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6. An Image Processing Protocol to Extract Variables Predictive of Human Embryo Fitness for Assisted Reproduction

Author

Cheles, DS, Ferreira, AS, de Jesus, IS, Fernandez, EI, Pinheiro, GM, Dal Molin, EA, Alves, W, Milanezi de Souza, Rebeca Colauto, Bori, L, Meseguer, M, Rocha, JC, and Gouveia Nogueira, Marcelo Fabio

Abstract

Despite the use of new techniques on embryo selection and the presence of equipment on the market, such as EmbryoScope(R) and Geri(R), which help in the evaluation of embryo quality, there is still a subjectivity between the embryologist's classifications, which are subjected to inter- and intra-observer variability, therefore compromising the successful implantation of the embryo. Nonetheless, with the acquisition of images through the time-lapse system, it is possible to perform digital processing of these images, providing a better analysis of the embryo, in addition to enabling the automatic analysis of a large volume of information. An image processing protocol was developed using well-established techniques to segment the image of blastocysts and extract variables of interest. A total of 33 variables were automatically generated by digital image processing, each one representing a different aspect of the embryo and describing a different characteristic of the blastocyst. These variables can be categorized into texture, gray-level average, gray-level standard deviation, modal value, relations, and light level. The automated and directed steps of the proposed processing protocol exclude spurious results, except when image quality (e.g., focus) prevents correct segmentation. The image processing protocol can segment human blastocyst images and automatically extract 33 variables that describe quantitative aspects of the blastocyst's regions, with potential utility in embryo selection for assisted reproductive technology (ART).

Published
2022

8. Near-normal aerobic capacity in long-term survivors after lung transplantation

Author

Saez-Gimenez B, Barrecheguren M, Ramon MA, Gomez-Garrido A, Bravo C, Monforte V, López-Meseguer M, Berastegui C, Revilla E, Romero C, Laporta R, Fernández-Rozas S, Redel-Montero J, Solé A, de la Torre M, Puente L, Roman A, Gómez-Ollés S, and Ojanguren I

Subjects
surgical procedures, operative, SINGLE, QUALITY-OF-LIFE, respiratory system, EXERCISE PERFORMANCE, respiratory tract diseases
Abstract

The clinical course of lung transplantation (LT) is diverse: some patients present chronic lung allograft dysfunction (CLAD) and progressive decline in pulmonary function, but others maintain normal spirometric values and active lives.

Published
2021

9. From Health-Related Quality of Life (HRQoL) of Patients with Pulmonary Hypertension to Patient Experience with the Care Received: Should We Be More Aware of Current Patient Needs?

Author

Martínez Meñaca A, Blanco Vich I, López Meseguer M, López Reyes R, Bedate Díaz P, Elías Hernández T, Fernández-Cuesta Peñafiel I, Fernández G, Álvez Liste A, and Escribano Subías P

Subjects
CAMPHOR, Chronic thromboembolic pulmonary hypertension, EQ-5D-5L, Empowerment, Health-related quality of life, IEXPAC, Information and communications technology (ICT), Patient engagement, Pulmonary arterial hypertension, Pulmonary hypertension, humanities
Abstract

Self-perceived health-related quality of life (HRQoL) of patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) and their experience with the care received are important for improving their management. We conducted a study to assess both patient-reported outcomes (PROs) and how they interrelate.

Published
2021

10. The morphokinetic signature of mosaic embryos: evidence in support of their own genetic identity

Author

Martin A, Rodrigo L, Beltran D, Meseguer M, Rubio C, Mercader A, and de Los Santos M

Subjects
animal structures, embryonic structures, Mosaicism, morphokinetics, next-generation sequencing, preimplantation genetic testing for aneuploidy
Abstract

OBJECTIVE: To provide full morphokinetic characterization of embryos ranked with different degrees of chromosomal mosaicism. DESIGN: Retrospective cohort study. SETTING: University-affiliated private invitro fertilization clinic. PATIENT(S): We analyzed 1,511 embryos from 424 intracytoplasmic sperm injection cycles by culturing embryos in a time-lapse imaging system and performing next-generation sequencing. We assessed 106 mosaic embryos. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Comparison of chromosomal, morphological, and morphokinetic characteristics of blastocysts classified as euploid, aneuploid, low-degree mosaic (30% to

Published
2021

11. An artificial intelligence model based on the proteomic profile of euploid embryos and blastocyst morphology: a preliminary study

Author

Bori L, Dominguez F, Fernandez EI, Del Gallego R, Alegre L, Hickman C, Quiñonero A, Nogueira MFG, Rocha JC, and Meseguer M

Subjects
Artificial intelligence, Artificial neural network, Blastocyst morphology, Live birth, Proteomics
Abstract

The study aimed to develop an artificial intelligence model based on artificial neural networks (ANNs) to predict the likelihood of achieving a live birth using the proteomic profile of spent culture media and blastocyst morphology.

Published
2021

12. Blastocyst formation is similar in obese and normal weight women: a morphokinetic study

Author

Bellver J, Brandão P, Alegre L, and Meseguer M

Subjects
animal structures, urogenital system, embryonic structures, BMI, IVF, blastocyst formation, morphokinetics, obesity, reproductive and urinary physiology
Abstract

Does the embryo cleavage pattern and rate of blastocyst formation differ between normal weight and obese women undergoing IVF?

Published
2021

13. Is there a procoagulant state long-term after lung transplantation? A prospective study

Author

Saez-Gimenez B, Clofent D, Meseguer M, Masgoret C, Monforte V, Berastegui C, Revilla-Lopez E, Barrecheguren M, Arjona-Peris M, Ruiz V, Ramon M, Gomez-Olles S, Santamaria A, and Roman A

Subjects
Lung transplantation, Organ transplantation, Thrombophilia, Blood coagulation, Venous thromboembolism
Abstract

Background: Venous thromboembolism (VTE) is a major complication after lung transplantation (LT). However, its pathophysiology remains unknown, and coagulation profiles have yet to be described. Objective: The aim of this study was to longitudinally assess coagulation status after LT. Methods: We performed a prospective study and described the coagulation profiles of 48 patients at 5 different time-points: before LT and at 24-72 h, 2 weeks, 4 months, and 1 year after LT. Results: At baseline, almost all analyzed coagulation factors were within the normal range, except for FVIII, which was above the normal range. Von Willebrand factor (vWF) and FVIII were increased after LT and remained high at 1 year after transplantation. The cumulative incidence of VTE was 22.9%. Patients who developed VTE had higher FVIII activity 2 weeks after LT. Conclusions: This is the first study to describe coagulation profiles up to 1 year after LT. We show that most markers of a procoagulant state normalize at 2 weeks after LT, but that values of FVIII and vWF remain abnormal at 1 year. This problem has received little attention in the literature. Larger studies are necessary to confirm the results and to design appropriate prophylactic strategies.

