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1. The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group.

Author

Siris, ES, Adler, R, Bilezikian, J, Bolognese, M, Dawson-Hughes, B, Favus, MJ, Harris, ST, Jan de Beur, SM, Khosla, S, Lane, NE, Lindsay, R, Nana, AD, Orwoll, ES, Saag, K, Silverman, S, and Watts, NB

Subjects
Femur Neck, Lumbar Vertebrae, Hip Joint, Humans, Osteoporosis, Osteoporosis, Postmenopausal, Absorptiometry, Photon, Risk Assessment, Age Factors, Bone Density, Algorithms, Aged, Middle Aged, Female, Male, Osteoporotic Fractures, Clinical diagnosis, Criteria, Position statement, Postmenopausal, Absorptiometry, Photon, Clinical Sciences, Endocrinology & Metabolism, Biomedical Engineering, Public Health and Health Services
Abstract

UnlabelledOsteoporosis causes an elevated fracture risk. We propose the continued use of T-scores as one means for diagnosis but recommend that, alternatively, hip fracture; osteopenia-associated vertebral, proximal humerus, pelvis, or some wrist fractures; or FRAX scores with ≥3% (hip) or 20% (major) 10-year fracture risk also confer an osteoporosis diagnosis.IntroductionOsteoporosis is a common disorder of reduced bone strength that predisposes to an increased risk for fractures in older individuals. In the USA, the standard criterion for the diagnosis of osteoporosis in postmenopausal women and older men is a T-score of  ≤ -2.5 at the lumbar spine, femur neck, or total hip by bone mineral density testing.MethodsUnder the direction of the National Bone Health Alliance, 17 clinicians and clinical scientists were appointed to a working group charged to determine the appropriate expansion of the criteria by which osteoporosis can be diagnosed.ResultsThe group recommends that postmenopausal women and men aged 50 years should be diagnosed with osteoporosis if they have a demonstrable elevated risk for future fractures. This includes having a T-score of less than or equal to -2.5 at the spine or hip as one method for diagnosis but also permits a diagnosis for individuals in this population who have experienced a hip fracture with or without bone mineral density (BMD) testing and for those who have osteopenia by BMD who sustain a vertebral, proximal humeral, pelvic, or, in some cases, distal forearm fracture. Finally, the term osteoporosis should be used to diagnose individuals with an elevated fracture risk based on the World Health Organization Fracture Risk Algorithm, FRAX.ConclusionsAs new ICD-10 codes become available, it is our hope that this new understanding of what osteoporosis represents will allow for an appropriate diagnosis when older individuals are recognized as being at an elevated risk for fracture.

Published
2014

2. Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures

Author

Austin, Matthew, Yang, Yu‐Ching, Vittinghoff, Eric, Adami, Silvano, Boonen, Steven, Bauer, Douglas C, Bianchi, Gerolamo, Bolognese, Michael A, Christiansen, Claus, Eastell, Richard, Grauer, Andreas, Hawkins, Federico, Kendler, David L, Oliveri, Beatriz, McClung, Michael R, Reid, Ian R, Siris, Ethel S, Zanchetta, Jose, Zerbini, Cristiano AF, Libanati, Cesar, Cummings, Steven R, and Trial, for the FREEDOM

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Osteoporosis, Physical Injury - Accidents and Adverse Effects, Musculoskeletal, Absorptiometry, Photon, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Bone Density, Bone Density Conservation Agents, Denosumab, Double-Blind Method, Female, Fractures, Bone, Humans, Middle Aged, Placebos, Risk Reduction Behavior, Spinal Fractures, DENOSUMAB, BONE MINERAL DENSITY, FRACTURE, SURROGATE, PERCENT OF TREATMENT EFFECT EXPLAINED, FREEDOM Trial, Biological Sciences, Engineering, Medical and Health Sciences, Anatomy & Morphology, Biological sciences, Biomedical and clinical sciences
Abstract

Dual-energy X-ray absorptiometric bone mineral density (DXA BMD) is a strong predictor of fracture risk in untreated patients. However, previous patient-level studies suggest that BMD changes explain little of the fracture risk reduction observed with osteoporosis treatment. We investigated the relevance of DXA BMD changes as a predictor for fracture risk reduction using data from the FREEDOM trial, which randomly assigned placebo or denosumab 60 mg every 6 months to 7808 women aged 60 to 90 years with a spine or total hip BMD T-score < -2.5 and not < -4.0. We took a standard approach to estimate the percent of treatment effect explained using percent changes in BMD at a single visit (months 12, 24, or 36). We also applied a novel approach using estimated percent changes in BMD from baseline at the time of fracture occurrence (time-dependent models). Denosumab significantly increased total hip BMD by 3.2%, 4.4%, and 5.0% at 12, 24, and 36 months, respectively. Denosumab decreased the risk of new vertebral fractures by 68% (p < 0.0001) and nonvertebral fracture by 20% (p = 0.01) over 36 months. Regardless of the method used, the change in total hip BMD explained a considerable proportion of the effect of denosumab in reducing new or worsening vertebral fracture risk (35% [95% confidence interval (CI): 20%-61%] and 51% [95% CI: 39%-66%] accounted for by percent change at month 36 and change in time-dependent BMD, respectively) and explained a considerable amount of the reduction in nonvertebral fracture risk (87% [95% CI: 35% - >100%] and 72% [95% CI: 24% - >100%], respectively). Previous patient-level studies may have underestimated the strength of the relationship between BMD change and the effect of treatment on fracture risk or this relationship may be unique to denosumab.

Published
2012

3. Incidence and Management of Restenosis After Treatment of Unprotected Left Main Disease With Drug-Eluting Stents 70 Restenotic Cases From a Cohort of 718 Patients: FAILS (Failure in Left Main Study)

Author

Sheiban, Imad, Sillano, Dario, Biondi-Zoccai, Giuseppe, Chieffo, Alaide, Colombo, Antonio, Vecchio, Sabine, Margheri, Massimo, Gunn, Julian P, Raina, Tushar, Liistro, Francesco, Bolognese, Leonardo, Lee, Michael S, Tobis, Jonathan, and Moretti, Claudio

Subjects
Assistive Technology, Atherosclerosis, Bioengineering, Heart Disease, Clinical Research, Heart Disease - Coronary Heart Disease, Cardiovascular, Aged, Aged, 80 and over, Angioplasty, Balloon, Coronary, Cohort Studies, Coronary Artery Bypass, Coronary Restenosis, Drug-Eluting Stents, Female, Graft Occlusion, Vascular, Humans, Incidence, Male, Middle Aged, Retrospective Studies, Treatment Failure, coronary artery disease, drug-eluting stent, left main coronary artery, percutaneous coronary intervention, restenosis, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

ObjectivesThis study sought to retrospectively appraise the incidence and management of restenosis after drug-eluting stent (DES) implantation for unprotected left main (ULM) disease.BackgroundThe promising role of DES for ULM has been reported. However, no detailed data are available on subsequent restenosis.MethodsFrom the total sample of patients with ULM treated with DES, we identified those presenting with angiographic ULM restenosis. The primary end point was the long-term rate of major adverse cardiac events (MACE), that is, death, myocardial infarction (MI), or target lesion revascularization (TLR). We also adjudicated stent thrombosis according to the Academic Research Consortium.ResultsPost-DES restenosis in ULM occurred in 70 of 718 patients (9.7%). Of these, 59 (84.3%) were treated percutaneously (34 [48.6%] with additional DES, 22 [31.4%] with standard or cutting balloons, 2 [2.9%] with rotational atherectomy, and 1 [1.4%] with a bare-metal stent), whereas 7 (10%) patients underwent bypass surgery and 4 (5.7%) were treated medically. In-hospital MACE included no periprocedural MI and only 1 (1.4%) death. After 27.2 +/- 15.4 months, MACE occurred cumulatively in 18 (25.7%) patients, with death in 4 (5.7%), MI in 2 (2.9%), and TLR in 15 (21.4%). Patients treated with medical, interventional, and surgical therapy had the following MACE rates, respectively: 50%, 25.4%, and 14.3%. Definite, probable, and possible stent thrombosis occurred in 0 (0%), 1 (1.4%), and 1 (1.4%) patient, respectively.ConclusionsDES restenosis in the ULM artery can be managed in most cases with a minimally invasive approach, achieving favorable early and late results.

Published
2009

4. Romosozumab Enhances Vertebral Bone Structure in Women With Low Bone Density

Author

Carlos Mautalen, Y.-C. Yang, K Poole, Christopher Recknor, Andreas Grauer, M. A. Bolognese, Graham M. Treece, David A. Hanley, RA Pearson, Tristan Whitmarsh, Andrew H. Gee, Jacques P. Brown, Cesar Libanati, Stefan Goemaere, Maria Rojeski, Poole, Kenneth Es [0000-0003-4546-7352], Bolognese, Michael A [0000-0002-7102-5518], Libanati, Cesar [0000-0003-1427-7839], Whitmarsh, Tristan [0000-0001-8272-9505], and Apollo - University of Cambridge Repository

Subjects
ANABOLICS, Endocrinology, Diabetes and Metabolism, Romosozumab, Dentistry, DISEASES AND DISORDERS OF/RELATED TO BONE, ANALYSIS/QUANTITATION OF BONE, Bone Density, Teriparatide, Low bone density, Medicine, Humans, Orthopedics and Sports Medicine, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), ComputingMilieux_MISCELLANEOUS, Vertebral bone, Osteoporosis, Postmenopausal, Lumbar Vertebrae, Bone Density Conservation Agents, business.industry, BONE QCT/microCT, Antibodies, Monoclonal, ANTIRESORPTIVES, THERAPEUTICS, Osteoporosis, Social care, Female, business
Abstract

Funder: NIHR Cambridge BRC; Id: http://dx.doi.org/10.13039/501100018956, Romosozumab monoclonal antibody treatment works by binding sclerostin and causing rapid stimulation of bone formation while decreasing bone resorption. The location and local magnitude of vertebral bone accrual by romosozumab and how it compares to teriparatide remains to be investigated. Here we analyzed the data from a study collecting lumbar computed tomography (CT) spine scans at enrollment and 12 months post-treatment with romosozumab (210 mg sc monthly, n = 17), open-label daily teriparatide (20 μg sc, n = 19), or placebo (sc monthly, n = 20). For each of the 56 women, cortical thickness (Ct.Th), endocortical thickness (Ec.Th), cortical bone mineral density (Ct.bone mineral density (BMD)), cancellous BMD (Cn.BMD), and cortical mass surface density (CMSD) were measured across the first lumbar vertebral surface. In addition, color maps of the changes in the lumbar vertebrae structure were statistically analyzed and then visualized on the bone surface. At 12 months, romosozumab improved all parameters significantly over placebo and resulted in a mean vertebral Ct.Th increase of 10.3% versus 4.3% for teriparatide, an Ec.Th increase of 137.6% versus 47.5% for teriparatide, a Ct.BMD increase of 2.1% versus a -0.1% decrease for teriparatide, and a CMSD increase of 12.4% versus 3.8% for teriparatide. For all these measurements, the differences between romosozumab and teriparatide were statistically significant (p < 0.05). There was no significant difference between the romosozumab-associated Cn.BMD gains of 22.2% versus 18.1% for teriparatide, but both were significantly greater compared with the change in the placebo group (-4.6%, p < 0.05). Cortical maps showed the topographical locations of the increase in bone in fracture-prone areas of the vertebral shell, walls, and endplates. This study confirms widespread vertebral bone accrual with romosozumab or teriparatide treatment and provides new insights into how the rapid prevention of vertebral fractures is achieved in women with osteoporosis using these anabolic agents. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Published
2021

5. Reduction of hospitalizations for myocardial infarction in Italy in the COVID-19 era

Author

De Rosa, Salvatore, Spaccarotella, Carmen, Basso, Cristina, Calabrò, Maria Pia, Curcio, Antonio, Filardi, Pasquale Perrone, Mancone, Massimo, Mercuro, Giuseppe, Muscoli, Saverio, Nodari, Savina, Pedrinelli, Roberto, Sinagra, Gianfranco, Indolfi, Ciro, Angelini, Filippo, Barillà, Francesco, Bartorelli, Antonio, Benedetto, Francesco, Bernabò, Paola, Bolognese, Leonardo, Briani, Martina, Cacciavillani, Luisa, Calabrese, Alice, Calabrò, Paolo, Caliendo, Luigi, Calò, Leonardo, Casella, Gianni, Casu, Gavino, Cavallini, Claudio, Ciampi, Quirino, Ciccone, Marco, Comito, Michele, Corrada, Elena, Crea, Filippo, D’Andrea, Antonello, D’Urbano, Maurizio, De Caterina, Raffaele, De Ferrari, Gaetano, De Ponti, Roberto, Della Mattia, Alessio, Di Mario, Carlo, Donazzan, Luca, Esposito, Giovanni, Fedele, Francesco, Ferraro, Alessandro, Galasso, Gennaro, Galiè, Nazzareno, Gnecchi, Massimiliano, Golino, Paolo, Golia, Bruno, Guarini, Pasquale, Leonardi, Sergio, Locuratolo, Nicola, Luzza, Francesco, Manganiello, Vincenzo, Francesca Marchetti, Maria, Marenzi, Giancarlo, Margonato, Alberto, Meloni, Luigi, Metra, Marco, Milo, Marco, Mongiardo, Annalisa, Monzo, Luca, Morisco, Carmine, Novo, Giuseppina, Pancaldi, Stefano, Parollo, Matteo, Paternò, Giovanni, Patti, Giuseppe, Priori, Silvia, Ravera, Amelia, Giuseppe Rebuzzi, Antonio, Rossi, Massimo, Scherillo, Marino, Semprini, Franco, Senni, Michele, Sibilio, Gerolamo, Siviglia, Massimo, Tamburino, Corrado, Tortorici, Gianfranco, Versace, Francesco, Villari, Bruno, Volpe, Massimo, De Rosa S., Spaccarotella C., Basso C., Calabro M.P., Curcio A., Filardi P.P., Mancone M., Mercuro G., Muscoli S., Nodari S., Pedrinelli R., Sinagra G., Indolfi C., Angelini F., Barilla F., Bartorelli A., Benedetto F., Bernabo P., Bolognese L., Briani M., Cacciavillani L., Calabrese A., Calabro P., Caliendo L., Calo L., Casella G., Casu G., Cavallini C., Ciampi Q., Ciccone M., Comito M., Corrada E., Crea F., D'Andrea A., D'Urbano M., De Caterina R., De Ferrari G., De Ponti R., Della Mattia A., DI Mario C., Donnazzan L., Esposito G., Fedele F., Ferraro A., Galasso G., Galie N., Gnecchi M., Golino P., Golia B., Guarini P., Leonardi S., Locuratolo N., Luzza F., Manganiello V., Francesca Marchetti M., Marenzi G., Margonato A., Meloni L., Metra M., Milo M., Mongiardo A., Monzo L., Morisco C., Novo G., Pancaldi S., Parollo M., Paterno G., Patti G., Priori S., Ravera A., Giuseppe Rebuzzi A., Rossi M., Scherillo M., Semprini F., Senni M., Sibilio G., Siviglia M., Tamburino C., Tortorici G., Versace F., Villari B., Volpe M., De Rosa, S., Spaccarotella, C., Basso, C., Calabro, M. P., Curcio, A., Filardi, P. P., Mancone, M., Mercuro, G., Muscoli, S., Nodari, S., Pedrinelli, R., Sinagra, G., Indolfi, C., Angelini, F., Barilla, F., Bartorelli, A., Benedetto, F., Bernabo, P., Bolognese, L., Briani, M., Cacciavillani, L., Calabrese, A., Calabro, P., Caliendo, L., Calo, L., Casella, G., Casu, G., Cavallini, C., Ciampi, Q., Ciccone, M., Comito, M., Corrada, E., Crea, F., D'Andrea, A., D'Urbano, M., De Caterina, R., De Ferrari, G., De Ponti, R., Della Mattia, A., DI Mario, C., Donnazzan, L., Esposito, G., Fedele, F., Ferraro, A., Galasso, G., Galie, N., Gnecchi, M., Golino, P., Golia, B., Guarini, P., Leonardi, S., Locuratolo, N., Luzza, F., Manganiello, V., Francesca Marchetti, M., Marenzi, G., Margonato, A., Meloni, L., Metra, M., Milo, M., Mongiardo, A., Monzo, L., Morisco, C., Novo, G., Pancaldi, S., Parollo, M., Paterno, G., Patti, G., Priori, S., Ravera, A., Giuseppe Rebuzzi, A., Rossi, M., Scherillo, M., Semprini, F., Senni, M., Sibilio, G., Siviglia, M., Tamburino, C., Tortorici, G., Versace, F., Villari, B., Volpe, M., De Rosa, S, Spaccarotella, C, Basso, C, Calabro, M, Curcio, A, Filardi, P, Mancone, M, Mercuro, G, Muscoli, S, Nodari, S, Pedrinelli, R, Sinagra, G, Indolfi, C, Angelini, F, Barilla, F, Bartorelli, A, Benedetto, F, Bernabo, P, Bolognese, L, Briani, M, Cacciavillani, L, Calabrese, A, Calabro, P, Caliendo, L, Calo, L, Casella, G, Casu, G, Cavallini, C, Ciampi, Q, Ciccone, M, Comito, M, Corrada, E, Crea, F, D'Andrea, A, D'Urbano, M, De Caterina, R, De Ferrari, G, De Ponti, R, Della Mattia, A, DI Mario, C, Donnazzan, L, Esposito, G, Fedele, F, Ferraro, A, Galasso, G, Galie, N, Gnecchi, M, Golino, P, Golia, B, Guarini, P, Leonardi, S, Locuratolo, N, Luzza, F, Manganiello, V, Francesca Marchetti, M, Marenzi, G, Margonato, A, Meloni, L, Metra, M, Milo, M, Mongiardo, A, Monzo, L, Morisco, C, Novo, G, Pancaldi, S, Parollo, M, Paterno, G, Patti, G, Priori, S, Ravera, A, Giuseppe Rebuzzi, A, Rossi, M, Scherillo, M, Semprini, F, Senni, M, Sibilio, G, Siviglia, M, Tamburino, C, Tortorici, G, Versace, F, Villari, B, Volpe, M, De Rosa, Salvatore, Spaccarotella, Carmen, Basso, Cristina, Calabrò, Maria Pia, Curcio, Antonio, Filardi, Pasquale Perrone, Mancone, Massimo, Mercuro, Giuseppe, Muscoli, Saverio, Nodari, Savina, Pedrinelli, Roberto, Sinagra, Gianfranco, and Indolfi, Ciro

Subjects
Male, Myocardial Infarction, 030204 cardiovascular system & hematology, Settore MED/11, 0302 clinical medicine, Acute myocardial infarction, Cardiac care units, STEMI, Aged, Aged, 80 and over, COVID-19, Female, Hospitalization, Humans, Italy, Male, Middle Aged, SARS-CoV-2, Betacoronavirus, Coronavirus Infections, Myocardial Infarction, Pandemics, Pneumonia, Viral, Case fatality rate, 80 and over, Medicine, 030212 general & internal medicine, Myocardial infarction, Viral, Aged, 80 and over, Acute myocardial infarction, Cardiac care units, COVID-19, SARS-CoV2, STEMI, Aged, Female, Hospitalization, Humans, Italy, Middle Aged, Betacoronavirus, Coronavirus Infections, Pandemics, Pneumonia, Viral, Cardiology and Cardiovascular Medicine, Human, medicine.medical_specialty, Fast Track Clinical Research, 03 medical and health sciences, Cardiac care unit, cardiovascular diseases, Betacoronaviru, Pandemic, business.industry, Coronavirus Infection, SARS-CoV-2, Pneumonia, medicine.disease, acute myocardial infarction, cardiac care units, Confidence interval, Relative risk, Emergency medicine, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Myocardial infarction complications, Observational study, Myocardial infarction diagnosis, business, Complication
Abstract

Aims To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs). Methods and Results We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019. We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001). The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7–32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3–70.3; P < 0.001). Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191). A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%). The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7–6.6; P < 0.001]. A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1–2.8; P = 0.009). Conclusion Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates. This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies.

Published
2020

6. A single dose of zoledronate preserves bone mineral density for up to 2 years after a second course of romosozumab

Author

Paul D Meisner, Andreas Grauer, Yifei Shi, Michael A. Bolognese, Michael R. McClung, Bente L. Langdahl, Judy Maddox, Jacques P. Brown, Jean-Yves Reginster, and Maria Rojeski

Subjects
0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Osteoporosis, Urology, Romosozumab, Phases of clinical research, 030209 endocrinology & metabolism, Placebo, Zoledronic Acid, Follow-on regimen, antiresorptive, 03 medical and health sciences, 0302 clinical medicine, Bone Density, Internal medicine, Bone mineral density, medicine, Humans, Osteoporosis, Postmenopausal, Aged, romosozumab, Bone mineral, Bone Density Conservation Agents, business.industry, Antibodies, Monoclonal, Middle Aged, follow-on regimen, medicine.disease, osteoporosis, Rheumatology, Antiresorptive, Regimen, Denosumab, Original Article, Female, 030101 anatomy & morphology, bone mineral density, business, medicine.drug
Abstract

Summary This phase 2 study evaluated the efficacy and safety of transitioning to zoledronate following romosozumab treatment in postmenopausal women with low bone mass. A single dose of 5 mg zoledronate generally maintained the robust BMD gains accrued with romosozumab treatment and was well tolerated. Introduction Follow-on therapy with an antiresorptive agent is necessary to maintain the skeletal benefits of romosozumab therapy. We evaluated the use of zoledronate following romosozumab treatment. Methods This phase 2, dose-finding study enrolled postmenopausal women with low bone mineral density (BMD). Subjects who received various romosozumab doses or placebo from months 0–24 were rerandomized to denosumab (60 mg SC Q6M) or placebo for 12 months, followed by open-label romosozumab (210 mg QM) for 12 months. At month 48, subjects who had received active treatment for 48 months were assigned to no further active treatment and all other subjects were assigned to zoledronate 5 mg IV. Efficacy (BMD, P1NP, and β-CTX) and safety were evaluated for 24 months, up to month 72. Results A total of 141 subjects entered the month 48–72 period, with 51 in the no further active treatment group and 90 in the zoledronate group. In subjects receiving no further active treatment, lumbar spine (LS) BMD decreased by 10.8% from months 48–72 but remained 4.2% above the original baseline. In subjects receiving zoledronate, LS BMD was maintained (percentage changes: − 0.8% from months 48–72; 12.8% from months 0–72). Similar patterns were observed for proximal femur BMD in both groups. With no further active treatment, P1NP and β-CTX decreased but remained above baseline at month 72. Following zoledronate, P1NP and β-CTX levels initially decreased but approached baseline by month 72. No new safety signals were observed. Conclusion A zoledronate follow-on regimen can maintain robust BMD gains achieved with romosozumab treatment. Electronic supplementary material The online version of this article (10.1007/s00198-020-05502-0) contains supplementary material, which is available to authorized users.

Published
2020
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7. Posterior fossa decompression with duraplasty in Chiari malformation type 1: a systematic review and meta-analysis

Author

Paolo A. Bolognese, Andrew Brodbelt, Sharon Ka Po Tam, and Mansoor Foroughi

Subjects
Adult, Male, Reoperation, medicine.medical_specialty, Adolescent, Decompression, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, medicine, Humans, Child, Chiari malformation, Neuroradiology, medicine.diagnostic_test, business.industry, Interventional radiology, Middle Aged, Decompression, Surgical, medicine.disease, Arnold-Chiari Malformation, Hydrocephalus, Surgery, Child, Preschool, Meta-analysis, Female, Dura Mater, Neurology (clinical), Neurosurgery, business, Craniotomy, 030217 neurology & neurosurgery, Syringomyelia
Abstract

Surgery for symptomatic Chiari type I malformation (CM-I) patients include posterior fossa decompression (PFD) involving craniectomy with or without dural opening, and posterior fossa decompression with duraplasty (PFDD). This review aims to examine the evidence to aid surgical decision-making. A medical database search was expanded to include article references to identify all relevant published case series. Animal studies, editorials, letters, and review articles were excluded. A systemic review and meta-analysis were performed to assess clinical and radiological improvement, complications, and reoperation rates. Seventeen articles, containing data on 3618 paediatric and adult participants, met the inclusion criteria. In the group, 5 papers included patients that had the dura left open. PFDD is associated with better clinical outcomes (RR 1.24, 95% CI, 1.07 to 1.44; P = 0.004), but has a higher complication rate (RR 4.51, 95% CI, 2.01 to 10.11; P = 0.0003). In adults, clinical outcomes differences did not reach statistical significance (P = 0.07) but re-operation rates were higher with PFD (RR 0.17, 95% CI 0.03 to 0.86; P = 0.03), whilst in children re-operation rates were no different (RR 0.97, 95% CI 0.41 to 2.30; P = 0.94). Patients with a syrinx did better with PFDD (P = 0.02). No significant differences were observed concerning radiological improvement. In the absence of hydrocephalus and craniocervical region instability, PFDD provides better clinical outcomes but with higher risk. The use of PFD may be justified in some cases in children, and in the absence of a syrinx. To help with future outcome assessments in patients with a CM-I, standardization of clinical and radiological grading systems are required. Trial registration: not required

Published
2020
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8. Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study

Author

Jonathan P Piccini, Valeria Caso, Stuart J Connolly, Keith A A Fox, Jonas Oldgren, W Schuyler Jones, Diana A Gorog, Václav Durdil, Thomas Viethen, Christoph Neumann, Hardi Mundl, Manesh R Patel, Johann Auer, Martin Hubauer, Sead Pandzic, Eva Preishuber, Carina Primus-Grabscheit, Dietmar Reitgruber, Florian Schmalzer, Christopher Adlbrecht, Andreas Schober, Johannes Hajos, Christoph Keil, Alexandra Schratter, Matthias Frick, Magdalena Anna Benda, Maximilian Mächler, Beatrix Mutschlechner, Christoph Saely, Lukas Sprenger, Michael Lichtenauer, Miriam Eber, Uta Hoppe, Tobias Kolbitsch, Peter Michael Jirak, Moritz Mirna, Robert Schönbauer, Jutta Bergler-Klein, Christian Hengstenberg, Stefan Stojkovic, Daniel Scherr, Martin Manninger-Wünscher, Ursula Rohrer, Markus Stühlinger, Wilfried Schgoer, Jana Schwarzl, Helmut Pürerfellner, Michael Derndorfer, Christian Ebner, Veronika Eder, Georgios Kollias, Thomas Sturmberger, Stefan Sieghartsleitner, Johan Vijgen, Peter Koopman, Karl Dujardin, Wim Anné, Michel De Ceuninck, Rene Tavernier, Mattias Duytschaever, Sébastien Knecht, Luc Missault, Yves Vandekerckhove, Tom Rossenbacker, Bavo Ector, Filip Charlier, Philippe Debruyne, Willem Dewilde, Luc Janssens, John Roosen, Bart Vankelecom, Hein Heidbuchel, Michiel Delesie, Gert Vervoort, Hans Rombouts, Thomas Vanassche, Matthias Engelen, Peter Verhamme, Rik Willems, Christian Constance, Nicolas Pranno, Jafna Cox, Iqbal Bata, Laurent Macle, Martin Aguilar, Julia Cadrin Tourigny, Marc Dubuc, Katia Dyrda, Peter Guerra, Paul Khairy, Blandine Mondésert, Léna Rivard, Denis Roy, Rafik Tadros, Mario Talajic, Bernard Thibault, Isabelle Nault, Louis Blier, Jean Champagne, Franck Molin, Gilles O'Hara, François Philippon, Benoit Plourde, Jean-François Sarrazin, Christian Steinberg, Zdenek Coufal, David Balazsik, Michal Mikulica, Jakub Zapeca, Ondrej Cermak, Tomas Drasnar, Matej Falc, Josef Hornof, Blazej Racz, Danica Weissova, Hana Linkova, Eva Paskova, Robert Petr, Andrea Sirakova, Jiri Kettner, Ales Benak, Martin Holek, Ivo Podpera, Monika Podperova, Vlastimil Vancura, Tomas Jandik, Jiri Smid, Vratislav Dedek, Jan Banik, Vaclav Durdil, Tomas Hnat, Nicolas Lellouche, Ségolène Rouffiac, Guillaume Taldir, Valentin Bridonneau, Philippe Couffon, Magalie Daudin, Cécile Hamon, Jonathan Lacaze, Anne Quentin, Christophe Thebault, Emmanuel Boiffard, Olivier Billon, Fabien Miette, Hervé Pouliquen, Guillaume Turlotte, Hervé Gorka, Franck Albert, Sandrine Bayle, Reda Bensaid, Madalina Dasoveanu, Thibaud Demichili, Teodora Dutoiu, Cliff Khalil, Caterina Loghin, Grégoire Range, Laurent Roussel, Pierre Socié, Christophe Thuaire, Fabrice Extramiana, Vincent Algalarrondo, Haten Boughanmi, Noreddine El Mansour, Usman Mohammad, Romain Sellier, Meyer Elbaz, Clémence Laperche, Philippe Maury, Robert Kiss, Tunde Borsanyi, Zoltan Gingl, Balaza Polgar, Bela Benczur, Alexandra Bodor, Tamas Hepp, Eva Malati, Laszlo Nagy, Norbert Erdei, Jozsef Kapus, Katalin Kapus, Brigitta Toth, Andras Matoltsy, Tunde Kiss, Bela Merkely, Szilvia Herczeg, Orsolya Kiss, Zoltan Sallo, Kalman Toth, Tamas Habon, Miklos Rabai, Kinga Totsimon, Zsolt Zilahi, Gabriella Bencze, Janos Santa, Daniel Aradi, Barbara Kelemen, Leonardo Bolognese, Martina Nesti, Pasquale Giovanni Notarstefano, Simona D'Orazio, Franco Cosmi, Cecilia Becattini, Giancarlo Agnelli, Belinda Broccatelli, Maria Giulia Mosconi, Maurizio Paciaroni, Chiara Urbini, Vito Maurizio Parato, Camilla Notaristefani, Michele Scarano, Pietro Ameri, Giorgio Ghigliotti, Giulia Guglielmi, Roberta Lotti, Andrea Carlo Merlo, Maria Lorenza Muiesan, Andrea Abondio, Caterina Berasi, Elena Mattiuzzo, Claudio Mutti, Massimo Salvetti, Pasquale Pignatelli, Danilo Menichelli, Daniele Pastori, Eiji Tamiya, Takahiro Matsumoto, Tomosato Takabe, Shoichi Yamamoto, Haruyo Yamashita, Shinichi Higashiue, Onichi Furuya, Norihiko Hiramatsu, Kensuke Kasuga, Saburo Kojima, Masatoshi Komooka, Satoshi Kuroyanagi, Makoto Matsuura, Tetsushi Takemoto, Shuji Yamamoto, Katusmi Saito, Takuro Abe, Issei Ishida, Yuji Iwanami, Shohei Kataoka, Tetsu Moriyama, Akira Murohashi, Akihito Sasaki, Yuichiro Nakamura, Tetsuya Ueno, Akira Shimane, Tomoyo Hamana, Hirotoshi Ichibori, Tomohiro Inoue, Mitsuaki Itoh, Seigo Iwane, Hiroya Kawai, Tatsuya Kokawa, Akiko Masumoto, Koki Matsuo, Taishi Miyata, Shinsuke Nakano, Shogo Oishi, Tetsuari Onishi, Takahiro Sawada, Takayuki Saito, Mitsuhiko Shoda, Nobuyuki Takahashi, Tomofumi Takaya, Yasuyo Taniguchi, Shota Tsukamoto, Yasue Tsukishiro, Yoshiro Tsukiyama, Hiroshi Tsunamoto, Kenzo Uzu, Hiroyuki Yamamoto, Tetsuya Yamamoto, Kiminobu Yokoi, Chiaki Yoshida, Nobuhiro Watanabe, Tetsuo Betsuyaku, Kumiko Adachi, Kouichi Awane, Daisuke Goto, Mamoru Sakakibara, Masashi Watanabe, Hideki Ueno, Yoshitaka Hiroe, Koshi Matsuo, Kenji Ayata, Ko Fukuda, Yoshiki Hata, Katsushi Hashimoto, Hiroaki Matsumi, Akira Nikaido, Shuichi Okamoto, Iveta Sime, Valters Stirna, Ilze Reinholde, Silvija Hansone, Anita Kozlovska, Janina Romanova, Dace Klincare, Natalja Pontaga, Igors Dirmans, Artis Kalnins, Dana Upite, Arcils Gersamija, Arturs Teleznikovs, Nadezda Rozkova, Jelena Safro, Ignasi Anguera Camós, Paolo Domenico Dallaglio, Rafael Salguero Bodes, Fernando Arnbas, Luis Borrego, Alvaro Marco, Javier Ramos Jimenez, Juan José Gómez-Doblas, Alejandro Pérez Cabeza, Ignacio Ferreira Gonzålez, Javier Limeres Freire, Merce Lopez Grau, Xavier Viñolas Prat, Zoraida Moreno Weidmann, Jose Maria Guerra Ramos, Maria Concepcion Alonso Martin, Bieito Campos Garcia, Javier Mauricio Mogro Carranza, Francisco Javier Mendez Zurita, Enrique Rodriguez Font, Carlos Eduardo Gonzales Matos, Víctor García Hernando, Carl-Johan Lindholm, Jörgen Thulin, Håkan Wallén, Kristina Hagwall, Ken Eliasson, Martin Lundvall, Jens Olsson, Björn Kjellman, Markus Lind, Lars Johansson, Niclas Svedberg, Stefan Berglund, Julia Söderberg, Christer Zedigh, Thomas Mooe, Mattias Axelsson, Emil Binsell, Daniel Huber, Christian Müller, Isabelle Danier, Michael Kühne, Bernhard Okamura, Hadrien Schoepfer, Cornelia Simmen, Tobias Reichlin, Laurève Chollet, Anna Lam, Severin Wittmer, Hans Rickli, Christian Gall, Greta Hametner, Stephanie Intorp, Daniel Luescher, Laurent Haegeli, Jan Christopher Berg, Ramin Ebrahimi, Angelo Auricchio, Carmela Crljenica, Tizziano Moccetti, Cristina Monti, Elena Pasotti, Iveta Petrova, Mariagrazia Rossi, François Mach, Mehdi Namdar, Joris de Groot, Virginnio Proost, Joline Neefs, Dominik Linz, Twan van Stipdonk, Dennis den Uijl, Marco Alings, Jeroen Schaap, Dolf Segers, Noemi Wouters, Louis Bartels, Robert Tieleman, Ron Pisters, Tim de Vries, Jaap Selig, Aaf Kuijper, Pieter Bot, Mitran Keijzers, Gerardus Verdel, Raymond Tukkie, Ewout van den Bos, Floris Kauer, Rohit Oemrawsingh, Jeroen Stevenhagen, Jan van Es, Gregory Lip, Dhiraj Gupta, Agnieszka Kotalczyk, Anthony Gunstone, Richard David Brixey, Diana Gorog, Danial Dinarvand, Ying Gue, Rahim Kanji, Vassilios Memtsas, Roxy Senior, Gabriel Bioh, Yuk-Ki Wong, Nick Child, Cardiology, and ACS - Heart failure & arrhythmias

