroem, A., Fontanella, M., Sturiale, C.L., Pola, R., Puca, A., Lawton, M.T., Young, W.L., Pawlikowska, L., Klijn, C.J.M., Kim, H., Weinsheimer, S., Bendjilali, N., Nelson, J., Guo, D.E., Zaroff, J.G., Sidney, S., McCulloch, C.E., Salman, R. Al-Shahi, Berg, J.N., Koeleman, B.P.C., Simon, M., Bostroem, A., Fontanella, M., Sturiale, C.L., Pola, R., Puca, A., Lawton, M.T., Young, W.L., Pawlikowska, L., Klijn, C.J.M., and Kim, H.

Abstract

Item does not contain fulltext, BACKGROUND: The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium. METHODS: The Caucasian discovery cohort included 515 BAVM cases and 1191 controls genotyped using Affymetrix genome-wide SNP arrays. Genotype data were imputed to 1000 Genomes Project data, and well-imputed SNPs (>0.01 minor allele frequency) were analysed for association with BAVM. 57 top BAVM-associated SNPs (51 SNPs with p<10(-05) or p<10(-04) in candidate pathway genes, and 6 candidate BAVM SNPs) were tested in a replication cohort including 608 BAVM cases and 744 controls. RESULTS: The estimated heritability of BAVM was 17.6% (SE 8.9%, age and sex-adjusted p=0.015). None of the SNPs were significantly associated with BAVM in the replication cohort after correction for multiple testing. 6 SNPs had a nominal p<0.1 in the replication cohort and map to introns in EGFEM1P, SP4 and CDKAL1 or near JAG1 and BNC2. Of the 6 candidate SNPs, 2 in ACVRL1 and MMP3 had a nominal p<0.05 in the replication cohort. CONCLUSIONS: We performed the first GWAS of sporadic BAVM in the largest BAVM cohort assembled to date. No GWAS SNPs were replicated, suggesting that common SNPs do not contribute strongly to BAVM susceptibility. However, heritability estimates suggest a modest but significant genetic contribution.

Published
2016

28. Genome-wide association study of sporadic brain arteriovenous malformations

Author

Weinsheimer, S., Bendjilali, N., Nelson, J., Guo, D.E., Zaroff, J.G., Sidney, S., McCulloch, C.E., Salman, R. Al-Shahi, Berg, J.N., Koeleman, B.P.C., Simon, M., Bostroem, A., Fontanella, M., Sturiale, C.L., Pola, R., Puca, A., Lawton, M.T., Young, W.L., Pawlikowska, L., Klijn, C.J.M., Kim, H., Weinsheimer, S., Bendjilali, N., Nelson, J., Guo, D.E., Zaroff, J.G., Sidney, S., McCulloch, C.E., Salman, R. Al-Shahi, Berg, J.N., Koeleman, B.P.C., Simon, M., Bostroem, A., Fontanella, M., Sturiale, C.L., Pola, R., Puca, A., Lawton, M.T., Young, W.L., Pawlikowska, L., Klijn, C.J.M., and Kim, H.

Abstract

Item does not contain fulltext, BACKGROUND: The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium. METHODS: The Caucasian discovery cohort included 515 BAVM cases and 1191 controls genotyped using Affymetrix genome-wide SNP arrays. Genotype data were imputed to 1000 Genomes Project data, and well-imputed SNPs (>0.01 minor allele frequency) were analysed for association with BAVM. 57 top BAVM-associated SNPs (51 SNPs with p<10(-05) or p<10(-04) in candidate pathway genes, and 6 candidate BAVM SNPs) were tested in a replication cohort including 608 BAVM cases and 744 controls. RESULTS: The estimated heritability of BAVM was 17.6% (SE 8.9%, age and sex-adjusted p=0.015). None of the SNPs were significantly associated with BAVM in the replication cohort after correction for multiple testing. 6 SNPs had a nominal p<0.1 in the replication cohort and map to introns in EGFEM1P, SP4 and CDKAL1 or near JAG1 and BNC2. Of the 6 candidate SNPs, 2 in ACVRL1 and MMP3 had a nominal p<0.05 in the replication cohort. CONCLUSIONS: We performed the first GWAS of sporadic BAVM in the largest BAVM cohort assembled to date. No GWAS SNPs were replicated, suggesting that common SNPs do not contribute strongly to BAVM susceptibility. However, heritability estimates suggest a modest but significant genetic contribution.

Published
2016

29. Genome-wide association study of sporadic brain arteriovenous malformations

Author

Weinsheimer, S., Bendjilali, N., Nelson, J., Guo, D.E., Zaroff, J.G., Sidney, S., McCulloch, C.E., Salman, R. Al-Shahi, Berg, J.N., Koeleman, B.P.C., Simon, M., Bostroem, A., Fontanella, M., Sturiale, C.L., Pola, R., Puca, A., Lawton, M.T., Young, W.L., Pawlikowska, L., Klijn, C.J.M., Kim, H., Weinsheimer, S., Bendjilali, N., Nelson, J., Guo, D.E., Zaroff, J.G., Sidney, S., McCulloch, C.E., Salman, R. Al-Shahi, Berg, J.N., Koeleman, B.P.C., Simon, M., Bostroem, A., Fontanella, M., Sturiale, C.L., Pola, R., Puca, A., Lawton, M.T., Young, W.L., Pawlikowska, L., Klijn, C.J.M., and Kim, H.

Abstract

Item does not contain fulltext, BACKGROUND: The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium. METHODS: The Caucasian discovery cohort included 515 BAVM cases and 1191 controls genotyped using Affymetrix genome-wide SNP arrays. Genotype data were imputed to 1000 Genomes Project data, and well-imputed SNPs (>0.01 minor allele frequency) were analysed for association with BAVM. 57 top BAVM-associated SNPs (51 SNPs with p<10(-05) or p<10(-04) in candidate pathway genes, and 6 candidate BAVM SNPs) were tested in a replication cohort including 608 BAVM cases and 744 controls. RESULTS: The estimated heritability of BAVM was 17.6% (SE 8.9%, age and sex-adjusted p=0.015). None of the SNPs were significantly associated with BAVM in the replication cohort after correction for multiple testing. 6 SNPs had a nominal p<0.1 in the replication cohort and map to introns in EGFEM1P, SP4 and CDKAL1 or near JAG1 and BNC2. Of the 6 candidate SNPs, 2 in ACVRL1 and MMP3 had a nominal p<0.05 in the replication cohort. CONCLUSIONS: We performed the first GWAS of sporadic BAVM in the largest BAVM cohort assembled to date. No GWAS SNPs were replicated, suggesting that common SNPs do not contribute strongly to BAVM susceptibility. However, heritability estimates suggest a modest but significant genetic contribution.