Published
2021

14. Invitro fertilization and andrology laboratory in 2030: expert visions

Author

Campbell A, Gardner D, Meseguer M, Miller K, Montag M, Palermo G, Cheung S, Keating D, Xie P, Rosenwaks Z, Rienzi L, Innocenti F, Cimadomo D, Ubaldi F, Sakkas D, Tucker M, Nel-Themaat L, and Simon C

Abstract

The aim of this article is to gather 9 thought leaders and their team members to present their ideas about the future of invitro fertilization and the andrology laboratory. Although we have seen much progress and innovation in the laboratory over the years, there is still much to come, and this article looks at what these leaders think will be important in the future development of technology and processes in the laboratory. Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Published
2021

15. Invitro fertilization and andrology laboratories in 2030

Author

Simon C, Campbell A, Gardner D, Meseguer M, Miller K, Montag M, Palermo G, Cheung S, Keating D, Xie P, Rosenwaks Z, Rienzi L, Innocenti F, Cimadomo D, Ubaldi F, Sakkas D, Tucker M, and Nel-Themaat L

Abstract

The invitro fertilization and andrology laboratories are at the center of assisted reproductive technologies and the place where technicians and embryologists manipulate gametes and preimplantation-stage embryos with the goal of achieving the best embryo for transfer. Through the years, these laboratories have seen developments in technique, technology, and testing. The goal of this Views and Interviews series is to bring together the thought leaders in the field and envision what the laboratories will look like in the next 10 years.

Published
2021

16. Will the introduction of automated ART laboratory systems render the majority of embryologists redundant?

Author

Bori L and Meseguer M

Subjects
Artificial Intelligence, Automation, Embryologist
Abstract

IVF techniques have changed over time with the aim of improving clinical results. Today, embryology is facing a change common to most areas of medicine, the introduction of automation. The use of automated systems in the IVF laboratory is already happening, for example, with electronic witnessing and the ranking of embryos according to their implantation potential. It is expected that in the near future, various systems in the IVF laboratory will be automated. In this way, gamete manipulation would cease to be manual and embryo culture and selection would be performed by means of microfluidics and artificial intelligence. Therefore, the tasks of the embryologist will inevitably be reduced. However, new functions related to data capture, management and analysis will emerge, along with other research skills and increased communication with other professionals and patients.

Published
2021

17. Frailty Assessment in a Stable COPD Cohort: Is There a COPD-Frail Phenotype?

Author

Naval E, González MC, Giraldós S, Calatayud J, Jornet M, Lluch I, Meseguer M, Cubillan JJR, Viña J, and Tarazona-Santabalbina FJ

Subjects
COPD-frail, phenotype, COPD, frailty, human activities, respiratory tract diseases
Abstract

The frailty syndrome increases the morbidity/mortality in older adults, and several studies have shown a higher prevalence of this syndrome in patients with Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to identify the characteristics of frail patients with COPD to define a new phenotype called "COPD-frail." We conducted a cross-sectional study in a cohort of patients with stable COPD, classified as either frail, pre-frail, or non-frail. Sociodemographic, clinical, and biochemical variables were compared between the three groups of patients. The study included 127 patients, of which 31 were frail, 64 were pre-frail, and 32 non-frail. All subjects had FEV1/FVC below the lower limit of normal (range Z-score: -1.66 and -5.32). Patients in the frail group showed significantly higher scores in the mMRC (modified Medical Research Council) scale, the CAT (COPD Assessment Test), and the BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index. They also showed differences in symptoms according to GOLD (Global Initiative for Chronic Obstructive Lung Disease), as well as more COPD exacerbations, less physical activity, more anxiety and depression symptoms based on HADS (Hospital Anxiety and Depression Scale), and lower hemoglobin, hematocrit, and 25-hydroxycholecalciferol levels. Variables with independent association with frailty included the mMRC score, the HAD index for depression and age. In summary, differential characteristics of frail patients with COPD encourage the definition of a "COPD-frail" phenotype that-if identified early-would allow performing interventions to prevent a negative impact on the morbidity/mortality of these patients.

Published
2021

18. Novel and conventional embryo parameters as input data for artificial neural networks: an artificial intelligence model applied for prediction of the implantation potential

Author

Bori L, Paya E, Alegre L, Viloria TA, Remohi JA, Naranjo V, and Meseguer M

Subjects
body regions, Embryo parameters, artificial intelligence, artificial neural network, implantation, time-lapse, ComputingMethodologies_PATTERNRECOGNITION, animal structures, Quantitative Biology::Tissues and Organs, embryonic structures, Computer Science::Neural and Evolutionary Computation, equipment and supplies
Abstract

To describe novel embryo features capable of predicting implantation potential as input data for an artificial neural network (ANN) model.

Published
2020

19. Portopulmonary hypertension: prognosis and management in the current treatment era. Results from the REHAP Registry

Author

Lázaro Salvador M, Quezada Loaiza CA, Rodríguez Padial L, Barberá JA, López-Meseguer M, López-Reyes R, Sala Llinas E, Alcolea S, Blanco I, and Escribano Subías P

Subjects
PAH-targeted therapy, Portal hypertension, Portopulmonary hypertension, Pulmonary arterial hypertension, survival
Abstract

Portopulmonary hypertension (PoPH) is a rare condition with poorer survival compared to idiopatic/familial pulmonary arterial hypertension (IPAH/FPAH).

Published
2020

20. COVID-19 in lung transplant recipients: A multicenter study

Author

Saez-Giménez B, Berastegui C, Barrecheguren M, Revilla-López E, Los Arcos I, Alonso R, Aguilar M, Mora VM, Otero I, Reig JP, Quezada CA, Pérez V, Valle M, Laporta R, Deu M, Sacanell J, Bravo C, Gavalda J, Lopez-Meseguer M, and Monforte V

Subjects
infectious, lung transplantation / pulmonology [clinical research / practice, critical care / intensive care management, drug toxicity, infection and infectious agents - viral, infectious disease, lung disease]
Abstract

This study describes the clinical presentation, treatment, and outcomes of SARS-CoV-2 infection in lung transplant recipients (LTRs). This is a multicenter, retrospective study of all adult LTRs with confirmed SARS-CoV-2 infection from March 4 until April 28, 2020 in six Spanish reference hospitals for lung transplantation. Clinical and radiological data, treatment characteristics, and outcomes were reviewed. Forty-four cases were identified in that period. The median time from transplantation was 4.2 (interquartile range: 1.11-7.3) years. Chest radiography showed acute parenchymal abnormalities in 32 (73%) cases. Hydroxychloroquine was prescribed in 41 (93%), lopinavir/ritonavir (LPV/r) in 14 (32%), and tocilizumab in 19 (43%) patients. There was a strong interaction between tacrolimus and LPV/r in all cases. Thirty-seven (84%) patients required some degree of respiratory support and/or oxygen therapy, and 13 (30%) were admitted to intermediate or intensive critical care units. Seventeen (39%) patients had died and 20 (45%) had been discharged at the time of the last follow-up. Deceased patients had a worse respiratory status and chest X-ray on admission and presented with higher D-dimer, interleukin-6, and lactate dehydrogenase levels. In this multicenter LTR cohort, SARS-CoV-2 presented with high mortality. Additionally, the severity of disease on presentation predicted subsequent mortality.

Published
2020

21. Preimplantation genetic testing for aneuploidy in patients with partial X monosomy using their own oocytes: is this a suitable indication?