Subjects
anticoagulants, factor xa inhibitors, General Medicine, aged, double-blind method, female, hemorrhage, humans, male, pyrazoles, pyridones, treatment outcome, atrial fibrillation, 610 Medicine & health
Abstract

BACKGROUND Direct-acting oral anticoagulant use for stroke prevention in atrial fibrillation is limited by bleeding concerns. Asundexian, a novel, oral small molecule activated coagulation factor XIa (FXIa) inhibitor, might reduce thrombosis with minimal effect on haemostasis. We aimed to determine the optimal dose of asundexian and to compare the incidence of bleeding with that of apixaban in patients with atrial fibrillation. METHODS In this randomised, double-blind, phase 2 dose-finding study, we compared asundexian 20 mg or 50 mg once daily with apixaban 5 mg twice daily in patients aged 45 years or older with atrial fibrillation, a CHA2DS2-VASc score of at least 2 if male or at least 3 if female, and increased bleeding risk. The study was conducted at 93 sites in 14 countries, including 12 European countries, Canada, and Japan. Participants were randomly assigned (1:1:1) to a treatment group using an interactive web response system, with randomisation stratified by whether patients were receiving a direct-acting oral anticoagulant before the study start. Masking was achieved using a double-dummy design, with participants receiving both the assigned treatment and a placebo that resembled the non-assigned treatment. The primary endpoint was the composite of major or clinically relevant non-major bleeding according to International Society on Thrombosis and Haemostasis criteria, assessed in all patients who took at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT04218266, and EudraCT, 2019-002365-35. FINDINGS Between Jan 30, 2020, and June 21, 2021, 862 patients were enrolled. 755 patients were randomly assigned to treatment. Two patients (assigned to asundexian 20 mg) never took any study medication, resulting in 753 patients being included in the analysis (249 received asundexian 20 mg, 254 received asundexian 50 g, and 250 received apixaban). The mean age of participants was 73·7 years (SD 8·3), 309 (41%) were women, 216 (29%) had chronic kidney disease, and mean CHA2DS2-VASc score was 3·9 (1·3). Asundexian 20 mg resulted in 81% inhibition of FXIa activity at trough concentrations and 90% inhibition at peak concentrations; asundexian 50 mg resulted in 92% inhibition at trough concentrations and 94% inhibition at peak concentrations. Ratios of incidence proportions for the primary endpoint were 0·50 (90% CI 0·14-1·68) for asundexian 20 mg (three events), 0·16 (0·01-0·99) for asundexian 50 mg (one event), and 0·33 (0·09-0·97) for pooled asundexian (four events) versus apixaban (six events). The rate of any adverse event occurring was similar in the three treatment groups: 118 (47%) with asundexian 20 mg, 120 (47%) with asundexian 50 mg, and 122 (49%) with apixaban. INTERPRETATION The FXIa inhibitor asundexian at doses of 20 mg and 50 mg once daily resulted in lower rates of bleeding compared with standard dosing of apixaban, with near-complete in-vivo FXIa inhibition, in patients with atrial fibrillation. FUNDING Bayer.

Published
2022

9. Efficacy and Safety of Glycoprotein IIb/IIIa Inhibitors on Top of Ticagrelor in STEMI: A Subanalysis of the ATLANTIC Trial

Author

Robert F. Storey, Angel Cequier, Shaun G. Goodman, Uwe Zeymer, Atlantic Investigators, Jean P. Collet, Anne H. Tavenier, Eric Vicaut, Abdourahmane Diallo, Jurriën M. ten Berg, Renicus S Hermanides, Enrico Fabris, Frank F. Willems, Arnoud W J van 't Hof, Jens Flensted Lassen, Patrick Ecollan, Béla Merkely, Christian W. Hamm, Mohamed Chettibi, Christopher J. Hammett, Warren J. Cantor, Magnus Janzon, Leonardo Bolognese, Johanne Silvain, Kurt Huber, Frédéric Lapostolle, Gilles Montalescot, University of Trieste, SAMU 93 [Bobigny], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), St. Antonius Hospital [Nieuwegein], University of Toronto, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Linköpings universitet, Semmelweis University of Medicine [Budapest], University of Sheffield [Sheffield], Hôpital Lariboisière-Fernand-Widal [APHP], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Tavenier, A. H., Hermanides, R. S., Fabris, E., Lapostolle, F., Silvain, J., Ten Berg, J. M., Lassen, J. F., Bolognese, L., Cantor, W. J., Cequier, A., Chettibi, M., Goodman, S. G., Hammett, C. J., Huber, K., Janzon, M., Merkely, B., Storey, R. F., Zeymer, U., Ecollan, P., Collet, J. -P., Willems, F. F., Diallo, A., Vicaut, E., Hamm, C. W., Montalescot, G., Van 'T Hof, A. W. J., Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), and RS: Carim - H01 Clinical atrial fibrillation

Subjects
0301 basic medicine, Male, st-segment elevation, tirofiban, medicine.medical_treatment, [SDV]Life Sciences [q-bio], high-dose tirofiban, PRIMARY ANGIOPLASTY, 030204 cardiovascular system & hematology, glycoprotein IIb/IIIa inhibitors, 0302 clinical medicine, Postoperative Complications, Myocardial infarction, iiia inhibitors, eptifibatide, Hematology, Middle Aged, Clopidogrel, primary percutaneous coronary intervention, 3. Good health, Treatment Outcome, Cardiology, Drug Therapy, Combination, Female, lipids (amino acids, peptides, and proteins), Ticagrelor, medicine.drug, medicine.medical_specialty, ACUTE MYOCARDIAL-INFARCTION, glycoprotein IIb/IIIa inhibitor, PERCUTANEOUS CORONARY INTERVENTION, Hemorrhage, Platelet Glycoprotein GPIIb-IIIa Complex, Revascularization, ticagrelor, STEMI, 03 medical and health sciences, abciximab, bailout, Double-Blind Method, IIB-IIIA INHIBITORS, Internal medicine, STENT THROMBOSIS, medicine, PREHOSPITAL INITIATION, Humans, cardiovascular diseases, Aged, INDIVIDUAL PATIENTS DATA, business.industry, Percutaneous coronary intervention, Thrombosis, Odds ratio, medicine.disease, Survival Analysis, platelet inhibition, 030104 developmental biology, Glycoprotein IIb/IIIa inhibitors, Conventional PCI, ST Elevation Myocardial Infarction, glycoprotein IIb, business, Platelet Aggregation Inhibitors
Abstract

Background Glycoprotein IIb/IIIa inhibitors (GPIs) in combination with clopidogrel improve clinical outcome in ST-elevation myocardial infarction (STEMI); however, finding a balance that minimizes both thrombotic and bleeding risk remains fundamental. The efficacy and safety of GPI in addition to ticagrelor, a more potent P2Y12-inhibitor, have not been fully investigated. Methods 1,630 STEMI patients who underwent primary percutaneous coronary intervention (PCI) were analyzed in this subanalysis of the ATLANTIC trial. Patients were divided in three groups: no GPI, GPI administration routinely before primary PCI, and GPI administration in bailout situations. The primary efficacy outcome was a composite of death, myocardial infarction, urgent target revascularization, and definite stent thrombosis at 30 days. The safety outcome was non-coronary artery bypass graft (CABG)-related PLATO major bleeding at 30 days. Results Compared with no GPI (n = 930), routine GPI (n = 525) or bailout GPI (n = 175) was not associated with an improved primary efficacy outcome (4.2% no GPI vs. 4.0% routine GPI vs. 6.9% bailout GPI; p = 0.58). After multivariate analysis, the use of GPI in bailout situations was associated with a higher incidence of non-CABG-related bleeding compared with no GPI (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.32–6.64; p = 0.03). However, routine GPI use compared with no GPI was not associated with a significant increase in bleeding (OR 1.78, 95% CI 0.88–3.61; p = 0.92). Conclusion Use of GPIs in addition to ticagrelor in STEMI patients was not associated with an improvement in 30-day ischemic outcome. A significant increase in 30-day non-CABG-related PLATO major bleeding was seen in patients who received GPIs in a bailout situation.

Published
2020
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10. Antisense oligonucleotide eluforsen improves CFTR function in F508del cystic fibrosis

Author

Kris De Boeck, J. Stuart Elborn, George M. Solomon, Wilhelmina den Hollander, Noreen Henig, Jerry A. Nick, Nicolas Paquette-Lamontagne, Steven M. Rowe, Florilene Bouisset, David P. Nichols, Marcus A. Mall, John P. Clancy, Nigel Tomkinson, Isabelle Sermet-Gaudelus, and James Bolognese

Subjects
Male, 0301 basic medicine, Epithelial sodium channel, Cystic Fibrosis, Respiratory System, Oligonucleotides, Cystic Fibrosis Transmembrane Conductance Regulator, Pharmacology, Compound heterozygosity, Cystic fibrosis, Basal (phylogenetics), 0302 clinical medicine, Pulmonary Medicine, Medicine, Regulator delta F508, education.field_of_study, biology, Nasal Potential Difference, Middle Aged, Clinical Trial, Cystic fibrosis transmembrane conductance regulator, TRANSMEMBRANE CONDUCTANCE REGULATOR, Female, Life Sciences & Biomedicine, Adult, Pulmonary and Respiratory Medicine, Adolescent, Sodium, Population, chemistry.chemical_element, Article, NASAL POTENTIAL DIFFERENCE, Young Adult, 03 medical and health sciences, Antisense Oligonucleotide, Humans, education, Science & Technology, business.industry, Oligonucleotides, Antisense, Cystic Fibrosis Transmembrane Conductance, medicine.disease, GENE, 030104 developmental biology, 030228 respiratory system, chemistry, Mutation, Pediatrics, Perinatology and Child Health, biology.protein, Nasal administration, business
Abstract

BACKGROUND: Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. In this study we assessed the effect of antisense oligonucleotide eluforsen on CFTR biological activity measured by Nasal Potential Difference (NPD) in patients with the most common mutation, F508del-CFTR. METHODS: This multi-centre, exploratory, open-label study recruited adults with CF homozygous or compound heterozygous for the F508del-CFTR mutation. Subjects received intranasal eluforsen three times weekly for 4 weeks. The primary endpoint was the within-subject change from baseline in total chloride transport (Cl-free+iso), as assessed by NPD. Secondary endpoints included within-subject change from baseline in sodium transport. RESULTS: In the homozygous cohort (n = 7; per-protocol population), mean change (90% confidence interval) in Cl-free+iso was -3.0 mV (-6.6; 0.6) at day 15, -4.1 mV (-7.8; -0.4, p = .04) at day 26 (end of treatment) and - 3.7 mV (-8.0; 0.6) at day 47. This was supported by improved sodium transport as assessed by an increase in average basal potential difference at day 26 of +9.4 mV (1.1; 17.7, p = .04). The compound heterozygous cohort (n = 7) did not show improved chloride or sodium transport NPD values. Eluforsen was well tolerated with a favourable safety profile. CONCLUSIONS: In F508del-CFTR homozygous subjects, repeated intranasal administration of eluforsen improved CFTR activity as measured by NPD, an encouraging indicator of biological activity. ispartof: Journal Of Cystic Fibrosis vol:18 issue:4 pages:536-542 ispartof: location:Netherlands status: published

Published
2019
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11. Trends in management and outcome of patients with non-ST elevation acute coronary syndromes and peripheral arterial disease

Author

Leonardo De Luca, Andrea Di Lenarda, Gianni Casella, Michele Massimo Gulizia, Leonardo Bolognese, Giuseppe Di Pasquale, Zoran Olivari, Alessandro Boccanelli, Lucio Gonzini, Stefano De Servi, Stefano Savonitto, Antonio Di Chiara, and Francesco Chiarella

Subjects
Male, Change over time, medicine.medical_specialty, Arterial disease, 030204 cardiovascular system & hematology, Coronary Angiography, Risk Assessment, Electrocardiography, Peripheral Arterial Disease, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, Risk Factors, Internal medicine, Epidemiology, Internal Medicine, medicine, Humans, Hospital Mortality, Registries, 030212 general & internal medicine, Acute Coronary Syndrome, Aged, Aged, 80 and over, business.industry, ST elevation, Middle Aged, Peripheral, Italy, Baseline characteristics, Multivariate Analysis, Female, business
Abstract

Patients with non ST-segment elevation acute coronary syndromes (NSTE-ACS) and peripheral arterial disease (PAD) present a worse prognosis compared to those without PAD. We sought to describe contemporary trends of in-hospital management and outcome of patients admitted for NSTE-ACS with associated PAD.We analyzed data from 6 Italian nationwide registries, conducted between 2001 and 2014, including consecutive NSTE-ACS patients.Out of 15,867 patients with NSTE-ACS enrolled in the 6 registries, 2226 (14.0%) had a history of PAD. As compared to non-PAD patients, those with PAD had significantly more risk factors and comorbidities (all p 0.0001) that increased over time. Patients with PAD underwent less frequently coronary angiography (72.0% vs 79.2%, p 0.0001) and percutaneous coronary intervention (PCI, 42.9% vs 51.8%, p 0.0001), compared to patients without PAD. Over the years, a progressive and similar increase occurred in the rates of invasive procedures both in patients with and without PAD (both p for trend0.0001). The crude in-hospital mortality rate did not significantly change over time (p for trend = 0.83). However, as compared to 2001, the risk of death was significantly lower in all other studies performed at different times, after adjustment for multiple comorbidities.. At multivariable analysis, PAD on admission was an independent predictor of in-hospital mortality [odds ratio (OR): 1.75; 95% confidence intervals (CI): 1.35-2.27; p 0.0001].Over the 14 years of observation, patients with PAD and NSTE-ACS exhibited worsening baseline characteristics and a progressive increase in invasive procedures. Whereas crude in-hospital mortality did not change over time, we observed a significant reduction in comorbidity-adjusted mortality, as compared to 2001.

Published
2019
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12. Is percutaneous coronary intervention safe during uninterrupted direct oral anticoagulant therapy in patients with atrial fibrillation and acute coronary syndromes?

Author

Massimo Uguccioni, Leonardo De Luca, Ilaria Meynet, Silvia Maria Brach Prever, Leonardo Bolognese, Jeness Campodonico, Donata Lucci, Andrea Di Lenarda, Andrea Rubboli, Michele Massimo Gulizia, Domenico Gabrielli, Matador-Pci Investigators, and Simonetta Blengino

Subjects
Male, medicine.medical_specialty, Acute coronary syndrome, medicine.medical_treatment, Administration, Oral, 030204 cardiovascular system & hematology, Risk Assessment, acute coronary syndrome, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Internal medicine, Antithrombotic, Atrial Fibrillation, medicine, Diseases of the circulatory (Cardiovascular) system, Humans, 030212 general & internal medicine, cardiovascular diseases, Prospective Studies, Registries, Aged, business.industry, Incidence, percutaneous coronary intervention, Percutaneous coronary intervention, Stent, Anticoagulants, Atrial fibrillation, Drug-Eluting Stents, medicine.disease, Interventional Cardiology, Survival Rate, Italy, RC666-701, Concomitant, Conventional PCI, Cardiology, Female, epidemiology, Cardiology and Cardiovascular Medicine, business, Mace, Follow-Up Studies
Abstract

ObjectivesNo data on optimal management of patients with acute coronary syndromes (ACS) on long-term direct oral anticoagulants (DOACs) undergoing percutaneous coronary intervention (PCI) are available. Using the data of the Management of Antithrombotic TherApy in Patients with Chronic or DevelOping AtRial Fibrillation During Hospitalization for PCI study, we sought to compare the outcome of patients with ACS and atrial fibrillation (AF) who underwent PCI during uninterrupted DOAC (UDOAC group) and those who interrupted DOAC before PCI (IDOAC group).MethodsThe primary outcomes of our analysis were the incidence of major adverse cardiovascular events (MACEs), a composite of death, cerebrovascular events, recurrent myocardial infarction or revascularisation and net adverse clinical events (NACEs), including major bleeding, at 6 months.ResultsAmong the 132 patients on long-term DOAC, 72 (54.6%) underwent PCI during UDOAC and 60 (45.4%) after IDOAC. The mean CHA2DS2-VASc score was 3.8±1.7 and 3.9±1.3 (p=0.89), while the HAS-BLED score was 2.5±1.0 and 2.5±0.9 (p=0.96), in UDOAC and IDOAC groups, respectively. The median time from hospital admission to PCI was 9.5 (IQR: 2.0–31.5) hours in UDOAC and 45.5 (IQR: 22-5–92.0) hours in IDOAC group (p2DS2-VASc score (HR: 1.39; 95% CIs 1.05 to 1.83; p=0.02) resulted as the only independent predictor of NACE.ConclusionsOur study shows that PCI is a safe procedure during UDOAC in patients with concomitant ACS and AF.

Published
2021

13. FGF10 and FGF13 genetic variation and tooth-size discrepancies

Author

Alexandre R. Vieira, Mônica Tirre de Souza Araújo, Arthur S. Cunha, Suyany Gabriely Weiss, Rafaela Scariot, Luiza Vertuan dos Santos, Guido Artemio Marañón-Vásquez, Ana Maria Bolognese, Erika Calvano Küchler, and Maria Bernadete Sasso Stuani

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Buccal swab, Orthodontics, Single-nucleotide polymorphism, Mandible, Gastroenterology, symbols.namesake, Young Adult, stomatognathic system, Polymorphism (computer science), Internal medicine, Genotype, medicine, Humans, Odontometry, Allele, Child, Fisher's exact test, Permanent teeth, Mouth Mucosa, Genetic Variation, Odds ratio, Original Articles, Fibroblast Growth Factors, stomatognathic diseases, symbols, Female, Fibroblast Growth Factor 10, Tooth
Abstract

ObjectivesTo explore whether variations in odontogenesis-related genes are associated with tooth-size discrepancies.Materials and MethodsMeasurements of the width of permanent teeth were obtained from dental casts of 62 orthodontic patients (age 15.65 ± 6.82 years; 29 males and 33 females). Participants were classified according to the anterior and overall Bolton ratios as without tooth-size discrepancy or with maxillary or mandibular tooth-size excess. Genomic DNA extracted from buccal cells was used, and 13 single nucleotide polymorphisms (SNPs) across nine genes were genotyped by polymerase chain reaction using TaqMan chemistry. χ2 or Fisher exact tests were applied to determine the overrepresentation of genotypes/alleles depending on the type of tooth-size discrepancy (α = .05; corrected P value: P < 5.556 × 10−3). Odds ratios (ORs) and their correspondent 95% confidence intervals (CIs) were also calculated to investigate the risk of this phenotype for the SNPs having significant association.ResultsIndividuals carrying the FGF10 rs900379 T allele were more likely to have larger mandibular teeth (OR = 3.74; 95% CI: 1.65–8.47; P = .002). This effect appeared to be stronger when two copies of the risk allele (TT) were found (recessive model, OR = 6.16; 95% CI: 1.71–22.16; P = .006). On the other hand, FGF13 rs5931572 rare homozygotes (AA, or male A hemizygotes) had increased risk of displaying tooth-size discrepancies when compared with the common homozygotes (GG, or male G hemizygotes; OR = 10.32; 95% CI: 2.20–48.26; P = .003).ConclusionsThe results suggest that FGF10 and FGF13 may contribute to the presence of tooth-size discrepancies.

Published
2021

14. Clinical impact and predictors of complete ST segment resolution after primary percutaneous coronary intervention: A subanalysis of the ATLANTIC Trial

Author

Warren J. Cantor, Shaun G. Goodman, Mathieu Kerneis, Frédéric Lapostolle, Jens Flensted Lassen, Gilles Montalescot, Enrico Fabris, Anne Tsatsaris, Robert F. Storey, Leonardo Bolognese, Jurriën M. ten Berg, Uwe Zeymer, Christopher J. Hammett, Béla Merkely, Kurt Huber, Christian W. Hamm, Mohamed Chettibi, Eric Vicaut, Angel Cequier, Abdourahmane Diallo, Magnus Janzon, Arnoud W J van 't Hof, Fabris, Enrico, van 't Hof, Arnoud, Hamm, Christian W, Lapostolle, Frédéric, Lassen, Jens F, Goodman, Shaun G, Ten Berg, Jurriën M, Bolognese, Leonardo, Cequier, Angel, Chettibi, Mohamed, Hammett, Christopher J, Huber, Kurt, Janzon, Magnu, Merkely, Béla, Storey, Robert F, Zeymer, Uwe, Cantor, Warren J, Tsatsaris, Anne, Kerneis, Mathieu, Diallo, Abdourahmane, Vicaut, Eric, Montalescot, Gilles, Cardiologie, RS: CARIM - R2.01 - Clinical atrial fibrillation, MUMC+: MA Med Staf Spec Cardiologie (9), and RS: Carim - H01 Clinical atrial fibrillation

Subjects
Male, prehospital ticagrelor, Ticagrelor, REPERFUSION THERAPY, st segment resolution, medicine.medical_treatment, PREHOSPITAL TICAGRELOR, PRIMARY ANGIOPLASTY, 030204 cardiovascular system & hematology, Coronary Angiography, Critical Care and Intensive Care Medicine, DOUBLE-BLIND, Electrocardiography, 0302 clinical medicine, TO-BALLOON TIME, ST segment, 030212 general & internal medicine, vasodilation, Coronary Vessel, Aspirin, medicine.diagnostic_test, General Medicine, Middle Aged, Coronary Vessels, reperfusion, ST-elevation myocardial infarction, Treatment Outcome, medicine.anatomical_structure, Combination, DELAY, Cardiology, Platelet aggregation inhibitor, Drug Therapy, Combination, Female, Cardiology and Cardiovascular Medicine, ST segment resolution, Human, medicine.drug, medicine.medical_specialty, st-elevation myocardial infarction, delay, ticagrelor, Aged, Coronary Circulation, Double-Blind Method, Humans, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, ST Elevation Myocardial Infarction, Time-to-Treatment, 03 medical and health sciences, Coronary circulation, Reperfusion therapy, Drug Therapy, Internal medicine, medicine, business.industry, MORTALITY, Platelet Aggregation Inhibitor, ELEVATION MYOCARDIAL-INFARCTION, Percutaneous coronary intervention, DIABETES-MELLITUS, business, VASODILATION
Abstract

Background: In the ATLANTIC (Administration of Ticagrelor in the catheterization laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery) trial the early use of aspirin, anticoagulation, and ticagrelor coupled with very short medical contact-to-balloon times represent good indicators of optimal treatment of ST-elevation myocardial infarction and an ideal setting to explore which factors may influence coronary reperfusion beyond a well-established pre-hospital system. Methods: This study sought to evaluate predictors of complete ST-segment resolution after percutaneous coronary intervention in ST-elevation myocardial infarction patients enrolled in the ATLANTIC trial. ST-segment analysis was performed on electrocardiograms recorded at the time of inclusion (pre-hospital electrocardiogram), and one hour after percutaneous coronary intervention (post-percutaneous coronary intervention electrocardiogram) by an independent core laboratory. Complete ST-segment resolution was defined as ≥70% ST-segment resolution. Results: Complete ST-segment resolution occurred post-percutaneous coronary intervention in 54.9% ( n=800/1456) of patients and predicted lower 30-day composite major adverse cardiovascular and cerebrovascular events (odds ratio 0.35, 95% confidence interval 0.19–0.65; pConclusions: This study confirmed that post-percutaneous coronary intervention complete ST-segment resolution is a valid surrogate marker for cardiovascular clinical outcomes. In the current era of ST-elevation myocardial infarction reperfusion, patients’ delay and diabetes mellitus are independent predictors of poor reperfusion and need specific attention in the future.

Published
2017
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15. Pre-hospital administration of ticagrelor in diabetic patients with ST-elevation myocardial infarction undergoing primary angioplasty: A sub-analysis of the ATLANTIC trial

Author

Shaun G. Goodman, Magnus Janzon, Robert F. Storey, Jurriën M. ten Berg, Christopher J. Hammett, Jens Flensted Lassen, Arnoud W J van 't Hof, Mathieu Kerneis, Christian W. Hamm, Béla Merkely, Warren J. Cantor, Abdourahmane Diallo, Leonardo Bolognese, Kurt Huber, Mohamed Chettibi, Eric Vicaut, Uwe Zeymer, Frédéric Lapostolle, Angel Cequier, Enrico Fabris, Gilles Montalescot, RS: Carim - H01 Clinical atrial fibrillation, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: CARIM - R2.01 - Clinical atrial fibrillation, Fabris, E., van't Hof, A., Hamm, C. W., Lapostolle, F., Lassen, J. F., Goodman, S. G., ten Berg, J. M., Bolognese, L., Cequier, A., Chettibi, M., Hammett, C. J., Huber, K., Janzon, M., Merkely, B., Storey, R. F., Zeymer, U., Cantor, W. J., Kerneis, M., Diallo, A., Vicaut, E., and Montalescot, G.

Subjects
Male, Time Factors, antithrombotic drug, medicine.medical_treatment, 030204 cardiovascular system & hematology, MELLITUS, 0302 clinical medicine, Risk Factors, Antithrombotic, 030212 general & internal medicine, Myocardial infarction, Prospective Studies, education.field_of_study, OUTCOMES, diabetes mellitu, General Medicine, Thrombolysis, Middle Aged, Treatment Outcome, CLOPIDOGREL, diabetes mellitus, Cardiology, PLATELET INHIBITION, Female, Cardiology and Cardiovascular Medicine, Ticagrelor, medicine.drug, medicine.medical_specialty, Population, Revascularization, Risk Assessment, Drug Administration Schedule, ticagrelor, STEMI, 03 medical and health sciences, Percutaneous Coronary Intervention, Double-Blind Method, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, education, Aged, business.industry, ACUTE CORONARY SYNDROMES, Percutaneous coronary intervention, medicine.disease, REACTIVITY, Conventional PCI, ST Elevation Myocardial Infarction, business, Platelet Aggregation Inhibitors
Abstract

Objective: We investigated, in the contemporary era of ST-elevation myocardial infarction (STEMI) treatment, the influence of diabetes mellitus (DM) on cardiovascular outcomes, and whether pre-hospital administration of ticagrelor may affect these outcomes in a subgroup of STEMI patients with DM. Background: DM patients have high platelet reactivity and a prothrombotic condition which highlight the importance of an effective antithrombotic regimen in this high-risk population. Methods: In toal 1,630 STEMI patients enrolled in the ATLANTIC trial who underwent primary percutaneous coronary intervention (PCI) were included. Multivariate analysis was used to explore the association of DM with outcomes and potential treatment-by-diabetes interaction was tested. Results: A total of 214/1,630 (13.1%) patients had DM. DM was an independent predictor of poor myocardial reperfusion as reflected by less frequent ST-segment elevation resolution (≥70%) after PCI (OR 0.59, 95% CI 0.43–0.82, P < 0.01) and was an independent predictor of the composite 30-day outcomes of death/new myocardial infarction (MI)/urgent revascularization/definite stent thrombosis (ST) (OR 2.80, 95% CI 1.62–4.85, P < 0.01), new MI or definite acute ST (OR 2.46, 95% CI 1.08–5.61, P = 0.03), and definite ST (OR 10.00, 95% CI 3.54–28.22, P < 0.01). No significant interaction between pre-hospital ticagrelor vs in-hospital ticagrelor administration and DM was present for the clinical, electrocardiographic and angiographic outcomes as well as for thrombolysis in myocardial infarction major bleeding. Conclusions: DM remains independently associated with poor myocardial reperfusion and worse 30-day clinical outcomes. No significant interaction was found between pre-hospital vs in-hospital ticagrelor administration and DM status. Further approaches for the treatment of DM patients are needed. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01347580.