Published
2016

30. Lack of association between Alzheimer's disease and Gln-Arg 192 Q/R polymorphism of the PON-1 gene in an Italian population

Author

Pola, R., Gaetani, E., Flex, A., Gerardino, L., Aloi, F., Flore, R., Serricchio, M., Pola, P., Bernabei, R., Pola R. (ORCID:0000-0001-5224-2931), Gaetani E. (ORCID:0000-0002-7808-1491), Flex A. (ORCID:0000-0003-2664-4165), Gerardino L. (ORCID:0000-0002-3806-5788), Flore R. (ORCID:0000-0003-1659-1338), Serricchio M. (ORCID:0000-0003-1832-9608), Bernabei R. (ORCID:0000-0002-9197-004X), Pola, R., Gaetani, E., Flex, A., Gerardino, L., Aloi, F., Flore, R., Serricchio, M., Pola, P., Bernabei, R., Pola R. (ORCID:0000-0001-5224-2931), Gaetani E. (ORCID:0000-0002-7808-1491), Flex A. (ORCID:0000-0003-2664-4165), Gerardino L. (ORCID:0000-0002-3806-5788), Flore R. (ORCID:0000-0003-1659-1338), Serricchio M. (ORCID:0000-0003-1832-9608), and Bernabei R. (ORCID:0000-0002-9197-004X)

Abstract

Alzheimer's disease (AD) is characterized by deposition of oxidized low-density lipoprotein (LDL) forming the senile plaque and by structural changes and cell death in acetylcholine-producing neurons. Paraoxonase-1 (PON-1) is a secreted protein primarily associated with high-density lipoproteins (HDL) and participates in the prevention of LDL oxidation. PON-1 is also an arylesterase that hydrolyzes paraoxon, an active toxic metabolite of parathion, thus providing protection against organo-phosphate poisoning and metabolization of environmental neurotoxins that might be responsible for neurodegeneration with aging. Serum levels of PON-1 are genetically determined and strongly influenced by a common polymorphism on the position 192 of the PON-1 gene. The aim of this study was to evaluate whether the polymorphism of the PON-1 gene is associated with AD. We studied 124 Italian subjects affected by probable AD and 135 age- and sex-matched controls. The distribution of PON-1 genotypes was 64 QQ, 46 QR, 14 RR in the AD patients and 57 QQ, 59 QR, 19 RR in the control subjects. No statistically significant difference was found between the two groups in our population (p = 0.130 for homozygous QQ, p = 0.279 for heterozygous QR, and p = 0.502 for homozygous RR). These results suggest that the human Gln-Arg 192 Q/R polymorphism of the PON-1 gene is not associated with AD in an Italian population. Copyright © 2003 S. Karger AG, Basel.

Published
2003

31. In vivo characterization of the physicochemical properties of polymer-linked TLR agonists that enhance vaccine immunogenicity

Author

Lynn, GM, Laga, R, Darrah, PA, Ishizuka, AS, Balaci, AJ, Dulcey, AE, Pechar, M, Pola, R, Gerner, MY, Yamamoto, A, Buechler, CR, Quinn, KM, Smelkinson, MG, Vanek, O, Cawood, R, Hills, T, Vasalatiy, O, Kastenmueller, K, Francica, JR, Stutts, L, Tom, JK, Ryu, KA, Esser-Kahn, AP, Etrych, T, Fisher, KD, Seymour, LW, Seder, RA, Lynn, GM, Laga, R, Darrah, PA, Ishizuka, AS, Balaci, AJ, Dulcey, AE, Pechar, M, Pola, R, Gerner, MY, Yamamoto, A, Buechler, CR, Quinn, KM, Smelkinson, MG, Vanek, O, Cawood, R, Hills, T, Vasalatiy, O, Kastenmueller, K, Francica, JR, Stutts, L, Tom, JK, Ryu, KA, Esser-Kahn, AP, Etrych, T, Fisher, KD, Seymour, LW, and Seder, RA

Abstract

The efficacy of vaccine adjuvants such as Toll-like receptor agonists (TLRa) can be improved through formulation and delivery approaches. Here, we attached small molecule TLR-7/8a to polymer scaffolds (polymer-TLR-7/8a) and evaluated how different physicochemical properties of the TLR-7/8a and polymer carrier influenced the location, magnitude and duration of innate immune activation in vivo. Particle formation by polymer-TLR-7/8a was the most important factor for restricting adjuvant distribution and prolonging activity in draining lymph nodes. The improved pharmacokinetic profile by particulate polymer-TLR-7/8a was also associated with reduced morbidity and enhanced vaccine immunogenicity for inducing antibodies and T cell immunity. We extended these findings to the development of a modular approach in which protein antigens are site-specifically linked to temperature-responsive polymer-TLR-7/8a adjuvants that self-assemble into immunogenic particles at physiologic temperatures in vivo. Our findings provide a chemical and structural basis for optimizing adjuvant design to elicit broad-based antibody and T cell responses with protein antigens.

Published
2015

32. A two-layered classifier based on the radial basis function for the screening of thalassaemia

Author

Masala, Giovanni Luca, Golosio, B., Cutzu, R., Pola, R., Masala, Giovanni Luca, Golosio, B., Cutzu, R., and Pola, R.

