Venous thromboembolism characteristics and outcomes among RIETE patients tested and untested for inherited thrombophilia

Publisher Copyright: © 2024 by The American Society of Hematology.Inherited thrombophilia (IT) workup is commonly pursued in patients with venous thromboembolism (VTE). Recent American Society of Hematology guidelines recommend a selective approach to IT testing, nevertheless, evidence on whether thrombophilia testing can actually improve patient-important outcomes through tailored management is limited. Data from the large, prospective Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry were analyzed to compare VTE risk factors, management, and outcomes between patients who were tested for IT and untested patients, during anticoagulant treatment and after its discontinuation. Among 103 818 patients enrolled in RIETE, 21 089 (20.3%) were tested for IT, 8422 (8.1%) tested positive, and 82 729 (79.7%) were not tested. IT testing was more frequent in patients with VTE provoked by minor risk factors and less common in those with major risk factors such as surgery or active cancer. Choices of anticoagulant treatment did not differ based on IT testing results. Untested patients exhibited inferior outcomes across all VTE categories, with higher rates of VTE recurrence, major bleeding, mortality, and notably, cancer-related mortality. After treatment discontinuation, IT-negative patients with surgically provoked VTE showed lower recurrence rates. For immobilization-related VTE as well as in estrogen-related VTE, no significant differences in recurrence rates were observed between IT-negative and IT-positive patients. However, IT-negative patients with pregnancy or postpartum-related VTE had significantly lower recurrence rates. Patients with unprovoked VTE, particularly those testing positive for IT, had high recurrence rates after treatment. These findings underscore the complex role of IT testing in managing VTE, supporting personalized treatment strategies that consider VTE risk factors and comorbidities. The trial was registered at www.clinicaltrials.gov as #NCT02832245.Peer reviewe

Development of a Risk Prediction Score for Occult Cancer in Patients With VTE

Background The benefits of a diagnostic workup for occult cancer in patients with VTE are controversial. Our aim was to provide and validate a risk score for occult cancer in patients with VTE. Methods We designed a nested case-control study in a cohort of patients with VTE included in the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry from 2001 to 2014. Cases included cancer detected beyond the first 30 days and up to 24 months after VTE. Control subjects were defined as patients with VTE with no cancer in the same period. Results Of 5,863 eligible patients, 444 (7.6%; 95% CI, 6.8%-8.2%) were diagnosed with occult cancer. On multivariable analysis, variables selected were male sex, age > 70 years, chronic lung disease, anemia, elevated platelet count, prior VTE, and recent surgery. We built a risk score assigning points to each variable. Internal validity was confirmed using bootstrap analysis. The proportion of patients with cancer who scored ≤ 2 points was 5.8% (241 of 4,150) and that proportion in those who scored ≥ 3 points was 12% (203 of 1,713). We also identified scores divided by sex and age subgroups. Conclusions This is the first risk score that has identified patients with VTE who are at increased risk for occult cancer. Our score needs to be externally validated

Timing and characteristics of venous thromboembolism after noncancer surgery

Background: Venous thromboembolism (VTE) is a major cause of morbidity and mortality postoperatively. The use of pharmacologic prophylaxis is effective in reducing the incidence of VTE. However, the prophylaxis is often discontinued at hospital discharge, especially for those with benign disease. The implications of this practice are not known. We assessed the data from a large, ongoing registry regarding the time course of VTE and outcomes after noncancer surgery. Methods: We analyzed the RIETE (Computerized Registry on Venous Thromboembolism) registry, which includes data from consecutive patients with symptomatic confirmed VTE. In the present study, we focused on general surgical patients who had developed symptomatic postoperative VTE in the first 8 weeks after noncancer surgery. The main objective was to assess the interval between surgery and the occurrence of VTE. Additional variables included the clinical presentation associated with the event, the use of thrombosis prophylaxis, and unfavorable outcomes. Results: The data from 3296 patients were analyzed. The median time from surgery to the detection of VTE was 16 days (interquartile range, 8-30 days). Of the VTE events, 77% were detected after the first postoperative week and 27% after 4 weeks. Overall, 43.9% of the patients with VTE had received pharmacologic prophylaxis after surgery for a median of 8 days (interquartile range, 5-14 days), and three quarters of the VTE events were detected after pharmacologic prophylaxis had been discontinued. Overall, 54% of the patients with VTE had presented with pulmonary embolism. For 15% of the patients, the clinical outcome was unfavorable, including 4% who had died within 90 days. Conclusions: The risk of VTE after noncancer general surgery remains high for ≤2 months. More than one half of the patients had presented with symptomatic PE as the VTE event, and 15% had had unfavorable outcomes. Only 44% of these patients had received pharmacologic prophylaxis for around 1 week