Published
2019
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16. Time Course of Ischemic and Bleeding Burden in Elderly Patients With Acute Coronary Syndromes Randomized to Low‐Dose Prasugrel or Clopidogrel

Author

Alessandro Mandurino Mirizzi, Michele Cacucci, Luigi Piatti, Giuseppe De Luca, Nuccia Morici, Gabriele Crimi, Federico Piscione, Luigi Raffaele Elia, Luca A. Ferri, Daniele Grosseto, Stefano De Servi, Marco De Carlo, Leonardo Bolognese, Bruno Trimarco, Maurizio Ferrario, Stefano Savonitto, Francesco Bovenzi, Anna Toso, Crimi, Gabriele, Morici, Nuccia, Ferrario, Maurizio, Ferri, Luca A., Piatti, Luigi, Grosseto, Daniele, Cacucci, Michele, Mirizzi, Alessandro Mandurino, Toso, Anna, Piscione, Federico, De Carlo, Marco, Elia, Luigi Raffaele, Trimarco, Bruno, Bolognese, Leonardo, Bovenzi, Francesco M., De Luca, Giuseppe, Savonitto, Stefano, and De Servi, Stefano

Subjects
Male, Aging, Antiplatelet drug, Prasugrel, Time Factors, P2Y12, medicine.medical_treatment, Myocardial Infarction, 030204 cardiovascular system & hematology, 0302 clinical medicine, Catheter-Based Coronary and Valvular Interventions, Stent, Single-Blind Method, 030212 general & internal medicine, Original Research, Incidence, Low dose, Congenital Heart Disease, Clopidogrel, Prognosis, Survival Rate, Editorial, Italy, Cardiology, Female, Cardiology and Cardiovascular Medicine, medicine.drug, medicine.medical_specialty, Acute coronary syndrome, Ticlopidine, Hemorrhage, elderly, acute coronary syndrome, 03 medical and health sciences, Percutaneous Coronary Intervention, Internal medicine, medicine, Humans, antiplatelet drug, Retrospective Studies, Aged, Pharmacology, Dose-Response Relationship, Drug, business.industry, Editorials, medicine.disease, prasugrel, Treatment, Time course, Purinergic P2Y Receptor Antagonists, business, Prasugrel Hydrochloride, Platelet Aggregation Inhibitors, Follow-Up Studies
Abstract

Background Elderly patients have high ischemic and bleeding rates after acute coronary syndrome; however, the occurrence of these complications over time has never been studied. This study sought to characterize average daily ischemic rates (ADIRs) and average daily bleeding rates (ADBRs) over 1 year in patients aged >74 years with acute coronary syndrome undergoing percutaneous coronary intervention who were randomized in the Elderly ACS 2 trial, comparing low‐dose prasugrel (5 mg daily) with clopidogrel (75 mg daily). Methods and Results ADIRs and ADBRs were calculated as the total number of events, including recurrent events, divided by the number of patient‐days of follow‐up and assessed within different clinical phases: acute (0–3 days), subacute (4–30 days), and late (31–365 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparisons of ADIRs and ADBRs and the pairwise comparison of clopidogrel versus prasugrel effects. Globally, ADIRs were 2.6 times (95% CI, 2.4–2.9) higher than ADBRs. ADIRs were significantly higher in the clopidogrel arm than in the low‐dose prasugrel arm in the subacute phase (P adj, See Editorial by Kinnaird

Published
2019

17. Ticagrelor Alone Versus Dual Antiplatelet Therapy From 1 Month After Drug-Eluting Coronary Stenting

Author

Christian W. Hamm, Peter Jüni, Leonardo Bolognese, Luc Janssens, Scot Garg, Ton Slagboom, Ivo Petrov, Edouard Benit, Janusz Prokopczuk, Patrick W. Serruys, Maurizio Ferrario, Glassy Investigators, Marco Valgimigli, Pascal Vranckx, Dik Heg, Adel Aminian, Christoph Naber, Roberto Diletti, Christoph Liebetrau, Carlo Tumscitz, Eugene P. McFadden, Stephan Windecker, Krzysztof Bryniarski, Anna Franzone, Aleksander Zurakowski, Kurt Huber, Sergio Leonardi, Raffaele Piccolo, Paweł Buszman, Marcello Dominici, Philippe Gabriel Steg, Mathias Vrolix, Cardiology, Franzone, A., Mcfadden, E., Leonardi, S., Piccolo, R., Vranckx, P., Serruys, P. W., Benit, E., Liebetrau, C., Janssens, L., Ferrario, M., Zurakowski, A., Diletti, R., Dominici, M., Huber, K., Slagboom, T., Buszman, P., Bolognese, L., Tumscitz, C., Bryniarski, K., Aminian, A., Vrolix, M., Petrov, I., Garg, S., Naber, C., Prokopczuk, J., Hamm, C., Steg, P. G., Heg, D., Juni, P., Windecker, S., and Valgimigli, M.

Subjects
Male, Ticagrelor, medicine.medical_specialty, medicine.medical_treatment, Coronary Artery Disease, 030204 cardiovascular system & hematology, Rate ratio, Drug Administration Schedule, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, Internal medicine, Statistical significance, medicine, Clinical endpoint, Humans, Prospective Studies, 030212 general & internal medicine, Myocardial infarction, 610 Medicine & health, Aged, Aspirin, business.industry, Dual Anti-Platelet Therapy, adjudication, Percutaneous coronary intervention, Drug-Eluting Stents, Middle Aged, medicine.disease, dual antiplatelet therapy, Confidence interval, Survival Rate, Treatment Outcome, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, Follow-Up Studies, medicine.drug
Abstract

Background: The GLOBAL LEADERS (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation) study randomly assigned 15,991 patients undergoing percutaneous coronary intervention to 1-month dual antiplatelet therapy (DAPT) followed by 23-month ticagrelor monotherapy or conventional 12-month DAPT followed by 12-month aspirin. Apart from Q-wave myocardial infarction (MI), all study endpoints were analyzed as investigator reported. Objectives: This was a pre-specified ancillary study assessing whether experimental therapy is noninferior, and if met, superior, to conventional treatment for the coprimary efficacy endpoint of all-cause death, nonfatal MI, nonfatal stroke, or urgent target vessel revascularization and superior in preventing BARC 3 (Bleeding Academic Research Consortium) or 5 bleeding (coprimary safety endpoint) at 2 years with a 0.025 significance level to preserve nominal 5% alpha error. Methods: An independent clinical event committee adjudicated investigator-reported and eventually unreported events of 7,585 patients from the 20 top-enrolling participating sites. Results: The 2-year coprimary efficacy endpoint occurred in 271 (7.14%) and in 319 (8.41%) patients in the experimental and conventional groups, respectively (rate ratio [RR]: 0.85; 95% confidence interval [CI]: 0.72 to 0.99), fulfilling noninferiority (p noninferiority

Published
2019

18. Group Nutrition Counseling or Individualized Prescription for Women With Obesity? A Clinical Trial

Author

Marciele Alves Bolognese, Carina Bertoldi Franco, Ariana Ferrari, Rose Mari Bennemann, Solange Munhoz Arroyo Lopes, Sônia Maria Marques Gomes Bertolini, Nelson Nardo Júnior, and Braulio Henrique Magnani Branco

Subjects
Adult, Counseling, medicine.medical_specialty, obesity, health promotion, Physical exercise, Overweight, Body fat percentage, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, business.industry, 030503 health policy & services, lcsh:Public aspects of medicine, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Middle Aged, Anthropometry, medicine.disease, women's health, Clinical Trial, Obesity, Prescriptions, multiprofessional research, Quality of Life, Lean body mass, Physical therapy, Female, Public Health, medicine.symptom, 0305 other medical science, business, Body mass index, Nutrition counseling, mental health
Abstract

Background: This study investigates the effects of group counseling vs. individual dietary prescription on physical, nutritional, and mental health in overweight or obese women.Methods: Seventy-four women aged 40–59 years with body mass index ≥ 25 kg/m2 were randomized into 2 intervention arms: group nutrition counseling (GNC) or individualized nutrition prescription (INP). Twenty-seven women completed the 12-week intervention protocol. The GNC received counseling once a week and the INP received an individualized prescription once a month. All participants attended physical exercise sessions 3 times a week following the same protocol. Body mass, body mass index, fat mass, body fat percentage, lean mass, lipid profile, hemoglobin A1c, insulin and liver transaminases were measured pre- and post-intervention in both arms. A 3 day food record was applied to calculate the intake of calories, carbohydrates, proteins, and lipids. Body image dissatisfaction, level of anxiety, self-esteem measure and pathological eating attitudes were measured.Results: Both dietary interventions decreased body mass, body mass index, fat mass, body fat percentage, total caloric intake, carbohydrates, proteins, lipids, body dissatisfaction, anxiety, and saturated and polyunsaturated fats (p < 0.05). Lean mass, metabolic variables, self-esteem and pathological eating attitudes remained unchanged (p > 0.05).Conclusion: Both nutritional interventions combined with concurrent exercise were effective to improve anthropometrics, body composition, food intake, and some mental health parameters. We suggest that the choice of nutritional intervention (GNC or INP) could be based on the participants preference, considering the adherence and satisfaction, to promote health and quality of life.

Published
2020
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19. Impact of preprocedural TIMI flow on clinical outcome in low-risk patients with ST-elevation myocardial infarction: Results from the ATLANTIC study

Author

Kurt Huber, Leonardo Bolognese, Timm Bauer, Angel Cequier, Christian W. Hamm, Abdourahmane Diallo, Arnoud W van 't Hof, Eric Vicaut, Uwe Zeymer, Atlantic Investigators, Gilles Montalescot, RS: Carim - H01 Clinical atrial fibrillation, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Maastricht University Medical Centre (MUMC), and Maastricht University [Maastricht]

Subjects
Male, Ticagrelor, prehospital ticagrelor, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], PRIMARY ANGIOPLASTY, 030204 cardiovascular system & hematology, 0302 clinical medicine, Risk Factors, Cause of Death, 030212 general & internal medicine, Myocardial infarction, Randomized Controlled Trials as Topic, stent thrombosis, artery patency, General Medicine, Thrombolysis, Middle Aged, reperfusion, stemi, Europe, surgical procedures, operative, Treatment Outcome, Cardiology, Female, Cardiology and Cardiovascular Medicine, TIMI, medicine.drug, medicine.medical_specialty, pci, Risk Assessment, Drug Administration Schedule, 03 medical and health sciences, Internal medicine, Coronary Circulation, medicine, Humans, Radiology, Nuclear Medicine and imaging, cardiovascular diseases, Aged, Retrospective Studies, business.industry, Coronary Thrombosis, percutaneous coronary intervention, Percutaneous coronary intervention, Odds ratio, medicine.disease, Confidence interval, TIMI flow grade, Conventional PCI, ST Elevation Myocardial Infarction, business, Platelet Aggregation Inhibitors
Abstract

International audience; Objectives: This study sought to analyze the impact of the preprocedural thrombolysis in myocardial infarction (TIMI) flow on clinical outcome in patients with ST-elevation myocardial infarction (STEMI).Background: Previous studies have shown that the TIMI flow 0/1 prior to primary percutaneous coronary intervention (PCI) is associated with a poor clinical outcome. However, it is unclear whether the same is true in patients with ongoing STEMI of less than 6 hr duration, rapid reperfusion, and modern guideline-adherent therapy.Methods: The ATLANTIC study compared prehospital versus inhospital treatment with ticagrelor in patients with acute STEMI. For this analysis, patients were divided into three groups according to the preprocedural TIMI flow grade of the infarct vessel: TIMI 0/1, TIMI 2, and TIMI 3.Results: From a total of 1,680 patients, 1,113 had TIMI 0/1, 279 TIMI 2, and 288 TIMI 3 flow before primary PCI. At 30 days, the composite ischemic endpoint (5.5, 2.9, and 2.1%, p < .05) and all-cause death (3.0, 1.4, and 2.1%, p = .30) were highest in patients with TIMI flow 0/1. After adjustment, preprocedural TIMI flow

Published
2020
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20. Professional Profiles, Technical Preferences, Surgical Opinions, and Management of Clinical Scenarios from a Panel of 63 International Experts in the Field of Chiari I Malformation

Author

Paolo A. Bolognese, Alexander B. Bloom, Roger W. Kula, and Andrew Brodbelt

Subjects
Male, medicine.medical_specialty, Internationality, business.industry, Disease Management, Preference, Arnold-Chiari Malformation, 03 medical and health sciences, 0302 clinical medicine, Neurosurgeons, Chiari I malformation, 030220 oncology & carcinogenesis, Surveys and Questionnaires, Medicine, Humans, Surgery, Medical physics, Complication rate, Female, Neurology (clinical), business, Expert Testimony, 030217 neurology & neurosurgery
Abstract

Background Chiari I Malformation (CMI) and the topics concerning it have been the subject of numerous discussions and polarizing controversies over the course of the past 20 years. Methods The opinions of 63 recognized international Neurosurgical CMI experts from 4 continents, with a collective surgical experience of more than 15,000 CMI cases, were gathered through a detailed questionnaire, divided in two parts: diagnostic and therapeutic. The therapeutic part was organized into four sections: Professional Profile, Technical Preferences, Surgical Opinions, and Clinical Scenarios. Results The data reflected a wide spectrum of opinions, approaches, and expertise. The second part of the questionnaire dealt with the surgical aspects of CMI care and painted a more complex picture: • 81% of the surgeons preferred the Intradural technique. • 88% of the experts agreed that CMI surgery is not indicated for minimal non-debilitating symptoms alone, or as prophylaxis. • In the face of given clinical scenarios, a wide spectrum of therapeutic approaches was chosen by the whole group, but the 4 Surgeons with the largest case series expressed the same opinion. • Eight out of 63 Surgeons had a surgical experience above 600 cases, were responsible for more than half of the total 15,000 declared CMI cases, and shared a similar profile in terms of technical surgical choices, therapeutic opinions, and low complication rate, with a marked preference for Intradural techniques and tonsillar manipulation. • Once large individual case series were accumulated, we did not see any differences in the opinions and preferences between Adult and Pediatric Neurosurgeons. Conclusion Surgeons who have focused on CMI have been able to accumulate large surgical series, have chosen in their practices the more aggressive (and intrinsically more effective) CMI surgical techniques, and have achieved a low complication rate which compares favorably with that one of the extradural techniques.

Published
2020

21. Deficiency of receptor-interacting protein kinase 3 (RIPK3) attenuates inflammation and organ injury in neonatal sepsis

Author

Gene F. Coppa, Asha Jacob, Jeffrey Nicastro, Jose M. Prince, Weng Lang Yang, Laura W. Hansen, Ping Wang, and Alexandra C. Bolognese

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Necroptosis, Inflammation, Lung injury, Systemic inflammation, Article, Sepsis, Mice, Random Allocation, 03 medical and health sciences, Internal medicine, medicine, Animals, Mice, Knockout, Lung, Neonatal sepsis, biology, business.industry, Lung Injury, General Medicine, medicine.disease, Intestines, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Receptor-Interacting Protein Serine-Threonine Kinases, Myeloperoxidase, Pediatrics, Perinatology and Child Health, Immunology, biology.protein, Female, Surgery, Neonatal Sepsis, medicine.symptom, business, Biomarkers
Abstract

Introduction Sepsis is the third leading cause of morbidity and mortality in neonates. Sepsis in neonates is characterized as the systemic inflammation owing to infection within the first 28days after birth. The molecular mechanism causing the exaggerated inflammation phenotype in neonates has not been completely elucidated. Receptor interacting protein kinase 3 (RIPK3) is a protein identified as a mediator in programmed necrosis or necroptosis. We hypothesize that RIPK3 could be responsible for the inflammatory response in neonates and that deficiency in the RIPK3 protein attenuates inflammation and organ injury in neonatal sepsis. Methods Male and female C57BL6 wild-type (WT) and RIPK3 knock-out (KO) newborn mice aged 5–7days (3–4g body weight) were injected intraperitoneally with 0.9mg/g cecal slurry (CS). At 10h after injection, the newborns were euthanized and blood, the lungs and gut tissues were collected. Results At 10h after CS injection, serum cytokines IL-6 and IL-1β in the WT mice were increased by 511- and 43-fold whereas in KO mice, these levels were increased by 166-fold and 22-fold, respectively. Lung IL-1β in the WT mice increased by 7-fold after CS injection whereas only a 4-fold increase was seen in the KO mice. In the lungs of CS injected KO mice, the injury score, MIP-2 mRNA, myeloperoxidase (MPO) activity and TUNEL staining were significantly reduced by 76%, 70%, 26% and 74%, respectively compared to the CS WT mice. Gut TUNEL staining was also reduced by 80%. Conclusion The deficiency in RIPK3 attenuated serum and lung cytokines, lung injury and neutrophil infiltration and lung and gut apoptosis. These data suggest that RIPK3, in part, is responsible for the systemic inflammatory response in neonatal sepsis.

Published
2018
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22. Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization

Author

Stefano Savonitto, Luca A. Ferri, Luigi Piatti, Daniele Grosseto, Giancarlo Piovaccari, Nuccia Morici, Irene Bossi, Paolo Sganzerla, Giovanni Tortorella, Michele Cacucci, Maurizio Ferrario, Ernesto Murena, Girolamo Sibilio, Stefano Tondi, Anna Toso, Sergio Bongioanni, Amelia Ravera, Elena Corrada, Matteo Mariani, Leonardo Di Ascenzo, A. Sonia Petronio, Claudio Cavallini, Giancarlo Vitrella, Renata Rogacka, Roberto Antonicelli, Bruno M. Cesana, Leonardo De Luca, Filippo Ottani, Giuseppe De Luca, Federico Piscione, Nadia Moffa, Stefano De Servi, Leonardo Bolognese, Francesco Bovenzi, Giuseppe Steffenino, Ignazio Santilli, Giorgio Bassanelli, Alice Sacco, Federico Canziani, Marco Ferri, Emilia Lo Jacono, Umberto Canosi, Giuseppe Fornaro, Mario Leoncini, Maria Rosa Conte, Rosario Farina, Catia Stefanin, Francesco Di Pede, Piersilvio Chella, M. Chiara Nardoni, Paola Tamburrini, Bruno Trimarco, Gennaro Galasso, Raffaele Elia, Simone Grotti, Lucia Borrelli, Corrado Tamburino, Piera Capranzano, Bruno Francaviglia, Carlo Campana, Roberto Bonatti, Alessandro Martinoni, Fabio Abate, Sebastian Coscarelli, Paolo Rubartelli, Giovanni Q. Villani, and Roberta Rossini

Subjects
Male, medicine.medical_specialty, Acute coronary syndrome, Prasugrel, medicine.medical_treatment, Myocardial Infarction, Hemorrhage, antiplatelet drugs, 030204 cardiovascular system & hematology, elderly, percutaneous coronary interventions, Disease-Free Survival, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine, Humans, acute coronary syndromes, 030212 general & internal medicine, Myocardial infarction, Acute Coronary Syndrome, Aged, Aged, 80 and over, Maintenance dose, business.industry, Hazard ratio, Percutaneous coronary intervention, Clopidogrel, medicine.disease, Survival Rate, Cardiology, Platelet aggregation inhibitor, Female, Cardiology and Cardiovascular Medicine, business, Prasugrel Hydrochloride, medicine.drug
Abstract

Background: Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome and display higher on-clopidogrel platelet reactivity compared with younger patients. Prasugrel 5 mg provides more predictable platelet inhibition compared with clopidogrel in the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding. Methods: In a multicenter, randomized, open-label, blinded end point trial, we compared a once-daily maintenance dose of prasugrel 5 mg with the standard clopidogrel 75 mg in patients >74 years of age with acute coronary syndrome undergoing percutaneous coronary intervention. The primary end point was the composite of mortality, myocardial infarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg. Results: Enrollment was interrupted, according to prespecified criteria, after a planned interim analysis, when 1443 patients (40% women; mean age, 80 years) had been enrolled with a median follow-up of 12 months, because of futility for efficacy. The primary end point occurred in 121 patients (17%) with prasugrel and 121 (16.6%) with clopidogrel (hazard ratio, 1.007; 95% confidence interval, 0.78–1.30; P =0.955). Definite/probable stent thrombosis rates were 0.7% with prasugrel versus 1.9% with clopidogrel (odds ratio, 0.36; 95% confidence interval, 0.13–1.00; P =0.06). Bleeding Academic Research Consortium types 2 and greater rates were 4.1% with prasugrel versus 2.7% with clopidogrel (odds ratio, 1.52; 95% confidence interval, 0.85–3.16; P =0.18). Conclusions: The present study in elderly patients with acute coronary syndromes showed no difference in the primary end point between reduced-dose prasugrel and standard-dose clopidogrel. However, the study should be interpreted in light of the premature termination of the trial. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01777503.

Published
2018
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23. Duration of ischemia and treatment effects of pre- versus in-hospital ticagrelor in patients with ST-segment elevation myocardial infarction

Author

Anne Tsatsaris, Christopher J. Hammett, Akshay Bagai, Angel Cequier, Jad El Khoury, Warren J. Cantor, Béla Merkely, Arnoud W. van't Hof, Leonardo Bolognese, Frédéric Lapostolle, Shaun G. Goodman, Uwe Zeymer, Jurriën M. ten Berg, Jens Flensted Lassen, Kurt Huber, Christian W. Hamm, Robert F. Storey, Gilles Montalescot, Mohamed Chettibi, Magnus Janzon, Eric Vicaut, Abdourahmane Diallo, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), and RS: CARIM - R2.01 - Clinical atrial fibrillation

Subjects
Male, Emergency Medical Services, Ticagrelor, Internationality, medicine.medical_treatment, PREHOSPITAL TICAGRELOR, Myocardial Ischemia, PRIMARY ANGIOPLASTY, 030204 cardiovascular system & hematology, Coronary Angiography, ST Elevation Myocardial Infarction/diagnostic imaging, law.invention, Electrocardiography, DOUBLE-BLIND, 0302 clinical medicine, Randomized controlled trial, law, ST segment, REPERFUSION, 030212 general & internal medicine, Myocardial infarction, PREDICTORS, Percutaneous Coronary Intervention/methods, Absolute risk reduction, Ticagrelor/administration & dosage, Middle Aged, Prognosis, TIME, Treatment Outcome, Cardiology, Disease Progression, Female, Stents, Cardiology and Cardiovascular Medicine, medicine.drug, Myocardial Ischemia/diagnostic imaging, medicine.medical_specialty, Electrocardiography/methods, PERCUTANEOUS CORONARY INTERVENTION, Risk Assessment, Time-to-Treatment, 03 medical and health sciences, Double-Blind Method, Internal medicine, Post-hoc analysis, STENT THROMBOSIS, medicine, Humans, Aged, Coronary Angiography/methods, business.industry, MORTALITY, Percutaneous coronary intervention, Emergency Medical Services/methods, medicine.disease, Survival Analysis, Surgery, SIZE, Conventional PCI, ST Elevation Myocardial Infarction, business
Abstract

BACKGROUND: Among patients with STEMI in the ATLANTIC study, pre-hospital administration of ticagrelor improved post-PCI ST-segment resolution and 30-day stent thrombosis. We investigated whether this clinical benefit with pre-hospital ticagrelor differs by ischemic duration.METHODS: In a post hoc analysis we compared absence of ST-segment resolution post-PCI and stent thrombosis at 30 days between randomized treatment groups (pre- versus in-hospital ticagrelor) stratified by symptom onset to first medical contact (FMC) duration [≤1 hour (n = 773), >1 to ≤3 hours (n = 772), and >3 hours (n = 311)], examining the interaction between randomized treatment strategy and duration of symptom onset to FMC for each outcome.RESULTS: Patients presenting later after symptom onset were older, more likely to be female, and have higher baseline risk. Patients with symptom onset to FMC >3 hours had the greatest improvement in post-PCI ST-segment elevation resolution with pre- versus in-hospital ticagrelor (absolute risk difference: ≤1 hour, 2.9% vs. >1 to ≤3 hours, 3.6% vs. >3 hours, 12.2%; adjusted p for interaction = 0.13), while patients with shorter duration of ischemia had greater improvement in stent thrombosis at 30 days with pre- versus in-hospital ticagrelor (absolute risk difference: ≤1 hour, 1.3% vs. >1 hour to ≤3 hours, 0.7% vs. >3 hours, 0.4%; adjusted p for interaction = 0.55). Symptom onset to active ticagrelor administration was independently associated with stent thrombosis at 30 days (adjusted OR 1.89 per 100 minute delay, 95%CI 1.20-2.97, P < .01), but not post-PCI ST-segment resolution (P = .41).CONCLUSIONS: The effect of pre-hospital ticagrelor to reduce stent thrombosis was most evident when given early within 3 hours after symptom onset, with delay in ticagrelor administration after symptom onset associated with higher rate of stent thrombosis. These findings re-emphasize the need for early ticagrelor administration in primary PCI treated STEMI patients.

Published
2018
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24. Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome : a Randomized Clinical Trial