Abstract

The thalassaemias are blood disorders with hereditary transmission. Their distribution is global, with particular incidence in areas affected by malaria. Their diagnosis is mainly based on haematologic and genetic analyses. The aim of this study was to differentiate between persons with the thalassaemia trait and normal subjects by inspecting characteristics of haemochromocytometric data. The paper proposes an original method that is useful in screening activity for thalassaemia classification. A complete working system with a friendly graphical user interface is presented. A unique feature of the presented work is the adoption of a two-layered classification system based on Radial basis function, which improves the performance of the system.

Published
2013

33. Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm.

Author

Gretarsdottir, S., Baas, A.F., Thorleifsson, G., Holm, H., Heijer, M. den, Vries, J.P. de, Kranendonk, S.E., Zeebregts, C.J.A., Sterkenburg, S.M. van, Geelkerken, R.H., Rij, A.M. van, Williams, M.J., Boll, A.P.M., Kostic, J., Jonasdottir, A., Walters, G.B., Masson, G., Sulem, P., Saemundsdottir, J., Mouy, M., Magnusson, K.P., Tromp, G., Elmore, J.B., Sakalihasan, N., Limet, R., Defraigne, J.O., Ferrell, R.E., Ronkainen, A., Ruigrok, Y.M., Wijmenga, C., Grobbee, D.E., Shah, S.H., Granger, C.B., Quyyumi, A.A., Vaccarino, V., Patel, R., Zafari, A.M., Levey, A.I., Austin, H., Girelli, D., Pignatti, P.F., Olivieri, O., Martinelli, N., Malerba, G., Trabetti, E., Becker, L.C., Becker, D.M., Reilly, M.P., Rader, D.J., Mueller, T., Dieplinger, B., Haltmayer, M., Urbonavicius, S., Lindblad, B., Gottsäter, A., Gaetani, E., Pola, R., Wells, P., Rodger, M., Forgie, M., Langlois, N., Corral, J., Vicente, V., Fontcuberta, J., España, F., Grarup, N., Jørgensen, T., Witte, D.R., Hansen, T., Pedersen, O., Aben, K.K.H., Graaf, J. de, Holewijn, S., Folkersen, L., Franco-Cereceda, A., Eriksson, P., Collier, D.A., Stefansson, H., Steinthorsdottir, V., Rafnar, T., Valdimarsson, E.M., Magnadottir, H.B., Sveinbjornsdottir, S., Olafsson, I., Magnusson, M.K., Palmason, R., Haraldsdottir, V., Andersen, K., Onundarson, P.T., Thorgeirsson, G., Kiemeney, L.A.L.M., Powell, J.T., Carey, D.J., Kuivaniemi, H., Lindholt, J.S., Jones, G.T., Blankensteijn, J.D., Gretarsdottir, S., Baas, A.F., Thorleifsson, G., Holm, H., Heijer, M. den, Vries, J.P. de, Kranendonk, S.E., Zeebregts, C.J.A., Sterkenburg, S.M. van, Geelkerken, R.H., Rij, A.M. van, Williams, M.J., Boll, A.P.M., Kostic, J., Jonasdottir, A., Walters, G.B., Masson, G., Sulem, P., Saemundsdottir, J., Mouy, M., Magnusson, K.P., Tromp, G., Elmore, J.B., Sakalihasan, N., Limet, R., Defraigne, J.O., Ferrell, R.E., Ronkainen, A., Ruigrok, Y.M., Wijmenga, C., Grobbee, D.E., Shah, S.H., Granger, C.B., Quyyumi, A.A., Vaccarino, V., Patel, R., Zafari, A.M., Levey, A.I., Austin, H., Girelli, D., Pignatti, P.F., Olivieri, O., Martinelli, N., Malerba, G., Trabetti, E., Becker, L.C., Becker, D.M., Reilly, M.P., Rader, D.J., Mueller, T., Dieplinger, B., Haltmayer, M., Urbonavicius, S., Lindblad, B., Gottsäter, A., Gaetani, E., Pola, R., Wells, P., Rodger, M., Forgie, M., Langlois, N., Corral, J., Vicente, V., Fontcuberta, J., España, F., Grarup, N., Jørgensen, T., Witte, D.R., Hansen, T., Pedersen, O., Aben, K.K.H., Graaf, J. de, Holewijn, S., Folkersen, L., Franco-Cereceda, A., Eriksson, P., Collier, D.A., Stefansson, H., Steinthorsdottir, V., Rafnar, T., Valdimarsson, E.M., Magnadottir, H.B., Sveinbjornsdottir, S., Olafsson, I., Magnusson, M.K., Palmason, R., Haraldsdottir, V., Andersen, K., Onundarson, P.T., Thorgeirsson, G., Kiemeney, L.A.L.M., Powell, J.T., Carey, D.J., Kuivaniemi, H., Lindholt, J.S., Jones, G.T., and Blankensteijn, J.D.

Abstract

Contains fulltext : 88507.pdf (publisher's version ) (Closed access)

Published
2010

34. Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm.