DVT Management and Outcome Trends, 2001 to 2014

Background A comprehensive evaluation of temporal trends in the treatment of patients who have DVT may assist with identification of modifiable factors that contribute to short-term outcomes. Methods We assessed temporal trends in length of hospital stay and use of pharmacological and interventional therapies among 26,695 adults with DVT enrolled in the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2014. We also examined temporal trends in risk-adjusted rates of all-cause, pulmonary embolism-related, and bleeding-related death to 30 days after diagnosis. Results The mean length of hospital stay decreased from 9.0 days in 2001 to 2005 to 7.6 days in 2010 to 2014 (P <01). For initial DVT treatment, the use of low-molecular-weight heparin decreased from 98% to 90% (P <01). Direct oral anticoagulants use increased from 0.5% in 2010 to 13.4% in 2014 (P <001). Risk-adjusted rates of 30-day all-cause mortality decreased from 3.9% in 2001 to 2005 to 2.7% in 2010 to 2014 (adjusted rate ratio per year, 0.84; 95% CI, 0.74-0.96; P <01). VTE-related mortality showed a nonstatistically significant downward trend (adjusted rate ratio per year, 0.70; 95% CI, 0.44-1.10; P =13), whereas 30-day bleeding-related mortality significantly decreased from 0.5% in 2001 to 2005 to 0.1% in 2010-2014 (adjusted rate ratio per year, 0.55; 95% CI, 0.40-0.77; P < .01). Conclusions This international registry-based temporal analysis identified reductions in length of stay for adults hospitalized for DVT. The study also found a decreasing trend in adjusted rates of all-cause and bleeding-related mortality

Analysis of noncatheter-associated upper extremity deep venous thrombosis from the RIETE registry

Objective We sought to determine the risk factors for subsequent bleeding and recurrent venous thromboembolism (VTE) events following isolated noncatheter-associated upper extremity deep venous thrombosis (non-CA-UEDVT) to better inform future treatment decisions for this group of patients. Methods The RIETE registry (Registro Informatizado de Enfermedad TromboEmb\uf3lica [Computerized Registry of Patients with Venous Thromboembolism]) is a prospective international registry of patients with objectively confirmed symptomatic VTE. Patients with a symptomatic, isolated, proximal UEDVT from March 2001 through March 2015 were analyzed. Any patient with an indwelling catheter or pacemaker lead at the DVT site and at the time of thrombosis was considered to have a CA-UEDVT and was excluded. Patient and treatment characteristics such as age, gender, comorbidities, VTE risk factors, treatment drug, and duration were collected. Outcomes examined included recurrent DVT, subsequent pulmonary embolism (PE), and hemorrhage. Multivariate analysis was performed using stepwise logistic regression. Results Of the 1100 patients who met the study criteria, 580 (53%) were male. The mean age of the patients was 50&nbsp;\ub1 20 years, and overall patient survival at 1 year was 85%. Recurrent VTE occurred in 59 patients (5.4%). Of these, 46 patients (4%) had recurrent DVT, 10 (0.9%) had a PE following UEDVT diagnosis, and 3 (0.3%) had both. PE was fatal in three patients (0.3%). Bleeding occurred in 50 patients (4.5%), major bleeding in 19 patients (1.7%), and fatal bleeding in 6 patients (0.5%). On multivariate analysis, malignant disease was associated with VTE recurrence (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.04-3.45; P&nbsp;&lt;.04), whereas hemorrhage was associated with age (OR, 1.03; 95% CI, 1.01-1.05; P&nbsp;=.002) and malignant disease (OR, 2.53; 95% CI, 1.34-4.76; P&nbsp;&lt;.005). Hemorrhage and recurrent VTE were also significantly associated (OR, 2.79; 95% CI, 1.16-6.76; P&nbsp;&lt;.03). Conclusions PE following non-CA-UEDVT is rare. Malignant disease was associated with VTE recurrence. Age and malignant disease were associated with hemorrhage, and VTE recurrence was associated with hemorrhage. Further prospective studies should be undertaken to best determine length of anticoagulation treatment for the varied populations of patients with UEDVT