Author

Cavalcanti, A. B., Suzumura, E. A., Laranjeira, L. N., De Moraes Paisani, D., Damiani, L. P., Guimaraes, H. P., Romano, E. R., De Moraes Regenga, M., Taniguchi, L. N. T., Teixeira, C., De Oliveira, R. P., Machado, F. R., Diaz-Quijano, F. A., De Alencar Filho, M. S., Maia, I. S., Caser, E. B., De Oliveira Filho, W., De Carvalho Borges, M., De Aquino Martins, P., Matsui, M., Ospina-Tascon, G. A., Giancursi, T. S., Giraldo-Ramirez, N. D., Vieira, S. R. R., De Lima Assef, M. D. G. P., Hasan, M. S., Szczeklik, W., Rios, F., Amato, M. B. P., Berwanger, O., De Carvalho, C. R. R., Tucci, M. R., Souza Dos Santos, L., Franca de Oliveira, M. C., Peres, I., Freitas, I., Reis, H., Verissimo, A., Torres, D., Barroso, A., Semboloni Bitencourt, W., Franco, M. R., Oliveira Lage, J., Aparecida Pessoa Conde, K., Charro, F. A., Naia, A., de Brito Sobrinho, E., Lameira Verissimo, A., Barros de Oliveira, M. E., Zampieri, F., Ladeira, J. P., Cordioli, R., Diogo Sala, A., Tadahiro Ikeoka, D., Baptista Filho, M. L. A., Ray, A., Guerra de Almeida, A., Nazareno Conceicao, C., Ribeiro Salgado, D., Rosso Verdeal, J. C., Martins, G. A., Junqueira Ribeiro, L., Vilela Siqueira, H., Flavio Costa Filho, F., Adler Maccagnan Pinheiro Besen, B., Vieira Do Nascimento Martins, E., Aparecida Pereira, J., Milioli Ferreira, D., Alves Ferreira Goncalves, F., de Souza Nobrega, M., Barros Duarte, I. J., Nobre, V., Miranda Barreto Mourao, L., Gomez Ravetti, C., Scalzo, A. C., Martins De Stefano, L., Gut, A. L., Nogueira Filho, W., Gatti Cirillo, C., Ishiwaki, S., Lobo, S., Elias de Oliveira, N., Fernandes Machado, L., Sisconetto, L., Rios Vieira, S. R., Fialkow, L., Fontoura Prado, K., Franke, C., Barberena Moraes, R., Christmann Wawrzeniak, I., Rech, T. H., Parolo, E., Almeida Victorino, J., Marques Barroso, C., Marcal de Vasconcelos, M. O., Souza da Silva, R., Lesti Esteves, A. R., Camassola, A. P., Antoniazzi, R., Griebler, M., Favretto, J., Romano, M., Franz da Costa, A., Werneck, V., Miura, M. C., Farran, J., Vasconcelos, R., Isola, A., Resende, E., Goulart, R., Luzzi, S., Rea-Neto, A., de Oliveira, M. C., Bruinje Cosentino, M. F., Martins Dzivielevski, B., Reese, F. B., Ferreira da Silva, S. D., Elias Aquim, E., Girotto, F., Helenditi Fernandes Camurca Martins, R., Lima de Andrade, A., Breckenfeld Heirel, D. C., Ryoji Takatani, R., Dias de Almeida, S., Medina Matos, A., Iwamoto, T., Do Val Tavares, P. E., Valiatti, J. L., de Lucca, F. C., Fornazari, J. C., Dias Brugugnolli, I., de Araujo Nazare, M., Nascimento Loureiro, N., Vasconcelos de Sousa, G., Staffa Gonzaga da Silva, L., Dos Anjos Sad, F. C., Stucchi, E. M., Melo Silva, R., Fonseca Silva, T., Mendes Filho, S. P., Borba Pereira, T., da Silva, P. N., Martines Moralez, G., Abrantes Saraiva, S., Abrunhosa, A., Chagas, C. E. R. C., Thompson, M. M., Pinto Goncalves, C. H., de Oliveira Dias, R., Schwan Filho, F., Magalhaes Carvalho Grion, C., Mezzaroba, A. L., Festti, J., Massariol, T. C., de Souza, G. F., Martins Lima Silva, M., de Souza Andrade Neto, J., Costa, G., Souza Ribeiro, M., Coelho, M., Cruz Carbonell, R. C., de Souza Trindade, R., Valente Barbas, C. S., Domingos Correa, T., Serpa Neto, A., Santucci Cesar de Assuncao, M., Vilela Costa Pinto, B., Goncalves Libanio, P., da Silva Motta, J., Santa Maria Lucin, G., Macedo Araujo, L., Anibal Leite Barros Agostinho, T., de Andrade, K. M., da Silva, M. S., Pereira da Silva, E., Mousinho Gomes, R. L., Campos, N. M. P., Fonseca de Sousa, J., Ramos Nicolau da Costa, L., de Carvalho Fonseca Assuncao, N. S., Martins de Lima, G., Pinheiro de Oliveira, R., Gasparetto Maccari, J., de Campos Balzano, P., Tagliari, L., Metran Nascente, A. P., de Carvalho, M. A., Buttignol, M., Henn Moura, R., Vinicius Pereira, M., Alberti da Silva, G., Akemi Higo, M., Morales, M., Andrade, A. H. V., de Paiva, A. P., da Silva, K. S., Andrioli de Araujo, P., Cordeiro de Abreu Filho, C. A., Abdalla, G., Loureiro Sebold, M., Moreira, R., Caldeira Filho, M., de Brito Cordeiro, R., Pfuetzenreiter, F., Costa Carvalho, L. F., da Silva Guimaraes, B. L., de Faria Cordeiro, H., Pimentel Alvim, S. H., Do Espirito Santo, J. A., Silva Maia, I., Pincelli, M., Zandonai, C. L., Burigo Grumann, A. C., Kretzer, L. P., Nedel, W., Manozzo Boniatti, M., Santos Pellegrini, J. A., da Silva Marques, L., Girardelli Baptista, W. C., da Silva Franco, R. S., Moreira de Sousa, M., de Marchi Benfica, A. F., Veiga de Oliveira, A. L., Reis, D. L., Morais, M. O., Santa Rosa Santana, H., Murilo Domingues, S., de Menezes Ferreira, C., Amado Rabelo, L., Menezes de Rezende, C., Riccio, P., Silva de Almeida, P., Rubini, P., da Graca Pasquotto de Lima Assef, M., Nardela, R., Locks Stahlhofer, L., Gatelli Noronha, C., de Azevedo Naves, S., Dias da Silva, F., Mazza, B. F., Longhi Simoes de Almeida, S., Mayumi Higa, R., Papacidero, C. H., Lima Silva, M. M., de Assuncao Melo, L., Miranda Mafra Oliveira, M., Matos Brito Coelho, C., Machado, J. A., de Souza Machado, Y. L., Vitor Fera, J., Dos Santos Ramos, N. C., Botelho Foernges, R., de Souza, R. R., Rutzen, W., Villasante Troncoso, E. M., Paiva, T. K. B., Vieira de Lacerda, N. M., Aires de Araujo Neto, J., de Oliveira Maia, M., Bastos de Moura, E., Brocco Magnan, G., Soares Nasrala, M. L., Campos Tonussi, R. L., Kohl Pinheiro, E., Simoes da Silva, F., Dal-Pizzol, F., Schmitz de Figueiredo, F., Ritter, C., de Vasconcellos Baldisserotto, S., Blattner, C., Saldanha Dos Santos, R., da Silva Bettega, F., Almeida Delfino Duarte, P., Tozo, T. C., Peliser, P., Deczka Morsch, R., Guimaraes Leal Guadalupe, E., Souza Amorim, D., Rezegue de Moraes Rego, L., Azevedo, L., Ramos, F., Pastore, L., Nery, P., Spegiorin Moreno, M., Nakad Orsatti, V., Yudi Horikawa, F., Samartino Zavanelli, G., Adrieno Westphal, G., Sperotto, G., Dadam, M., Nunes, M., Pantaleao, S. L., Camargo Narciso, R., Bernadete Caser, E., Falcao, J. G., Genelhu, G., Lessa Soares, F., Silva Sales, B., Rebello de Jesus, K., Correia Santos Bonomo, D., Martins Arruda, J., de Pinho, J. C., Belacho Azeredo Coutinho, J., Braga Hagreaves Ribeiro de Freitas, R., de Souza Oliveira Garcia, T., Frizera Vassallo, P., Buarque Souza de Lima, M. H., Eberhart Neto, E., Satoshi Inagaki, A., Oliveira de Paula, A. E., Amador Correia, T., Nomoto, S., Seiji Ueno Gil, F., Florizel Almeida de Araujo, M., Bezerra Lima, Z., Simoes Giancursi, T., Rejane de Lima, C., Costa, M., Osaku, E. F., Jorge, A. C., Rodrigues da Cruz, M., da Cunha, S., Silva Cavallaro Torres, K., Rocha Rodrigues da Silva, F., Lisboa de Souza, R., Osni Machado, F., Buss, E. K., Cattelan Bonorino, K., Germano, A., Bin da Silva, S. R., Herek, A., Tavares Gurgel, S. J., Sanches Laranjeira, A., Toshiyuki Tanita, M., Tibery Queiroz Cardoso, L., Osorio Guerreiro, M., Peres Bainy, M., de Oliveira Teixeira, L., Colozza Mecatti, G., Carolina Salomao, M., Ribeiro Moreira, A., Vantini Capasso Palamim, C., Deucher, R. A. O., Castro Escobar Furlan, F., Rodrigues Torres de Carvalho, F., Muniz, R., Penna Guimaraes, H., Conceicao Andrade, L., Abrahao Hajjar, L., Barbosa Gomes Galas, F. R., Pinheiro de Almeida, J., Marco, R., Peixoto, E., Hirata, F., Yen Ju, C., Bonaccorsi Fernandino, B., Lage de Assis Rocha, D., Azzi Barbosa, N., Dias Alves, J., Furtado Lamego, L., de Linhares, J. M., Ferreira Sousa, M., Ferreira de Souza, M. M., Guimaraes de Carvalho, F. L., Aparecida Leite, M., Torres, P., Bolognese, D., Lacerda, V., Cisari, G., Souza Marques, A., Amarante Costa, A., Bonin Campos, L., Lovato, W. J., Guimaraes Dantas, B., Ribeiro Campos, D., Pires Barrientto, L. C., Rossi Peras Americo, V., Barboza Carnevalli Bueno, T., Morales, D., Mara Gomes, T., Barbosa Cerantola, R., Hoher, J., Sa Malbouisson, L. M., Matheus Cadamuro, F., Bassi, E., Maia, R., Dias E Santos, J. A., Oliveira, C., Balzi, A. P., Tierno, P., Marques Andrade, G., Delascio Lopes, R., Ramos Mello, M., Vendrame, L. S., Ribeiro Machado, F., Baccaro Rossetti Santana, H., de Carvalho, A., Marques Ferreira Mendez, V., de Araujo Macedo Pinto, W., Dos Santos Francisco, R., Steponovicius Piedade Cruz, F., Silva de Araujo, A., Paiva de Souza, A., Teixeira Pinheiro, T., Martins Santos, T., Gontijo-Coutinho, C. M., Franci, D., de Carvalho-Filho, M. A., Ribas Rosa de Oliveira, A. M., Silva, J. M., Costa Lisboa, T., Peretti Torelly, A., Silva de Souza, A., Hadrich, M., Schwarz, P., Berto, P., Teixeira de Gois, A. F., Silva, M., Gessolo Lins, P., Cavalcante Lola Biazzoto, E. P., Dragosavac, D., Ribeiro de Carvalho, C. R., Passos Amato, M. B., Toufen, C., Ribeiro de Santis Santiago, R., Hirota, A. S., Rodrigues, M., Dias Chiavegato, L., Bastos Vieira, P. C., de Almeida, M. M. M. F., Barbosa, P. G., Pereira Santos, J. R., Nogueira de Paula, L., Piras, C., Giuberti, J., Siqueira da Silva, A., Conti Ramos, R., Plata Valdivieso, R., Gonzalez, H. H., Ortiz, M., Bautista-Rincon, D. F., Quinones, E., Calderon, L. E., Vargas, M., Pizarro, C., Orozco Levi, M., Espitia Hernandez, A. M., Cadavid Gutierrez, C., Giraldo Ramirez, N., Gallego, D. A., Naranjo Sierra, S., Ortiz, G., Esneda Rocha Gaona, M., Garay, M., Vieda, E., Bermudez, W. F., Castaneda, J. A., Cortegiani, A., Russotto, V., Raineri, S. M., Giarratano, A., Shahnaz Hasan, M., Rai Hakumat Rai, V., Fadhil Hadi Bin Jamaluddin, M., Afiq Syahmi Ramli, M., Gorka, J., Nowak, I., Seczynska, B., Sega, A., Paulino, C., Povoa, P., Belda, F. J., Ferrando, C., Carbonell, J. A., Puig, J., Soro, M., Nin, N., Hurtado, J., Gacel, A., Gaudin, A., Sande, L., Cavalcanti, A, Suzumura, E, Laranjeira, L, De Moraes Paisani, D, Damiani, L, Guimaraes, H, Romano, E, De Moraes Regenga, M, Taniguchi, L, Teixeira, C, De Oliveira, R, Machado, F, Diaz-Quijano, F, De Alencar Filho, M, Maia, I, Caser, E, De Oliveira Filho, W, De Carvalho Borges, M, De Aquino Martins, P, Matsui, M, Ospina-Tascon, G, Giancursi, T, Giraldo-Ramirez, N, Vieira, S, De Lima Assef, M, Hasan, M, Szczeklik, W, Rios, F, Amato, M, Berwanger, O, De Carvalho, C, Tucci, M, Souza Dos Santos, L, Franca de Oliveira, M, Peres, I, Freitas, I, Reis, H, Verissimo, A, Torres, D, Barroso, A, Semboloni Bitencourt, W, Franco, M, Oliveira Lage, J, Aparecida Pessoa Conde, K, Charro, F, Naia, A, de Brito Sobrinho, E, Lameira Verissimo, A, Barros de Oliveira, M, Zampieri, F, Ladeira, J, Cordioli, R, Diogo Sala, A, Tadahiro Ikeoka, D, Baptista Filho, M, Ray, A, Guerra de Almeida, A, Nazareno Conceicao, C, Ribeiro Salgado, D, Rosso Verdeal, J, Martins, G, Junqueira Ribeiro, L, Vilela Siqueira, H, Flavio Costa Filho, F, Adler Maccagnan Pinheiro Besen, B, Vieira Do Nascimento Martins, E, Aparecida Pereira, J, Milioli Ferreira, D, Alves Ferreira Goncalves, F, de Souza Nobrega, M, Barros Duarte, I, Nobre, V, Miranda Barreto Mourao, L, Gomez Ravetti, C, Scalzo, A, Martins De Stefano, L, Gut, A, Nogueira Filho, W, Gatti Cirillo, C, Ishiwaki, S, Lobo, S, Elias de Oliveira, N, Fernandes Machado, L, Sisconetto, L, Rios Vieira, S, Fialkow, L, Fontoura Prado, K, Franke, C, Barberena Moraes, R, Christmann Wawrzeniak, I, Rech, T, Parolo, E, Almeida Victorino, J, Marques Barroso, C, Marcal de Vasconcelos, M, Souza da Silva, R, Lesti Esteves, A, Camassola, A, Antoniazzi, R, Griebler, M, Favretto, J, Romano, M, Franz da Costa, A, Werneck, V, Miura, M, Farran, J, Vasconcelos, R, Isola, A, Resende, E, Goulart, R, Luzzi, S, Rea-Neto, A, de Oliveira, M, Bruinje Cosentino, M, Martins Dzivielevski, B, Reese, F, Ferreira da Silva, S, Elias Aquim, E, Girotto, F, Helenditi Fernandes Camurca Martins, R, Lima de Andrade, A, Breckenfeld Heirel, D, Ryoji Takatani, R, Dias de Almeida, S, Medina Matos, A, Iwamoto, T, Do Val Tavares, P, Valiatti, J, de Lucca, F, Fornazari, J, Dias Brugugnolli, I, de Araujo Nazare, M, Nascimento Loureiro, N, Vasconcelos de Sousa, G, Staffa Gonzaga da Silva, L, Dos Anjos Sad, F, Stucchi, E, Melo Silva, R, Fonseca Silva, T, Mendes Filho, S, Borba Pereira, T, da Silva, P, Martines Moralez, G, Abrantes Saraiva, S, Abrunhosa, A, Chagas, C, Thompson, M, Pinto Goncalves, C, de Oliveira Dias, R, Schwan Filho, F, Magalhaes Carvalho Grion, C, Mezzaroba, A, Festti, J, Massariol, T, de Souza, G, Martins Lima Silva, M, de Souza Andrade Neto, J, Costa, G, Souza Ribeiro, M, Coelho, M, Cruz Carbonell, R, de Souza Trindade, R, Valente Barbas, C, Domingos Correa, T, Serpa Neto, A, Santucci Cesar de Assuncao, M, Vilela Costa Pinto, B, Goncalves Libanio, P, da Silva Motta, J, Santa Maria Lucin, G, Macedo Araujo, L, Anibal Leite Barros Agostinho, T, de Andrade, K, da Silva, M, Pereira da Silva, E, Mousinho Gomes, R, Campos, N, Fonseca de Sousa, J, Ramos Nicolau da Costa, L, de Carvalho Fonseca Assuncao, N, Martins de Lima, G, Pinheiro de Oliveira, R, Gasparetto Maccari, J, de Campos Balzano, P, Tagliari, L, Metran Nascente, A, de Carvalho, M, Buttignol, M, Henn Moura, R, Vinicius Pereira, M, Alberti da Silva, G, Akemi Higo, M, Morales, M, Andrade, A, de Paiva, A, da Silva, K, Andrioli de Araujo, P, Cordeiro de Abreu Filho, C, Abdalla, G, Loureiro Sebold, M, Moreira, R, Caldeira Filho, M, de Brito Cordeiro, R, Pfuetzenreiter, F, Costa Carvalho, L, da Silva Guimaraes, B, de Faria Cordeiro, H, Pimentel Alvim, S, Do Espirito Santo, J, Silva Maia, I, Pincelli, M, Zandonai, C, Burigo Grumann, A, Kretzer, L, Nedel, W, Manozzo Boniatti, M, Santos Pellegrini, J, da Silva Marques, L, Girardelli Baptista, W, da Silva Franco, R, Moreira de Sousa, M, de Marchi Benfica, A, Veiga de Oliveira, A, Reis, D, Morais, M, Santa Rosa Santana, H, Murilo Domingues, S, de Menezes Ferreira, C, Amado Rabelo, L, Menezes de Rezende, C, Riccio, P, Silva de Almeida, P, Rubini, P, da Graca Pasquotto de Lima Assef, M, Nardela, R, Locks Stahlhofer, L, Gatelli Noronha, C, de Azevedo Naves, S, Dias da Silva, F, Mazza, B, Longhi Simoes de Almeida, S, Mayumi Higa, R, Papacidero, C, Lima Silva, M, de Assuncao Melo, L, Miranda Mafra Oliveira, M, Matos Brito Coelho, C, Machado, J, de Souza Machado, Y, Vitor Fera, J, Dos Santos Ramos, N, Botelho Foernges, R, de Souza, R, Rutzen, W, Villasante Troncoso, E, Paiva, T, Vieira de Lacerda, N, Aires de Araujo Neto, J, de Oliveira Maia, M, Bastos de Moura, E, Brocco Magnan, G, Soares Nasrala, M, Campos Tonussi, R, Kohl Pinheiro, E, Simoes da Silva, F, Dal-Pizzol, F, Schmitz de Figueiredo, F, Ritter, C, de Vasconcellos Baldisserotto, S, Blattner, C, Saldanha Dos Santos, R, da Silva Bettega, F, Almeida Delfino Duarte, P, Tozo, T, Peliser, P, Deczka Morsch, R, Guimaraes Leal Guadalupe, E, Souza Amorim, D, Rezegue de Moraes Rego, L, Azevedo, L, Ramos, F, Pastore, L, Nery, P, Spegiorin Moreno, M, Nakad Orsatti, V, Yudi Horikawa, F, Samartino Zavanelli, G, Adrieno Westphal, G, Sperotto, G, Dadam, M, Nunes, M, Pantaleao, S, Camargo Narciso, R, Bernadete Caser, E, Falcao, J, Genelhu, G, Lessa Soares, F, Silva Sales, B, Rebello de Jesus, K, Correia Santos Bonomo, D, Martins Arruda, J, de Pinho, J, Belacho Azeredo Coutinho, J, Braga Hagreaves Ribeiro de Freitas, R, de Souza Oliveira Garcia, T, Frizera Vassallo, P, Buarque Souza de Lima, M, Eberhart Neto, E, Satoshi Inagaki, A, Oliveira de Paula, A, Amador Correia, T, Nomoto, S, Seiji Ueno Gil, F, Florizel Almeida de Araujo, M, Bezerra Lima, Z, Simoes Giancursi, T, Rejane de Lima, C, Costa, M, Osaku, E, Jorge, A, Rodrigues da Cruz, M, da Cunha, S, Silva Cavallaro Torres, K, Rocha Rodrigues da Silva, F, Lisboa de Souza, R, Osni Machado, F, Buss, E, Cattelan Bonorino, K, Germano, A, Bin da Silva, S, Herek, A, Tavares Gurgel, S, Sanches Laranjeira, A, Toshiyuki Tanita, M, Tibery Queiroz Cardoso, L, Osorio Guerreiro, M, Peres Bainy, M, de Oliveira Teixeira, L, Colozza Mecatti, G, Carolina Salomao, M, Ribeiro Moreira, A, Vantini Capasso Palamim, C, Deucher, R, Castro Escobar Furlan, F, Rodrigues Torres de Carvalho, F, Muniz, R, Penna Guimaraes, H, Conceicao Andrade, L, Abrahao Hajjar, L, Barbosa Gomes Galas, F, Pinheiro de Almeida, J, Marco, R, Peixoto, E, Hirata, F, Yen Ju, C, Bonaccorsi Fernandino, B, Lage de Assis Rocha, D, Azzi Barbosa, N, Dias Alves, J, Furtado Lamego, L, de Linhares, J, Ferreira Sousa, M, Ferreira de Souza, M, Guimaraes de Carvalho, F, Aparecida Leite, M, Torres, P, Bolognese, D, Lacerda, V, Cisari, G, Souza Marques, A, Amarante Costa, A, Bonin Campos, L, Lovato, W, Guimaraes Dantas, B, Ribeiro Campos, D, Pires Barrientto, L, Rossi Peras Americo, V, Barboza Carnevalli Bueno, T, Morales, D, Mara Gomes, T, Barbosa Cerantola, R, Hoher, J, Sa Malbouisson, L, Matheus Cadamuro, F, Bassi, E, Maia, R, Dias E Santos, J, Oliveira, C, Balzi, A, Tierno, P, Marques Andrade, G, Delascio Lopes, R, Ramos Mello, M, Vendrame, L, Ribeiro Machado, F, Baccaro Rossetti Santana, H, de Carvalho, A, Marques Ferreira Mendez, V, de Araujo Macedo Pinto, W, Dos Santos Francisco, R, Steponovicius Piedade Cruz, F, Silva de Araujo, A, Paiva de Souza, A, Teixeira Pinheiro, T, Martins Santos, T, Gontijo-Coutinho, C, Franci, D, de Carvalho-Filho, M, Ribas Rosa de Oliveira, A, Silva, J, Costa Lisboa, T, Peretti Torelly, A, Silva de Souza, A, Hadrich, M, Schwarz, P, Berto, P, Teixeira de Gois, A, Silva, M, Gessolo Lins, P, Cavalcante Lola Biazzoto, E, Dragosavac, D, Ribeiro de Carvalho, C, Passos Amato, M, Toufen, C, Ribeiro de Santis Santiago, R, Hirota, A, Rodrigues, M, Dias Chiavegato, L, Bastos Vieira, P, de Almeida, M, Barbosa, P, Pereira Santos, J, Nogueira de Paula, L, Piras, C, Giuberti, J, Siqueira da Silva, A, Conti Ramos, R, Plata Valdivieso, R, Gonzalez, H, Ortiz, M, Bautista-Rincon, D, Quinones, E, Calderon, L, Vargas, M, Pizarro, C, Orozco Levi, M, Espitia Hernandez, A, Cadavid Gutierrez, C, Giraldo Ramirez, N, Gallego, D, Naranjo Sierra, S, Ortiz, G, Esneda Rocha Gaona, M, Garay, M, Vieda, E, Bermudez, W, Castaneda, J, Cortegiani, A, Russotto, V, Raineri, S, Giarratano, A, Shahnaz Hasan, M, Rai Hakumat Rai, V, Fadhil Hadi Bin Jamaluddin, M, Afiq Syahmi Ramli, M, Gorka, J, Nowak, I, Seczynska, B, Sega, A, Paulino, C, Povoa, P, Belda, F, Ferrando, C, Carbonell, J, Puig, J, Soro, M, Nin, N, Hurtado, J, Gacel, A, Gaudin, A, Sande, L, Cavalcanti A.B., Suzumura E.A., Laranjeira L.N., De Moraes Paisani D., Damiani L.P., Guimaraes H.P., Romano E.R., De Moraes Regenga M., Taniguchi L.N.T., Teixeira C., De Oliveira R.P., Machado F.R., Diaz-Quijano F.A., De Alencar Filho M.S., Maia I.S., Caser E.B., De Oliveira Filho W., De Carvalho Borges M., De Aquino Martins P., Matsui M., Ospina-Tascon G.A., Giancursi T.S., Giraldo-Ramirez N.D., Vieira S.R.R., De Lima Assef M.D.G.P., Hasan M.S., Szczeklik W., Rios F., Amato M.B.P., Berwanger O., De Carvalho C.R.R., Tucci M.R., Souza Dos Santos L., Franca de Oliveira M.C., Peres I., Freitas I., Reis H., Verissimo A., Torres D., Barroso A., Semboloni Bitencourt W., Franco M.R., Oliveira Lage J., Aparecida Pessoa Conde K., Charro F.A., Naia A., de Brito Sobrinho E., Lameira Verissimo A., Barros de Oliveira M.E., Zampieri F., Ladeira J.P., Cordioli R., Diogo Sala A., Tadahiro Ikeoka D., Baptista Filho M.L.A., Ray A., Guerra de Almeida A., Nazareno Conceicao C., Ribeiro Salgado D., Rosso Verdeal J.C., Martins G.A., Junqueira Ribeiro L., Vilela Siqueira H., Flavio Costa Filho F., Adler Maccagnan Pinheiro Besen B., Vieira Do Nascimento Martins E., Aparecida Pereira J., Milioli Ferreira D., Alves Ferreira Goncalves F., de Souza Nobrega M., Barros Duarte I.J., Nobre V., Miranda Barreto Mourao L., Gomez Ravetti C., Scalzo A.C., Martins De Stefano L., Gut A.L., Nogueira Filho W., Gatti Cirillo C., Ishiwaki S., Lobo S., Elias de Oliveira N., Fernandes Machado L., Sisconetto L., Rios Vieira S.R., Fialkow L., Fontoura Prado K., Franke C., Barberena Moraes R., Christmann Wawrzeniak I., Rech T.H., Parolo E., Almeida Victorino J., Marques Barroso C., Marcal de Vasconcelos M.O., Souza da Silva R., Lesti Esteves A.R., Camassola A.P., Antoniazzi R., Griebler M., Favretto J., Romano M., Franz da Costa A., Werneck V., Miura M.C., Farran J., Vasconcelos R., Isola A., Resende E., Goulart R., Luzzi S., Rea-Neto A., de Oliveira M.C., Bruinje Cosentino M.F., Martins Dzivielevski B., Reese F.B., Ferreira da Silva S.D., Elias Aquim E., Girotto F., Helenditi Fernandes Camurca Martins R., Lima de Andrade A., Breckenfeld Heirel D.C., Ryoji Takatani R., Dias de Almeida S., Medina Matos A., Iwamoto T., Do Val Tavares P.E., Valiatti J.L., de Lucca F.C., Fornazari J.C., Dias Brugugnolli I., de Araujo Nazare M., Nascimento Loureiro N., Vasconcelos de Sousa G., Staffa Gonzaga da Silva L., Dos Anjos Sad F.C., Stucchi E.M., Melo Silva R., Fonseca Silva T., Mendes Filho S.P., Borba Pereira T., da Silva P.N., Martines Moralez G., Abrantes Saraiva S., Abrunhosa A., Chagas C.E.R.C., Thompson M.M., Pinto Goncalves C.H., de Oliveira Dias R., Schwan Filho F., Magalhaes Carvalho Grion C., Mezzaroba A.L., Festti J., Massariol T.C., de Souza G.F., Martins Lima Silva M., de Souza Andrade Neto J., Costa G., Souza Ribeiro M., Coelho M., Cruz Carbonell R.C., de Souza Trindade R., Valente Barbas C.S., Domingos Correa T., Serpa Neto A., Santucci Cesar de Assuncao M., Vilela Costa Pinto B., Goncalves Libanio P., da Silva Motta J., Santa Maria Lucin G., Macedo Araujo L., Anibal Leite Barros Agostinho T., de Andrade K.M., da Silva M.S., Pereira da Silva E., Mousinho Gomes R.L., Campos N.M.P., Fonseca de Sousa J., Ramos Nicolau da Costa L., de Carvalho Fonseca Assuncao N.S., Martins de Lima G., Pinheiro de Oliveira R., Gasparetto Maccari J., de Campos Balzano P., Tagliari L., Metran Nascente A.P., de Carvalho M.A., Buttignol M., Henn Moura R., Vinicius Pereira M., Alberti da Silva G., Akemi Higo M., Morales M., Andrade A.H.V., de Paiva A.P., da Silva K.S., Andrioli de Araujo P., Cordeiro de Abreu Filho C.A., Abdalla G., Loureiro Sebold M., Moreira R., Caldeira Filho M., de Brito Cordeiro R., Pfuetzenreiter F., Costa Carvalho L.F., da Silva Guimaraes B.L., de Faria Cordeiro H., Pimentel Alvim S.H., Do Espirito Santo J.A., Silva Maia I., Pincelli M., Zandonai C.L., Burigo Grumann A.C., Kretzer L.P., Nedel W., Manozzo Boniatti M., Santos Pellegrini J.A., da Silva Marques L., Girardelli Baptista W.C., da Silva Franco R.S., Moreira de Sousa M., de Marchi Benfica A.F., Veiga de Oliveira A.L., Reis D.L., Morais M.O., Santa Rosa Santana H., Murilo Domingues S., de Menezes Ferreira C., Amado Rabelo L., Menezes de Rezende C., Riccio P., Silva de Almeida P., Rubini P., da Graca Pasquotto de Lima Assef M., Nardela R., Locks Stahlhofer L., Gatelli Noronha C., de Azevedo Naves S., Dias da Silva F., Mazza B.F., Longhi Simoes de Almeida S., Mayumi Higa R., Papacidero C.H., Lima Silva M.M., de Assuncao Melo L., Miranda Mafra Oliveira M., Matos Brito Coelho C., Machado J.A., de Souza Machado Y.L., Vitor Fera J., Dos Santos Ramos N.C., Botelho Foernges R., de Souza R.R., Rutzen W., Villasante Troncoso E.M., Paiva T.K.B., Vieira de Lacerda N.M., Aires de Araujo Neto J., de Oliveira Maia M., Bastos de Moura E., Brocco Magnan G., Soares Nasrala M.L., Campos Tonussi R.L., Kohl Pinheiro E., Simoes da Silva F., Dal-Pizzol F., Schmitz de Figueiredo F., Ritter C., de Vasconcellos Baldisserotto S., Blattner C., Saldanha Dos Santos R., da Silva Bettega F., Almeida Delfino Duarte P., Tozo T.C., Peliser P., Deczka Morsch R., Guimaraes Leal Guadalupe E., Souza Amorim D., Rezegue de Moraes Rego L., Azevedo L., Ramos F., Pastore L., Nery P., Spegiorin Moreno M., Nakad Orsatti V., Yudi Horikawa F., Samartino Zavanelli G., Adrieno Westphal G., Sperotto G., Dadam M., Nunes M., Pantaleao S.L., Camargo Narciso R., Bernadete Caser E., Falcao J.G., Genelhu G., Lessa Soares F., Silva Sales B., Rebello de Jesus K., Correia Santos Bonomo D., Martins Arruda J., de Pinho J.C., Belacho Azeredo Coutinho J., Braga Hagreaves Ribeiro de Freitas R., de Souza Oliveira Garcia T., Frizera Vassallo P., Buarque Souza de Lima M.H., Eberhart Neto E., Satoshi Inagaki A., Oliveira de Paula A.E., Amador Correia T., Nomoto S., Seiji Ueno Gil F., Florizel Almeida de Araujo M., Bezerra Lima Z., Simoes Giancursi T., Rejane de Lima C., Costa M., Osaku E.F., Jorge A.C., Rodrigues da Cruz M., da Cunha S., Silva Cavallaro Torres K., Rocha Rodrigues da Silva F., Lisboa de Souza R., Osni Machado F., Buss E.K., Cattelan Bonorino K., Germano A., Bin da Silva S.R., Herek A., Tavares Gurgel S.J., Sanches Laranjeira A., Toshiyuki Tanita M., Tibery Queiroz Cardoso L., Osorio Guerreiro M., Peres Bainy M., de Oliveira Teixeira L., Colozza Mecatti G., Carolina Salomao M., Ribeiro Moreira A., Vantini Capasso Palamim C., Deucher R.A.O., Castro Escobar Furlan F., Rodrigues Torres de Carvalho F., Muniz R., Penna Guimaraes H., Conceicao Andrade L., Abrahao Hajjar L., Barbosa Gomes Galas F.R., Pinheiro de Almeida J., Marco R., Peixoto E., Hirata F., Yen Ju C., Bonaccorsi Fernandino B., Lage de Assis Rocha D., Azzi Barbosa N., Dias Alves J., Furtado Lamego L., de Linhares J.M., Ferreira Sousa M., Ferreira de Souza M.M., Guimaraes de Carvalho F.L., Aparecida Leite M., Torres P., Bolognese D., Lacerda V., Cisari G., Souza Marques A., Amarante Costa A., Bonin Campos L., Lovato W.J., Guimaraes Dantas B., Ribeiro Campos D., Pires Barrientto L.C., Rossi Peras Americo V., Barboza Carnevalli Bueno T., Morales D., Mara Gomes T., Barbosa Cerantola R., Hoher J., Sa Malbouisson L.M., Matheus Cadamuro F., Bassi E., Maia R., Dias E Santos J.A., Oliveira C., Balzi A.P., Tierno P., Marques Andrade G., Delascio Lopes R., Ramos Mello M., Vendrame L.S., Ribeiro Machado F., Baccaro Rossetti Santana H., de Carvalho A., Marques Ferreira Mendez V., de Araujo Macedo Pinto W., Dos Santos Francisco R., Steponovicius Piedade Cruz F., Silva de Araujo A., Paiva de Souza A., Teixeira Pinheiro T., Martins Santos T., Gontijo-Coutinho C.M., Franci D., de Carvalho-Filho M.A., Ribas Rosa de Oliveira A.M., Silva J.M., Costa Lisboa T., Peretti Torelly A., Silva de Souza A., Hadrich M., Schwarz P., Berto P., Teixeira de Gois A.F., Silva M., Gessolo Lins P., Cavalcante Lola Biazzoto E.P., Dragosavac D., Ribeiro de Carvalho C.R., Passos Amato M.B., Toufen C., Ribeiro de Santis Santiago R., Hirota A.S., Rodrigues M., Dias Chiavegato L., Bastos Vieira P.C., de Almeida M.M.M.F., Barbosa P.G., Pereira Santos J.R., Nogueira de Paula L., Piras C., Giuberti J., Siqueira da Silva A., Conti Ramos R., Plata Valdivieso R., Gonzalez H.H., Ortiz M., Bautista-Rincon D.F., Quinones E., Calderon L.E., Vargas M., Pizarro C., Orozco Levi M., Espitia Hernandez A.M., Cadavid Gutierrez C., Giraldo Ramirez N., Gallego D.A., Naranjo Sierra S., Ortiz G., Esneda Rocha Gaona M., Garay M., Vieda E., Bermudez W.F., Castaneda J.A., Cortegiani A., Russotto V., Raineri S.M., Giarratano A., Shahnaz Hasan M., Rai Hakumat Rai V., Fadhil Hadi Bin Jamaluddin M., Afiq Syahmi Ramli M., Gorka J., Nowak I., Seczynska B., Sega A., Paulino C., Povoa P., Belda F.J., Ferrando C., Carbonell J.A., Puig J., Soro M., Nin N., Hurtado J., Gacel A., Gaudin A., and Sande L.

Subjects
Adult, Male, ARDS, medicine.medical_specialty, acure respitatory distress syndrome, medicine.medical_treatment, mechanical ventilation, law.invention, Positive-Pressure Respiration, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Intensive care, Tidal Volume, medicine, Humans, Treatment Failure, ARDS, ventilation, PEEP, MED/41 - ANESTESIOLOGIA, PEEP, Tidal volume, Positive end-expiratory pressure, Aged, intensive care, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, Hazard ratio, Pneumothorax, 030208 emergency & critical care medicine, General Medicine, Middle Aged, medicine.disease, Surgery, Intensive Care Units, Editorial, 030228 respiratory system, Anesthesia, Female, business
Abstract

Importance The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain. Objective To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy. Design, Setting, and Participants Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS. Interventions An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory–system compliance (n = 501; experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning. Main Outcomes and Measures The primary outcome was all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality. Results A total of 1010 patients (37.5% female; mean [SD] age, 50.9 [17.4] years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio [HR], 1.20; 95% CI, 1.01 to 1.42; P = .041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; P = .04), decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, −1.1; 95% CI, −2.1 to −0.1; P = .03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; P = .03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; P = .001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality. Conclusions and Relevance In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients. Trial Registration clinicaltrials.gov Identifier:NCT01374022

Published
2017

25. Treatment with milk fat globule epidermal growth factor-factor 8 (MFG-E8) reduces inflammation and lung injury in neonatal sepsis

Author

Tracy Chen, Jose M. Prince, Asha Jacob, Weng Lang Yang, Alexandra C. Bolognese, Jeffrey Nicastro, Gene F. Coppa, Ping Wang, and Laura W. Hansen

Subjects
Male, 0301 basic medicine, medicine.medical_treatment, Intraperitoneal injection, Inflammation, Lung injury, Article, law.invention, Andrology, Sepsis, Mice, Random Allocation, 03 medical and health sciences, law, Epidermal growth factor, medicine, Animals, Lung, Neonatal sepsis, business.industry, Lung Injury, Milk Proteins, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Animals, Newborn, Antigens, Surface, Immunology, Recombinant DNA, Female, Surgery, Neonatal Sepsis, medicine.symptom, business
Abstract

Background Sepsis remains one of the leading causes of infant death worldwide. It is characterized by uncontrolled inflammatory responses due to proven bacterial infection. Despite improvement in supportive care and the availability of effective antibiotics, no specific therapy targeting the dysregulated inflammatory response is available for neonatal sepsis. Milk fat globule epidermal growth factor-factor 8 (MFG-E8) is a secretory glycoprotein abundantly present in human milk. MFG-E8 suppresses the systemic inflammatory responses in adult murine injury models by improving the clearance of dying cells. We hypothesized that exogenous administration of recombinant mouse MFG-E8 could inhibit the exaggerated inflammatory response and lung injury in a murine model of neonatal sepsis. Methods Neonatal sepsis was induced in 5- to 7-day-old male and female C57BL6 mice using an intraperitoneal injection of cecal slurry. At 1 hour after sepsis induction, a single dose of 40 μg/kg recombinant mouse MFG-E8 or vehicle was administered via retro-orbital injection. All neonates were returned to their mothers as a group. At 10 hours after cecal slurry injection, pups were killed and blood and lung tissues were collected. Control mice underwent a similar procedure with the exception of cecal slurry intraperitoneal injection. Results Serum lactate dehydrogenase, IL-1β, and IL-6 were significantly increased 10 hours after cecal slurry injection. Treatment with recombinant mouse MFG-E8 decreased these levels by 30%, 56%, and 37%, respectively. Lung morphology was significantly compromised in the vehicle group after cecal slurry injection, whereas the recombinant mouse MFG-E8–treated groups demonstrated a 48% improvement in the lung injury score. Lung IL-6 and MIP-2 protein levels were significantly reduced with recombinant mouse MFG-E8 treatment. Lung neutrophil infiltration as observed by Gr-1 staining and, TUNEL-positive cells were also significantly reduced with recombinant mouse MFG-E8 treatment. Conclusion Treatment with recombinant mouse MFG-E8 attenuated inflammation and lung injury in murine neonatal sepsis. Thus, MFG-E8 could be developed as a possible therapy for neonatal sepsis.