Author

Gretarsdottir, S., Baas, A.F., Thorleifsson, G., Holm, H., Heijer, M. den, Vries, J.P. de, Kranendonk, S.E., Zeebregts, C.J.A., Sterkenburg, S.M. van, Geelkerken, R.H., Rij, A.M. van, Williams, M.J., Boll, A.P.M., Kostic, J., Jonasdottir, A., Walters, G.B., Masson, G., Sulem, P., Saemundsdottir, J., Mouy, M., Magnusson, K.P., Tromp, G., Elmore, J.B., Sakalihasan, N., Limet, R., Defraigne, J.O., Ferrell, R.E., Ronkainen, A., Ruigrok, Y.M., Wijmenga, C., Grobbee, D.E., Shah, S.H., Granger, C.B., Quyyumi, A.A., Vaccarino, V., Patel, R., Zafari, A.M., Levey, A.I., Austin, H., Girelli, D., Pignatti, P.F., Olivieri, O., Martinelli, N., Malerba, G., Trabetti, E., Becker, L.C., Becker, D.M., Reilly, M.P., Rader, D.J., Mueller, T., Dieplinger, B., Haltmayer, M., Urbonavicius, S., Lindblad, B., Gottsäter, A., Gaetani, E., Pola, R., Wells, P., Rodger, M., Forgie, M., Langlois, N., Corral, J., Vicente, V., Fontcuberta, J., España, F., Grarup, N., Jørgensen, T., Witte, D.R., Hansen, T., Pedersen, O., Aben, K.K.H., Graaf, J. de, Holewijn, S., Folkersen, L., Franco-Cereceda, A., Eriksson, P., Collier, D.A., Stefansson, H., Steinthorsdottir, V., Rafnar, T., Valdimarsson, E.M., Magnadottir, H.B., Sveinbjornsdottir, S., Olafsson, I., Magnusson, M.K., Palmason, R., Haraldsdottir, V., Andersen, K., Onundarson, P.T., Thorgeirsson, G., Kiemeney, L.A.L.M., Powell, J.T., Carey, D.J., Kuivaniemi, H., Lindholt, J.S., Jones, G.T., Blankensteijn, J.D., Gretarsdottir, S., Baas, A.F., Thorleifsson, G., Holm, H., Heijer, M. den, Vries, J.P. de, Kranendonk, S.E., Zeebregts, C.J.A., Sterkenburg, S.M. van, Geelkerken, R.H., Rij, A.M. van, Williams, M.J., Boll, A.P.M., Kostic, J., Jonasdottir, A., Walters, G.B., Masson, G., Sulem, P., Saemundsdottir, J., Mouy, M., Magnusson, K.P., Tromp, G., Elmore, J.B., Sakalihasan, N., Limet, R., Defraigne, J.O., Ferrell, R.E., Ronkainen, A., Ruigrok, Y.M., Wijmenga, C., Grobbee, D.E., Shah, S.H., Granger, C.B., Quyyumi, A.A., Vaccarino, V., Patel, R., Zafari, A.M., Levey, A.I., Austin, H., Girelli, D., Pignatti, P.F., Olivieri, O., Martinelli, N., Malerba, G., Trabetti, E., Becker, L.C., Becker, D.M., Reilly, M.P., Rader, D.J., Mueller, T., Dieplinger, B., Haltmayer, M., Urbonavicius, S., Lindblad, B., Gottsäter, A., Gaetani, E., Pola, R., Wells, P., Rodger, M., Forgie, M., Langlois, N., Corral, J., Vicente, V., Fontcuberta, J., España, F., Grarup, N., Jørgensen, T., Witte, D.R., Hansen, T., Pedersen, O., Aben, K.K.H., Graaf, J. de, Holewijn, S., Folkersen, L., Franco-Cereceda, A., Eriksson, P., Collier, D.A., Stefansson, H., Steinthorsdottir, V., Rafnar, T., Valdimarsson, E.M., Magnadottir, H.B., Sveinbjornsdottir, S., Olafsson, I., Magnusson, M.K., Palmason, R., Haraldsdottir, V., Andersen, K., Onundarson, P.T., Thorgeirsson, G., Kiemeney, L.A.L.M., Powell, J.T., Carey, D.J., Kuivaniemi, H., Lindholt, J.S., Jones, G.T., and Blankensteijn, J.D.

Abstract

Contains fulltext : 88507.pdf (publisher's version ) (Closed access)

Published
2010

35. Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm.

Author

Gretarsdottir, S., Baas, A.F., Thorleifsson, G., Holm, H., Heijer, M. den, Vries, J.P. de, Kranendonk, S.E., Zeebregts, C.J.A., Sterkenburg, S.M. van, Geelkerken, R.H., Rij, A.M. van, Williams, M.J., Boll, A.P.M., Kostic, J., Jonasdottir, A., Walters, G.B., Masson, G., Sulem, P., Saemundsdottir, J., Mouy, M., Magnusson, K.P., Tromp, G., Elmore, J.B., Sakalihasan, N., Limet, R., Defraigne, J.O., Ferrell, R.E., Ronkainen, A., Ruigrok, Y.M., Wijmenga, C., Grobbee, D.E., Shah, S.H., Granger, C.B., Quyyumi, A.A., Vaccarino, V., Patel, R., Zafari, A.M., Levey, A.I., Austin, H., Girelli, D., Pignatti, P.F., Olivieri, O., Martinelli, N., Malerba, G., Trabetti, E., Becker, L.C., Becker, D.M., Reilly, M.P., Rader, D.J., Mueller, T., Dieplinger, B., Haltmayer, M., Urbonavicius, S., Lindblad, B., Gottsäter, A., Gaetani, E., Pola, R., Wells, P., Rodger, M., Forgie, M., Langlois, N., Corral, J., Vicente, V., Fontcuberta, J., España, F., Grarup, N., Jørgensen, T., Witte, D.R., Hansen, T., Pedersen, O., Aben, K.K.H., Graaf, J. de, Holewijn, S., Folkersen, L., Franco-Cereceda, A., Eriksson, P., Collier, D.A., Stefansson, H., Steinthorsdottir, V., Rafnar, T., Valdimarsson, E.M., Magnadottir, H.B., Sveinbjornsdottir, S., Olafsson, I., Magnusson, M.K., Palmason, R., Haraldsdottir, V., Andersen, K., Onundarson, P.T., Thorgeirsson, G., Kiemeney, L.A.L.M., Powell, J.T., Carey, D.J., Kuivaniemi, H., Lindholt, J.S., Jones, G.T., Blankensteijn, J.D., Gretarsdottir, S., Baas, A.F., Thorleifsson, G., Holm, H., Heijer, M. den, Vries, J.P. de, Kranendonk, S.E., Zeebregts, C.J.A., Sterkenburg, S.M. van, Geelkerken, R.H., Rij, A.M. van, Williams, M.J., Boll, A.P.M., Kostic, J., Jonasdottir, A., Walters, G.B., Masson, G., Sulem, P., Saemundsdottir, J., Mouy, M., Magnusson, K.P., Tromp, G., Elmore, J.B., Sakalihasan, N., Limet, R., Defraigne, J.O., Ferrell, R.E., Ronkainen, A., Ruigrok, Y.M., Wijmenga, C., Grobbee, D.E., Shah, S.H., Granger, C.B., Quyyumi, A.A., Vaccarino, V., Patel, R., Zafari, A.M., Levey, A.I., Austin, H., Girelli, D., Pignatti, P.F., Olivieri, O., Martinelli, N., Malerba, G., Trabetti, E., Becker, L.C., Becker, D.M., Reilly, M.P., Rader, D.J., Mueller, T., Dieplinger, B., Haltmayer, M., Urbonavicius, S., Lindblad, B., Gottsäter, A., Gaetani, E., Pola, R., Wells, P., Rodger, M., Forgie, M., Langlois, N., Corral, J., Vicente, V., Fontcuberta, J., España, F., Grarup, N., Jørgensen, T., Witte, D.R., Hansen, T., Pedersen, O., Aben, K.K.H., Graaf, J. de, Holewijn, S., Folkersen, L., Franco-Cereceda, A., Eriksson, P., Collier, D.A., Stefansson, H., Steinthorsdottir, V., Rafnar, T., Valdimarsson, E.M., Magnadottir, H.B., Sveinbjornsdottir, S., Olafsson, I., Magnusson, M.K., Palmason, R., Haraldsdottir, V., Andersen, K., Onundarson, P.T., Thorgeirsson, G., Kiemeney, L.A.L.M., Powell, J.T., Carey, D.J., Kuivaniemi, H., Lindholt, J.S., Jones, G.T., and Blankensteijn, J.D.