Author

Giles J, Meseguer M, Mercader A, Rubio C, Alegre L, Vidal C, Trabalon M, and Bosch E

Abstract

OBJECTIVE: To describe the outcome of preimplantation genetic testing (PGT-A) using their own oocytes in patients with mosaic Turner Syndrome (MTS). The impact of the assisted reproduction technique (ART) performed (PGT-A or oocyte donation) and the type of absence of the X chromosome (total or partial) were considered.; DESIGN: Retrospective observational multicenter study.; SETTING: University-affiliated private invitro fertilization center.; PATIENT(S): Fifty-six patients with MTS with whom 65 ovarian stimulation cycles for PGT-A (fluorescence in situ hybridization/arrays-next generation sequencing) were performed. The study included 90 women with MTS and 20 women with pure Turner Syndrome (PTS) who underwent 140 and 25 oocyte donation (OD) cycles, respectively.; INTERVENTION(S): Invitro fertilization for PGT-A (fluorescence in situ hybridization/arrays-next generation sequencing) or OD.; MAIN OUTCOME MEASURE (S): Reproductive outcome and feto-maternal outcomes.; RESULTS: The live birth rate (LBR) per embryo transfer in patients with MTS tended to be higher in OD 37.7% (95% confidence interval [CI]: 29.3-46.1) than that observed for PGT-A 22.5% (95% CI 7.8-38.2), and the cumulative LBR (CLBR), with 77.6% vs. 43.3%, respectively. Likewise, the LBR per patient was significant when comparing PGT-A vs. OD, with 12.5% (95 CI 3.9-21.1) vs. 51.1% (40.7-61.4), respectively. While focusing on the X chromosome, partial MTS (PTS), we found significant differences in the CLBR per embryo transfer, with 77.6% vs. 29.2%, and also in the LBR per patient: 51.1% (40.7-61.4) in MTS vs. 15% (95 CI 0.0-30.1) in PTS.; CONCLUSION(S): Oocyte donation is the best reproductive option in females with Turner Syndrome with or without mosaicisms. Nevertheless, PGT-A is a valid therapeutic option in patients with MTS using their own oocytes, and OD should not necessarily be directly recommended. Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Published
2020

22. Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness

Author

Spyropoulos A. C., Ageno W., Albers G. W., Elliott C. G., Halperin J. L., Hiatt W. R., Maynard G. A., Steg P. G., Weitz J. I., Suh E., Spiro T. E., Barnathan E. S., Raskob G. E., Douketis J., Turpie A. G., Schulman S., Kearon C., Linkins L. A., Schellong S., Bauer K., Geerts W., Roberts R., Casais P., Gallus A., Karrasch J., Eichinger-Hasenauer S., Krivenchuk V., Hadzovic-Dzuvo A., Trbojevic S., Lopes R., Mincheva V., Carrier M., Dennis R., Tudoric N., Spinar J., Nielsen H., Marandi T., Shaburishvili T., Beyer-Westendorf J., Vardas P., Boda Z., Brenner B., Piovella F., Krievins D., Petrauskiene B., Dejanova-Ilijevska V., Virgen Carrillo L. R., Middeldorp S., Castillo Leon R. P., Torbicki A., Saraiva de Sousa M., Dorobantu M., Militaru C., Yavelov I., Vuckovic B., Reuter H., Basson M., Monreal M., Kucukoglu S., Parkhomenko A., Alikhan R., Rosenberg D., Yusen R., Khorana A., Tapson V., Pollack C., Hazelrigg M., Jure H., Alvarisqueta A., Cartasegna L., Hominal M., Cursack G., Alzogaray M., Maillo M., Parody M., Caccavo A., Dran R. D., Muntaner J. A., Casas M., Schmidberg J., Sarjanovich R., Gabito A., Garrido M., Amuchastegui M., Fernandez A., Loureyro J., Giumelli C., Heazlewood V., Colquhoun D., White H., Sabet A., Bowler S., Carroll P., Khalafallah A., Baker R., Hedger S., Simpson F. G., Jackson D., Chong B., Siostrzonek P., Gary T., Hoppe U., Dosta N., Prystrom A., Gorokhovsky S., Yanushko V., Skrahin A., Kulik A., Maslianski B., Yakubtsevich R., Timkin I., Moguchaya O., Tanaskovic N., Miljkovic S., Stojkovic S., Kovacevic-Preradovic T., Jovic D., Basagic E., Radjen M., Mutapcic M., Rizvanovic-Vojic E., Galic K., Terzic I., Pojskic B., Stevanovic D., Cehajic M., Rech R., Annichino-Bizzacchi J., Stelmach R., Blanco D., Castro I., Backes L. M., Saraiva J. F., Ramacciotti E., de Barros e Silva P. G. M., Reis G., Moreira Vieira E., Leaes P., Zimmermann S., Van Bellen B., Precoma D., Luiz Silvestrini T., Hernandes M. E., Kyoleyan M., Kalinova T., Tiholov R., Petrov I., Mihov A., Chompalova B., Velikov C., Pencheva G., Atanasov P., Raev D., Kinova E., Peltegov V., Marchev S., Siulemezova S., Ayryanova I. D., Grigorov M., Naydenova I., Koteva N., Dimov B., Runev N., Getov D., Metev H., Donchev K., Taseva M., Hadzhieva A., Benov H., Stoyanov M., Tisheva-Gospodinova S., Mihaylova N., Abadzhiev S., Atzev B., Georgiev R., Mollov M., Stoikov A., Mazhdrakov G., Karastanev K., Dube F., Roth S., Mansour S., Wu C., Dolan S., Pesant Y., Pietrangelo M., Dresser G., Kahn S., Kruisselbrink R., Cadena Bonfanti A., Botero R., Quintero Ossa A., Poveda C. M., Cedano J., Gomez Isaza L., Villaquiran Torres C., Gomez Mesa J., Vargas Alonso R., Espinosa D., Rodriguez J. M., Sanchez G., Accini Mendoza J. L., Gomez Florez C. C., Cuervo Millan F., Pesek K., Horvat D., Fuckar K., Ruzic A., Ostricki B., Knezevic A., Breitenfeld T., Laganovic M., Samodol A., Sikic J., Starcevic B., Babic Z., Samarzija M., Milas K., Votocek S., Kvapil M., Kolman P., Bindas P., Simon V., Adamek T., Svobodova J., Gergely L., Lastuvka J., Macel I., Navratil K., Gregor P., Lacnak B., Janousek J., Kellnerova I., Hulinsky V., Matusek Z., Prucek L., Dunaj M., Pirchala M., Vencour D., Pavolko M., Gorican K., Fiksa J., Tuxen C., Meyer C., Suppli Ulrik C., Uuetoa T., Otarishvili N., Khintibidze I., Emukhvari N., Kipiani Z., Gochitashvili D., Mamatsashvili M., Megreladze I., Paposhvili K., Agladze R., Eradze Z., Chelidze K., Lominadze S., Chukhrukidze A., Chumburidze V., Metreveli S., Danelia V., Orjonikidze S., Kobulia B., Nikolaishvili G., Gvenetadze R., Melia A., Tsinamdzgvrishvili B., Sekhniashvili M., Sikharulidze I., Meuser M., Licka M., Rauch-Kroehnert U., Graf K., Brachmann J., Akin I., Toumbis M., Vassilikos V., Konstantinides S., Steiropoulos P., Gogos C., Andrikopoulos G., Parthenakis F., Karydi P., Tsivgoulis G., Mertzanos G., Olympios C., Karapanayiotides T., Paraskevopoulou E., Kifnidis K., Hahalis G., Skoutelis A., Vadikolias K., Nyirati G., Nagy L., Matoltsy A., Komoly S., Lippai J., Kiss K., Toth K., Pozsegovits K., Kiraly C., Bereczki D., Zolyomi S., Szakal I., Pall D., Futo L., Forster T., Lovasz O., Papp A., Kiraly Z., Pozsonyi Z., Hajko E., Kristof P., Lakatos F., Ples Z., Kirschner R., Lupkovics G., Timar G., Pinter I., Kristof T., Kis E., Kovacs A., Jakab G., Palinkas A., Muller G., Turi T., Horvath C., Kondakor I., Csanyi A., Frankfurter Z., Gurzo M., Gafter-Gvili A., Kuchuk M., Azzam Z., Elis A., Halabi M., Hussein O., Blum A., Tsoran-Rosenthal I., Lishner M., Hochberg-Klein S., Caraco Y., Atar S., Elias N., Gavish D., Butnaru A., Cosmi F., Garbelotto R., Giorgi Pierfranceschi M., Simioni L., Gronda E., Pesci A., D'Angelo A., Fedele F., Ghirarduzzi A., Piovaccari G., Lembo G., Ria L., Monaco G. L., Brunelli C., Tosetto A., Capucci A., Zanatta N., Pistolesi M., Mazzi V., Testa S., Scherillo M., Di Biase M., Antonicelli R., Lodigiani C., Nassiacos D., Viksne I., Lapkovska Z., Rancane G., Sime I., Pontaga N., Eglite R., Puzule S., Smolova R., Butkiene Z., Bagdonas A., Raugaliene R., Norkiene S., Norviliene R., Basijokiene V., Stonkus S., Griskeviciene V., Miskiniene A., Norvaisiene R., Skripkauskiene I., Jovkovska-Kaeva B., Kochovska-Kamchevska N., Antovski A., Nechevska L., Celeska V., Ilievska-Poposka B., Kostojchinoska M., Donchovska S., Kedev S., Kuzmanovski I., Bushletikj O., Stojchev S., Bakrachevski N., Kuzmanovska B., Angusheva T., Llamas Esperon G., Valdez Lopez H., Medina Pech C., Cortes Hernandez M., Virgen Carrillo L., Gans S., Smulders S., Swart H., Boersma W., Goosens M., Hovens M., Semplonius G., Sohne M., Lema Osores J., Salas Perez M. D., Rodriguez A., Rios Oliva C., Cotrina R., Berrospi Argandona P., Toce Yanez L., Chavez Ayala C., Mirek-Bryniarska E., Goch A., Skucha W., Skorski M., Miekus P., Szyszka A., Piotrowski G., Gniot J., Czerski T., Debich P., Zaluska R., Bebenek W., Wozakowska-Kaplon B., Sciborski R., Ilkowski J., Wojnowski P., Uscinska E., Gaciong Z., Bonek R., Sobkowicz B., Berkowski P., Bejgier K., Polonski L., Kosior D., Lata S., Kolodziej P., Gessek J., Kachel T., Talalaj M., Musial J., Lewczuk J., Krysiak W., Kucharski L., Wysokinski A., Minc P., Martinez J., Gregorio T., Almeida F., Monteiro P., Stanciulescu G., Mercea C. D., Iosipescu L. C., Ciobotaru V., Crisu D., Burca M., Tudoran M., Savu A., Negrean