Real-Time Dissemination of Aggregate Data on Presentation and Outcomes of Patients With Venous Thromboembolism: The RIETE Infographics Project

In the current era of patient empowerment and precision medicine, access to timely information is critical to decision-making. Unfortunately, we currently lack patient-specific, real-time data about clinical presentation, risk of thrombotic or hemorrhagic events, key risk factors, and adverse outcomes in patients with venous thromboembolism (VTE). Accordingly, the Registro Informatizado Enfermedad TromboEmb\uf3lica (RIETE) investigators developed a tool to provide an open-source, real-time graphic representation of VTE-related data derived from over 90 000 patients with confirmed VTE. This information is intended to facilitate discussion in the informed decision-making process. The current article describes the aims, rationale, methods, and ongoing and future efforts of the real-time VTE infographics developed by the RIETE registry collaborators

Vitamin K Antagonists After 6 Months of Low-Molecular-Weight Heparin in Cancer Patients with Venous Thromboembolism

Background: Low-molecular-weight heparin (LMWH) is the treatment of choice in cancer patients with venous thromboembolism. However, data on continuing LMWH treatment beyond 6 months remain scanty. Methods: We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to compare the rate of venous thromboembolism recurrences and major bleeding appearing beyond the first 6 months of anticoagulant therapy in cancer patients with venous thromboembolism, according to therapy with LMWH or vitamin K antagonists (VKA). We performed a propensity score-matched cohort study. Results: After propensity matching, 482 cancer patients continued to receive LMWH and 482 switched to VKA. During the course of anticoagulant therapy (mean 275.5 days), 57 patients developed venous thrombosis recurrences (recurrent pulmonary embolism 26, recurrent deep vein thrombosis 29, both 2), 28 had major bleeding, 38 had nonmajor bleeding, and 129 died. No patient died of recurrent venous thrombosis, and 5 patients died of bleeding (2 were on LMWH, 3 on VKA). Patients who continued with LMWH had a similar rate of deep vein thrombosis recurrences (relative risk [RR] 1.41; 95% confidence interval [CI], 0.68-2.93), pulmonary embolism recurrences (RR 0.73; 95% CI, 0.34-1.58), major bleeding (RR 0.96; 95% CI, 0.51-1.79), or nonmajor bleeding (RR 1.15; 95% CI, 0.55-2.40), compared with those who switched to VKA, but a higher mortality rate (RR 1.58; 95% CI, 1.13-2.20). Conclusions: In cancer patients with venous thromboembolism who completed 6 months of LMWH therapy, switching to VKA was associated with a similar risk of venous thrombosis recurrences or bleeding when compared with patients who continued LMWH

Derivation and validation of a clinical prediction rule for thrombolysis-associated major bleeding in patients with acute pulmonary embolism: The BACS score

Background: Improved prediction of the risk of major bleeding in patients with acute pulmonary embolism (PE) receiving systemic thrombolysis is crucial to guide the choice of therapy. Methods: The study included consecutive patients with acute PE who received systemic thrombolysis in the RIETE registry. We used multivariable logistic regression analysis to create a risk score to predict 30-day major bleeding episodes. We externally validated the risk score in patients from the COMMAND VTE registry. In addition, we compared the newly created risk score against the Kuijer and RIETE scores. Results: Multivariable logistic regression identified four predictors for major bleeding: recent major bleeding (3 points), age &gt;75 years (1 point), active cancer (1 point) and syncope (1 point) (BACS). Among 1172 patients receiving thrombolytic therapy in RIETE, 446 (38%) were classified as having low risk (none of the variables present, 0 points) of major bleeding according to the BACS score, and the overall 30-day major bleeding rate of this group was 2.9% (95% CI 1.6–4.9%), compared with 44% (95% CI 14–79%) in the high-risk group (&gt;3 points). In the validation cohort, 51% (149 out of 290) of patients were classified as having low risk, and the overall 30-day major bleeding rate of this group was 1.3%. In RIETE, the 30-day major bleeding event rates in the Kuijer and RIETE low-risk strata were 5.3% and 4.4%, respectively. Conclusions: The BACS score is an easily applicable aid for prediction of the risk of major bleeding in the population of PE patients who receive systemic thrombolysis