Abstract

Contains fulltext : 88507.pdf (publisher's version ) (Closed access)

Published
2010

36. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm.

Author

Helgadottir, A., Thorleifsson, G., Magnusson, K.P., Gretarsdottir, S., Steinthorsdottir, V., Manolescu, A., Jones, G.T., Rinkel, G.J., Blankensteijn, J.D., Ronkainen, A., Jaaskelainen, J.E., Kyo, Y., Lenk, G.M., Sakalihasan, N., Kostulas, K., Gottsater, A., Flex, A., Stefansson, H., Hansen, T., Andersen, G., Weinsheimer, S., Borch-Johnsen, K., Jorgensen, T., Shah, S.H., Quyyumi, A.A., Granger, C.B., Reilly, M.P., Austin, H., Levey, A.I., Vaccarino, V., Palsdottir, E., Walters, G.B., Jonsdottir, T., Snorradottir, S., Magnusdottir, D., Gudmundsson, G., Ferrell, R.E., Sveinbjornsdottir, S., Hernesniemi, J., Niemela, M., Limet, R., Andersen, K., Sigurdsson, G., Benediktsson, R., Verhoeven, E.L., Teijink, J.A., Grobbee, D.E., Rader, D.J., Collier, D.A., Pedersen, O., Pola, R., Hillert, J., Lindblad, B., Valdimarsson, E.M., Magnadottir, H.B., Wijmenga, C., Tromp, G., Baas, A.F., Ruigrok, Y.M., Rij, A.M. van, Kuivaniemi, H., Powell, J.T., Matthiasson, S.E., Gulcher, J.R., Thorgeirsson, G., Kong, A., Thorsteinsdottir, U., Stefansson, K., Helgadottir, A., Thorleifsson, G., Magnusson, K.P., Gretarsdottir, S., Steinthorsdottir, V., Manolescu, A., Jones, G.T., Rinkel, G.J., Blankensteijn, J.D., Ronkainen, A., Jaaskelainen, J.E., Kyo, Y., Lenk, G.M., Sakalihasan, N., Kostulas, K., Gottsater, A., Flex, A., Stefansson, H., Hansen, T., Andersen, G., Weinsheimer, S., Borch-Johnsen, K., Jorgensen, T., Shah, S.H., Quyyumi, A.A., Granger, C.B., Reilly, M.P., Austin, H., Levey, A.I., Vaccarino, V., Palsdottir, E., Walters, G.B., Jonsdottir, T., Snorradottir, S., Magnusdottir, D., Gudmundsson, G., Ferrell, R.E., Sveinbjornsdottir, S., Hernesniemi, J., Niemela, M., Limet, R., Andersen, K., Sigurdsson, G., Benediktsson, R., Verhoeven, E.L., Teijink, J.A., Grobbee, D.E., Rader, D.J., Collier, D.A., Pedersen, O., Pola, R., Hillert, J., Lindblad, B., Valdimarsson, E.M., Magnadottir, H.B., Wijmenga, C., Tromp, G., Baas, A.F., Ruigrok, Y.M., Rij, A.M. van, Kuivaniemi, H., Powell, J.T., Matthiasson, S.E., Gulcher, J.R., Thorgeirsson, G., Kong, A., Thorsteinsdottir, U., and Stefansson, K.

Abstract

Contains fulltext : 70663.pdf (publisher's version ) (Closed access), Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.

Published
2008

37. A variant associated with nicotine dependence, lung cancer and peripheral arterial disease.

Author

Thorgeirsson, T.E., Geller, F., Sulem, P., Rafnar, T., Wiste, A., Magnusson, K.P., Manolescu, A., Thorleifsson, G., Stefansson, H., Ingason, A., Stacey, S.N., Bergthorsson, J.T., Thorlacius, S., Gudmundsson, J., Jonsson, T., Jakobsdottir, M., Saemundsdottir, J., Olafsdottir, O., Gudmundsson, L.J., Bjornsdottir, G., Kristjansson, K., Skuladottir, H., Isaksson, H.J., Gudbjartsson, T., Jones, G.T., Mueller, T., Gottsater, A., Flex, A., Aben, K.K.H., Vegt, F. de, Mulders, P.F.A., Isla, D., Vidal, M.J., Asin, L., Saez, B., Murillo, L., Blondal, T., Kolbeinsson, H., Stefansson, J.G., Hansdottir, I., Runarsdottir, V., Pola, R., Lindblad, B., Rij, A.M. van, Dieplinger, B., Haltmayer, M., Mayordomo, J.I., Kiemeney, L.A.L.M., Matthiasson, S.E., Oskarsson, H., Tyrfingsson, T., Gudbjartsson, D.F., Gulcher, J.R., Jonsson, S., Thorsteinsdottir, U., Kong, A., Stefansson, K., Thorgeirsson, T.E., Geller, F., Sulem, P., Rafnar, T., Wiste, A., Magnusson, K.P., Manolescu, A., Thorleifsson, G., Stefansson, H., Ingason, A., Stacey, S.N., Bergthorsson, J.T., Thorlacius, S., Gudmundsson, J., Jonsson, T., Jakobsdottir, M., Saemundsdottir, J., Olafsdottir, O., Gudmundsson, L.J., Bjornsdottir, G., Kristjansson, K., Skuladottir, H., Isaksson, H.J., Gudbjartsson, T., Jones, G.T., Mueller, T., Gottsater, A., Flex, A., Aben, K.K.H., Vegt, F. de, Mulders, P.F.A., Isla, D., Vidal, M.J., Asin, L., Saez, B., Murillo, L., Blondal, T., Kolbeinsson, H., Stefansson, J.G., Hansdottir, I., Runarsdottir, V., Pola, R., Lindblad, B., Rij, A.M. van, Dieplinger, B., Haltmayer, M., Mayordomo, J.I., Kiemeney, L.A.L.M., Matthiasson, S.E., Oskarsson, H., Tyrfingsson, T., Gudbjartsson, D.F., Gulcher, J.R., Jonsson, S., Thorsteinsdottir, U., Kong, A., and Stefansson, K.