V., Cojocaru C., Minescu B., Popa V., Blajan D., Nastase-Melicovici D., Fruntelata A., Barbulescu S., Lukinyh L., Akhunova S., Vishneva E., Semenova I., Nikolaev K. Y., Shaydyuk O., Nilk R., Shalnev V., Apartsin K., Goloshchekin B. M., Shpagina L., Khlevchuk T., Arkhipov M., Malygin A., Shvarts Y., Khaisheva L., Popov D., Kobalava Z., Lipchenko A., Shapovalova Y., Zrazhevsky K., Greshnova I., Maslova N., Karabenenko A., Shogenov Z., Budankova E., Barbarash O., Uspenskiy Y., Kosmacheva E., Berns S., Kostenko V., Zateyshchikov D., Vishnevsky A., Boldueva S., Podzolkov V., Sergeeva E., Grinshtein Y., Khrustalev O., Bugrova O., Repin A., Andreev D., Petrovic P., Boskovic Matic T., Apostolovic S., Lazic Z., Stankovic D., Stankovic A., Mitov V., Sofronic D., Kopitovic I., Zdravkovic V., Joksimovic Z., Lazovic N., Petrovic-Stanojevic N., Ilic A., Vujadinovic O., Pencic-Popovic B., Andjelkovic N., Sekularac N., Hinic S., Radjen G., Zivkovic A., Putnikovic B., Ivanov I., Babic R., Van Zyl L., Hobson B., Engelbrecht J., Mitha I., Siebert H., Jacobson B., Breedt J., Prozesky H., Ntsekhe M., Bayat J., Ellis G., Tarr G., Adler D., Van Dyk C., Ismail S. M., Spargo C. E., Abdool-Gaffar M., Saaiman J., Venter K., Lorente Aroca M. L., Fernandez Portales F., Pedrajas Navas J., Rodriguez Botaro A., Santa Cruz Siminiani A., Lopez Reyes R., Bisbe i Company J., Piedecausa Selfa M., Velasco Garrido J., Sobrino-Martinez J., Munoz Delgado G., Sala Llinas E., Blanco Coronado J., Almenar Bonet L., Vida Gutierrez M., Sanchez Lora F., Sanchez Martinez R., Calderon E. J., Villalta Blanch J., De la Hera Galarza J. M., Bustamante Ruiz A., Garcia-Fuster M. J., Ripoll Vera T., Alvarez-Sala Walter L., Todoli Parra J. A., Diaz Fernandez J., Bosa Ojeda F., Pellicer-Ciscar C., Jara Palomares L., Quiles Granado J., Trigo Bautista A., Ruiz Bustillo S., Ordi Ros J., Tolosa-Vilella C., Marin Ortuno F., Garcia Sanchez F., Barba Martin R., Segovia Cubero J., Cuervas-Mons Martinez V., Galan Montejano M., Lopez Meseguer M., Sener Comert S., Koksal N., Tertemiz K., Ernam D., Dursun A. B., Yildiz O., Rudenko L., Abrahamovych O., Goloborodko A., Holovchenko N., Kulyk A., Yagensky A., Batushkin V., Zolotaikina V., Kozyolkin O., Faynyk A., Maslovskyy V., Petrovskyy R., Koshlia V., Chopey I., Burmak I., Malynovsky Y., Voronkov L., Karpenko O., Dziublyk O., Godlevska O., Borovyk V., Bezrodna L., Serik S., Ovsyannikova N., Vynnychenko L., Kopytsya M., Rudkovskiy V., Grishyna O., Vyshnyvetskyy I., Prystupa L., Tseluyko V., Perepeliuk M., Koval O., Sychov O., Church A., Goudie A., Elliott M., Ferguson C., Welker J., Kao C. K., Bhagwat R., Serota H., Bozorgchami H., Nambiar R., Spilseth S., Bhagwath G., Syed F., Morrow L., Updegrove J., Bercz P., Kambo V., Henderson D., Wright P., Dang N., Nadar V., Jaffrani N., El-Shahawy M., Grossman C. H., Pearle J., Weinstein D., Galanis T. P., Gazmuri R., Kastelic R., Martinez R., Laman D., Macchiavelli A., Kmetzo J., Thurm C., Kayembe T., Chandrashekhar Y., Bassetti D., Jaoude P., Williams H., Dewhurst R., Naqvi S., Burr J., Rodriguez-Cintron W., Jeanfreau R., Kosinski E., Ndukwu I. M., Sotolongo C., Daboul N., Wilmer C., Simon P., Tak T., Rees C., Gupta N., Lerner R., Graffagnino C., Reed R. M., Alford C. M., Mody F., Wellmon B., Hamroff G., Rajan R., Kaatz S., OMÜ, Spyropoulos, A, Ageno, W, Albers, G, Elliott, C, Halperin, J, Hiatt, W, Maynard, G, Steg, P, Weitz, J, Suh, E, Spiro, T, Barnathan, E, Raskob, G, Douketis, J, Turpie, A, Schulman, S, Kearon, C, Linkins, L, Schellong, S, Bauer, K, Geerts, W, Roberts, R, Casais, P, Gallus, A, Karrasch, J, Eichinger-Hasenauer, S, Krivenchuk, V, Hadzovic-Dzuvo, A, Trbojevic, S, Lopes, R, Mincheva, V, Carrier, M, Dennis, R, Tudoric, N, Spinar, J, Nielsen, H, Marandi, T, Shaburishvili, T, Beyer-Westendorf, J, Vardas, P, Boda, Z, Brenner, B, Piovella, F, Krievins, D, Petrauskiene, B, Dejanova-Ilijevska, V, Virgen Carrillo, L, Middeldorp, S, Castillo Leon, R, Torbicki, A, Saraiva de Sousa, M, Dorobantu, M, Militaru, C, Yavelov, I, Vuckovic, B, Reuter, H, Basson, M, Monreal, M, Kucukoglu, S, Parkhomenko, A, Alikhan, R, Rosenberg, D, Yusen, R, Khorana, A, Tapson, V, Pollack, C, Hazelrigg, M, Jure, H, Alvarisqueta, A, Cartasegna, L, Hominal, M, Cursack, G, Alzogaray, M, Maillo, M, Parody, M, Caccavo, A, Dran, R, Muntaner, J, Casas, M, Schmidberg, J, Sarjanovich, R, Gabito, A, Garrido, M, Amuchastegui, M, Fernandez, A, Loureyro, J, Giumelli, C, Heazlewood, V, Colquhoun, D, White, H, Sabet, A, Bowler, S, Carroll, P, Khalafallah, A, Baker, R, Hedger, S, Simpson, F, Jackson, D, Chong, B, Siostrzonek, P, Gary, T, Hoppe, U, Dosta, N, Prystrom, A, Gorokhovsky, S, Yanushko, V, Skrahin, A, Kulik, A, Maslianski, B, Yakubtsevich, R, Timkin, I, Moguchaya, O, Tanaskovic, N, Miljkovic, S, Stojkovic, S, Kovacevic-Preradovic, T, Jovic, D, Basagic, E, Radjen, M, Mutapcic, M, Rizvanovic-Vojic, E, Galic, K, Terzic, I, Pojskic, B, Stevanovic, D, Cehajic, M, Rech, R, Annichino-Bizzacchi, J, Stelmach, R, Blanco, D, Castro, I, Backes, L, Saraiva, J, Ramacciotti, E, de Barros e Silva, P, Reis, G, Moreira Vieira, E, Leaes, P, Zimmermann, S, Van Bellen, B, Precoma, D, Luiz Silvestrini, T, Hernandes, M, Kyoleyan, M, Kalinova, T, Tiholov, R, Petrov, I, Mihov, A, Chompalova, B, Velikov, C, Pencheva, G, Atanasov, P, Raev, D, Kinova, E, Peltegov, V, Marchev, S, Siulemezova, S, Ayryanova, I, Grigorov, M, Naydenova, I, Koteva, N, Dimov, B, Runev, N, Getov, D, Metev, H, Donchev, K, Taseva, M, Hadzhieva, A, Benov, H, Stoyanov, M, Tisheva-Gospodinova, S, Mihaylova, N, Abadzhiev, S, Atzev, B, Georgiev, R, Mollov, M, Stoikov, A, Mazhdrakov, G, Karastanev, K, Dube, F, Roth, S, Mansour, S, Wu, C, Dolan, S, Pesant, Y, Pietrangelo, M, Dresser, G, Kahn, S, Kruisselbrink, R, Cadena Bonfanti, A, Botero, R, Quintero Ossa, A, Poveda, C, Cedano, J, Gomez Isaza, L, Villaquiran Torres, C, Gomez Mesa, J, Vargas Alonso, R, Espinosa, D, Rodriguez, J, Sanchez, G, Accini Mendoza, J, Gomez Florez, C, Cuervo Millan, F, Pesek, K, Horvat, D, Fuckar, K, Ruzic, A, Ostricki, B, Knezevic, A, Breitenfeld, T, Laganovic, M, Samodol, A, Sikic, J, Starcevic, B, Babic, Z, Samarzija, M, Milas, K, Votocek, S, Kvapil, M, Kolman, P, Bindas, P, Simon, V, Adamek, T, Svobodova, J, Gergely, L, Lastuvka, J, Macel, I, Navratil, K, Gregor, P, Lacnak, B, Janousek, J, Kellnerova, I, Hulinsky, V, Matusek, Z, Prucek, L, Dunaj, M, Pirchala, M, Vencour, D, Pavolko, M, Gorican, K, Fiksa, J, Tuxen, C, Meyer, C, Suppli