Clinical characteristics and 3-month outcomes in cancer patients with incidental versus clinically suspected and confirmed pulmonary embolism

230sinoneBackground Current guidelines suggest treating cancer patients with incidental pulmonary embolism (PE) similarly to those with clinically suspected and confirmed PE. However, the natural history of these presentations has not been thoroughly compared. Methods We used the data from the RIETE (Registro Informatizado de Enfermedad TromboEmbólica) registry to compare the 3-month outcomes in patients with active cancer and incidental PE versus those with clinically suspected and confirmed PE. The primary outcome was 90-day all-cause mortality. Secondary outcomes were PE-related mortality, symptomatic PE recurrences and major bleeding. Results From July 2012 to January 2019, 946 cancer patients with incidental asymptomatic PE and 2274 with clinically suspected and confirmed PE were enrolled. Most patients (95% versus 90%) received low-molecular-weight heparin therapy. During the first 90 days, 598 patients died, including 42 from PE. Patients with incidental PE had a lower all-cause mortality rate than those with suspected and confirmed PE (11% versus 22%; OR 0.43, 95% CI 0.34-0.54). Results were consistent for PE-related mortality (0.3% versus 1.7%; OR 0.18, 95% CI 0.06-0.59). Multivariable analysis confirmed that patients with incidental PE were at lower risk of death (adjusted OR 0.43, 95% CI 0.34-0.56). Overall, 29 (0.9%) patients developed symptomatic PE recurrences, and 122 (3.8%) had major bleeding. There were no significant differences in PE recurrences (OR 0.62, 95% CI 0.25-1.54) or major bleeding (OR 0.78, 95% CI 0.51-1.18). Conclusions Cancer patients with incidental PE had a lower mortality rate than those with clinically suspected and confirmed PE. Further studies are required to validate these findings, and to explore optimal management strategies in these patients.nonePeris M.; Lopez-Nunez J.J.; Maestre A.; Jimenez D.; Muriel A.; Bikdeli B.; Weinberg I.; Ay C.; Mazzolai L.; Lorenzo A.; Monreal M.; Monreel M.; Prandoni P.; Brenner B.; Farge-Bancel D.; Barba R.; Di Micco P.; Bertoletti L.; Schellong S.; Tzoran I.; Reis A.; Bosevski M.; Bounameaux H.; Maly R.; Verhamme P.; Caprini J.A.; Bui H.M.; Adarraga M.D.; Agud M.; Aibar J.; Aibar M.A.; Alfonso J.; Amado C.; Aramberri M.; Arcelus J.I.; Ballaz A.; Barba R.; Barbagelata C.; Barron M.; Barron-Andres B.; Blanco-Molina A.; Camon A.M.; Canas I.; Cerda P.; Criado J.; de Ancos C.; de Miguel J.; del Toro J.; Demelo-Rodriguez P.; Diaz-Pedroche M.C.; Diaz-Peromingo J.A.; Diez-Sierra J.; Dominguez I.M.; Encabo M.; Escribano J.C.; Farfan A.I.; Fernandez-Capitan C.; Fernandez-Reyes J.L.; de Roitegui F.K.; Fidalgo M.A.; Flores K.; Font C.; Font L.; Francisco I.; Gabara C.; Galeano-Valle F.; Garcia