Abstract

Contains fulltext : 69066.pdf (publisher's version ) (Closed access), Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases.

Published
2008

38. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm.

Author

Helgadottir, A., Thorleifsson, G., Magnusson, K.P., Gretarsdottir, S., Steinthorsdottir, V., Manolescu, A., Jones, G.T., Rinkel, G.J., Blankensteijn, J.D., Ronkainen, A., Jaaskelainen, J.E., Kyo, Y., Lenk, G.M., Sakalihasan, N., Kostulas, K., Gottsater, A., Flex, A., Stefansson, H., Hansen, T., Andersen, G., Weinsheimer, S., Borch-Johnsen, K., Jorgensen, T., Shah, S.H., Quyyumi, A.A., Granger, C.B., Reilly, M.P., Austin, H., Levey, A.I., Vaccarino, V., Palsdottir, E., Walters, G.B., Jonsdottir, T., Snorradottir, S., Magnusdottir, D., Gudmundsson, G., Ferrell, R.E., Sveinbjornsdottir, S., Hernesniemi, J., Niemela, M., Limet, R., Andersen, K., Sigurdsson, G., Benediktsson, R., Verhoeven, E.L., Teijink, J.A., Grobbee, D.E., Rader, D.J., Collier, D.A., Pedersen, O., Pola, R., Hillert, J., Lindblad, B., Valdimarsson, E.M., Magnadottir, H.B., Wijmenga, C., Tromp, G., Baas, A.F., Ruigrok, Y.M., Rij, A.M. van, Kuivaniemi, H., Powell, J.T., Matthiasson, S.E., Gulcher, J.R., Thorgeirsson, G., Kong, A., Thorsteinsdottir, U., Stefansson, K., Helgadottir, A., Thorleifsson, G., Magnusson, K.P., Gretarsdottir, S., Steinthorsdottir, V., Manolescu, A., Jones, G.T., Rinkel, G.J., Blankensteijn, J.D., Ronkainen, A., Jaaskelainen, J.E., Kyo, Y., Lenk, G.M., Sakalihasan, N., Kostulas, K., Gottsater, A., Flex, A., Stefansson, H., Hansen, T., Andersen, G., Weinsheimer, S., Borch-Johnsen, K., Jorgensen, T., Shah, S.H., Quyyumi, A.A., Granger, C.B., Reilly, M.P., Austin, H., Levey, A.I., Vaccarino, V., Palsdottir, E., Walters, G.B., Jonsdottir, T., Snorradottir, S., Magnusdottir, D., Gudmundsson, G., Ferrell, R.E., Sveinbjornsdottir, S., Hernesniemi, J., Niemela, M., Limet, R., Andersen, K., Sigurdsson, G., Benediktsson, R., Verhoeven, E.L., Teijink, J.A., Grobbee, D.E., Rader, D.J., Collier, D.A., Pedersen, O., Pola, R., Hillert, J., Lindblad, B., Valdimarsson, E.M., Magnadottir, H.B., Wijmenga, C., Tromp, G., Baas, A.F., Ruigrok, Y.M., Rij, A.M. van, Kuivaniemi, H., Powell, J.T., Matthiasson, S.E., Gulcher, J.R., Thorgeirsson, G., Kong, A., Thorsteinsdottir, U., and Stefansson, K.

Abstract

Contains fulltext : 70663.pdf (publisher's version ) (Closed access), Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.

Published
2008

39. A variant associated with nicotine dependence, lung cancer and peripheral arterial disease.

Author

Thorgeirsson, T.E., Geller, F., Sulem, P., Rafnar, T., Wiste, A., Magnusson, K.P., Manolescu, A., Thorleifsson, G., Stefansson, H., Ingason, A., Stacey, S.N., Bergthorsson, J.T., Thorlacius, S., Gudmundsson, J., Jonsson, T., Jakobsdottir, M., Saemundsdottir, J., Olafsdottir, O., Gudmundsson, L.J., Bjornsdottir, G., Kristjansson, K., Skuladottir, H., Isaksson, H.J., Gudbjartsson, T., Jones, G.T., Mueller, T., Gottsater, A., Flex, A., Aben, K.K.H., Vegt, F. de, Mulders, P.F.A., Isla, D., Vidal, M.J., Asin, L., Saez, B., Murillo, L., Blondal, T., Kolbeinsson, H., Stefansson, J.G., Hansdottir, I., Runarsdottir, V., Pola, R., Lindblad, B., Rij, A.M. van, Dieplinger, B., Haltmayer, M., Mayordomo, J.I., Kiemeney, L.A.L.M., Matthiasson, S.E., Oskarsson, H., Tyrfingsson, T., Gudbjartsson, D.F., Gulcher, J.R., Jonsson, S., Thorsteinsdottir, U., Kong, A., Stefansson, K., Thorgeirsson, T.E., Geller, F., Sulem, P., Rafnar, T., Wiste, A., Magnusson, K.P., Manolescu, A., Thorleifsson, G., Stefansson, H., Ingason, A., Stacey, S.N., Bergthorsson, J.T., Thorlacius, S., Gudmundsson, J., Jonsson, T., Jakobsdottir, M., Saemundsdottir, J., Olafsdottir, O., Gudmundsson, L.J., Bjornsdottir, G., Kristjansson, K., Skuladottir, H., Isaksson, H.J., Gudbjartsson, T., Jones, G.T., Mueller, T., Gottsater, A., Flex, A., Aben, K.K.H., Vegt, F. de, Mulders, P.F.A., Isla, D., Vidal, M.J., Asin, L., Saez, B., Murillo, L., Blondal, T., Kolbeinsson, H., Stefansson, J.G., Hansdottir, I., Runarsdottir, V., Pola, R., Lindblad, B., Rij, A.M. van, Dieplinger, B., Haltmayer, M., Mayordomo, J.I., Kiemeney, L.A.L.M., Matthiasson, S.E., Oskarsson, H., Tyrfingsson, T., Gudbjartsson, D.F., Gulcher, J.R., Jonsson, S., Thorsteinsdottir, U., Kong, A., and Stefansson, K.