Published
2017
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26. Incidence and outcome of switching of oral platelet P2Y12 receptor inhibitors in patients with acute coronary syndromes undergoing percutaneous coronary intervention: the SCOPE registry

Author

Sergio Berti, Fabrizio D'Ascenzo, Ferdinando Varbella, Leonardo Bolognese, Giuseppe Musumeci, Stefano De Servi, Francesco Saia, Guido Parodi, Leonardo De Luca, and Alfredo Marchese

Subjects
Blood Platelets, Male, medicine.medical_specialty, Ticlopidine, medicine.medical_treatment, Hemorrhage, 030204 cardiovascular system & hematology, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, Internal medicine, medicine, Adjunctive pharmacotherapy, Humans, Cumulative incidence, Prospective Studies, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, Acute Coronary Syndrome, Prospective cohort study, Aged, Aged, 80 and over, business.industry, Incidence, Incidence (epidemiology), Percutaneous coronary intervention, medicine.disease, Clopidogrel, Conventional PCI, Purinergic P2Y Receptor Antagonists, Cardiology, Cardiology and Cardiovascular Medicine, Female, business, Platelet Aggregation Inhibitors, Mace, medicine.drug
Abstract

Aims In patients with acute coronary syndromes (ACS) undergoing a percutaneous coronary intervention (PCI), switching of oral P2Y12 receptor inhibitors may frequently occur. We aimed to assess the current incidence of switching of oral P2Y12 receptor inhibitors and its safety in consecutive ACS patients undergoing PCI over a three-month period. Methods and results The SCOPE registry was a multicentre, observational, prospective study. A total of 1,363 consecutive patients were enrolled in 39 PCI centres across Italy. Switching of oral antiplatelet therapies occurred in 2.3% in the cathlab, 3.3% at discharge and 5.1% at follow-up. The cumulative incidence of major adverse cerebrovascular events (MACE) and net adverse cerebrovascular events (NACE: a combination of MACE and bleeding events) was 1.6% and 5.6%, respectively. Among patients receiving an upgrade switching (change from old to novel P2Y12 receptor inhibitors), no ischaemic or bleeding events occurred during the whole study period. On the other hand, downgrade switching (from novel to old P2Y12 receptor inhibitors) was an independent predictor of NACE (OR 5.3; CI: 2.1-18.2; p=0.04). Conclusions Switching of oral antiplatelet therapies is not uncommon among ACS patients undergoing PCI. Notably, switching from clopidogrel to novel P2Y12 receptor inhibitors appears safe, while a downgrade switching in early phases of ACS is associated with adverse clinical events.

Published
2017
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27. Impact of recruitment and retention on all-cause mortality in a large all-comers randomised controlled trial: insights from the GLOBAL LEADERS trial

Author

Mariusz Tomaniak, Pascal Vranckx, Mathias Vrolix, Joanna J. Wykrzykowska, Stephan Windecker, Chun Chin Chang, Aleksander Zurakowski, Robert-Jan van Geuns, Carlo Tumscitz, Kuniaki Takahashi, Edouard Benit, Ply Chichareon, Kurt Huber, Christoph Liebetrau, Krzysztof Żmudka, Maurizio Ferrario, Scot Garg, Yoshinobu Onuma, Paweł Buszman, Marcello Dominici, Rodrigo Modolo, Norihiro Kogame, Philippe Gabriel Steg, Adel Aminian, Marco Valgimigli, Christian W. Hamm, Robbert J. de Winter, Luc Janssens, Patrick W. Serruys, Leonardo Bolognese, Ivo Petrov, University of Zurich, Graduate School, ACS - Atherosclerosis & ischemic syndromes, Cardiology, ACS - Heart failure & arrhythmias, and ACS - Microcirculation

Subjects
Male, medicine.medical_specialty, Ticagrelor, Biomedical Research, Patient Dropouts, medicine.medical_treatment, 610 Medicine & health, Coronary Artery Disease, 030204 cardiovascular system & hematology, 11171 Cardiocentro Ticino, 2705 Cardiology and Cardiovascular Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, Percutaneous Coronary Intervention, Randomized controlled trial, law, Internal medicine, Medicine, Humans, In patient, 030212 general & internal medicine, Aged, Randomised controlled trial, business.industry, Dual Anti-Platelet Therapy, Patient Selection, Hazard ratio, Percutaneous coronary intervention, General Medicine, Middle Aged, All-cause mortality, All-comers, Confidence interval, Clinical trial, Retention, Vital Status, Cardiology, Female, Stents, Recruitment, Cardiology and Cardiovascular Medicine, business, All cause mortality, Platelet Aggregation Inhibitors
Abstract

Objective: Recruitment and retention in trials may bias the results and subsequently complicate their interpretation and validity. The aim of this study is to evaluate the impact of recruitment and retention on all-cause mortality in a large all-comers trial. Methods: The recruitment rate in each investigating center of the GLOBAL LEADERS trial was assessed and the 130 centers were subdivided into low and high recruiters according to the median, with all-cause mortality then compared between the two groups. Vital status was obtained from public records in patients with incomplete follow-up. Results: The trial randomized 15,991 (7.86%) of 203,483 eligible patients with percutaneous coronary intervention during the recruitment period, of whom 15,267 (95.47%) completed follow-up, 23 (0.14%) patients withdrew consent and formally requested to be deleted from the database; 183 (1.14%) withdrew consent but only objected to future data collection; 303 (1.89%) discontinued the study; and 215 (1.34%) were lost to follow-up. Vital status was finally obtained in all but 31 patients (99.81%). Patients from low recruiters had a significantly lower all-cause mortality than high ones (2.26% vs. 3.24%; hazard ratio: 0.69; 95% confidence interval: 0.55–0.87; p = 0.002). There was a significant difference in all-cause mortality among the incomplete follow-up groups (log-rank p < 0.001) with a significantly higher mortality in the 183 patients who withdrew consent than those who completed follow-up (7.38% vs. 2.99%, p = 0.002). Conclusions: Recruitment and retention significantly impacted all-cause mortality. Search for vital status through public domains is of paramount importance in the interpretation and validity of large clinical trials. Graphic abstract: [Figure not available: see fulltext.].

Published
2019

28. Interval From Initiation of Prasugrel to Coronary Angiography in Patients With Non–ST-Segment Elevation Myocardial Infarction

Author

Patrick Goldstein, Leonardo Bolognese, Petr Widimsky, Dariusz Dudek, Debra L. Miller, Johanne Silvain, Zhenyu Liu, Accoast Investigators, Jean-Jacques Portal, Jean-François Tanguay, Jean-Philippe Collet, Christian W. Hamm, Jur ten Berg, Benoit Lattuca, Tomasz Rakowski, Eric Vicaut, Gilles Montalescot, Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Peking Union Medical College Hospital [Beijing] (PUMCH), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Justus-Liebig-Universität Gießen (JLU), Montreal Heart Institute - Institut de Cardiologie de Montréal, St. Antonius Hospital [Nieuwegein], Charles University [Prague] (CU), Eli Lilly and Company [Indianapolis], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Pitié-Salpêtrière [APHP], Jagiellonian University [Krakow] (UJ), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Hôpital Lariboisière, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7)

Subjects
Male, medicine.medical_specialty, Acute coronary syndrome, Prasugrel, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Placebo, Coronary Angiography, acute coronary syndrome, 03 medical and health sciences, Electrocardiography, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Cause of Death, Medicine, ST segment, Humans, In patient, 030212 general & internal medicine, Myocardial infarction, cardiovascular diseases, Non-ST Elevated Myocardial Infarction, Dose-Response Relationship, Drug, business.industry, percutaneous coronary intervention, Percutaneous coronary intervention, Middle Aged, pretreatment, medicine.disease, 3. Good health, prasugrel, Survival Rate, Treatment Outcome, myocardial infarction, Conventional PCI, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Prasugrel Hydrochloride, Platelet Aggregation Inhibitors, medicine.drug, Follow-Up Studies
Abstract

International audience; BACKGROUND:In the ACCOAST (A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction) trial, the prasugrel pre-treatment strategy versus placebo was associated with excess bleeding complications and no improved ischemic outcome in non-ST-segment elevation myocardial infarction (MI). Whether patients with the longest pre-treatment duration had an ischemic benefit is unknown.OBJECTIVES:This pre-specified analysis of the ACCOAST trial aimed to assess the effect of pre-treatment duration with prasugrel (time from randomization to angiography) on outcomes.METHODS:Within the 4,033 patients randomized in the ACCOAST trial, pre-treatment duration was available in 4,001 patients (99.2%). The population of the trial was divided into quartiles of pre-treatment duration (0.1 to 2.5 h, 2.5 to 3.9 h, 3.9 to 13.6 h, and >13.6 h) with an evaluation of the primary efficacy endpoint of cardiovascular death, MI, stroke, urgent revascularization or glycoprotein IIb/IIIa inhibitor bailout use. Secondary efficacy outcomes including cardiovascular death, MI, or stroke; all-cause death; stent thrombosis and safety outcomes (all coronary artery bypass graft [CABG] or non-CABG TIMI [Thrombolysis In Myocardial Infarction] major bleeding) were also evaluated at 7 days.RESULTS:The primary efficacy outcome of cardiovascular death, MI, stroke, urgent revascularization or glycoprotein IIb/IIIa inhibitor bailout use did not differ between the quartiles of pre-treatment duration in the trial population (p = 0.17 for interaction). None of the secondary efficacy outcomes were found to be dependent on pre-treatment duration. The safety outcome of all CABG or non-CABG TIMI major bleeding did not differ between the quartiles of pre-treatment duration (p = 0.37 for interaction).CONCLUSIONS:In non-ST-segment elevation MI patients, the excess risk of bleeding and the absence of ischemic benefit were consistent across the quartiles of increasing duration of prasugrel pre-treatment. (A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction [ACCOAST]; NCT01015287).

Published
2019
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29. Drug-Eluting Balloon Versus Drug-Eluting Stent for Complex Femoropopliteal Arterial Lesions: The DRASTICO Study

Author

Francesco, Liistro, Paolo, Angioli, Italo, Porto, Kenneth, Ducci, Giovanni, Falsini, Giorgio, Ventoruzzo, Lucia, Ricci, Alessia, Scatena, Simone, Grotti, and Leonardo, Bolognese

Subjects
Aged, 80 and over, Femoral Artery, Male, Drug Delivery Systems, Self Expandable Metallic Stents, Humans, Arterial Occlusive Diseases, Drug-Eluting Stents, Female, Popliteal Artery, Prospective Studies, Aged
Abstract

Drug-eluting technologies improve 12-month angiographic results of femoropopliteal (FP) interventions, but few data on the comparison between drug-coated balloons (DCBs) and drug-eluting stents (DES) are available.The aim of this study was to compare, after balloon pre-dilation, a strategy of DCB followed by provisional self-expanding nitinol bare-metal stent implantation with a strategy of systematic DES implantation in patients at high risk for FP restenosis.Patients presenting with either intermittent claudication or critical limb ischemia undergoing FP intervention were randomly assigned 1:1 to DCB or DES after successful target lesion pre-dilation. The primary endpoint was 12-month target lesion binary restenosis, assessed using Doppler ultrasound. Secondary endpoints were freedom from target lesion revascularization and from major amputation.A total of 192 patients, 96 in the DCB group and 96 in the DES group, with 240 lesions in 225 limbs, were included. Diabetes and critical limb ischemia were present in50% in both groups. Mean lesion length was 14 cm, and baseline target lesion occlusion reached about 60% of cases in both groups. The systematic DES strategy yielded larger post-procedural minimal luminal diameter and a lower incidence of residual dissection compared to DCB, in which nitinol stents were used in only 21% of the lesions. Twelve-month target lesion restenosis was observed in 22% of DCB-treated versus 21% of DES-treated patients (p = 0.90). Clinically driven target lesion revascularization was necessary in 14% of DCB patients versus 17% of DES patients (p = 0.50).DCB was not superior to DES in the treatment of complex FP lesions in a high-risk population, yielding similar rate of restenosis and clinically driven target lesion revascularization. (Paclitaxel-Eluting Balloon Angioplasty With Provisional Use of Nitinol Stent Versus Systematic Implantation of Paclitaxel-Eluting Stent for the Treatment of Femoropopliteal De Novo Lesions; NCT01969630).

Published
2019

30. Impact of long-term ticagrelor monotherapy following 1-month dual antiplatelet therapy in patients who underwent complex percutaneous coronary intervention: insights from the Global Leaders trial

Author

Joanna J. Wykrzykowska, Antonio Colombo, Leonardo Bolognese, Hidenori Komiyama, Chun Chin Chang, Peter Jüni, Osama Ibrahim Ibrahim Soliman, Edouard Benit, Hans-Peter Stoll, Pascal Vranckx, Rodrigo Modolo, Patrick W. Serruys, Paweł Buszman, Marcello Dominici, Christian W. Hamm, Marco Valgimigli, Maurizio Ferrario, Robbert J. de Winter, Philippe Gabriel Steg, Ply Chichareon, Mariusz Tomaniak, Carlo Tumscitz, Yoshinobu Onuma, Stephan Windecker, Norihiro Kogame, Kuniaki Takahashi, Graduate School, ACS - Heart failure & arrhythmias, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, and Cardiology

Subjects
Male, Ticagrelor, medicine.medical_specialty, medicine.medical_treatment, Myocardial Infarction, Hemorrhage, 610 Medicine & health, 030204 cardiovascular system & hematology, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, Cause of Death, Internal medicine, Myocardial Revascularization, medicine, Clinical endpoint, Humans, Prospective Studies, 030212 general & internal medicine, Myocardial infarction, cardiovascular diseases, Acute Coronary Syndrome, Aged, Aspirin, business.industry, Hazard ratio, Stent, Percutaneous coronary intervention, Drug-Eluting Stents, Middle Aged, medicine.disease, Stroke, Drug-eluting stent, Case-Control Studies, Conventional PCI, Purinergic P2Y Receptor Antagonists, Cardiology, Drug Therapy, Combination, Female, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract

Aims To evaluate the impact of an experimental strategy [23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT)] vs. a reference regimen (12-month aspirin monotherapy following 12-month DAPT) after complex percutaneous coronary intervention (PCI). Methods and results In the present post hoc analysis of the Global Leaders trial, the primary endpoint [composite of all-cause death or new Q-wave myocardial infarction (MI)] at 2 years was assessed in patients with complex PCI, which includes at least one of the following characteristics: multivessel PCI, ≥3 stents implanted, ≥3 lesions treated, bifurcation PCI with ≥2 stents, or total stent length >60 mm. In addition, patient-oriented composite endpoint (POCE) (composite of all-cause death, any stroke, any MI, or any revascularization) and net adverse clinical events (NACE) [composite of POCE or Bleeding Academic Research Consortium (BARC) Type 3 or 5 bleeding] were explored. Among 15 450 patients included in this analysis, 4570 who underwent complex PCI had a higher risk of ischaemic and bleeding events. In patients with complex PCI, the experimental strategy significantly reduced risks of the primary endpoint [hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.48–0.85] and POCE (HR: 0.80, 95% CI: 0.69–0.93), but not in those with non-complex PCI (P interaction = 0.015 and 0.017, respectively). The risk of BARC Type 3 or 5 bleeding was comparable (HR: 0.97, 95% CI: 0.67–1.40), resulting in a significant risk reduction in NACE (HR: 0.80, 95% CI: 0.69–0.92; P interaction = 0.011). Conclusion Ticagrelor monotherapy following 1-month DAPT could provide a net clinical benefit for patients with complex PCI. However, in view of the overall neutral results of the trial, these findings of a post hoc analysis should be considered as hypothesis generating.

Published
2019
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31. Morphine and Ticagrelor Interaction in Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction:ATLANTIC-Morphine

Author

Lapostolle, Frederic, van't Hof, Arnoud W., Hamm, Christian W., Stibbe, Olivier, Ecollan, Patrick, Collet, Jean-Philippe, Silvain, Johanne, Lassen, Jens Flensted, Heutz, Wim M. J. M., Bolognese, Leonardo, Cantor, Warren J., Cequier, Angel, Chettibi, Mohamed, Goodman, Shaun G., Hammett, Christopher, Huber, Kurt, Janzon, Magnus, Merkely, Bela, Storey, Robert F., ten Berg, Jur, Zeymer, Uwe, Licour, Muriel, Tsatsaris, Anne, Montalescot, Gilles, Bougherbal, Rachid, Bouafia, Mohamed Tahar, Nibouche, Djamaleddine, Moklati, Abdelkader, Benalia, Ahmed, Krim, Messaad, Garraby, Paul, Jayasinghe, Rohan, Rashford, Stephen, Neunteufl, Thomas, Brussee, Helmut, Alber, Hannes, Weidinger, Franz, Baubin, Michael, Sebald, Dieter, Cantor, Warren, Vijayaraghavan, Ram, Bata, Iqbal, Lavoie, Andrea, Ravkilde, Jan, Jensen, Lisette Okkels, Christensen, Alf Mol, Université Sorbonne Paris Cité (USPC), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Brigade de sapeurs pompiers de Paris (BSPP), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Aarhus University Hospital, University of Toronto, University of Barcelona, Centre Hospitalo-Universitaire de Blida (CHU Blida), St. Michael's Hospital, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Linköping University (LIU), Semmelweis University of Medicine [Budapest], University of Sheffield [Sheffield], St. Antonius Hospital [Nieuwegein], AstraZeneca, RS: Carim - H01 Clinical atrial fibrillation, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), and RS: CARIM - R2.01 - Clinical atrial fibrillation

Subjects
Male, Ticagrelor, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Chest pain, DOUBLE-BLIND, 0302 clinical medicine, PRASUGREL, REPERFUSION, Pharmacology (medical), 030212 general & internal medicine, Myocardial infarction, Stroke, OUTCOMES, Morphine, General Medicine, Thrombolysis, ASSOCIATION, Middle Aged, 3. Good health, Analgesics, Opioid, INSIGHTS, Treatment Outcome, surgical procedures, operative, Cardiology, Female, TRIAL, medicine.symptom, Cardiology and Cardiovascular Medicine, TIMI, medicine.drug, Adult, medicine.medical_specialty, Pain, Platelet Glycoprotein GPIIb-IIIa Complex, Revascularization, 03 medical and health sciences, Percutaneous Coronary Intervention, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, cardiovascular diseases, Aged, Retrospective Studies, business.industry, Percutaneous coronary intervention, medicine.disease, ST Elevation Myocardial Infarction, business, Platelet Aggregation Inhibitors
Abstract

Background: Morphine adversely impacts the action of oral adenosine diphosphate (ADP)-receptor blockers in ST-segment elevation myocardial infarction (STEMI) patients, and is possibly associated with differing patient characteristics. This retrospective analysis investigated whether interaction between morphine use and pre-percutaneous coronary intervention (pre-PCI) ST-segment elevation resolution in STEMI patients in the ATLANTIC study was associated with differences in patient characteristics and management. Methods: ATLANTIC was an international, multicenter, randomized study of treatment in the acute ambulance/hospital setting where STEMI patients received ticagrelor 180 mg ± morphine. Patient characteristics, cardiovascular history, risk factors, management, and outcomes were recorded. Results: Opioids (97.6% morphine) were used in 921 out of 1862 patients (49.5%). There were no significant differences in age, sex or cardiovascular history, but more morphine-treated patients had anterior myocardial infarction and left-main disease. Time from chest pain to electrocardiogram and ticagrelor loading was shorter with morphine (both p = 0.01) but not total ischemic time. Morphine-treated patients more frequently received glycoprotein IIb/IIIa inhibitors (p = 0.002), thromboaspiration and stent implantation (both p < 0.001). No significant difference between the two groups was found regarding pre-PCI ≥ 70% ST-segment elevation resolution, death, myocardial infarction, stroke, urgent revascularization and definitive acute stent thrombosis. More morphine-treated patients had an absence of pre-PCI Thrombolysis in Myocardial Infarction (TIMI) 3 flow (85.8% vs. 79.7%; p = 0.001) and more had TIMI major bleeding (1.1% vs. 0.1%; p = 0.02). Conclusions: Morphine-treatment was associated with increased GP IIb/IIIa inhibitor use, less pre-PCI TIMI 3 flow, and more bleeding. Judicious morphine use is advised with non-opioid analgesics preferred for non-severe acute pain. Trial Registration: clinicaltrials.gov identifier: NCT01347580.

Published
2019
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32. Impact of presentation and transfer delays on complete ST-segment resolution before primary percutaneous coronary intervention: insights from the ATLANTIC trial

Author

Arnoud W J van 't Hof, Jurriën M. ten Berg, Jens Flensted Lassen, Eric Vicaut, Enrico Fabris, Béla Merkely, Shaun G. Goodman, Hélène Rousseau, Leonardo Bolognese, Mohamed Chettibi, Magnus Janzon, Angel Cequier, Warren J. Cantor, Christian W. Hamm, Christopher H Hammett, Frédéric Lapostolle, Kurt Huber, Gilles Montalescot, Robert F. Storey, Uwe Zeymer, Fabris, E., Van't Hof, A., Hamm, C. W., Lapostolle, F., Lassen, J. F., Goodman, S. G., Ten Berg, J. M., Bolognese, L., Cequier, A., Chettibi, M., Hammett, C. J., Huber, K., Janzon, M., Merkely, B., Storey, R. F., Zeymer, U., Cantor, W. J., Rousseau, H., Vicaut, E., and Montalescot, G.

Subjects
Male, ST-elevation myocardial infrarction (STEMI), Emergency Medical Services, PRIMARY PCI, medicine.medical_treatment, PREHOSPITAL TICAGRELOR, Coronary, Myocardial Infarction, 030204 cardiovascular system & hematology, THERAPY, Clinical research, Electrocardiography, 0302 clinical medicine, Clinical trials, Risk Factors, 80 and over, REPERFUSION, Medicine, ST segment, Thrombolytic Therapy, 030212 general & internal medicine, Myocardial infarction, Angioplasty, Balloon, Coronary, Aged, 80 and over, Anticoagulant, Middle Aged, TIME, clinical reserch, Clinical trial, Treatment Outcome, Cardiology, Platelet aggregation inhibitor, Female, Cardiology and Cardiovascular Medicine, Ticagrelor, Human, medicine.drug, medicine.medical_specialty, medicine.drug_class, INHIBITION, clinical trails, 03 medical and health sciences, Percutaneous Coronary Intervention, Angioplasty, Internal medicine, PATENCY, Adjunctive pharmacotherapy, Humans, cardiovascular diseases, ARTERY, Aged, Emergency Medical Service, business.industry, Platelet Aggregation Inhibitor, Risk Factor, ELEVATION MYOCARDIAL-INFARCTION, Percutaneous coronary intervention, medicine.disease, ST-elevation myocardial infarction (STEMI), Platelet Aggregation Inhibitors, Surgery, Conventional PCI, HEPARIN, business, Balloon
Abstract

Aims: The aim of this study was to identify predictors of complete ST-segment resolution (STR) pre-primary percutaneous coronary intervention (PCI) in patients enrolled in the ATLANTIC trial. Methods and results: ECGs recorded at the time of inclusion (pre-hospital [pre-H]-ECG) and in the catheterisation laboratory before angiography (pre-PCI-ECG) were analysed by an independent core laboratory. Complete STR was defined as ≥70%. Complete STR occurred pre-PCI in 12.8% (204/1, 598) of patients and predicted lower 30-day composite MACCE (OR=0.10, 95% CI: 0.002-0.57, p=0.001) and total mortality (OR=0.16, 95% CI: 0.004-0.95, p=0.035). Independent predictors of complete STR included the time from index event to pre-H-ECG (OR=0.94, 95% CI: 0.89-1.00, p=0.035), use of heparins before pre- PCI-ECG (OR=1.75, 95% CI: 1.25-2.45, p=0.001) and time from pre-H-ECG to pre-PCI-ECG (OR=1.09, 95% CI: 1.03-1.16, p=0.005). In the pre-H ticagrelor group, patients with complete STR had a significantly longer delay between pre-H-ECG and pre-PCI-ECG compared to patients without complete STR (median 53 [44-73] vs. 49 [38.5-61] mins, p=0.001); however, this was not observed in the control group (in-hospital ticagrelor) (50 [40-67] vs. 49 [39-61] mins, p=0.258). Conclusions: Short patient delay, early administration of anticoagulant and ticagrelor if a long transfer delay is expected may help to achieve reperfusion prior to PCI. Pre-H treatment may be beneficial in patients with longer transfer delays, allowing the drug to become biologically active. ClinicalTrials.gov Identifier: NCT01347580.

Published
2017
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33. Prognostic Impact of Diabetes and Prediabetes on Survival Outcomes in Patients With Chronic Heart Failure: A Post-Hoc Analysis of the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) Trial