M.A.; Garcia-Bragado F.; Garcia-Raso A.; Gavin-Blanco O.; Gavin-Sebastian O.; Gayol M.C.; Gil-Diaz A.; Gomez-Cuervo C.; Gonzalez-Martinez J.; Grau E.; Gutierrez J.; Hernandez-Blasco L.; Iglesias M.; Jara-Palomares L.; Jaras M.J.; Jimenez D.; Joya M.D.; Jou I.; Lacruz B.; Lalueza A.; Lecumberri R.; Lima J.; Llamas P.; Lobo J.L.; Lopez-Jimenez L.; Lopez-Miguel P.; Lopez-Nunez J.J.; Lopez-Reyes R.; Lopez-Saez J.B.; Lorente M.A.; Lorenzo A.; Loring M.; Lumbierres M.; Madridano O.; Maestre A.; Manrique-Abos I.; Marchena P.J.; Martin-Asenjo M.; Martin-Fernandez M.; Martin-Guerra J.M.; Martin-Martos F.; Mellado M.; Mercado M.I.; Moises J.; Monreal M.; Morales M.V.; Munoz-Blanco A.; Munoz-Guglielmetti D.; Nieto J.A.; Nunez M.J.; Olivares M.C.; Ortega-Recio M.D.; Osorio J.; Otero R.; Paredes D.; Parra P.; Parra V.; Pedrajas J.M.; Pellejero G.; Perez-Ductor C.; Perez-Jacoiste M.A.; Peris M.L.; Pesantez D.; Porras J.A.; Portillo J.; Ramos E.; Reig L.; Riera-Mestre A.; Rivas A.; Rodriguez-Cobo A.; Rodriguez-Fernandez L.; Rodriguez-Galan I.; Rodriguez-Matute C.; Rosa V.; Rubio C.M.; Ruiz-Artacho P.; Ruiz-Gimenez N.; Ruiz-Ruiz J.; Ruiz-Sada P.; Ruiz-Torregrosa P.; Sahuquillo J.C.; Salgueiro G.; Samperiz A.; Sanchez-Munoz-Torrero J.F.; Sancho T.; Sanmartin R.; Soler S.; Suarez S.; Surinach J.M.; Tiberio G.; Tolosa C.; Torres M.I.; Trujillo-Santos J.; Uresandi F.; Usandizaga E.; Valle R.; Vela; Vidal G.; Villares P.; Zamora C.; Gutierrez P.; Vazquez F.J.; Vanassche T.; Vandenbriele C.; Verhamme P.; Hirmerova J.; Maly R.; Salgado E.; Benzidia I.; Bertoletti L.; Bura-Riviere A.; Crichi B.; Debourdeau P.; Farge-Bancel D.; Helfer H.; Mahe I.; Moustafa F.; Poenou G.; Schellong S.; Braester A.; Brenner B.; Tzoran I.; Amitrano M.; Bilora F.; Bortoluzzi C.; Brandolin B.; Bucherini E.; Ciammaichella M.; Colaizzo D.; Dentali F.; Di Micco P.; Giammarino E.; Grandone E.; Maida R.; Mangiacapra S.; Mastroiacovo D.; Pace F.; Pesavento R.; Pomero F.; Prandoni P.; Quintavalla R.; Rocci A.; Siniscalchi C.; Tiraferri E.; Tufano A.; Ventresca A.; Visona A.; Vo Hong N.; Zalunardo B.; Kigitovica D.; Make K.; Skride A.; Ferreira M.; Meireles J.; Bosevski M.; Zdraveska M.; Bounameaux H.; Mazzolai L.; Bikdeli B.; Caprini J.A.; Tafur A.J.; Weinberg I.; Wilkins H.; Bui H.M.Peris, M.; Lopez-Nunez, J. J.; Maestre, A.; Jimenez, D.; Muriel, A.; Bikdeli, B.; Weinberg, I.; Ay, C.; Mazzolai, L.; Lorenzo, A.; Monreal, M.; Monreel, M.; Prandoni, P.; Brenner, B.; Farge-Bancel, D.; Barba, R.; Di Micco, P.; Bertoletti, L.; Schellong, S.; Tzoran, I.; Reis, A.; Bosevski, M.; Bounameaux, H.; Maly, R.; Verhamme, P.; Caprini, J. A.; Bui, H. M.; Adarraga, M. D.; Agud, M.; Aibar, J.; Aibar, M. A.; Alfonso, J.; Amado, C.; Aramberri, M.; Arcelus, J. I.; Ballaz, A.; Barba, R.; Barbagelata, C.; Barron, M.; Barron-Andres, B.; Blanco-Molina, A.; Camon, A. M.; Canas, I.; Cerda, P.; Criado, J.; de