Abstract

Contains fulltext : 69066.pdf (publisher's version ) (Closed access), Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases.

Published
2008

40. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm.

Author

Helgadottir, A., Thorleifsson, G., Magnusson, K.P., Gretarsdottir, S., Steinthorsdottir, V., Manolescu, A., Jones, G.T., Rinkel, G.J., Blankensteijn, J.D., Ronkainen, A., Jaaskelainen, J.E., Kyo, Y., Lenk, G.M., Sakalihasan, N., Kostulas, K., Gottsater, A., Flex, A., Stefansson, H., Hansen, T., Andersen, G., Weinsheimer, S., Borch-Johnsen, K., Jorgensen, T., Shah, S.H., Quyyumi, A.A., Granger, C.B., Reilly, M.P., Austin, H., Levey, A.I., Vaccarino, V., Palsdottir, E., Walters, G.B., Jonsdottir, T., Snorradottir, S., Magnusdottir, D., Gudmundsson, G., Ferrell, R.E., Sveinbjornsdottir, S., Hernesniemi, J., Niemela, M., Limet, R., Andersen, K., Sigurdsson, G., Benediktsson, R., Verhoeven, E.L., Teijink, J.A., Grobbee, D.E., Rader, D.J., Collier, D.A., Pedersen, O., Pola, R., Hillert, J., Lindblad, B., Valdimarsson, E.M., Magnadottir, H.B., Wijmenga, C., Tromp, G., Baas, A.F., Ruigrok, Y.M., Rij, A.M. van, Kuivaniemi, H., Powell, J.T., Matthiasson, S.E., Gulcher, J.R., Thorgeirsson, G., Kong, A., Thorsteinsdottir, U., Stefansson, K., Helgadottir, A., Thorleifsson, G., Magnusson, K.P., Gretarsdottir, S., Steinthorsdottir, V., Manolescu, A., Jones, G.T., Rinkel, G.J., Blankensteijn, J.D., Ronkainen, A., Jaaskelainen, J.E., Kyo, Y., Lenk, G.M., Sakalihasan, N., Kostulas, K., Gottsater, A., Flex, A., Stefansson, H., Hansen, T., Andersen, G., Weinsheimer, S., Borch-Johnsen, K., Jorgensen, T., Shah, S.H., Quyyumi, A.A., Granger, C.B., Reilly, M.P., Austin, H., Levey, A.I., Vaccarino, V., Palsdottir, E., Walters, G.B., Jonsdottir, T., Snorradottir, S., Magnusdottir, D., Gudmundsson, G., Ferrell, R.E., Sveinbjornsdottir, S., Hernesniemi, J., Niemela, M., Limet, R., Andersen, K., Sigurdsson, G., Benediktsson, R., Verhoeven, E.L., Teijink, J.A., Grobbee, D.E., Rader, D.J., Collier, D.A., Pedersen, O., Pola, R., Hillert, J., Lindblad, B., Valdimarsson, E.M., Magnadottir, H.B., Wijmenga, C., Tromp, G., Baas, A.F., Ruigrok, Y.M., Rij, A.M. van, Kuivaniemi, H., Powell, J.T., Matthiasson, S.E., Gulcher, J.R., Thorgeirsson, G., Kong, A., Thorsteinsdottir, U., and Stefansson, K.

Abstract

Contains fulltext : 70663.pdf (publisher's version ) (Closed access), Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.

Published
2008

41. Serum macrophage migration inhibitory factor (MIF) in the intercritical phase of hereditary periodic fevers and its relationship with the MIF-173G/C polymorphism

Author

Rigante, Donato, Flex, Andrea, Federico, G., Pola, Roberto, Candelli, Marcello, Manna, Raffaele, Pugliese, A. L., Cerquaglia, Claudia, Compagnone, A., Stabile, A., Rigante D. (ORCID:0000-0001-7032-7779), Flex A. (ORCID:0000-0003-2664-4165), Pola R. (ORCID:0000-0001-5224-2931), Candelli M. (ORCID:0000-0001-8443-7880), Manna R. (ORCID:0000-0003-1560-3907), Cerquaglia C., Rigante, Donato, Flex, Andrea, Federico, G., Pola, Roberto, Candelli, Marcello, Manna, Raffaele, Pugliese, A. L., Cerquaglia, Claudia, Compagnone, A., Stabile, A., Rigante D. (ORCID:0000-0001-7032-7779), Flex A. (ORCID:0000-0003-2664-4165), Pola R. (ORCID:0000-0001-5224-2931), Candelli M. (ORCID:0000-0001-8443-7880), Manna R. (ORCID:0000-0003-1560-3907), and Cerquaglia C.