Ulrik, C, Uuetoa, T, Otarishvili, N, Khintibidze, I, Emukhvari, N, Kipiani, Z, Gochitashvili, D, Mamatsashvili, M, Megreladze, I, Paposhvili, K, Agladze, R, Eradze, Z, Chelidze, K, Lominadze, S, Chukhrukidze, A, Chumburidze, V, Metreveli, S, Danelia, V, Orjonikidze, S, Kobulia, B, Nikolaishvili, G, Gvenetadze, R, Melia, A, Tsinamdzgvrishvili, B, Sekhniashvili, M, Sikharulidze, I, Meuser, M, Licka, M, Rauch-Kroehnert, U, Graf, K, Brachmann, J, Akin, I, Toumbis, M, Vassilikos, V, Konstantinides, S, Steiropoulos, P, Gogos, C, Andrikopoulos, G, Parthenakis, F, Karydi, P, Tsivgoulis, G, Mertzanos, G, Olympios, C, Karapanayiotides, T, Paraskevopoulou, E, Kifnidis, K, Hahalis, G, Skoutelis, A, Vadikolias, K, Nyirati, G, Nagy, L, Matoltsy, A, Komoly, S, Lippai, J, Kiss, K, Toth, K, Pozsegovits, K, Kiraly, C, Bereczki, D, Zolyomi, S, Szakal, I, Pall, D, Futo, L, Forster, T, Lovasz, O, Papp, A, Kiraly, Z, Pozsonyi, Z, Hajko, E, Kristof, P, Lakatos, F, Ples, Z, Kirschner, R, Lupkovics, G, Timar, G, Pinter, I, Kristof, T, Kis, E, Kovacs, A, Jakab, G, Palinkas, A, Muller, G, Turi, T, Horvath, C, Kondakor, I, Csanyi, A, Frankfurter, Z, Gurzo, M, Gafter-Gvili, A, Kuchuk, M, Azzam, Z, Elis, A, Halabi, M, Hussein, O, Blum, A, Tsoran-Rosenthal, I, Lishner, M, Hochberg-Klein, S, Caraco, Y, Atar, S, Elias, N, Gavish, D, Butnaru, A, Cosmi, F, Garbelotto, R, Giorgi Pierfranceschi, M, Simioni, L, Gronda, E, Pesci, A, D'Angelo, A, Fedele, F, Ghirarduzzi, A, Piovaccari, G, Lembo, G, Ria, L, Monaco, G, Brunelli, C, Tosetto, A, Capucci, A, Zanatta, N, Pistolesi, M, Mazzi, V, Testa, S, Scherillo, M, Di Biase, M, Antonicelli, R, Lodigiani, C, Nassiacos, D, Viksne, I, Lapkovska, Z, Rancane, G, Sime, I, Pontaga, N, Eglite, R, Puzule, S, Smolova, R, Butkiene, Z, Bagdonas, A, Raugaliene, R, Norkiene, S, Norviliene, R, Basijokiene, V, Stonkus, S, Griskeviciene, V, Miskiniene, A, Norvaisiene, R, Skripkauskiene, I, Jovkovska-Kaeva, B, Kochovska-Kamchevska, N, Antovski, A, Nechevska, L, Celeska, V, Ilievska-Poposka, B, Kostojchinoska, M, Donchovska, S, Kedev, S, Kuzmanovski, I, Bushletikj, O, Stojchev, S, Bakrachevski, N, Kuzmanovska, B, Angusheva, T, Llamas Esperon, G, Valdez Lopez, H, Medina Pech, C, Cortes Hernandez, M, Gans, S, Smulders, S, Swart, H, Boersma, W, Goosens, M, Hovens, M, Semplonius, G, Sohne, M, Lema Osores, J, Salas Perez, M, Rodriguez, A, Rios Oliva, C, Cotrina, R, Berrospi Argandona, P, Toce Yanez, L, Chavez Ayala, C, Mirek-Bryniarska, E, Goch, A, Skucha, W, Skorski, M, Miekus, P, Szyszka, A, Piotrowski, G, Gniot, J, Czerski, T, Debich, P, Zaluska, R, Bebenek, W, Wozakowska-Kaplon, B, Sciborski, R, Ilkowski, J, Wojnowski, P, Uscinska, E, Gaciong, Z, Bonek, R, Sobkowicz, B, Berkowski, P, Bejgier, K, Polonski, L, Kosior, D, Lata, S, Kolodziej, P, Gessek, J, Kachel, T, Talalaj, M, Musial, J, Lewczuk, J, Krysiak, W, Kucharski, L, Wysokinski, A, Minc, P, Martinez, J, Gregorio, T, Almeida, F, Monteiro, P, Stanciulescu, G, Mercea, C, Iosipescu, L, Ciobotaru, V, Crisu, D, Burca, M, Tudoran, M, Savu, A, Negrean, V, Cojocaru, C, Minescu, B, Popa, V, Blajan, D, Nastase-Melicovici, D, Fruntelata, A, Barbulescu, S, Lukinyh, L, Akhunova, S, Vishneva, E, Semenova, I, Nikolaev, K, Shaydyuk, O, Nilk, R, Shalnev, V, Apartsin, K, Goloshchekin, B, Shpagina, L, Khlevchuk, T, Arkhipov, M, Malygin, A, Shvarts, Y, Khaisheva, L, Popov, D, Kobalava, Z, Lipchenko, A, Shapovalova, Y, Zrazhevsky, K, Greshnova, I, Maslova, N, Karabenenko, A, Shogenov, Z, Budankova, E, Barbarash, O, Uspenskiy, Y, Kosmacheva, E, Berns, S, Kostenko, V, Zateyshchikov, D, Vishnevsky, A, Boldueva, S, Podzolkov, V, Sergeeva, E, Grinshtein, Y, Khrustalev, O, Bugrova, O, Repin, A, Andreev, D, Petrovic, P, Boskovic Matic, T, Apostolovic, S, Lazic, Z, Stankovic, D, Stankovic, A, Mitov, V, Sofronic, D, Kopitovic, I, Zdravkovic, V, Joksimovic, Z, Lazovic, N, Petrovic-Stanojevic, N, Ilic, A, Vujadinovic, O, Pencic-Popovic, B, Andjelkovic, N, Sekularac, N, Hinic, S, Radjen, G, Zivkovic, A, Putnikovic, B, Ivanov, I, Babic, R, Van Zyl, L, Hobson, B, Engelbrecht, J, Mitha, I, Siebert, H, Jacobson, B, Breedt, J, Prozesky, H, Ntsekhe, M, Bayat, J, Ellis, G, Tarr, G, Adler, D, Van Dyk, C, Ismail, S, Spargo, C, Abdool-Gaffar, M, Saaiman, J, Venter, K, Lorente Aroca, M, Fernandez Portales, F, Pedrajas Navas, J, Rodriguez Botaro, A, Santa Cruz Siminiani, A, Lopez Reyes, R, Bisbe i Company, J, Piedecausa Selfa, M, Velasco Garrido, J, Sobrino-Martinez, J, Munoz Delgado, G, Sala Llinas, E, Blanco Coronado, J, Almenar Bonet, L, Vida Gutierrez, M, Sanchez Lora, F, Sanchez Martinez, R, Calderon, E, Villalta Blanch, J, De la Hera Galarza, J, Bustamante Ruiz, A, Garcia-Fuster, M, Ripoll Vera, T, Alvarez-Sala Walter, L, Todoli Parra, J, Diaz Fernandez, J, Bosa Ojeda, F, Pellicer-Ciscar, C, Jara Palomares, L, Quiles Granado, J, Trigo Bautista, A, Ruiz Bustillo, S, Ordi Ros, J, Tolosa-Vilella, C, Marin Ortuno, F, Garcia Sanchez, F, Barba Martin, R, Segovia Cubero, J, Cuervas-Mons Martinez, V, Galan Montejano, M, Lopez Meseguer, M, Sener Comert, S, Koksal, N, Tertemiz, K, Ernam, D, Dursun, A, Yildiz, O, Rudenko, L, Abrahamovych, O, Goloborodko, A, Holovchenko, N, Kulyk, A, Yagensky, A, Batushkin, V, Zolotaikina, V, Kozyolkin, O, Faynyk, A, Maslovskyy, V, Petrovskyy, R, Koshlia, V, Chopey, I, Burmak, I, Malynovsky, Y, Voronkov, L, Karpenko, O, Dziublyk, O, Godlevska, O, Borovyk, V, Bezrodna, L, Serik, S, Ovsyannikova, N, Vynnychenko, L, Kopytsya, M, Rudkovskiy, V, Grishyna, O, Vyshnyvetskyy, I, Prystupa, L, Tseluyko, V, Perepeliuk, M, Koval, O, Sychov, O, Church, A, Goudie, A, Elliott, M, Ferguson, C, Welker, J, Kao, C, Bhagwat, R, Serota, H, Bozorgchami, H, Nambiar, R, Spilseth, S, Bhagwath, G, Syed, F, Morrow, L, Updegrove, J, Bercz, P, Kambo, V, Henderson, D, Wright, P, Dang, N, Nadar, V, Jaffrani, N, El-Shahawy, M, Grossman, C, Pearle, J, Weinstein, D, Galanis, T, Gazmuri, R, Kastelic, R, Martinez, R, Laman, D, Macchiavelli, A, Kmetzo, J, Thurm, C, Kayembe, T, Chandrashekhar, Y, Bassetti, D, Jaoude, P, Williams, H, Dewhurst, R, Naqvi, S, Burr, J, Rodriguez-Cintron, W, Jeanfreau, R, Kosinski, E, Ndukwu, I, Sotolongo, C, Daboul, N, Wilmer, C, Simon, P, Tak, T, Rees, C, Gupta, N, Lerner, R, Graffagnino, C, Reed, R, Alford, C, Mody, F, Wellmon, B, Hamroff, G, Rajan, R, and Kaatz, S