Author

Marco Dauriz, Giovanni Targher, Pier Luigi Temporelli, Donata Lucci, Lucio Gonzini, Gian Luigi Nicolosi, Roberto Marchioli, Gianni Tognoni, Roberto Latini, Franco Cosmi, Luigi Tavazzi, Aldo Pietro Maggioni, Simona Barlera, Maria Grazia Franzosi, Aldo P. Maggioni, Maurizio Porcu, Salim Yusuf, Fulvio Camerini, Jay N. Cohn, Adriano Decarli, Bertram Pitt, Peter Sleight, Philip A. Poole‐Wilson, Enrico Geraci, Marino Scherillo, Gianna Fabbri, Barbara Bartolomei, Daniele Bertoli, Franco Cobelli, Claudio Fresco, Antonietta Ledda, Giacomo Levantesi, Cristina Opasich, Franco Rusconi, Gianfranco Sinagra, Fabio Turazza, Alberto Volpi, Martina Ceseri, Gianluca Alongi, Antonio Atzori, Filippo Bambi, Desiree Bastarolo, Francesca Bianchini, Iacopo Cangioli, Vittoriana Canu, Concetta Caporusso, Gabriele Cenni, Laura Cintelli, Michele Cocchio, Alessia Confente, Eva Fenicia, Giorgio Friso, Marco Gianfriddo, Gianluca Grilli, Beatrice Lazzaro, Giuseppe Lonardo, Alessia Luise, Rachele Nota, Mariaelena Orlando, Rosaria Petrolo, Chiara Pierattini, Valeria Pierota, Alessandro Provenzani, Velia Quartuccio, Anna Ragno, Chiara Serio, Alvise Spolaor, Arianna Tafi, Elisa Tellaroli, Stefano Ghio, Elisa Ghizzardi, Serge Masson, Lella Crociati, Maria Teresa La Rovere, Ugo Corrà, Andrea Finzi, Marco Gorini, Valentina Milani, Giampietro Orsini, Elisa Bianchini, Silvia Cabiddu, Ilaria Cangioli, Laura Cipressa, Maria Lucia Cipressa, Giuseppina Di Bitetto, Barbara Ferri, Luisa Galbiati, Andrea Lorimer, Carla Pera, Paola Priami, Antonella Vasamì, T. Moccetti, M.G. Rossi, E. Pasotti, F. Vaghi, P. Roncarolo, M.T. Zunino, F. Matta, E. Actis Perinetto, F. Gaita, G. Azzaro, M. Zanetta, A.M. Paino, U. Parravicini, D. Vegis, R. Conte, P. Ferraro, A. De Bernardi, S. Morelloni, M. Fagnani, P. Greco Lucchina, L. Montagna, E. Bellone, D. Sappè, F. Ferraro, M. Delucchi, S.G. Reynaud, M. Dore, A. La Brocca, N. Massobrio, L. Bo, R. Trinchero, M. Imazio, G. Brocchi, A. Nejrotti, L. Rissone, S. Gabasio, C. Zocchi, S. Randazzo, A. Crenna, P. Giannuzzi, E. Bonanomi, A. Mezzani, M. De Marchi, G. Begliuomini, C.A. Gianonatti, A. Gavazzi, A. Grosu, L. Dei Cas, S. Nodari, P. Garyfallidis, A. Bertoletti, C. Bonifazi, S. Arisi, F. Mascaro, M. Fraccarollo, S. Dell'Orto, M. Sfolcini, F. Bortolini, D. Raccagni, A. Turelli, M. Santarone, E. Miglierina, L. Sormani, R. Jemoli, F. Tettamanti, S. Pirelli, C. Bianchi, S. Verde, M. Mariani, V. Ziacchi, A. Ferrazza, A. Russo, M. Bortolotti, G.F. Pasini, A. Volpi, K.N. Jones, D. Cuzzucrea, G. Gullace, C. Carbone, A. Granata, S. De Servi, G. Del Rosso, C. Inserra, E. Renaldini, C. Zappa, M. Moretti, R. Zanini, M. Ferrari, E. Moroni, A. Cei, C. Lissi, E. Dovico, C. Fiorentini, P. Palermo, B. Brusoni, M. Negrini, J. Heyman, G.B. Danzi, A. Finzi, M. Frigerio, F. Turazza, L. Beretta, A. Sachero, F. Casazza, L. Squadroni, F. Lombardi, L. Marano, A. Margonato, G. Fragasso, O.C. Febo, E. Aiolfi, F. Olmetti, A. Grieco, V. Antonazzo, G. Specchia, A. Mortara, F. Robustelli, M.G. Songini, C. Schweiger, A. Frisinghelli, M. Palvarini, C. Campana, L. Scelsi, N. Ajmone Marsan, F. Cobelli, A. Gualco, C. Opasich, S. De Feo, R. Mazzucco, M.A. Iannone, T. Diaco, D. Zaniboni, G. Milanesi, D. Nassiacos, S. Meloni, P. Giani, T. Nicoli, C. Malinverni, A. Gusmini, L. Pozzoni, G. Bisiani, P. Margaroli, A. Schizzarotto, A. Daverio, G. Occhi, N. Partesana, P. Bandini, M.G. Rosella, S. Giustiniani, G. Cucchi, R. Pedretti, R. Raimondo, R. Vaninetti, A. Fedele, I. Ghezzi, E. Rezzonico, J.A. Salerno Uriarte, F. Morandi, F. Salvucci, C. Valenti, G. Graziano, M. Romanò, C. Cimminiello, I. Mangone, M. Lombardo, P. Quorso, G. Marinoni, M. Breghi, M. Erckert, A. Dienstl, G. Mirante Marini, C. Stefenelli, G. Cioffi, E. Buczkowska, A. Bonanome, F. Bazzanini, L. Parissenti, C. Serafini, G. Catania, L. Tarantini, G. Rigatelli, S. Boni, A. Pasini, E. Masini, A.A. Zampiero, M. Zanchetta, L. Franceschetto, P. Delise, C. Marcon, A. Sacchetta, L. Borgese, L. Artusi, P. Casolino, F. Corbara, A. Banzato, M. Barbiero, M.P. Aldegheri, R. Bazzucco, G. Crivellenti, A. Raviele, C. Zanella, P. Pascotto, P. Sarto, S. Milan, E. Barbieri, P. Girardi, W. Dalla Villa, J. Dalle Mule, M.L. Di Sipio, R. Cazzin, D. Milan, P. Zonzin, M. Carraro, R. Rossi, E. Carbonieri, I. Rossi, P. Stritoni, P. Meneghetti, G. Risica, P.L. Tenderini, C. Vassanelli, L. Zanolla, G. Perini, G. Brighetti, R. Chiozza, G. Giuliano, R. Gortan, R. Cesanelli, G.L. Nicolosi, R. Piazza, L. Mos, O. Vriz, D. Pavan, G. Pascottini, E. Alberti, M. Werren, L. Solinas, G. Sinagra, F. Longaro, P. Fioretti, M.C. Albanese, D. Miani, R. Gianrossi, A. Pende, P. Rubartelli, O. Magaia, S. Domenicucci, D. Caruso, A.S. Faraguti, L. Magliani, F. Miccoli, G. Guglielmino, D. Bertoli, A. Cantarelli, S. Orlandi, A. Vallebona, A. Pozzati, G. Brega, L.G. Pancaldi, R. Vandelli, S. Urbinati, M.G. Poci, M. Zoli, G.M. Costa, U. Guiducci, G. Zobbi, F. Tartagni, A. Tisselli, A. Gentili, P. Pieri, E. Cagnetta, S. Bendinelli, A. Barbieri, R. Conti, R. Ferrari, F. Merlini, A. Fucili, P. Moruzzi, E. Buia, M. Galvani, D. Ferrini, G. Baggioni, P. Yiannacopulu, G. Canè, A. Bonfiglioli, R. Zandomeneghi, L. Brugioni, A. Giannini, R. Di Ruvo, M. Giuliani, L. Rusconi, P. Del Corso, G. Piovaccari, F. Bologna, P. Venturi, F. Melandri, E. Bagni, L. Bolognese, R. Perticucci, A. Zuppiroli, M. Nannini, N. Consoli, P. Petrone, C. Pipitò, L. Colombi, D. Bernardi, P.R. Mariani, R. Testa, F. Mazzinghi, F. Cosmi, D. Cosmi, A. Zipoli, A. Cecchi, G. Castelli, M. Ciaccheri, F. Mori, F. Pieri, P. Valoti, D. Chiarantini, G.M. Santoro, C. Minneci, F. Marchi, M. Milli, G. Zambaldi, A.A. Brandinelli Geri, M. Cipriani, M. Alessandri, S. Severi, S. Stefanelli, A. Comella, R. Poddighe, A. Digiorgio, M. Carluccio, S. Berti, A. Rizza, V. Bonatti, V. Molendi, A. Brancato, N. D'Aprile, G. Giappichini, S. Del Vecchio, G. Mantini, F. De Tommasi, G. Meucci, M. Cordoni, S. Bechi, L. Barsotti, P. Baldini, M. Romei, G. Scopelliti, G. Lauri, F. Pestelli, F. Furiozzi, M. Cocchieri, D. Severini, F. Patriarchi, P. Chiocchi, M. Buccolieri, S. Martinelli, A. Wee, F. Angelici, M. Bernardinangeli, G. Proietti, B. Biscottini, R. Panciarola, L. Marinacci, G.P. Perna, D. Gabrielli, A. Moraca, L. Moretti, L. Partemi, G. Gregori, R. Amici, G. Patteri, P. Capone, E. Savini, G.L. Morgagni, L. Paccaloni, F. Pezzuoli, S. Carincola, S. Papi, S. De Crescentini, P. Gerardi, P. Midi, E. Gallenzi, G. Pajes, C. Mancone, V. Di Spirito, M. Di Gennaro, S. Calcagno, S. Toscano, S. Antonicoli, F. Carta, G. Giorgi, F. Comito, E. Daniele, O. Ciarla, P.G. Gelfo, A. Acquaviva, D. Testa, G. Testa, F.A. Pagliaro, F. Russo, F. Vetta, I. Marchese, G. Di Sciascio, A. D'Ambrosio, F. Leggio, D. Del Sindaco, A. Lacchè, A. Avallone, M.P. Risa, P. Azzolini, E. Baldo, E. Giovannini, G. Pulignano, C. Tondo, E. Picchio, E. ani, P. Tanzi, F. Pozzar, F. Farnetti, M. Azzarito, M. Santini, A. Varveri, G. Ferraiuolo, C. Valtorta, A. Gaspardone, G. Barbato, V. Ceci, N. Aspromonte, F. Bellocci, C. Colizzi, F. Fedele, F.I. Perez, A. Galati, A. Rossetti, A. Mainella, D. etta, C. Matteucci, G. Busi, A. De Angelis, G. Farina, A. Granatelli, F. Leone, F. Frasca, R. Di Giovambattista, G. Castellani, G. Massaro, G. Mastrogiuseppe, A. Vacri, F. De Sanctis, M. Cioli, S. Di Luzio, C. Napoletano, L.L. Piccioni, G. De Simone, A. Ottaviano, V. Mazza, C. Spedaliere, D. Staniscia, E. Calgione, G. De Marco, T. Chiacchio, T. Di Napoli, S. Romanzi, G. Salvatore, P. Golino, A. Palermo, F. Mascia, A. Vetrano, A. Vinciguerra, L. Caliendo, R. Longobardi, G. De Caro, R. Di Nola, F. Piemonte, D. Prinzi, P. De Rosa, V. De Rosa, F. Riello, V. Capuano, G. Vecchio, M. Landi, S. Amato, M. Garofalo, M. D'Avino, P. Sensale, O. Maiolica, R. Santoro, P. Caso, D. Miceli, N. Maurea, U. Bianchi, C. Crispo, M. Chiariello, P. Perrone Filardi, L. Russo, N. Capuano, G. Ungaro, G. Vergara, F. Scafuro, G. D'Angelo, C. Campaniello, P. Bottiglieri, A. Volpe, R. Battista, L. De Risi, G. Cardillo, G. Sibilio, A.P. Marino, F. Silvestri, P. Predotti, A. Iervoglini, C. De Matteis, P. Sarnicola, M.M. Matarazzo, S. Baldi, V. Iuliano, C. Astarita, P. Cuccaro, A. Liguori, G. Liguori, G. Gregorio, L. Petraglia, G. Antonelli, G. Amodio, I. De Luca, D. Traversa, G. Franchini, M.L. Lenti, D. Cavallari, C. D'Agostino, G. Scalera, C.M. Altamura, M. Russo, A.R. Mascolo, G. Pettinati, S.A. Ciricugno, D. Scrutinio, A. Passantino, D. Mastrangelo, A. Di Masi, R. De Carne, M. Cannone, F. Dibiase, M. Pensato, F. Loliva, F. Trapani, I. Panettieri, L. Leone, M. Di Biase, M. Carrone, V. Gallone, F. Cocco, M. Costantini, C. Tritto, F. Cavalieri, L. Stella, F. Magliari, M. Callerame, A. De Giorgi, L. Pellegrino, M. Correra, V. Portulano, G.L. Nisi, G. Grassi, E. Cristallo, D. De Laura, C. Salerno, R. Fanelli, M. Villella, S. Pede, A. Renna, E. De Lorenzi, L. Urso, V. Lenti, A. Peluso, N. Baldi, G. Polimeni, P. Palma, R. Lauletta, E. Tagliamonte, T. Cirillo, B. Silvestri, G. Centonze, B. D'Alessandro, L. Truncellito, D. Mecca, M.A. Petruzzi, R.O.M. Coviello, A. Lopizzo, M. telli, S. Barbuzzi, S. Gubelli, G. Germinario, N. Cosentino, A. Mingrone, R. Vico, G. Borrello, M.L. Mazza, R. Cimino, D. Galasso, F. Cassadonte, U. Talarico, F. Perticone, S. Cassano, F. Catapano, S. Calemme, E. Feraco, C. Cloro, G. Misuraca, R. Caporale, L. Vigna, V. Spagnuolo, F. De Rosa, G. Spadafora, G. Zampaglione, R. Russo, F.A. Schipani, A.F. Ferragina, D. Stranieri, G. Musca, C. Carpino, P. Bencardino, F. Raimondo, D. Musacchio, G. Pulitanò, A. Ruggeri, A. Provenzano, S. Salituri, M. Musolino, S. Calandruccio, A. Marrari, E. Tripodi, R. Scali, L. Anastasio, A. Arone, P. Aragona, L. Donnangelo, M.G.A. Comito, F. Bilotta, I. Vaccaro, R. Rametta, V. Ventura, A. Bonvegna, A. Alì, C. Cinnirella, M. Raineri, F. Pompeo, N. Cascio Ingurgio, V. Carini, R. Coco, G. Giunta, G. Leonardi, V. Randazzo, V. Di Blasi, C. Tamburino, G. Russo, S. Mangiameli, R. Cardillo, D. Castelli, V. Inserra, A. Arena, M.M. Gulizia, S. Raciti, G. Rapisarda, R. Romano, P. Prestifilippo, G.B. Braschi, G. Ledda, R. Terrazzino, M. De Caro, G. Scilabra, B. agnino, R. Grassi, G. Di Tano, G.F. Scimone, L. Vasquez, C. Coppolino, A. Casale, M. Castelli, G. D'Urso, E. D'Antonio, L. Lo Presti, E. Badalamenti, P. Conti, N. Sanfilippo, V. Cirrincione, M.T. Cinà, G. Cusimano, A. Taormina, P. Giuliano, A. Bajardi, V. Mandalà, A. Canonico, G. Geraci, F.P. Sabella, F. Enia, A.M. Floresta, I. Lo Cascio, D. Gumina, A. Cavallaro, G. Piccione, R. Ferrante, M. Blandino, M.S. Iudicello, E. Mossuti, G. Romano, L. Lombardo, P. Monastra, D. Di Vincenzo, M. Porcu, P. Orrù, F. Muscas, G. Giardina, M. Corda, G. Locci, A. Podda, M. Ledda, P. Siddi, C. Lai, G. Pili, G. Mercuro, G. Mureddu, A. Ganau, G. Meloni, G. Poddighe, G. Sanna, Dauriz, Marco, Targher, Giovanni, Temporelli, Pier Luigi, Lucci, Donata, Gonzini, Lucio, Nicolosi, Gian Luigi, Marchioli, Roberto, Tognoni, Gianni, Latini, Roberto, Cosmi, Franco, Tavazzi, Luigi, Maggioni, Aldo Pietro, on behalf of the GISSI-HF, Investigator, Margonato, Alberto, Moccetti, T., Rossi, M. G., Pasotti, E., Vaghi, F., Roncarolo, P., Zunino, M. T., Matta, F., Actis Perinetto, E., Gaita, F., Azzaro, G., Zanetta, M., Paino, A. M., Parravicini, U., Vegis, D., Conte, R., Ferraro, P., De Bernardi, A., Morelloni, S., Fagnani, M., Greco Lucchina, P., Montagna, L., Bellone, E., Sappè, D., Ferraro, F., Delucchi, M., Reynaud, S. G., Dore, M., La Brocca, A., Massobrio, N., Bo, L., Trinchero, R., Imazio, M., Brocchi, G., Nejrotti, A., Rissone, L., Gabasio, S., Zocchi, C., Randazzo, S., Crenna, A., Giannuzzi, P., Bonanomi, E., Mezzani, A., De Marchi, M., Begliuomini, G., Gianonatti, C. A., Gavazzi, A., Grosu, A., Dei Cas, L., Nodari, S., Garyfallidis, P., Bertoletti, A., Bonifazi, C., Arisi, S., Mascaro, F., Fraccarollo, M., Dell'Orto, S., Sfolcini, M., Bortolini, F., Raccagni, D., Turelli, A., Santarone, M., Miglierina, E., Sormani, L., Jemoli, R., Tettamanti, F., Pirelli, S., Bianchi, C., Verde, S., Mariani, M., Ziacchi, V., Ferrazza, A., Russo, A., Bortolotti, M., Pasini, G. F., Volpi, A., Jones, K. N., Cuzzucrea, D., Gullace, G., Carbone, C., Granata, A., De Servi, S., Del Rosso, G., Inserra, C., Renaldini, E., Zappa, C., Moretti, M., Zanini, R., Ferrari, M., Moroni, E., Cei, A., Lissi, C., Dovico, E., Fiorentini, C., Palermo, P., Brusoni, B., Negrini, M., Heyman, J., Danzi, G. 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L., Paccaloni, L., Pezzuoli, F., Carincola, S., Papi, S., De Crescentini, S., Gerardi, P., Midi, P., Gallenzi, E., Pajes, G., Mancone, C., Di Spirito, V., Di Gennaro, M., Calcagno, S., Toscano, S., Antonicoli, S., Carta, F., Giorgi, G., Comito, F., Daniele, E., Ciarla, O., Gelfo, P. G., Acquaviva, A., Testa, D., Testa, G., Pagliaro, F. A., Russo, F., Vetta, F., Marchese, I., Di Sciascio, G., D'Ambrosio, A., Leggio, F., Del Sindaco, D., Lacchè, A., Avallone, A., Risa, M. P., Azzolini, P., Baldo, E., Giovannini, E., Pulignano, G., Tondo, C., Picchio, E., Biffani, E., Tanzi, P., Pozzar, F., Farnetti, F., Azzarito, M., Santini, M., Varveri, A., Ferraiuolo, G., Valtorta, C., Gaspardone, A., Barbato, G., Ceci, V., Aspromonte, N., Bellocci, F., Colizzi, C., Fedele, F., Perez, F. I., Galati, A., Rossetti, A., Mainella, A., Ciuffetta, D., Matteucci, C., Busi, G., De Angelis, A., Farina, G., Granatelli, A., Leone, F., Frasca, F., Di Giovambattista, R., Castellani, G., Massaro, G., Mastrogiuseppe, G., Vacri, A., De Sanctis, F., Cioli, M., Di Luzio, S., Napoletano, C., Piccioni, L. L., De Simone, G., Ottaviano, A., Mazza, V., Spedaliere, C., Staniscia, D., Calgione, E., De Marco, G., Chiacchio, T., Di Napoli, T., Romanzi, S., Salvatore, G., Golino, P., Palermo, A., Mascia, F., Vetrano, A., Vinciguerra, A., Caliendo, L., Longobardi, R., De Caro, G., Di Nola, R., Piemonte, F., Prinzi, D., De Rosa, P., De Rosa, V., Riello, F., Capuano, V., Vecchio, G., Landi, M., Amato, S., Garofalo, M., D'Avino, M., Sensale, P., Maiolica, O., Santoro, R., Caso, P., Miceli, D., Maurea, N., Bianchi, U., Crispo, C., Chiariello, M., Perrone Filardi, P., Russo, L., Capuano, N., Ungaro, G., Vergara, G., Scafuro, F., D'Angelo, G., Campaniello, C., Bottiglieri, P., Volpe, A., Battista, R., De Risi, L., Cardillo, G., Sibilio, G., Marino, A. P., Silvestri, F., Predotti, P., Iervoglini, A., De Matteis, C., Sarnicola, P., Matarazzo, M. 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F., Stranieri, D., Musca, G., Carpino, C., Bencardino, P., Raimondo, F., Musacchio, D., Pulitanò, G., Ruggeri, A., Provenzano, A., Salituri, S., Musolino, M., Calandruccio, S., Marrari, A., Tripodi, E., Scali, R., Anastasio, L., Arone, A., Aragona, P., Donnangelo, L., Comito, M. G. A., Bilotta, F., Vaccaro, I., Rametta, R., Ventura, V., Bonvegna, A., Alì, A., Cinnirella, C., Raineri, M., Pompeo, F., Cascio Ingurgio, N., Carini, V., Coco, R., Giunta, G., Leonardi, G., Randazzo, V., Di Blasi, V., Tamburino, C., Russo, G., Mangiameli, S., Cardillo, R., Castelli, D., Inserra, V., Arena, A., Gulizia, M. M., Raciti, S., Rapisarda, G., Romano, R., Prestifilippo, P., Braschi, G. B., Ledda, G., Terrazzino, R., De Caro, M., Scilabra, G., Graffagnino, B., Grassi, R., Di Tano, G., Scimone, G. F., Vasquez, L., Coppolino, C., Casale, A., Castelli, M., D'Urso, G., D'Antonio, E., Lo Presti, L., Badalamenti, E., Conti, P., Sanfilippo, N., Cirrincione, V., Cinà, M. T., Cusimano, G., Taormina, A., Giuliano, P., Bajardi, A., Mandalà, V., Canonico, A., Geraci, G., Sabella, F. P., Enia, F., Floresta, A. M., Lo Cascio, I., Gumina, D., Cavallaro, A., Piccione, G., Ferrante, R., Blandino, M., Iudicello, M. S., Mossuti, E., Romano, G., Lombardo, L., Monastra, P., Di Vincenzo, D., Porcu, M., Orrù, P., Muscas, F., Giardina, G., Corda, M., Locci, G., Podda, A., Ledda, M., Siddi, P., Lai, C., Pili, G., Mercuro, G., Mureddu, G., Ganau, A., Meloni, G., Poddighe, G., Sanna, G., Barlera, Simona, Franzosi, Maria Grazia, Porcu, Maurizio, Yusuf, Salim, Camerini, Fulvio, Cohn, Jay N., Decarli, Adriano, Pitt, Bertram, Sleight, Peter, Poole-Wilson, Philip A., Geraci, Enrico, Scherillo, Marino, Fabbri, Gianna, Bartolomei, Barbara, Bertoli, Daniele, Cobelli, Franco, Fresco, Claudio, Ledda, Antonietta, Levantesi, Giacomo, Opasich, Cristina, Rusconi, Franco, Sinagra, Gianfranco, Turazza, Fabio, Volpi, Alberto, Ceseri, Martina, Alongi, Gianluca, Atzori, Antonio, Bambi, Filippo, Bastarolo, Desiree, Bianchini, Francesca, Cangioli, Iacopo, Canu, Vittoriana, Caporusso, Concetta, Cenni, Gabriele, Cintelli, Laura, Cocchio, Michele, Confente, Alessia, Fenicia, Eva, Friso, Giorgio, Gianfriddo, Marco, Grilli, Gianluca, Lazzaro, Beatrice, Lonardo, Giuseppe, Luise, Alessia, Nota, Rachele, Orlando, Mariaelena, Petrolo, Rosaria, Pierattini, Chiara, Pierota, Valeria, Provenzani, Alessandro, Quartuccio, Velia, Ragno, Anna, Serio, Chiara, Spolaor, Alvise, Tafi, Arianna, Tellaroli, Elisa, Ghio, Stefano, Ghizzardi, Elisa, Masson, Serge, Crociati, Lella, La Rovere, Maria Teresa, Corrà, Ugo, Di Giulio, Paola, Finzi, Andrea, Gorini, Marco, Milani, Valentina, Orsini, Giampietro, Bianchini, Elisa, Cabiddu, Silvia, Cangioli, Ilaria, Cipressa, Laura, Cipressa, Maria Lucia, Di Bitetto, Giuseppina, Ferri, Barbara, Galbiati, Luisa, Lorimer, Andrea, Pera, Carla, Priami, Paola, and Vasamì, Antonella

Subjects
Blood Glucose, Male, Glycated Hemoglobin A, heart failure, Kaplan-Meier Estimate, prediabetes, 030204 cardiovascular system & hematology, time factors, Settore MED/11, cause of death, 0302 clinical medicine, Glycemic control, prediabetic state, Cause of Death, italy, middle aged, Prevalence, 80 and over, double-blind method, blood glucose, risk factors, 030212 general & internal medicine, Prediabetes, Rosuvastatin Calcium, humans, rosuvastatin calcium, Cause of death, Original Research, Metabolic Syndrome, Aged, 80 and over, adult, Chronic heart failure, Diabetes mellitus, Heart failure, Mortality, Cardiology and Cardiovascular Medicine, Hazard ratio, chronic heart failure, diabetes mellitus, glycemic control, mortality, Treatment Outcome, Adolescent, Biomarkers, Chronic Disease, Diabetes Mellitus, Fatty Acids, Omega-3, Double-Blind Method, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hospitalization, Heart Failure, Italy, Prediabetic State, Risk Assessment, Proportional Hazards Models, Risk Factors, Time Factors, risk assessment, Middle Aged, kaplan-meier estimate, aged, female, Prediabete, young adult, Female, omega-3, Human, hospitalization, Adult, medicine.medical_specialty, Diabetes mellitu, proportional hazards models, Time Factor, hydroxymethylglutaryl-coa reductase inhibitors, prevalence, fatty acids, 03 medical and health sciences, Young Adult, male, Internal medicine, Post-hoc analysis, glycated hemoglobin a, medicine, Intensive care medicine, Aged, Glycated Hemoglobin, Proportional hazards model, business.industry, Risk Factor, biomarkers, Biomarker, medicine.disease, Clinical trial, adolescent, Proportional Hazards Model, treatment outcome, aged, 80 and over, chronic disease, fatty acids, omega-3, cardiology and cardiovascular medicine, Hydroxymethylglutaryl-CoA Reductase Inhibitor, business
Abstract

Background The independent prognostic impact of diabetes mellitus ( DM ) and prediabetes mellitus (pre‐ DM ) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐ DM on survival outcomes in the GISSI ‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial. Methods and Results We assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI ‐ HF trial, who were stratified by presence of DM (n=2852), pre‐ DM (n=2013), and non‐ DM (n=2070) at baseline. Compared with non‐ DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐ DM patients and those with pre‐ DM . Cox regression analysis showed that DM , but not pre‐ DM , was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI , 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI , 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI , 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI , 1.01–1.29, respectively). Conclusions Presence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00336336.

Published
2017
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34. Comparative assessment of 'plaque/media' change on three modalities of IVUS immediately after implantation of either everolimus-eluting bioresorbable vascular scaffold or everolimus-eluting metallic stent in Absorb II study

Author

Dieter Horstkotte, Yohei Sotomi, Hans Jonker, Erhan Tenekecioglu, Rafael Cavalcante, Leonardo Bolognese, Javier Goicolea, Shaoping Nie, Bernard Chevalier, Manfred Zehender, Yoshinobu Onuma, Rosario Fiorilli, Patrick W. Serruys, Pannipa Suwannasom, Franck Digne, Carlos Collet, Ciro Indolfi, Francesco Saia, Mahammad Abdelghani, Yaping Zeng, Cardiology, Graduate School, Amsterdam Cardiovascular Sciences, ACS - Heart failure & arrhythmias, and ACS - Atherosclerosis & ischemic syndromes

Subjects
Carotid Artery Diseases, Male, Time Factors, Databases, Factual, medicine.medical_treatment, 030204 cardiovascular system & hematology, 0302 clinical medicine, Absorbable Implants, Intravascular ultrasound, Medicine, Single-Blind Method, Prospective Studies, 030212 general & internal medicine, Cardiac imaging, medicine.diagnostic_test, Ultrasound, Drug-Eluting Stents, Middle Aged, Coronary Vessels, Plaque, Atherosclerotic, Bioresorbable vascular scaffold, Treatment Outcome, Metals, Radiology Nuclear Medicine and imaging, Female, Absorb II, Radiology, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Lumen (anatomy), Prosthesis Design, 03 medical and health sciences, Percutaneous Coronary Intervention, Predictive Value of Tests, Image Interpretation, Computer-Assisted, Humans, Radiology, Nuclear Medicine and imaging, Everolimus, Ultrasonography, Interventional, Aged, IVUS, Original Paper, Plaque/media volume, business.industry, Echogenicity, Stent, Percutaneous coronary intervention, Cardiovascular Agents, Cardiovascular agent, business
Abstract

The purpose of the study to assess the comparability of immediate changes in plaque/media volume (PV) on three modalities of intravascular ultrasound (IVUS) after implantation of either bioresorbable vascular scaffold (BVS) or everolimus-eluting metallic stent (EES) in Absorb II Study. The two devices have different device volume and ultrasound backscattering that may interfere with the “plaque/media” assessed by three modalities on IVUS: grayscale, backscattering of radiofrequency and brightness function. In a multicenter randomized controlled trial, 501 patients with stable or unstable angina underwent documentary IVUS pre- and post- implantation. The change in plaque/media volume (PV) was categorized into three groups according to the relative PV change in device segment: PV “increased” >+5% (PVI), PV unchanged ±5% (PVU), and PV decreased

Published
2016
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35. Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates

Author

C. Wang, M. A. Bolognese, Jean-Yves Reginster, Steve Cummings, Henry G. Bone, Rachel B. Wagman, A. Singer, Edward Czerwiński, Nicola Pannacciulli, Paul D. Miller, Jorge Malouf, Jacques P. Brown, and Bettina S. Nedergaard

Subjects
0301 basic medicine, medicine.medical_specialty, Bone density, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Osteoporosis, Urology, Administration, Oral, 030209 endocrinology & metabolism, Context (language use), Zoledronic Acid, Biochemistry, Bone remodeling, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Double-Blind Method, Bone Density, Internal medicine, medicine, Humans, Osteoporosis, Postmenopausal, Aged, Femoral neck, Bone mineral, Bone Density Conservation Agents, Diphosphonates, Drug Substitution, business.industry, Biochemistry (medical), Imidazoles, Original Articles, Middle Aged, medicine.disease, Surgery, 030104 developmental biology, Zoledronic acid, Denosumab, medicine.anatomical_structure, Female, business, medicine.drug
Abstract

Context: Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis. Objective: The objective of the study was to compare the effect of transitioning from oral bisphosphonates to denosumab or ZOL on bone mineral density (BMD) and bone turnover. Design and Setting: This was an international, multicenter, randomized, double-blind trial. Participants: A total of 643 postmenopausal women with osteoporosis previously treated with oral bisphosphonates participated in the study. Interventions: Subjects were randomized 1:1 to sc denosumab 60 mg every 6 months plus iv placebo once or ZOL 5 mg iv once plus sc placebo every 6 months for 12 months. Main Outcome Measures: Changes in BMD and bone turnover markers were measured. Results: BMD change from baseline at month 12 was significantly greater with denosumab compared with ZOL at the lumbar spine (primary end point; 3.2% vs 1.1%; P < .0001), total hip (1.9% vs 0.6%; P < .0001), femoral neck (1.2% vs −0.1%; P < .0001), and one-third radius (0.6% vs 0.0%; P < .05). The median decrease from baseline was greater with denosumab than ZOL for serum C-telopeptide of type 1 collagen at all time points after day 10 and for serum procollagen type 1 N-terminal propeptide at month 1 and at all time points after month 3 (all P < .05). Median percentage changes from baseline in serum intact PTH were significantly greater at months 3 and 9 with denosumab compared with ZOL (all P < .05). Adverse events were similar between groups. Three events consistent with the definition of atypical femoral fracture were observed (two denosumab and one ZOL). Conclusions: In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL., Postmenopausal women with osteoporosis transitioned from oral bisphosphonates had greater BMD increases and greater inhibition of bone turnover with denosumab compared with zoledronic acid.

Published
2016
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36. A Longitudinal Study of Skeletal Histomorphometry at 6 and 24 Months Across Four Bone Envelopes in Postmenopausal Women With Osteoporosis Receiving Teriparatide or Zoledronic Acid in the SHOTZ Trial

Author

David W. Dempster, Valerie A Ruff, Robert R. Recker, Eileen R Gallagher, David A. Hanley, Grattan Woodson, Sudhaker D Rao, Neil Binkley, Michael A. Bolognese, Jahangir Alam, David L. Kendler, Hua Zhou, Christopher Recknor, Paul D. Miller, Robert Lindsay, E. Michael Lewiecki, Kathleen A. Taylor, and Jacques P. Brown

Subjects
0301 basic medicine, Longitudinal study, Time Factors, Bone density, Endocrinology, Diabetes and Metabolism, Osteoporosis, Dentistry, 030209 endocrinology & metabolism, Zoledronic Acid, 03 medical and health sciences, 0302 clinical medicine, Bone Density, Osteogenesis, Periosteum, Teriparatide, Biopsy, medicine, Humans, Orthopedics and Sports Medicine, Longitudinal Studies, Osteoporosis, Postmenopausal, Aged, Diphosphonates, medicine.diagnostic_test, business.industry, Imidazoles, Middle Aged, medicine.disease, Postmenopause, 030104 developmental biology, medicine.anatomical_structure, Zoledronic acid, Cancellous Bone, Female, Cortical bone, business, Cancellous bone, medicine.drug
Abstract

Previously, we reported the effects of teriparatide (TPTD) and zoledronic acid (ZOL) on bone formation based on biochemical markers and bone histomorphometry of the cancellous envelope at month 6 in postmenopausal women with osteoporosis who participated in the 12-month primary Skeletal Histomorphometry in Subjects on Teriparatide or Zoledronic Acid Therapy (SHOTZ) study. Patients were eligible to enter a 12-month extension on their original treatment regimen: TPTD 20 μg/day (s.c. injection) or ZOL 5 mg/year (i.v. infusion). A second biopsy was performed at month 24. Here we report longitudinal changes between and within each treatment group in the cancellous, endocortical, intracortical, and periosteal bone envelopes in patients with evaluable biopsies at months 6 and 24 (paired data set: TPTD, n = 10; ZOL, n = 9). Between-group differences are also reported in the larger set of patients with evaluable biopsies at month 6 (TPTD, n = 28; ZOL, n = 30). Data from the cancellous envelope at month 6 or month 24 provided a reference to compare differences across envelopes within each treatment group. The 24-month results extend our earlier report that TPTD and ZOL possess different tissue-level mechanisms of action. Moreover, these differences persisted for at least 2 years in all four bone envelopes. Few longitudinal differences were observed within or across bone envelopes in ZOL-treated patients, suggesting that the low bone formation indices at month 6 persisted to month 24. Conversely, the magnitude of the effect of TPTD on bone formation varied across individual envelopes: median values for mineralizing surface (MS/BS) and bone formation rate (BFR/BS) at month 6 were approximately 3-fold to 5-fold higher in the endocortical and intracortical envelopes compared to the cancellous envelope. Although MS/BS and BFR/BS declined in these envelopes at month 24, median values continued to exceed, or were not significantly different from, those in the cancellous envelope. This study demonstrates for the first time that bone formation indices are higher with TPTD treatment than with ZOL in all four bone envelopes and the difference persists for at least 2 years. Moreover, the magnitude of the effect of TPTD in cortical bone remains robust at 24 months. © 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).