Abstract

Objectives: To examine the association of the -173 single-nucleotide G/C polymorphism of the macrophage migration inhibitory factor gene (MIF) and serum macrophage migration inhibitory factor (MIF) concentrations in a group of Italian patients with hereditary periodic fevers (HPF), tested during a symptom-free phase of their disease. Methods: Genomic DNA for MIF and serum MIF were evaluated in 22 patients with HPF and compared with healthy controls of the same ethnic group. The MIF-173G/C polymorphism was genotyped using polymerase chain reaction (PCR) and visualized by ethidium bromide staining. Serum MIF levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: MIF-173*C allele frequency and MIF serum concentrations were significantly higher in patients with HPF than in controls, with no statistically significant difference between familial Mediterranean fever (FMF) and hyperimmunoglobulinaemia D/periodic fever syndrome (HIDS) and no correlation with specific MIF genotypes. Conclusions: The MIF-173*C allele was found more frequently in patients with HPF than in controls and MIF serum concentrations were considerably elevated in attack-free phases, suggesting a persistent state of subclinical cytokine activation with MIF involvement in the autoinflammatory cascade. © 2007 Taylor & Francis on license from Scandinavian Rheumatology Research Foundation.

Published
2007

42. Vascular endothelial growth factor (VEGF) expression in noise-induced hearing loss

Author

Picciotti, Pasqualina Maria, Fetoni, Anna Rita, Paludetti, Gaetano, Wolf, F I, Torsello, A, Troiani, Diana, Ferraresi, A, Pola, Roberto, Sergi, Bruno, Picciotti, P M (ORCID:0000-0002-1502-6508), Fetoni, A R (ORCID:0000-0001-5405-4301), Paludetti, G (ORCID:0000-0003-2480-1243), Troiani, D (ORCID:0000-0002-5665-7410), Pola, R (ORCID:0000-0001-5224-2931), Sergi, B (ORCID:0000-0001-8648-5966), Picciotti, Pasqualina Maria, Fetoni, Anna Rita, Paludetti, Gaetano, Wolf, F I, Torsello, A, Troiani, Diana, Ferraresi, A, Pola, Roberto, Sergi, Bruno, Picciotti, P M (ORCID:0000-0002-1502-6508), Fetoni, A R (ORCID:0000-0001-5405-4301), Paludetti, G (ORCID:0000-0003-2480-1243), Troiani, D (ORCID:0000-0002-5665-7410), Pola, R (ORCID:0000-0001-5224-2931), and Sergi, B (ORCID:0000-0001-8648-5966)

Abstract

Noise-induced hearing loss has been associated with alterations in cochlear blood flow. Our study analyzed the expression of Vascular Endothelial Growth Factor (VEGF) and its functional receptors, Flt-1 and Flk-1, in the cochlear structures of noise-exposed and unexposed guinea pigs. VEGF is a prototypical angiogenic agent, with multiple functions on vascular biology, ranging from vascular permeability to endothelial cell migration, proliferation, differentiation, and survival.Acoustic trauma was induced by a continuous pure tone of 6 kHz, at 120 dB SPL for 30 min. Auditory function was evaluated by electrocochleographic recordings at 2-20 kHz for 7 days. Noise-induced cochlear morphological changes were studied by immunohistochemistry and scanning electron microscopy. The expression of VEGF and its receptors was examined by immunohistochemistry and western blotting analysis. The hearing threshold shift reached a level of 60 dB SPL on day I after trauma and underwent a partial recovery over time, reaching a value of about 20 dB SPL on day 7. Outer hair cell loss was more prominent in the area located 14-16 min from the apex. Increased cochlear VEGF expression was observed in noise-exposed animals, in particular at the level of stria vascularis, spiral ligament, and spiral ganglion cells. No changes were observed in the expression of VEGF-receptors.Our data suggest a role for VEGF in the regulation of the vascular network in the inner ear after acoustic trauma and during auditory recovery, with potentially important clinical and therapeutic implications. (c) 2006 Elsevier B.V. All rights reserved.

Published
2006

43. Intercellular adhesion molecule-1 K469E gene polymorphism and Alzheimer's disease

Author

Pola, Roberto, Flex, Andrea, Gaetani, Eleonora, Santoliquido, Angelo, Serricchio, Michele Lorenzo, Pola, P., Bernabei, Roberto, Pola R. (ORCID:0000-0001-5224-2931), Flex A. (ORCID:0000-0003-2664-4165), Gaetani E. (ORCID:0000-0002-7808-1491), Santoliquido A. (ORCID:0000-0003-1539-4017), Serricchio M. (ORCID:0000-0003-1832-9608), Bernabei R. (ORCID:0000-0002-9197-004X), Pola, Roberto, Flex, Andrea, Gaetani, Eleonora, Santoliquido, Angelo, Serricchio, Michele Lorenzo, Pola, P., Bernabei, Roberto, Pola R. (ORCID:0000-0001-5224-2931), Flex A. (ORCID:0000-0003-2664-4165), Gaetani E. (ORCID:0000-0002-7808-1491), Santoliquido A. (ORCID:0000-0003-1539-4017), Serricchio M. (ORCID:0000-0003-1832-9608), and Bernabei R. (ORCID:0000-0002-9197-004X)

Abstract

Inflammatory processes are considered important in the pathogenesis of Alzheimer's disease (AD). Intercellular adhesion molecule-1 (ICAM-1) is an important mediator of inflammatory response and immune cell activation, is expressed on cerebrovascular endothelium and neuritic plaques in brain of AD patients, and seems to be implicated in the process of neuro-degeneration. A common polymorphism of the ICAM-1 gene (K469E) has been recently reported. In this case-control study, we evaluated the distribution of E/K alleles and genotypes of the ICAM-1 gene in 98 patients affected by sporadic AD and 115 age- and sex-matched controls. The frequency of the EE genotype was significantly higher in AD patients (P<0.01). Logistic regression analysis indicated that the presence of EE genotype significantly increased the risk of AD (odds ratio 3.01 [1.1-8.0], P<0.05). This study shows for the first time an association between ICAM-1 E/K gene polymorphism and AD, suggesting that polymorphisms of the ICAM-1 gene may be clinically important and confirming that inflammatory mechanisms may be crucial in the pathophysiology of neuro-degenerative diseases. © 2002 Elsevier Science Inc. All rights reserved.

Published
2003

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