Subjects
Male, medicine.medical_specialty, Aftercare, Aged, Double-Blind Method, Drug Administration Schedule, Factor Xa Inhibitors, Female, Hemorrhage, Humans, Kaplan-Meier Estimate, Middle Aged, Patient Discharge, Rivaroxaban, Treatment Outcome, Venous Thromboembolism, Venous Thrombosis, Hospitalization, Medicine (all), 030204 cardiovascular system & hematology, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Medical illness, Internal medicine, Hospital discharge, Medicine, Venous Thrombosi, 030212 general & internal medicine, Thromboprophylaxis, business.industry, General Medicine, medicine.disease, Venous thrombosis, Increased risk, rivaroxaban, thromboprophylaxis, medical illness, business, Venous thromboembolism, Factor Xa Inhibitor, Human, medicine.drug
Abstract

Zateyshchikov, Dmitry A/0000-0001-7065-2045; Vyshnyvetskyy, Ivan/0000-0001-7228-3052; Bustillo, Sonia Ruiz/0000-0002-6074-914X; Maslovskyi, Valentyn/0000-0001-5184-1799; Ruzic, Alen/0000-0001-5031-2975; Nikolaev, Konstantin/0000-0003-4601-6203; Musial, Jacek/0000-0002-8994-0036; Malynovsky, Yaroslav V/0000-0002-9118-1104; Tsivgoulis, Georgios/0000-0002-0640-3797; Maslovskyi, Valentyn/0000-0001-5184-1799; Grinshtein, Yury/0000-0001-8847-235X; Shpagina, Lyubov/0000-0003-0871-7551; Yildiz, Oznur/0000-0002-5379-6829; Marchev, Sotir/0000-0001-9250-510X; Weitz, Jeffrey/0000-0002-1092-7550; Apartsin, Konstantin A/0000-0003-0577-9001; Reis, Gilmar/0000-0002-4847-1034; Baker, Ross/0000-0002-2728-6788; Koziolkin, Olexandr/0000-0001-9878-5798; Barbarash, Olga/0000-0002-4642-3610; Sala-Llinas, Ernest/0000-0002-6499-1638; Gallus, Alexander/0000-0001-7347-9989; lodigiani, corrado/0000-0002-9152-9385; Kosmacheva, Elena/0000-0001-8600-0199; Ramacciotti, Eduardo/0000-0002-5735-1333; Khorana, Alok/0000-0002-9509-0998; Giorgi-Pierfranceschi, Matteo/0000-0002-7988-9652; Torbicki, Adam/0000-0003-3475-8832; Abragamovic, Orest/0000-0001-6862-6809; Jara-Palomares, Luis/0000-0002-4125-3376; Prozesky, Hans/0000-0001-9715-3449; Andreev, Denis/0000-0002-0276-7374; Cuervas-Mons Martinez, Valentin/0000-0003-3086-9463; Apostolovic, Svetlana/0000-0001-9015-297X; Gregorio, Tiago/0000-0002-0131-9430; Sanchez Martinez, Rosario/0000-0003-0408-3029; Antonicelli, Roberto/0000-0002-5921-1828; Konstantinides, Stavros/0000-0001-6359-7279; Karapanayiotides, Theodoros/0000-0002-2357-7967; Repin, Alexey/0000-0001-7123-0645 WOS: 000445020900006 PubMed: 30145946 BACKGROUND Patients who are hospitalized for medical illness remain at risk for venous thromboembolism after discharge, but the role of extended thromboprophylaxis in the treatment of such patients is a subject of controversy. METHODS In this randomized, double-blind trial, medically ill patients who were at increased risk for venous thromboembolism on the basis of a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score of 4 or higher (scores range from 0 to 10, with higher scores indicating a higher risk of venous thromboembolism) or a score of 2 or 3 plus a plasma n-dimer level of more than twice the upper limit of the normal range (defined according to local laboratory criteria) were assigned at hospital discharge to either once-daily rivaroxaban at a dose of 10 mg (with the dose adjusted for renal insufficiency) or placebo for 45 days. The primary efficacy outcome was a composite of symptomatic venous thromboembolism or death due to venous thromboembolism. The principal safety outcome was major bleeding. RESULTS Of the 12,024 patients who underwent randomization, 12,019 were included in the intention-to-treat analysis. The primary efficacy outcome occurred in 50 of 6007 patients (0.83%) who were given rivaroxaban and in 66 of 6012 patients (1.10%) who were given placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.52 to 1.09; P=0.14). The prespecified secondary outcome of symptomatic nonfatal venous thromboembolism occurred in 0.18% of patients in the rivaroxaban group and 0.42% of patients in the placebo group (hazard ratio, 0.44; 95% CI, 0.22 to 0.89). Major bleeding occurred in 17 of 5982 patients (0.28%) in the rivaroxaban group and in 9 of 5980 patients (0.15%) in the placebo group (hazard ratio, 1.88; 95% CI, 0.84 to 4.23). CONCLUSIONS Rivaroxaban, given to medical patients for 45 days after hospital discharge, was not associated with a significantly lower risk of symptomatic venous thromboembolism and death due to venous thromboembolism than placebo. The incidence of major bleeding was low. Janssen Research and Development; Daiichi SankyoDaiichi Sankyo Company Limited; Portola; Boehringer IngelheimBoehringer Ingelheim; JanssenJohnson & Johnson USAJanssen Biotech Inc; BayerBayer AG; BMS PfizerPfizer; Aspen; Sanofi; University of Cincinnati and Spectrum Health; PfizerPfizer; ATLAS Group (Colorado Prevention Center); Johnson JohnsonJohnson & Johnson USA; Ortho-McNeil-JanssenJohnson & Johnson USAJanssen Biotech Inc; Bayer/JanssenJohnson & Johnson USAJanssen Biotech IncBayer AG; MerckMerck & Company; AmgenAmgen Supported by Janssen Research and Development.r Dr. Spyropoulos reports receiving advisory board fees from Daiichi Sankyo and Portola, grant support, consulting fees, and advisory board fees from Boehringer Ingelheim and Janssen, consulting fees and advisory board fees from Bayer, and a stipend from ATLAS Group (Colorado Prevention Center); Dr. Ageno, receiving grant support and advisory board fees from Bayer and BMS Pfizer and advisory board fees from Portola, Daiichi Sankyo, Aspen, Boehringer Ingelheim, and Sanofi; Dr. Albers, receiving consulting fees from Bayer; Dr. Elliott, receiving fees for serving on a steering committee from Bayer and lecture fees from the University of Cincinnati and Spectrum Health; Dr. Halperin, receiving consulting fees from Boehringer Ingelheim, Daiichi Sankyo, Pfizer, ATLAS Group (Colorado Prevention Center), Johnson & Johnson, and Ortho-McNeil-Janssen; Dr. Hiatt, receiving grant support from Janssen and Bayer; Dr. Steg, receiving grant support and fees for serving on a steering committee from Bayer/Janssen, grant support and lecture fees from Merck, grant support, consulting fees, lecture fees, and fees for serving as cochair of the ODYSSEY outcomes trial and the SCORED trial from Sanofi, grant support and fees for serving as chair of the CLARIFY registry from Servier, consulting fees and fees for serving on the executive steering committee for the REDUCE IT trial from Amarin, consulting fees and lecture fees from Amgen, consulting fees, lecture fees, and fees for critical event committee work from Bristol-Myers Squibb, fees for serving on the executive steering committee of the REDUAL PCI trial from Boehringer Ingelheim, fees for critical event committee work from Pfizer, consulting fees and fees for serving on the executive steering committee for the PARADISE MI trial from Novartis, consulting fees from Regeneron and Lilly, and consulting fees and fees for serving as cochair of the THEMIS trial from AstraZeneca; Dr. Weitz, receiving consulting fees and honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Ionis, Janssen, Merck, Novartis, Pfizer and Portola; Dr. Suh and Dr. Barnathan, being employed by Janssen Research and Development and owning stock in Johnson & Johnson; Dr. Spiro, being employed by and owning shares in Bayer U.S.; and Dr. Raskob, receiving consulting fees from Bayer, BMS, Boehringer Ingelheim, Eli Lilly, Portola, and Novartis and consulting fees and honoraria from Daiichi Sankyo and Pfizer. No other potential conflict of interest relevant to this article was reported.