Published
2016
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37. Impact of age on the effect of pre-hospital P2Y12 receptor inhibition in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: the ATLANTIC-Elderly analysis

Author

Jean-Philippe Collet, Mathieu Kerneis, Benoit Lattuca, Yan Yan, Guillaume Cayla, Johanne Silvain, Frédéric Lapostolle, Patrick Ecollan, Abdourahmane Diallo, Eric Vicaut, Christian W. Hamm, Arnoud W. Van ‘t Hof, Gilles Montalescot, Jens Flensted Lassen, Leonardo Bolognese, Warren J. Cantor, Àngel Cequier, Mohamed Chettibi, Shaun G. Goodman, Christopher J. Hammett, Kurt Huber, Magnus Janzon, Béla Merkely, Robert F. Storey, Jurrien M. ten Berg, Uwe Zeymer, Muriel Licour, Anne Tsatsaris, Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)

Subjects
medicine.medical_specialty, Adenosine, medicine.medical_treatment, Myocardial Infarction, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Percutaneous Coronary Intervention, Double-Blind Method, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, ST segment, Humans, 030212 general & internal medicine, Myocardial infarction, Stroke, Aged, business.industry, Percutaneous coronary intervention, medicine.disease, 3. Good health, Regimen, Treatment Outcome, Heart failure, Cardiology, Purinergic P2Y Receptor Antagonists, ST Elevation Myocardial Infarction, Female, Cardiology and Cardiovascular Medicine, business, Ticagrelor, TIMI, medicine.drug
Abstract

International audience; AIMS:The aim of the study was to examine the main results of the ATLANTIC trial in patients with ST-elevation myocardial infarction (STEMI), randomised to pre- versus in-hospital ticagrelor, according to age.METHODS AND RESULTS:Patients were evaluated by age class (

Published
2018
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38. Electroanatomic and Pathologic Right Ventricular Outflow Tract Abnormalities in Patients With Brugada Syndrome

Author

Pasquale Notarstefano, Ramon Brugada, Maurizio Pieroni, Oscar Campuzano, Monica Coll, Pasquale Santangeli, Aureliano Fraticelli, Leonardo Bolognese, Martina Nesti, Andrea Carnevali, Simone Grassi, Anna Iglesias, and Antonio Oliva

Subjects
Adult, Male, medicine.medical_specialty, Brugada syndrome, electroanatomic mapping, endomyocardial biopsy, genetic analysis, myocardial inflammation, sudden cardiac death, Cardiology and Cardiovascular Medicine, 030204 cardiovascular system & hematology, Sudden cardiac death, Endomyocardial biopsy, Ventricular Outflow Obstruction, 03 medical and health sciences, Electrocardiography, 0302 clinical medicine, Imaging, Three-Dimensional, Internal medicine, mental disorders, medicine, Ventricular outflow tract, Humans, In patient, 030212 general & internal medicine, Endocardium, Brugada Syndrome, business.industry, Body Surface Potential Mapping, Myocardial inflammation, Middle Aged, medicine.disease, Defibrillators, Implantable, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Risk stratification, Cardiology, Female, business, Follow-Up Studies
Abstract

Background The prevalence and significance of structural abnormalities in Brugada syndrome (BrS) are still largely debated. Objectives The authors investigated the relationship between genetic background, electroanatomic abnormalities, and pathologic substrate in BrS. Methods They performed 3-dimensional electroanatomic unipolar and bipolar mapping in 30 patients with BrS. Twenty patients underwent 3-dimensional electroanatomic unipolar and bipolar mapping–guided right ventricular outflow tract (RVOT) endomyocardial biopsy. Programmed ventricular stimulation and genetic analysis were performed in all patients. Results Low-voltage areas (LVAs) were observed at unipolar map in 93% of patients and at bipolar map in 50% of cases. Unipolar LVAs were always larger than bipolar LVAs, were always colocalized, and in all cases included RVOT. Disease-causing mutations were detected in 10 (33%) patients. Programmed ventricular stimulation was positive in 16 cases (53%). In 75% of patients, RVOT histology showed pathologic findings with myocardial inflammation in 80% of them. Among patients with abnormal bipolar map submitted to endomyocardial biopsy, 9 (81%) showed evidence of myocardial inflammation. Conversely, bipolar map was abnormal in 83% of patients with myocardial inflammation. Myocardial inflammation was also more prevalent among inducible patients (83% vs. 25% in noninducible; p = 0.032). Conclusions BrS is characterized by electroanatomical and structural abnormalities localized to RVOT with a gradient of the pathologic substrate from epicardium to endocardium possibly driven by myocardial inflammation. These findings reclassify BrS as a combination of structural and electrical defects opening the way to new risk stratification and therapeutic strategies.

Published
2018

39. Activation of Invariant Natural Killer T Cells Redirects the Inflammatory Response in Neonatal Sepsis

Author

Alexandra C. Bolognese, Weng-Lang Yang, Laura W. Hansen, Archna Sharma, Jeffrey M. Nicastro, Gene F. Coppa, and Ping Wang

Subjects
0301 basic medicine, Antigens, Differentiation, T-Lymphocyte, neonatal sepsis, Mice, TGF-β1, Immunology and Allergy, IFN-γ, Original Research, Mice, Knockout, education.field_of_study, Neonatal sepsis, biology, CD69, 3. Good health, CD1D, Female, medicine.symptom, lcsh:Immunologic diseases. Allergy, Population, Immunology, Inflammation, Galactosylceramides, Lung injury, CD1d, Sepsis, Immunomodulation, Transforming Growth Factor beta1, 03 medical and health sciences, Interferon-gamma, Immune system, Adjuvants, Immunologic, Antigens, CD, medicine, invariant natural killer T cells, Animals, Lectins, C-Type, lung injury, education, KRN7000, business.industry, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, Animals, Newborn, biology.protein, Natural Killer T-Cells, Antigens, CD1d, business, lcsh:RC581-607
Abstract

Sepsis is the third leading cause of death in the neonatal population, due to susceptibility to infection conferred by immaturity of both the innate and adaptive components of the immune system. Invariant natural killer T (iNKT) cells are specialized adaptive immune cells that possess important innate-like characteristics and have not yet been well-studied in septic neonates. We hypothesized that iNKT cells would play an important role in mediating the neonatal immune response to sepsis. To study this, we subjected 5- to 7-day-old neonatal C57BL/6 mice to sepsis by intraperitoneal (i.p.) cecal slurry (CS) injection. Thirty hours prior to or immediately following sepsis induction, pups received i.p. injection of the iNKT stimulator KRN7000 (KRN, 0.2 µg/g) or vehicle. Ten hours after CS injection, blood and tissues were collected for various analyses. Thirty-hour pretreatment with KRN resulted in better outcomes in inflammation, lung injury, and survival, while immediate treatment with KRN resulted in worse outcomes compared to vehicle treatment. We further analyzed the activation status of neonatal iNKT cells for 30 h after KRN administration, and showed a peak in frequency of CD69 expression on iNKT cells and serum IFN-γ levels at 5 and 10 h, respectively. We then used CD1d knockout neonatal mice to demonstrate that KRN acts through the major histocompatibility complex-like molecule CD1d to improve outcomes in neonatal sepsis. Finally, we identified that KRN pretreatment exerts its protective effect by increasing systemic levels of TGF-β1. These findings support the importance of iNKT cells for prophylactic immunomodulation in neonates susceptible to sepsis.

Published
2018

40. Teaching NeuroImages: Visual loss as a rare complication of mechanical thrombectomy

Author

Florian Jordi, Manuel Bolognese, and Alexander von Hessling

Subjects
medicine.medical_specialty, Mechanical Thrombolysis, Vision Disorders, Physical examination, Retina, 030218 nuclear medicine & medical imaging, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Retinal Diseases, Aphasia, Occlusion, Medicine, Humans, cardiovascular diseases, medicine.diagnostic_test, business.industry, Emergency department, Cerebral Infarction, Middle Aged, Trunk, nervous system diseases, Surgery, Mechanical thrombectomy, Female, Neurology (clinical), medicine.symptom, Complication, business, 030217 neurology & neurosurgery
Abstract

A 46-year-old woman was admitted to the emergency department with a severe left hemispheric syndrome (NIH Stroke Scale [NIHSS] 11). CT showed an occlusion of the left middle cerebral artery, reaching from the distal main trunk (M1) to the inferior division (M2) (figure 1). IV thrombolysis was started and mechanical thrombectomy performed successfully. Postinterventional clinical examination showed mild aphasia (NIHSS 1). However, the patient also complained about impaired (“foggy”) vision of the left eye.

Published
2018

41. Takotsubo (Stress) Cardiomyopathy

Author

Leonardo Bolognese and Maurizio Pieroni

Subjects
Male, business.industry, Cardiomyopathy, MEDLINE, General Medicine, medicine.disease, Bioinformatics, Text mining, Takotsubo Cardiomyopathy, Stress (linguistics), Humans, Medicine, Female, business
Published
2015
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42. Treatment of Anemia with Darbepoetin Alfa in Systolic Heart Failure

Author

Karl Swedberg, James B. Young, Inder S. Anand, Sunfa Cheng, Akshay S. Desai, Rafael Diaz, Aldo P. Maggioni, John J. V. McMurray, Christopher O'Connor, Marc A. Pfeffer, Scott D. Solomon, Yan Sun, Michal Tendera, Dirk J. van Veldhuisen, Young J, Grinfeld L, Krum H, Vanhaecke J, Olivera Clausell N, Goudev A, Howlett J, Corbalan R, Hradec J, Kober L, Eha J, Cohen Solal A, Anker SD, Chopra V, Lewis B, Erglis A, Sakalyte G, Cardona Munoz E, Dunselman P, Dickstein K, Ponikowski P, Seabra Gomes R, Apetrei E, Mareev V, Murin J, Dalby A, Lopez Sendon J, Willenheimer R, Cleland J, Adams K, Anand I, Butler J, Dunlap M, Felker M, Ghali J, Levy W, Carson P, Cohn J, Drexler H, Pocock S, Ryden L, Poole Wilson P, Fishbane S, Ivanovich P, Nissenson A, Katz S, Barkoudah E, Campbell P, Desai A, Finn PV, Hartley L, Kasabov R, Odutayo KA, Rajesh V, Solomon S, Weinrauch LA, Albizem M, Cheng S, Chou W, Deegenaars M, Dougherty M, Fouqueray B, Froissart M, Froment A, Gadd S, Ghosh S, Grazette L, Guillet S, Gulabani D, Haddock B, Harris C, Jaffer A, Kerns C, Kim J, Knussel B, Law H, Mather R, Mix C, Moore L, Moyes R, Polu K, Rossert J, Scarlata D, Smirnakis K, Smith L, Snyder W, Sun Y, Trotman ML, Wasserman S, Watkins A, Wong M, Zhang Y, Amuchastegui M, Belziti C, Bluguermann J, Caccavo M, Cartasegna L, Colque R, Cuneo C, Fernandez A, Gabito A, Goicochea R, Gonzalez M, Gorosito V, Hominal M, Kevorkian R, Litvak Bruno M, Llanos J, Mackinnon I, Manuale O, Marzetti E, Nul D, Perna E, Riccitelli M, Sanchez A, Santos D, Schygiel P, Toblli J, Vogel D, Aggarwal A, Amerena J, De Looze F, Fletcher P, Hare D, Ireland M, Lattimore J, Marwick T, Sindone A, Thompson P, Waites J, Altenberger J, Ebner C, Lenz K, Pacher R, Poelzl G, Charlier F, de Ceuninck M, De Keulenaer G, Dendale P, Maréchal P, Mullens W, Thoeng J, Vanderheyden M, Weytjens C, Wollaert B, Albuquerque D, Almeida D, Aspe y. Rosas J, Bocchi E, Bordignon S, Clausell N, Kaiser S, Leaes P, Martins Alves S, Montera M, Moura L, Pereira de Castro R, Rassi S, Reis A, Saraiva J, Simões M, Souza Neto J, Teixeira M, Benov H, Chompalova B, Donova T, Georgiev P, Gotchev D, Grigorov M, Guenova D, Hergeldjieva V, Ivanov D, Kostova E, Manolova A, Marchev S, Nikolov F, Popov A, Raev D, Tzekova M, Czarnecki W, Giannetti N, Haddad H, Heath J, Huynh T, Lepage S, Liu P, Lonn E, Ma P, Manyari D, Moe G, Parker J, Pesant Y, Rajda M, Ricci J, Roth S, Sestier F, Sluzar V, Sussex B, Vizel S, Antezana G, Bugueno C, Castro P, Conejeros C, Manriquez L, Martinez D, Potthoff S, Stockins B, Vukasovic J, Gregor P, Herold M, Jerabek O, Jirmar R, Kuchar R, Linhart A, Podzemska B, Soucek M, Spac J, Spacek R, Vodnansky P, Bronnum Schou J, Clemmensen K, Egstrup K, Jensen G, Kjoller Hansen L, Markenvard J, Rokkedal J, Skagen K, Torp Pedersen C, Tuxen C, Videbak L, Laks T, Vahula V, Harjola V, Kettunen R, Kotila M, Bauer F, Coisne D, Davy J, De Groote P, Dos Santos P, Funck F, Galinier M, Gibelin P, Isnard R, Neuder Y, Roul G, Sabatier R, Trochu J, Denny S, Dreykluft T, Flesch M, Genth Zotz S, Hambrecht R, Hein J, Jeserich M, John M, Kreider Stempfle H, Laufs U, Muellerleile K, Natour M, Sandri M, Schäufele T, von Hodenberg E, Weyland K, Winkelmann B, Tse H, Yan B, Barsi B, Csikasz J, Dezsi C, Edes I, Forster T, Karpati P, Kerekes C, Kis E, Kosa I, Lupkovics G, Nagy A, Preda I, Ronaszeki A, Tomcsanyi J, Zamolyi K, Agarwal D, Bahl V, Bordoloi A, Chockalingam K, Chopda M, Dugal J, Ghaisas N, Grant P, Hiremath S, Iyengar S, Jagadeesa Subramania B, Jain P, Joshi A, Khan A, Mullasari A, Naik S, Oomman A, Pai V, Pareppally Gopal R, Parikh K, Patel T, Prakash V, Sastry B, Sathe S, Sinha N, Srikanthan V, Subburamakrishnan P, Thacker H, Wander G, Admon D, Katz A, Klainman E, Marmor A, Moriel M, Mosseri M, Shotan A, Weinstein J, Zimlichman R, Agostoni P, Albanese M, Alunni G, Bini R, Boccanelli A, Bolognese L, Campana C, Carbonieri E, Carpino C, Checco L, Cosmi F, Angelo GD, De Cristofaro M, Floresta A, Fucili A, Galvani M, Ivleva A, Marra S, Musca G, Peccerillo N, Picchio E, Russo T, Scelsi L, Senni M, Tavazzi L, Jasinkevica I, Kakurina N, Veze I, Volans E, Bagdonas A, Berukstis E, Celutkiene J, Dambrauskaite A, Jarasuniene D, Luksiene D, Rudys A, Sliaziene S, Aguilar Romero R, Cardona Muñoz E, Castro Jimenez J, Chavez Herrera J, Chuquiure Valenzuela E, De la Pena G, Herrera E, Leiva Pons J, Lopez Alvarado A, Mendez Machado G, Ramos Lopez G, Basart D, Buijs E, Cornel J, de Leeuw M, Dijkgraaf R, Freericks M, Hamraoui K, Lenderlink T, Linssen G, Lodewick P, Lodewijks C, Lok D, Nierop P, Ronner E, Somsen A, van Dantzig J, van der Burgh P, van Kempen L, van Vlies B, Voors A, Wardeh A, Willems F, Gundersen T, Hole T, Thalamus J, Westheim A, Dabrowski M, Gorski J, Korewicki J, Kuc K, Miekus P, Musial W, Niegowska J, Piotrowski W, Podolec P, Polonski L, Rynkiewicz A, Szelemej R, Trusz Gluza M, Ujda M, Wojciechowski D, Wysokinski A, Camacho A, Fonseca C, Monteiro P, Bruckner I, Carasca E, Coman I, Datcu M, Dragulescu S, Ionescu P, Iordachescu Petica D, Manitiu I, Popa V, Pop Moldovan A, Radoi M, Stamate S, Tomescu M, Vita I, Aroutiounov G, Ballyuzek M, Bart B, Churina S, Glezer M, Goloshchekin B, Kobalava Z, Kostenko V, Lopatin Y, Martynov A, Orlov V, Semernin E, Shogenov Z, Sidorenko B, Skvortsov A, Storzhakov G, Sulimov V, Talibov O, Tereshenko S, Tsyrline V, Zadionchenko V, Zateyshchikov D, Dzupina A, Hranai M, Kmec J, Micko K, Pella D, Sojka G, Spisak V, Vahala P, Vinanska D, Badat A, Bayat J, Dawood S, Delport E, Ellis G, Garda R, Klug E, Mabin T, Naidoo D, Pretorius M, Ranjith N, Van Zyl L, Weich H, Anguita M, Berrazueta J, Bruguera i. 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Brien T, Oellerich W, Oren R, Pamboukian S, Pereira N, Pitt W, Porter C, Prabhu S, Promisloff S, Ratkovec R, Richardson R, Ross A, Saleh N, Saltzberg M, Sarkar S, Schmedtje J, Schneider R, Schuyler G, Shanes J, Sharma A, Siegel C, Siegel R, Silber D, Singh N, Singh J, Singh V, Sklar J, Small R, Smith A, Smith E, Smull D, Sotolongo R, Staniloae C, Stapleton D, Steele P, Stehlik J, Stein M, Tang W, Thadani U, Torre Amoine G, Trichon B, Tsai C, Tummala R, Van Bakel A, Vicari R, Vijay N, Vijayaraghavan K, Vittorio T, Vossler M, Wagoner L, Wallis D, Ward N, Widmer M, Wight J, Wilkins C, Williams C, Williams G, Winchester M, Winkel E, Wittmer B, Wood D, Wormer D, Wright R, Xu Z, Yasin M, Zolty R., PERRONE FILARDI, PASQUALE, Karl, Swedberg, James B., Young, Inder S., Anand, Sunfa, Cheng, Akshay S., Desai, Rafael, Diaz, Aldo P., Maggioni, John J. V., Mcmurray, Christopher, O'Connor, Marc A., Pfeffer, Scott D., Solomon, Yan, Sun, Michal, Tendera, Dirk J., van Veldhuisen, Young, J, Grinfeld, L, Krum, H, Vanhaecke, J, Olivera Clausell, N, Goudev, A, Howlett, J, Corbalan, R, Hradec, J, Kober, L, Eha, J, Cohen Solal, A, Anker, Sd, Chopra, V, Lewis, B, Erglis, A, Sakalyte, G, Cardona Munoz, E, Dunselman, P, Dickstein, K, Ponikowski, P, Seabra Gomes, R, Apetrei, E, Mareev, V, Murin, J, Dalby, A, Lopez Sendon, J, Willenheimer, R, Cleland, J, Adams, K, Anand, I, Butler, J, Dunlap, M, Felker, M, Ghali, J, Levy, W, Carson, P, Cohn, J, Drexler, H, Pocock, S, Ryden, L, Poole Wilson, P, Fishbane, S, Ivanovich, P, Nissenson, A, Katz, S, Barkoudah, E, Campbell, P, Desai, A, Finn, Pv, Hartley, L, Kasabov, R, Odutayo, Ka, Rajesh, V, Solomon, S, Weinrauch, La, Albizem, M, Cheng, S, Chou, W, Deegenaars, M, Dougherty, M, Fouqueray, B, Froissart, M, Froment, A, Gadd, S, Ghosh, S, Grazette, L, Guillet, S, Gulabani, D, Haddock, B, Harris, C, Jaffer, A, Kerns, C, Kim, J, Knussel, B, Law, H, Mather, R, Mix, C, Moore, L, Moyes, R, Polu, K, Rossert, J, Scarlata, D, Smirnakis, K, Smith, L, Snyder, W, Sun, Y, Trotman, Ml, Wasserman, S, Watkins, A, Wong, M, Zhang, Y, Amuchastegui, M, Belziti, C, Bluguermann, J, Caccavo, M, Cartasegna, L, Colque, R, Cuneo, C, Fernandez, A, Gabito, A, Goicochea, R, Gonzalez, M, Gorosito, V, Hominal, M, Kevorkian, R, Litvak Bruno, M, Llanos, J, Mackinnon, I, Manuale, O, Marzetti, E, Nul, D, Perna, E, Riccitelli, M, Sanchez, A, Santos, D, Schygiel, P, Toblli, J, Vogel, D, Aggarwal, A, Amerena, J, De Looze, F, Fletcher, P, Hare, D, Ireland, M, Lattimore, J, Marwick, T, Sindone, A, Thompson, P, Waites, J, Altenberger, J, Ebner, C, Lenz, K, Pacher, R, Poelzl, G, Charlier, F, de Ceuninck, M, De Keulenaer, G, Dendale, P, Maréchal, P, Mullens, W, Thoeng, J, Vanderheyden, M, Weytjens, C, Wollaert, B, Albuquerque, D, Almeida, D, Aspe y., Rosas J, Bocchi, E, Bordignon, S, Clausell, N, Kaiser, S, Leaes, P, Martins Alves, S, Montera, M, Moura, L, Pereira de Castro, R, Rassi, S, Reis, A, Saraiva, J, Simões, M, Souza Neto, J, Teixeira, M, Benov, H, Chompalova, B, Donova, T, Georgiev, P, Gotchev, D, Grigorov, M, Guenova, D, Hergeldjieva, V, Ivanov, D, Kostova, E, Manolova, A, Marchev, S, Nikolov, F, Popov, A, Raev, D, Tzekova, M, Czarnecki, W, Giannetti, N, Haddad, H, Heath, J, Huynh, T, Lepage, S, Liu, P, Lonn, E, Ma, P, Manyari, D, Moe, G, Parker, J, Pesant, Y, Rajda, M, Ricci, J, Roth, S, Sestier, F, Sluzar, V, Sussex, B, Vizel, S, Antezana, G, Bugueno, C, Castro, P, Conejeros, C, Manriquez, L, Martinez, D, Potthoff, S, Stockins, B, Vukasovic, J, Gregor, P, Herold, M, Jerabek, O, Jirmar, R, Kuchar, R, Linhart, A, Podzemska, B, Soucek, M, Spac, J, Spacek, R, Vodnansky, P, Bronnum Schou, J, Clemmensen, K, Egstrup, K, Jensen, G, Kjoller Hansen, L, Markenvard, J, Rokkedal, J, Skagen, K, Torp Pedersen, C, Tuxen, C, Videbak, L, Laks, T, Vahula, V, Harjola, V, Kettunen, R, Kotila, M, Bauer, F, Coisne, D, Davy, J, De Groote, P, Dos Santos, P, Funck, F, Galinier, M, Gibelin, P, Isnard, R, Neuder, Y, Roul, G, Sabatier, R, Trochu, J, Denny, S, Dreykluft, T, Flesch, M, Genth Zotz, S, Hambrecht, R, Hein, J, Jeserich, M, John, M, Kreider Stempfle, H, Laufs, U, Muellerleile, K, Natour, M, Sandri, M, Schäufele, T, von Hodenberg, E, Weyland, K, Winkelmann, B, Tse, H, Yan, B, Barsi, B, Csikasz, J, Dezsi, C, Edes, I, Forster, T, Karpati, P, Kerekes, C, Kis, E, Kosa, I, Lupkovics, G, Nagy, A, Preda, I, Ronaszeki, A, Tomcsanyi, J, Zamolyi, K, Agarwal, D, Bahl, V, Bordoloi, A, Chockalingam, K, Chopda, M, Dugal, J, Ghaisas, N, Grant, P, Hiremath, S, Iyengar, S, Jagadeesa Subramania, B, Jain, P, Joshi, A, Khan, A, Mullasari, A, Naik, S, Oomman, A, Pai, V, Pareppally Gopal, R, Parikh, K, Patel, T, Prakash, V, Sastry, B, Sathe, S, Sinha, N, Srikanthan, V, Subburamakrishnan, P, Thacker, H, Wander, G, Admon, D, Katz, A, Klainman, E, Marmor, A, Moriel, M, Mosseri, M, Shotan, A, Weinstein, J, Zimlichman, R, Agostoni, P, Albanese, M, Alunni, G, Bini, R, Boccanelli, A, Bolognese, L, Campana, C, Carbonieri, E, Carpino, C, Checco, L, Cosmi, F, Angelo, Gd, De Cristofaro, M, Floresta, A, Fucili, A, Galvani, M, Ivleva, A, Marra, S, Musca, G, Peccerillo, N, PERRONE FILARDI, Pasquale, Picchio, E, Russo, T, Scelsi, L, Senni, M, Tavazzi, L, Jasinkevica, I, Kakurina, N, Veze, I, Volans, E, Bagdonas, A, Berukstis, E, Celutkiene, J, Dambrauskaite, A, Jarasuniene, D, Luksiene, D, Rudys, A, Sliaziene, S, Aguilar Romero, R, Cardona Muñoz, E, Castro Jimenez, J, Chavez Herrera, J, Chuquiure Valenzuela, E, De la Pena, G, Herrera, E, Leiva Pons, J, Lopez Alvarado, A, Mendez Machado, G, Ramos Lopez, G, Basart, D, Buijs, E, Cornel, J, de Leeuw, M, Dijkgraaf, R, Freericks, M, Hamraoui, K, Lenderlink, T, Linssen, G, Lodewick, P, Lodewijks, C, Lok, D, Nierop, P, Ronner, E, Somsen, A, van Dantzig, J, van der Burgh, P, van Kempen, L, van Vlies, B, Voors, A, Wardeh, A, Willems, F, Gundersen, T, Hole, T, Thalamus, J, Westheim, A, Dabrowski, M, Gorski, J, Korewicki, J, Kuc, K, Miekus, P, Musial, W, Niegowska, J, Piotrowski, W, Podolec, P, Polonski, L, Rynkiewicz, A, Szelemej, R, Trusz Gluza, M, Ujda, M, Wojciechowski, D, Wysokinski, A, Camacho, A, Fonseca, C, Monteiro, P, Bruckner, I, Carasca, E, Coman, I, Datcu, M, Dragulescu, S, Ionescu, P, Iordachescu Petica, D, Manitiu, I, Popa, V, Pop Moldovan, A, Radoi, M, Stamate, S, Tomescu, M, Vita, I, Aroutiounov, G, Ballyuzek, M, Bart, B, Churina, S, Glezer, M, Goloshchekin, B, Kobalava, Z, Kostenko, V, Lopatin, Y, Martynov, A, Orlov, V, Semernin, E, Shogenov, Z, Sidorenko, B, Skvortsov, A, Storzhakov, G, Sulimov, V, Talibov, O, Tereshenko, S, Tsyrline, V, Zadionchenko, V, Zateyshchikov, D, Dzupina, A, Hranai, M, Kmec, J, Micko, K, Pella, D, Sojka, G, Spisak, V, Vahala, P, Vinanska, D, Badat, A, Bayat, J, Dawood, S, Delport, E, Ellis, G, Garda, R, Klug, E, Mabin, T, Naidoo, D, Pretorius, M, Ranjith, N, Van Zyl, L, Weich, H, Anguita, M, Berrazueta, J, Bruguera i., Cortada J, de Teresa, E, Gómez Sánchez, M, González Juanatey, J, Gonzalez Maqueda, I, Jordana, R, Lupon, J, Manzano, L, Pascual Figal, D, Pulpón, L, Recio, J, Ridocci Soriano, F, Rodríguez Lambert, J, Roig Minguell, E, Romero, J, Valdovinos, P, Klintberg, L, Kronvall, T, Lycksell, M, Morner, S, Rydberg, E, Swedberg, K, Timberg, I, Wikstrom, G, Moccetti, T, Ashok, J, Banerjee, P, Carr White, G, Connolly, E, Francis, M, Greenbaum, R, Kadr, H, Lindsay, S, Mcmurray, J, Megarry, S, Memon, A, Murdoch, D, Senior, R, Squire, I, Tan, L, Witte, K, Adamson, P, Adler, A, Altschul, L, Altschuller, A, Amirani, H, Andreou, C, Ansari, M, Antonishen, M, Banchs, H, Banerjee, S, Banish, D, Bank, A, Barbagelata, A, Barnard, D, Bellinger, R, Benn, A, Berk, M, Berry, B, Bethala, V, Bilazarian, S, Bisognano, J, Bleyer, F, Blum, M, Boehmer, J, Bouchard, A, Boyle, A, Bozkurt, B, Brown, C, Burlew, B, Burnham, K, Call, J, Cambier, P, Cappola, T, Carlson, R, Chandler, B, Chandra, R, Chandraratna, P, Chernick, R, Colan, D, Colfer, H, Colucci, W, Connelly, T, Costantini, O, Dadkhah, S, Dauber, I, Davis, J, Davis, S, Denning, S, Drazner, M, Dunlap, S, Egbujiobi, L, Elkayam, U, Elliott, J, El Shahawy, M, Essandoh, L, Ewald, G, Fang, J, Farhoud, H, Felker, G, Fernandez, J, Festin, R, Fishbein, G, Florea, V, Flores, E, Floro, J, Gabris, M, Garg, M, Gatewood, R, Geller, M, Ghumman, W, Gibbs, G, Gillespie, E, Gilmore, R, Gogia, H, Goldberg, L, Gradus Pizlo, I, Grainger, T, Gudmundsson, G, Gunawardena, D, Gupta, D, Hack, T, Hall, S, Hamroff, G, Hankins, S, Hanna, M, Hargrove, J, Haught, W, Hauptman, P, Hazelrigg, M, Herzog, C, Heywood, J, Hill, T, Hilton, T, Hirsch, H, Hunter, J, Ibrahim, H, Imburgia, M, Iteld, B, Jackson, B, Jaffrani, N, Jain, D, Jain, A, James, M, Jimenez, J, Johnson, E, Kale, P, Kaneshige, A, Kapadia, S, Karia, D, Karlsberg, R, Katholi, R, Kerut, E, Khoury, W, Kipperman, R, Klapholz, M, Kosinski, E, Kozinn, M, Kraus, D, Krueger, S, Kumar, S, Lader, E, Lee, C, Lewis, E, Light McGroary, K, Loh, I, Lombardi, W, Machado, C, Maislos, F, Mancini, D, Markus, T, Mather, P, Mccants, K, Mcgrew, F, Mclaurin, B, Mcmillan, E, Mcnamara, D, Meyer, T, Meymandi, S, Miller, A, Minami, E, Modi, M, Mody, F, Mohanty, P, Moscoso, R, Moskowitz, R, Moustafa, M, Mullen, M, Naz, T, Noonan, T, O., Brien T, Oellerich, W, Oren, R, Pamboukian, S, Pereira, N, Pitt, W, Porter, C, Prabhu, S, Promisloff, S, Ratkovec, R, Richardson, R, Ross, A, Saleh, N, Saltzberg, M, Sarkar, S, Schmedtje, J, Schneider, R, Schuyler, G, Shanes, J, Sharma, A, Siegel, C, Siegel, R, Silber, D, Singh, N, Singh, J, Singh, V, Sklar, J, Small, R, Smith, A, Smith, E, Smull, D, Sotolongo, R, Staniloae, C, Stapleton, D, Steele, P, Stehlik, J, Stein, M, Tang, W, Thadani, U, Torre Amoine, G, Trichon, B, Tsai, C, Tummala, R, Van Bakel, A, Vicari, R, Vijay, N, Vijayaraghavan, K, Vittorio, T, Vossler, M, Wagoner, L, Wallis, D, Ward, N, Widmer, M, Wight, J, Wilkins, C, Williams, C, Williams, G, Winchester, M, Winkel, E, Wittmer, B, Wood, D, Wormer, D, Wright, R, Xu, Z, Yasin, M, Zolty, R., Faculteit Medische Wetenschappen/UMCG, and Cardiovascular Centre (CVC)

Subjects
Male, CHRONIC KIDNEY-DISEASE, Darbepoetin alfa, Ciencias de la Salud, Kaplan-Meier Estimate, law.invention, Hemoglobins, DOUBLE-BLIND, Randomized controlled trial, law, hemic and lymphatic diseases, Treatment Failure, Hazard ratio, Ética Médica, Anemia, General Medicine, Middle Aged, Shock, Septic, Stroke, purl.org/becyt/ford/3 [https], Female, medicine.drug, medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, Placebo, CONTROLLED-TRIAL, purl.org/becyt/ford/3.3 [https], MORBIDITY, Double-Blind Method, Darbepoetin, Internal medicine, Thromboembolism, parasitic diseases, medicine, Humans, Adverse effect, Erythropoietin, Aged, Proportional Hazards Models, CITY CARDIOMYOPATHY QUESTIONNAIRE, business.industry, Proportional hazards model, MORTALITY, equipment and supplies, medicine.disease, Surgery, REDUCTION, EPOETIN, Heart failure, Hematinics, business, Systolic heart failure, Heart Failure, Systolic
Abstract