Ancos, C.; de Miguel, J.; del Toro, J.; Demelo-Rodriguez, P.; Diaz-Pedroche, M. C.; Diaz-Peromingo, J. A.; Diez-Sierra, J.; Dominguez, I. M.; Encabo, M.; Escribano, J. C.; Farfan, A. I.; Fernandez-Capitan, C.; Fernandez-Reyes, J. L.; de Roitegui, F. K.; Fidalgo, M. A.; Flores, K.; Font, C.; Font, L.; Francisco, I.; Gabara, C.; Galeano-Valle, F.; Garcia, M. A.; Garcia-Bragado, F.; Garcia-Raso, A.; Gavin-Blanco, O.; Gavin-Sebastian, O.; Gayol, M. C.; Gil-Diaz, A.; Gomez-Cuervo, C.; Gonzalez-Martinez, J.; Grau, E.; Gutierrez, J.; Hernandez-Blasco, L.; Iglesias, M.; Jara-Palomares, L.; Jaras, M. J.; Jimenez, D.; Joya, M. D.; Jou, I.; Lacruz, B.; Lalueza, A.; Lecumberri, R.; Lima, J.; Llamas, P.; Lobo, J. L.; Lopez-Jimenez, L.; Lopez-Miguel, P.; Lopez-Nunez, J. J.; Lopez-Reyes, R.; Lopez-Saez, J. B.; Lorente, M. A.; Lorenzo, A.; Loring, M.; Lumbierres, M.; Madridano, O.; Maestre, A.; Manrique-Abos, I.; Marchena, P. J.; Martin-Asenjo, M.; Martin-Fernandez, M.; Martin-Guerra, J. M.; Martin-Martos, F.; Mellado, M.; Mercado, M. I.; Moises, J.; Monreal, M.; Morales, M. V.; Munoz-Blanco, A.; Munoz-Guglielmetti, D.; Nieto, J. A.; Nunez, M. J.; Olivares, M. C.; Ortega-Recio, M. D.; Osorio, J.; Otero, R.; Paredes, D.; Parra, P.; Parra, V.; Pedrajas, J. M.; Pellejero, G.; Perez-Ductor, C.; Perez-Jacoiste, M. A.; Peris, M. L.; Pesantez, D.; Porras, J. A.; Portillo, J.; Ramos, E.; Reig, L.; Riera-Mestre, A.; Rivas, A.; Rodriguez-Cobo, A.; Rodriguez-Fernandez, L.; Rodriguez-Galan, I.; Rodriguez-Matute, C.; Rosa, V.; Rubio, C. M.; Ruiz-Artacho, P.; Ruiz-Gimenez, N.; Ruiz-Ruiz, J.; Ruiz-Sada, P.; Ruiz-Torregrosa, P.; Sahuquillo, J. C.; Salgueiro, G.; Samperiz, A.; Sanchez-Munoz-Torrero, J. F.; Sancho, T.; Sanmartin, R.; Soler, S.; Suarez, S.; Surinach, J. M.; Tiberio, G.; Tolosa, C.; Torres, M. I.; Trujillo-Santos, J.; Uresandi, F.; Usandizaga, E.; Valle, R.; Vela, ; Vidal, G.; Villares, P.; Zamora, C.; Gutierrez, P.; Vazquez, F. J.; Vanassche, T.; Vandenbriele, C.; Verhamme, P.; Hirmerova, J.; Maly, R.; Salgado, E.; Benzidia, I.; Bertoletti, L.; Bura-Riviere, A.; Crichi, B.; Debourdeau, P.; Farge-Bancel, D.; Helfer, H.; Mahe, I.; Moustafa, F.; Poenou, G.; Schellong, S.; Braester, A.; Brenner, B.; Tzoran, I.; Amitrano, M.; Bilora, F.; Bortoluzzi, C.; Brandolin, B.; Bucherini, E.; Ciammaichella, M.; Colaizzo, D.; Dentali, F.; Di Micco, P.; Giammarino, E.; Grandone, E.; Maida, R.; Mangiacapra, S.; Mastroiacovo, D.; Pace, F.; Pesavento, R.; Pomero, F.; Prandoni, P.; Quintavalla, R.; Rocci, A.; Siniscalchi, C.; Tiraferri, E.; Tufano, A.; Ventresca, A.; Visona, A.; Vo Hong, N.; Zalunardo, B.; Kigitovica, D.; Make, K.; Skride, A.; Ferreira, M.; Meireles, J.; Bosevski, M.; Zdraveska, M.; Bounameaux, H.; Mazzolai, L.; Bikdeli, B.; Caprini, J. A.; Tafur, A. J.; Weinberg, I.; Wilkins, H.; Bui, H. M