Published
2018

23. Design and manufacturing of a prototype of a lightweight robot arm

Author

Gutiérrez, S. C., Zotovic Stanisic, Ranko, Navarro, M.D., and Meseguer, M. D.

Subjects
Fused filament fabrication, 0209 industrial biotechnology, Engineering, business.industry, Work (physics), Process (computing), INGENIERIA DE LOS PROCESOS DE FABRICACION, 3D printing, 02 engineering and technology, Light robot arm, INGENIERIA DE SISTEMAS Y AUTOMATICA, Industrial and Manufacturing Engineering, 03 medical and health sciences, 020901 industrial engineering & automation, 0302 clinical medicine, Artificial Intelligence, Rapid portotyping, business, Control parameters, Robotic arm, Fused filament fabricaction, 030217 neurology & neurosurgery, Simulation
Abstract

[EN] The aim of this work is to manufacture a prototype of a lightweight robot arm with a low cost budget, fully functional. This prototype is used to test and fix the elements for driving and controlling. During the development process, several tests and studies were performed, such as, strength simulations, dimensional effects after a post-process treatment with acetone, adjustment of control parameters to improve the accuracy, testing of behaviour of transmissions, etc. The prototype must have a low weight overall and a right operation. The results and conclusions, related with material, reinforcements, geometry/shape of the parts, etc., become recommendations for the manufacture of the final lightweight robot arm. The one that will not be prototype., The authors are grateful to the financial support of Spanish Ministry of Economy and European Union, grant DPI2016-81002-R (AEI/FEDER, UE).

Published
2017
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25. Real-life experience of inhaled iloprost for patients with pulmonary arterial hypertension: Insights from the Spanish REHAP registry

Author

Del Pozo R, Blanco I, Hernández-González I, López-Meseguer M, López-Reyes R, Lázaro-Salvador M, Elías-Hernández T, Álvarez-Vega P, Pérez-Peñate GM, Martínez-Meñaca A, Bedate P, Escribano-Subias P, and REHAP investigators

Subjects
respiratory system, Effectiveness, Iloprost, Prostanoids, Pulmonary arterial hypertension, Pulmonary hypertension, Real-life experience, Registry, Survival, respiratory tract diseases
Abstract

REHAP is a voluntary, observational Spanish registry of patients with pulmonary arterial hypertension. We analyzed the experience (use and effectiveness) with inhaled iloprost (inh-ILO) in real-life conditions during a 3-year period.

Published
2019

31. Prophylaxis with enoxaparin for prevention of venous thromboembolism after lung transplantation: a retrospective study

Author

Saez-Gimenez B, Berastegui C, Sintes H, Perez-Miranda J, Figueredo A, Lopez Meseguer M, Monforte V, Bravo C, Santamaria A, Ramon M, Gomez-Olles S, and Roman A

Subjects
venous thromboembolism, lung transplantation
Abstract

Venous thromboembolism (VTE) is a frequent complication after solid organ transplantation (SOT) and, specifically, after lung transplantation (LT). The objectives of this study were to evaluate prophylaxis with enoxaparin and to describe risk factors for VTE after LT. We retrospectively reviewed the clinical records of 333 patients who underwent LT in our institution between 2009 and 2014. We compared two consecutive cohorts: one that received enoxaparin only during post-transplant hospital admissions and a second cohort that received 90-day extended prophylaxis with enoxaparin. Cumulative incidence function for competing risk analysis was used to determine incidence of VTE during the first year after transplantation. Risk factors were analyzed using a Cox proportional hazards regression model. The cumulative incidence of VTE was 15.3% (95% CI: 11.6-19.4). Median time from transplant to the event was 40 (p25-p75, 14-112) days. Ninety-day extended prophylaxis did not reduce the incidence of VTE. In this study, the risk factors associated with VTE were male gender and interstitial lung disease. VTE is a major complication after LT, and 90-day extended prophylaxis was not able to prevent it. Large, multicenter, randomized clinical trials should be performed to define the best strategy for preventing VTE.

Published
2017

48. New strategy for diagnosing embryo implantation potential by combining proteomics and time-lapse technologies

Author

Dominguez F, Meseguer M, Aparicio-Ruiz B, Piqueras P, Quiñonero A, and Simón C

Subjects
IL-6, proteomics, blastocyst, time lapse, Embryo kinetics, implantation potential
Abstract

Objective: To develop a diagnostic tool for embryo implantation potential with the use of proteomic fingerprinting combined with time-lapse morphokinetic analysis. Design: Retrospective cohort study. Setting: University-affiliated private in vitro fertilization center. Patient(s): Seventeen infertile patients undergoing intracytoplasmic sperm injection (ICSI) from our ovum donation program. Intervention(s): No patient intervention. We examined morphokinetic data and proteomic data from the spent media of 16 embryos that implanted and 12 embryos that did not implant. Main Outcome Measure(s): We analyzed seven proteins in the embryo spentmedia-SCF, TNFR1, PIGF-1, IFN-alpha 2, IL-6, CXCL13, and GM-CSF-with the use of a bead-based multiplexing technology and combined this data with the exact timing (in hours) of cell cycle duration (cc2), blastomere synchrony (s2), and 5-blastomere cleavage (t5) with the use of an incubator equipped with time-lapse videography. Result(s): Logistic regression analysis with the use of the forward-step likelihood selection method revealed that the presence/absence of interleukin (IL) 6 and the duration of cc2 were the most relevant embryo features for embryo selection. We combined these two parameters to obtain a hierarchic model that established four categories (A/B/C/D), based on the presence of IL-6 and a cc2 range of 5-12 hours. A direct relationship was observed between the morphologic categories and implantation rates: Those with the presence of IL-6 and 5-12 h cc2 had significantly higher implantation rates. Conclusion(s): The strategy we report here combines time-lapse and proteome analysis to improve embryo selection while minimizing handling and monitoring by the embryologist. Our results describe the utility of a combined biochemical/morphokinetic approach to select embryos for transfer according to their implantation potential. Clinical validation with larger sample sizes is mandatory to confirm the effectiveness of this initial study. (C) 2015 by American Society for Reproductive Medicine.

Published
2015

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