BACKGROUND: Patients with systolic heart failure and anemia have worse symptoms, functional capacity, and outcomes than those without anemia. We evaluated the effects of darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anemia. METHODS: In this randomized, double-blind trial, we assigned 2278 patients with systolic heart failure and mild-to-moderate anemia (hemoglobin level, 9.0 to 12.0 g per deciliter) to receive either darbepoetin alfa (to achieve a hemoglobin target of 13 g per deciliter) or placebo. The primary outcome was a composite of death from any cause or hospitalization for worsening heart failure. RESULTS: The primary outcome occurred in 576 of 1136 patients (50.7%) in the darbepoetin alfa group and 565 of 1142 patients (49.5%) in the placebo group (hazard ratio in the darbepoetin alfa group, 1.01; 95% confidence interval, 0.90 to 1.13; P=0.87). There was no significant between-group difference in any of the secondary outcomes. The neutral effect of darbepoetin alfa was consistent across all prespecified subgroups. Fatal or nonfatal stroke occurred in 42 patients (3.7%) in the darbepoetin alfa group and 31 patients (2.7%) in the placebo group (P=0.23). Thromboembolic adverse events were reported in 153 patients (13.5%) in the darbepoetin alfa group and 114 patients (10.0%) in the placebo group (P=0.01). Cancer-related adverse events were similar in the two study groups. CONCLUSIONS: Treatment with darbepoetin alfa did not improve clinical outcomes in patients with systolic heart failure and mild-to-moderate anemia. Our findings do not support the use of darbepoetin alfa in these patients. (Funded by Amgen; RED-HF ClinicalTrials.gov number, NCT00358215.). Fil: Swedberg, Karl. University of Gothenburg; Suecia Fil: Young, James B.. Cleveland Clinic; Estados Unidos Fil: Anand, Inder S.. University of Minnesota; Estados Unidos Fil: Cheng, Sunfa. Amgen; Estados Unidos Fil: Desai, Akshay S.. Brigham and Women’s Hospital; Estados Unidos Fil: Diaz, Rafael. Estudios Clínicos Latinoamérica; Argentina Fil: Maggioni, Aldo P.. Italian Association of Hospital Cardiologists Research Center; Italia Fil: McMurray, John J.V.. University of Glasgow; Reino Unido Fil: O’Connor, Christopher. University of Duke; Estados Unidos Fil: Pfeffer, Marc A.. Brigham and Women’s Hospital; Estados Unidos Fil: Solomon, Scott D.. Brigham and Women’s Hospital; Estados Unidos Fil: Sun, Yan. Amgen; Estados Unidos Fil: Tendera, Michal. Medical University of Silesia; Polonia Fil: van Veldhuisen, Dirk J.. University of Groningen; Países Bajos Fil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Published
2013
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43. An Intra-Articular, Extended-Release Formulation of Triamcinolone Acetonide Prolongs and Amplifies Analgesic Effect in Patients with Osteoarthritis of the Knee

Author

Rahul Ballal, Christina Willwerth, Neil Bodick, Anjali Kumar, David J. Hunter, James Bolognese, Joelle Lufkin, Michael D. Clayman, and Chris Schoonmaker

Subjects
Male, Analgesic effect, medicine.medical_specialty, Triamcinolone acetonide, Anti-Inflammatory Agents, Osteoarthritis, Triamcinolone Acetonide, Injections, Intra-Articular, law.invention, Intra articular, Double-Blind Method, Randomized controlled trial, Musculoskeletal Pain, law, Humans, Medicine, Orthopedics and Sports Medicine, In patient, Adverse effect, Analgesics, Dose-Response Relationship, Drug, business.industry, General Medicine, Middle Aged, Osteoarthritis, Knee, medicine.disease, Surgery, Clinical trial, Treatment Outcome, Delayed-Action Preparations, Anesthesia, Female, business, medicine.drug
Abstract

Background: Intra-articular corticosteroids are a mainstay in the treatment of knee osteoarthritis, and in clinical trials, they demonstrate a large initial analgesic effect that wanes over one to four weeks with the rapid efflux of drug from the joint. The present study was undertaken to determine if FX006, an extended-release formulation of triamcinolone acetonide, can provide pain relief that is superior to the current standard of care, immediate-release triamcinolone acetonide. Methods: In this Phase-2, double-blind, multicenter study, 228 patients with moderate to severe knee osteoarthritis pain were randomized to a single intra-articular injection of FX006 (containing 10, 40, or 60 mg of triamcinolone acetonide) or 40 mg of immediate-release triamcinolone acetonide. Data on the mean daily pain on the 11-point Numeric Rating Scale were collected over twelve weeks; the primary efficacy end point was the change from baseline to each of eight, ten, and twelve weeks in the weekly mean of the mean daily pain intensity scores analyzed with a longitudinal mixed-effects model. Results: The 10-mg dose of FX006 produced pain relief that was improved relative to immediate-release triamcinolone acetonide at two through twelve weeks, although the difference in pain relief was not significant (p ≥ 0.05). The 40-mg dose of FX006 produced pain relief that was improved at two through twelve weeks and was significantly superior to immediate-release triamcinolone acetonide at five to ten weeks (p < 0.05 at each time point). At the 40-mg dose of FX006, prespecified secondary analyses, including responder analyses and all Western Ontario and McMaster Universities subscales, were significantly superior (p < 0.05) to immediate-release triamcinolone acetonide at eight weeks, and the time-weighted mean pain relief (assessed with mean daily pain intensity scores) was significantly superior to immediate-release triamcinolone acetonide over one to twelve weeks (p = 0.04). The 60-mg dose did not provide additional improvement relative to the 40-mg dose. Adverse events were generally mild and similar across all treatments. Conclusions: Intra-articular injection of FX006, an extended-release formulation of triamcinolone acetonide, provided a clinically relevant improvement in pain relief in patients with knee osteoarthritis relative to immediate-release triamcinolone acetonide, the current standard of care. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Published
2015
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44. Feasibility of Combined Unipolar and Bipolar Voltage Maps to Improve Sensitivity of Endomyocardial Biopsy

Author

Andrea Carnevali, Marta Giovannardi, Giulia d'Amati, Stefania Riva, Corrado Carbucicchio, Gaetano Fassini, Michela Casella, Pasquale Notarstefano, Leonardo Bolognese, Fabrizio Tundo, Claudio Tondo, Luigi Di Biase, Ghaliah Al-Mohani, Elena Sommariva, Maurizio Pieroni, Andrea Natale, Francesca Pizzamiglio, Eleonora Russo, Antonio Russo, and Pasquale Santangeli

Subjects
Adult, Male, medicine.medical_specialty, Myocarditis, Sarcoidosis, Biopsy, Cardiomyopathy, Action Potentials, Endomyocardial biopsy, Young Adult, Predictive Value of Tests, Physiology (medical), Internal medicine, mental disorders, Humans, Medicine, Bipolar voltage, arrhythmogenic right ventricular dysplasia, myocarditis, biopsy, Arrhythmogenic Right Ventricular Dysplasia, Endocardium, medicine.diagnostic_test, business.industry, Middle Aged, medicine.disease, Arrhythmogenic right ventricular dysplasia, Predictive value of tests, Cardiology, Feasibility Studies, Female, Electrophysiologic Techniques, Cardiac, Cardiology and Cardiovascular Medicine, business
Abstract

Background— Endomyocardial biopsy (EMB) has a low sensitivity. Electroanatomic voltage mapping (EVM) is effective in guiding EMB thanks to its ability in identifying and locating low-voltage regions. The analysis of unipolar EVM can correlate with epicardial pathological involvement. We evaluated the unipolar EVM in EMB areas to determine whether it can increase EMB sensitivity in diagnosing epicardial diseases. Methods and Results— We performed endocardial bipolar EVM-guided EMBs in 29 patients and we analyzed unipolar EVM at withdrawal sites. Eighty myocardial samples were collected (mean, 2.8±0.9; median, 3 fragments per patient) and 60 were suitable for histological analysis. Ten specimens (17%) were collected from an area with discordant normal bipolar/low-voltage unipolar EVM and they were diagnostic or suggestive for arrhythmogenic right ventricular dysplasia/cardiomyopathy in 6 patients, for myocarditis and sarcoidosis in 1 patient each. Six samples (10%) were collected from an area with discordant low-voltage bipolar/normal unipolar EVM and they showed nonspecific features. The sensitivity of unipolar EVMs for a diagnostic biopsy finding EMB was significantly higher compared with bipolar EVMs analyzed according to samples ( P P =0.008). The specificity of unipolar EMB was better than bipolar EMB when analyzed for all samples ( P =0.0014) but the difference did not reach statistical significance when analyzed by patient ( P =0.083). The diagnostic yield was 63.3% for the bipolar and 83.3% for the unipolar EVM. Conclusions— These findings suggest that use of a combined bipolar/unipolar map may be able to improve the diagnostic yield of endomyocardial ventricular biopsy.

Published
2015
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45. Optimal timing of initiation of oral P2Y12-receptor antagonist therapy in patients with non-ST elevation acute coronary syndromes. Lessons learnt from the ACCOAST-trial

Author

Diego Ardissino, Gilles Montalescot, Peter Clemmensen, Leonardo Bolognese, Jean-Philippe Collet, Jose Lopez-Sendon, Uwe Zeymer, and Petr Widimsky

Subjects
Male, medicine.medical_specialty, Prasugrel, medicine.medical_treatment, Administration, Oral, 030204 cardiovascular system & hematology, Coronary Angiography, Critical Care and Intensive Care Medicine, Non ST elevation myocardial infarction, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, P2Y12, Internal medicine, medicine, Humans, 030212 general & internal medicine, Acute Coronary Syndrome, Intensive care medicine, Clinical Trials as Topic, medicine.diagnostic_test, business.industry, ST elevation, Antagonist, Percutaneous coronary intervention, General Medicine, Clopidogrel, Treatment Outcome, Practice Guidelines as Topic, Conventional PCI, Angiography, Purinergic P2Y Receptor Antagonists, Cardiology, Female, P2Y12 antagonists, Cardiology and Cardiovascular Medicine, business, Prasugrel Hydrochloride, Pretreatment, medicine.drug
Abstract

The optimal time-point of the initiation of P2Y12 antagonist therapy in patients with non-ST elevation acute coronary syndromes (NTSE-ACS) is still a matter of debate. European guidelines recommend P2Y12 as soon as possible after first medical contact. However, the only trial which compared the two strategies did not demonstrate any benefit of pre-treatment with prasugrel before angiography compared to starting therapy after angiography and just prior to percutaneous coronary intervention (PCI). This paper summarizes the results of pharmacodynamic and previous studies, and gives recommendations for the initiation of P2Y12 antagonist therapy in NSTE-ACS in different clinical situations.

Published
2015
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46. Contemporary antithrombotic strategies in patients with acute coronary syndromes managed without revascularization: insights from the EYESHOT study

Author

De Luca, Leonardo, Leonardi, Sergio, Smecca, Ignazio Maria, Formigli, Dario, Lucci, Donata, Gonzini, Lucio, Tuccillo, Bernardino, Olivari, Zoran, Gulizia, Michele Massimo, Bovenzi, Francesco Maria, De Servi, Stefano, Caporale, R., Cavallini, C., Ceravolo, R., Lupi, A., Musumeci, G., Rakar, S., Maggioni, A. P., Lorimer, A., Orsini, G., Fabbri, Giorgio, Bianchini, E., Abrignani, M. G., Bonura, F., Trimarco, B., Galasso, Giorgia, Misuraca, G., Manes, M. T., Irace, Lorenzo, Totis, O., Ledda, A., Mauro, C., Boccalatte, M., Iliceto, S., Cacciavillani, L., Savonitto, S., Tortorella, G., Esposito, L., DE ROSA, Paolo, Calabrò, P., Bianchi, R., Napoletano, C., Lalla Piccioni, L., Pavesi, P. C., Boni, Allegra, Merenda, R., Wolff, S., De Ferrari, G. M., Camporotondo, R., Gambino, Paolo, Cutaia, A., Picariello, C., Cemin, R., Chiarella, F., Grazioli Gauthier, L., Mircoli, L., Del Pinto, M., Finocchiaro, M. L., Scioli, R., Farina, R., Naddeo, C., Scherillo, M., Santopietro, S., Metra, M., Costa, F., Calculli, G., Troito, G., Pennisi, V., Adornato, E. M. F., Pirelli, S., Fadin, B. M., Di Biase, M., Ieva, R., Zuin, G., Sanfilippo, N., Mancuso, LAURA CATERINA, Pani, Luisa Anna, Serra, Eleonora, Marenzi, G., Assanelli, E. M., Ansalone, G., Cacciotti, L., Morocutti, G., Fresco, C., Berti, S., Paradossi, U., Bozzano, A., Mauro, A., Noussan, P., Zanini, P., Bolognese, L., Falsini, G., Costa, P., Manca, G., Caldarola, P., Locuratolo, N., Cipolla, T., Becchina, M., Cocco, Gabriele, Scalera, G., Stefanelli, S., Giunta, N., Sinagra, G., Meloni, L., Lai, O., Chiaranda, G., Luca, G., Sleiman Helou, J., Biscottini, E., Magliari, F., Callerame, M., Uguccioni, M., Pugliese, M., Sanchez, F., Tartaglione, S., Ignone, G., Mavilio, G., Mantovan, R., Bini, R., Caico, S. I., Demolli, V., Proietti, F., Michisanti, M., Musmeci, G., Cantamessa, P., Sicuso, G., Micalef, S. S., Accogli, M., Zaccaria, MICHELA MARIA, Caputo, M., Di Paolo, G., Piatti, L., Farina, A., Vicinelli, P., Paloscia, L., Di Clemente, D., Felis, S., Castini, D., Rota, C., Casu, Gabriella, Bonano, S., Margheri, M., Ricci Lucchi, G., Serdoz, R., Proietti, P., Autore, C., Conti, E., Russo, V., Orlando, P., Ramondo, A. B., Bontorin, M., Marcolongo, M., Marrara, F., Maestroni, A., Vitti, P., Rodella, P., Bonetti, P., Elia, M., Lumare, R., Politi, A., Gritti, S., Poletti, F., Mafrici, A., Fusco, R., Bongo, A. S., Bacchini, S., Gasparetto, V., Ferraiuolo, G., Campana, C., Bonatti, R., Gaita, F., Bergerone, S., Bonmassari, R., Zeni, P., Langialonga, T., Scarcia, A., Caravita, L., Musacchio, E., Augello, G., Usmiani, T., Stomaci, B., Cirino, D., Pierini, S., Bottiglieri, G., Liso, A., Mussardo, M., Tosi, P., Sala, R., Belloni, A., Blengino, S., Lisi, E., Delfino, P., Auguadro, C., Brunazzi, M. C., Pacchioni, E., Fattore, L., Bosco, B., Blandizzi, S., Pajes, G., Patruno, N., Perna, G. P., Francioni, M., Favale, S., Vestito, D., Lombardi, A., Capecchi, A., Ferrero, P., De Vincenzo, C., Magri, G., Indolfi, C., De Rosa, S., Rossi, M., Collarini, L., Agnelli, D., Conti, G., Tonelli, C., Spadaro, C., Negroni, S., Di Noto, G., Lanari, A., Casolo, G., Del Meglio, J., Negrini, M., Celentano, A., Sifola, C., Rellini, G., Della Mattia, A., Molero, U., Piovaccari, G., Grosseto, D., Callegarin, L., Fiasconaro, G., Crivello, R., Thiebat, B., Leone, G., Tamburino, C., Caruso, G., Cassadonte, F., Sassone, B., Fuca, G., Sormani, L., Percoco, G. F., Mazzucco, R., Cazzani, E., Gianni, M., Limido, A., Luvini, M., Guglielmi, R., Mannarini, A., Moruzzi, P., Pastori, P., Golia, B., Marzano, A., Orazi, S., Marchese, I., Anselmi, M., Girardi, P., Nassiacos, D., Meloni, S., Busacca, P., Generali, C. A., Corda, S., Costanza, G., Montalto, S., Argenziano, L., Tommasini, P., Emdin, M., Pasanisi, E. M., Colivicchi, F., Tubaro, M., Azzolini, P., Luciani, C., Doronzo, B., Coppolino, A., Dellavesa, P., Zenone, F., Di Marco, A., De Conti, F., Piccinni, G. C., Gualtieri, M. R., Bisignani, G., Leone, A., Arcuri, G. M., Marinacci, L., Rossi, P., Perotti, S., Cotti Cometti, V., Arcidiacono, S., Tramontana, M., Bazzucchi, M., Mezzetti, P., Romano, M., Villani, R., Di Giovambattista, R., Volpe, B., Tedesco, L., Carini, M., Vinci, S., Paolini, E. A., Busoni, F., Piergentili, C., Navazio, A., Manca, F., Cocco, F., Pennetta, C. A., Maggiolini, S., Galbiati, R., Bruna, C., Ferrero, L., Brigido, S., Barducci, E., Musacchio, D., Manduca, B., Marchese, D., Patrassi, L. A., Pattarino, F. A., Rocchi, M., Briglia, S., Fanelli, R., Villella, M., Gronda, E., Massa, D., Lenti, V., Di Gregorio, L., Bottero, M., Bazzanini, F., Braggion, G., Antoniceli, R., Caraceni, D., Guzzo, V., Di Giovanni, P., Scarpini, S., Severgnini, B., Musolino, M. F., Della Casa, S., Gobbi, M., Arena, G., Bonizzato, S., Agnoletto, V., Sansoni, S., Pes, R. A. M., Denti, S., Polizzi, G. M., Pino, R., Commisso, B., Merlino, A., Di Lorenzo, L., Porchetta, I., Del Furia, F., Colombi, E., Covini, D., Cavalieri, F., Antonaci, S., Rubino, G., Ciulla, A., Bui, F., Casorelli, E., Caliendo, L., Laezza, A., Americo, L., Schillaci, A. M., Cordoni, M., Barsotti, L., Gaudio, C., Barilla, F., Cannone, M., Memeo, R., Truncellito, L., Andriani, A., Salituri, S., Verrina, F., Pafi, M., Sebastiani, M. L., Amico, A. F., Scolozzi, D., D'Alea, A., Catanzariti, D., Angheben, C., Ottaviano, A., and Levantesi, G.

Subjects
Male, Ticagrelor, medicine.medical_specialty, Acute coronary syndrome, medicine.medical_treatment, Conservative strategy, Population, Acute coronary syndromes, Revascularization, acute coronary syndromes, anticoagulant, antithrombotic therapy, conservative strategy, prasugrel, ticagrelor, aged, coronary care units, female, fibrinolytic agents, follow-up studies, hospital mortality, humans, iItaly, length of stay, male, myocardial revascularization, retrospective studies, survival rate, thrombolytic therapy, practice guidelines as topic, Fibrinolytic Agents, Anticoagulant, Antithrombotic therapy, Prasugrel, Acute Coronary Syndrome, Aged, Coronary Care Units, Female, Follow-Up Studies, Hospital Mortality, Humans, Italy, Length of Stay, Myocardial Revascularization, Retrospective Studies, Survival Rate, Thrombolytic Therapy, Practice Guidelines as Topic, Cardiology and Cardiovascular Medicine, Pharmacology (medical), Internal medicine, Antithrombotic, medicine, education, Survival rate, education.field_of_study, business.industry, Clopidogrel, medicine.disease, Cardiology, business, Fibrinolytic agent, medicine.drug
Abstract

Aims Patients with acute coronary syndromes (ACSs) who are managed without coronary revascularization represent a mixed and understudied population that seems to receive suboptimal pharmacological treatment. Methods and results We assessed patterns of antithrombotic therapies employed during the hospitalization and in-hospital clinical events of medically managed patients with ACS enrolled in the prospective, multicentre, nationwide EYESHOT (EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units) registry. Among the 2585 consecutive ACS patients enrolled in EYESHOT, 783 (30.3%) did not receive any revascularization during hospital admission. Of these, 478 (61.0%) underwent coronary angiography (CA), whereas 305 (39.0%) did not. The median GRACE and CRUSADE risk scores were significantly higher among patients who did not undergo CA compared with those who did (180 vs. 145, P < 0.0001 and 50 vs. 33, P < 0.0001, respectively). Antithrombotic therapies employed during hospitalization significantly differ between patients who received CA and those who did not with unfractioned heparin and novel P2Y12 inhibitors more frequently used in the first group, and low-molecular-weight heparins and clopidogrel in the latter group. During the index hospitalization, patients who did not receive CA presented a higher incidence of ischaemic cerebrovascular events and of mortality compared with those who underwent CA (1.6 vs. 0.2%, P = 0.04 and 7.9 vs. 2.7%, P = 0.0009, respectively). Conclusion Almost one-third of ACS patients are managed without revascularization during the index hospitalization. In this population, a lower use of recommended antiplatelet therapy and worse clinical outcome were observed in those who did not undergo CA when compared with those who did. Clinical Trial Registration Unique identifier: [NCT02015624][1], . [10.1093/ehjcvp/pvv017][2] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02015624&atom=%2Fehjcardpharm%2F1%2F3%2F168.atom [2]: /lookup/doi/10.1093/ehjcvp/pvv017

Published
2015
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47. A Randomized, Double‐Blind Phase 2 Clinical Trial of Blosozumab, a Sclerostin Antibody, in Postmenopausal Women with Low Bone Mineral Density

Author

Robert R. Recker, Hideaki Sowa, Leijun Hu, Bruce H. Mitlak, Charles Benson, Alan Y Chiang, Stephen L. Myers, Michael A. Bolognese, Toshio Matsumoto, Deborah A. Robins, John H. Krege, and Jahangir Alam

Subjects
Genetic Markers, musculoskeletal diseases, medicine.medical_specialty, Bone density, Blosozumab, Endocrinology, Diabetes and Metabolism, Osteoporosis, Urology, Romosozumab, Antibodies, Monoclonal, Humanized, Bone resorption, Bone remodeling, Placebos, chemistry.chemical_compound, Double-Blind Method, Bone Density, Internal medicine, medicine, Humans, Orthopedics and Sports Medicine, Osteoporosis, Postmenopausal, Adaptor Proteins, Signal Transducing, Aged, Bone mineral, business.industry, medicine.disease, Postmenopause, Treatment Outcome, Endocrinology, chemistry, Bone Morphogenetic Proteins, Sclerostin, Female, Bone Remodeling, business, Biomarkers
Abstract

Sclerostin, a SOST protein secreted by osteocytes, negatively regulates formation of mineralized bone matrix and bone mass. We report the results of a randomized, double-blind, placebo-controlled multicenter phase 2 clinical trial of blosozumab, a humanized monoclonal antibody targeted against sclerostin, in postmenopausal women with low bone mineral density (BMD). Postmenopausal women with a lumbar spine T-score -2.0 to -3.5, inclusive, were randomized to subcutaneous blosozumab 180 mg every 4 weeks (Q4W), 180 mg every 2 weeks (Q2W), 270 mg Q2W, or matching placebo for 1 year, with calcium and vitamin D. Serial measurements of spine and hip BMD and biochemical markers of bone turnover were performed. Overall, 120 women were enrolled in the study (mean age 65.8 years, mean lumbar spine T-score -2.8). Blosozumab treatment resulted in statistically significant dose-related increases in spine, femoral neck, and total hip BMD as compared with placebo. In the highest dose group, BMD increases from baseline reached 17.7% at the spine, and 6.2% at the total hip. Biochemical markers of bone formation increased rapidly during blosozumab treatment, and trended toward pretreatment levels by study end. However, bone specific alkaline phosphatase remained higher than placebo at study end in the highest-dose group. CTx, a biochemical marker of bone resorption, decreased early in blosozumab treatment to a concentration less than that of the placebo group by 2 weeks, and remained reduced throughout blosozumab treatment. Mild injection site reactions were reported more frequently with blosozumab than placebo. In conclusion, treatment of postmenopausal women with an antibody targeted against sclerostin resulted in substantial increases in spine and hip BMD. These results support further study of blosozumab as a potential anabolic therapy for osteoporosis.

Published
2015
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48. Long-term prognostic value of delirium in elderly patients with acute cardiac diseases admitted to two cardiac intensive care units: a prospective study (DELIRIUM CORDIS)

Author

Paolo Angioli, Leonardo Bolognese, Tamara Taddei, Italo Porto, Giulio Toccafondi, Kenneth Ducci, Simone Grotti, Francesco Liistro, Roberto Rossi, Aureliano Fraticelli, Giovanni Falsini, Maurizio Pieroni, and Serena Romanelli

Subjects
Male, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, law.invention, 0302 clinical medicine, law, Risk Factors, Delirium, cardiac intensive care unit, confusion assessment method, elderly, mortality, Acute Disease, Aged, Aged, 80 and over, Female, Heart Diseases, Humans, Incidence, Intensive Care Units, Italy, Length of Stay, Prevalence, Prognosis, Prospective Studies, Survival Rate, Risk Assessment, 80 and over, 030212 general & internal medicine, Prospective cohort study, Incidence (epidemiology), General Medicine, Intensive care unit, medicine.symptom, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, behavioral disciplines and activities, 03 medical and health sciences, Intensive care, mental disorders, medicine, Intensive care medicine, Survival rate, business.industry, Emergency medicine, Coronary care unit, Complication, business
Abstract

Background: Delirium is a frequent in-hospital complication in elderly patients, and is associated with poor clinical outcome. Its clinical impact, however, has not yet been fully addressed in the setting of the cardiac intensive care unit (CICU). The present study is a prospective, two-centre registry aimed at assessing the incidence, prevalence and significance of delirium in elderly patients with acute cardiac diseases. Methods: Between January 2014 and March 2015, all consecutive patients aged 65 years or older admitted to the CICU of our institutions were enrolled and followed for 6 months. Delirium was defined according to the confusion assessment method. Results: During the study period, 726 patients were screened for delirium. The mean age was 79.1±7.8 years. A total of 111 individuals (15.3%) were diagnosed with delirium; of them, 46 (41.4%) showed prevalent delirium (PD), while 65 (58.6%) developed incident delirium (ID). Patients 85 years or older showed a delirium rate of 52.3%. Hospital stay was longer in delirious versus non-delirious patients. Patients with delirium showed higher in-hospital, 30-day and 6-month mortality compared to non-delirious patients, irrespective of the onset time (overall, ID or PD). Six-month re-hospitalisation was significantly higher in overall delirium and the PD group, as compared to non-delirious patients. Kaplan–Meier analysis showed a significant reduction of 6-month survival in patients with delirium compared to those without, irrespective of delirium onset time (i.e. ID or PD). A positive confusion assessment method was an independent predictor of short and long-term mortality. Conclusions: Delirium is a common complication in elderly CICU patients, and is associated with a longer and more complicated hospital stay and increased short and long-term mortality. Our findings suggest the usefulness of a protocol for the early identification of delirium in the CICU. Clinicaltrials.gov: NCT02004665

Published
2017

49. Effects of 24 Months of Treatment With Romosozumab Followed by 12 Months of Denosumab or Placebo in Postmenopausal Women With Low Bone Mineral Density: A Randomized, Double-Blind, Phase 2, Parallel Group Study

Author

Michael R, McClung, Jacques P, Brown, Adolfo, Diez-Perez, Heinrich, Resch, John, Caminis, Paul, Meisner, Michael A, Bolognese, Stefan, Goemaere, Henry G, Bone, Jose R, Zanchetta, Judy, Maddox, Sarah, Bray, and Andreas, Grauer

Subjects
Time Factors, Antibodies, Monoclonal, Middle Aged, Bone and Bones, Drug Administration Schedule, Placebos, Postmenopause, Editorial Commentary, Treatment Outcome, Double-Blind Method, Bone Density, Humans, Female, Bone Remodeling, Denosumab, Biomarkers, Aged
Abstract

Over 12 months, romosozumab increased bone formation and decreased bone resorption, resulting in increased bone mineral density (BMD) in postmenopausal women with low BMD (NCT00896532). Herein, we report the study extension evaluating 24 months of treatment with romosozumab, discontinuation of romosozumab, alendronate followed by romosozumab, and romosozumab followed by denosumab. Postmenopausal women aged 55 to 85 years with a lumbar spine (LS), total hip (TH), or femoral neck T-score ≤-2.0 and ≥-3.5 were enrolled and randomly assigned to placebo, one of five romosozumab regimens (70 mg, 140 mg, 210 mg monthly [QM]; 140 mg Q3M; 210 mg Q3M) for 24 months, or open-label alendronate for 12 months followed by romosozumab 140 mg QM for 12 months. Eligible participants were then rerandomized 1:1 within original treatment groups to placebo or denosumab 60 mg Q6M for an additional 12 months. Percentage change from baseline in BMD and bone turnover markers (BTMs) at months 24 and 36 and safety were evaluated. Of 364 participants initially randomized to romosozumab, placebo, or alendronate, 315 completed 24 months of treatment and 248 completed the extension. Romosozumab markedly increased LS and TH BMD through month 24, with largest gains observed with romosozumab 210 mg QM (LS = 15.1%; TH = 5.4%). Women receiving romosozumab who transitioned to denosumab continued to accrue BMD, whereas BMD returned toward pretreatment levels with placebo. With romosozumab 210 mg QM, bone formation marker P1NP initially increased after treatment initiation and gradually decreased to below baseline by month 12, remaining below baseline through month 24; bone resorption marker β-CTX rapidly decreased after treatment, remaining below baseline through month 24. Transition to denosumab further decreased both BTMs, whereas after transition to placebo, P1NP returned to baseline and β-CTX increased above baseline. Adverse events were balanced between treatment groups through month 36. These data suggest that treatment effects of romosozumab are reversible upon discontinuation and further augmented by denosumab. © 2018 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.

Published
2017

50. Antithrombotic strategies in the catheterization laboratory for patients with acute coronary syndromes undergoing percutaneous coronary interventions: insights from the EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units Registry

Author

De Luca, L., Musumeci, G., Leonardi, S., Gonzini, L., Cavallini, C., Calabro, P., Mauro, C., Cacciavillani, L., Savonitto, S., De Servi, S., Caporale, R., Ceravolo, R., Formigli, D., Lupi, A., Rakar, S., Smecca, I. M., Maggioni, A. P., Lucci, D., Lorimer, A., Orsini, G., Fabbri, G., Bianchini, E., Abrignani, M. G., Bonura, F., Trimarco, B., Galasso, G., Misuraca, G., Manes, M. T., Tuccillo, B., Irace, L., Olivari, Z., Totis, O., Ledda, A., Boccalatte, M., Iliceto, S., Tortorella, G., Esposito, L., De Rosa, P., Bianchi, R., Napoletano, C., Piccioni, L. L., Pavesi, P. C., Bovenzi, F. M., Boni, A., Merenda, R., Wolff, S., De Ferrari, G. M., Camporotondo, R., Gambino, P., Cutaia, A., Picariello, C., Cemin, R., Chiarella, F., Gauthier, L. G., Mircoli, L., Del Pinto, M., Finocchiaro, M. L., Scioli, R., Farina, R., Naddeo, C., Scherillo, M., Santopietro, S., Metra, M., Costa, F., Calculli, G., Troito, G., Pennisi, V., Adornato, E. M. F., Pirelli, S., Fadin, B. M., DI Biase, M., Ieva, R., Zuin, G., Sanfilippo, N., Mancuso, L., Pani, A., Serra, E., Marenzi, G., Assanelli, E. M., Ansalone, G., Cacciotti, L., Morocutti, G., Fresco, C., Berti, S., Paradossi, U., Bozzano, A., Mauro, A., Noussan, P., Zanini, P., Bolognese, L., Falsini, G., Costa, P., Manca, G., Caldarola, P., Locuratolo, N., Cipolla, T., Becchina, M., Cocco, G., Scalera, G., Stefanelli, S., Giunta, N., Sinagra, G., Meloni, L., Lai, O., Chiaranda, G., Luca, G., Helou, J. S., Biscottini, E., Magliari, F., Callerame, M., Uguccioni, M., Pugliese, M., Sanchez, F., Tartaglione, S., Ignone, G., Mavilio, G., Mantovan, R., Bini, R., Caico, S. I., Demolli, V., Proietti, F., Michisanti, M., Musmeci, G., Cantamessa, P., Sicuso, G., Micalef, S. S., Accogli, M., Zaccaria, M., Caputo, M., DI Paolo, G., Piatti, L., Farina, A., Vicinelli, P., Paloscia, L., DI Clemente, D., Felis, S., Castini, D., Rota, C., Casu, G., Bonano, S., Margheri, M., Lucchi, G. R., Serdoz, R., Proietti, P., Autore, C., Conti, E., Russo, V., Orlando, P., Ramondo, A. B., Bontorin, M., Marcolongo, M., Santagostino, M., Maestroni, A., Vitti, P., Rodella, P., Bonetti, P., Elia, M., Lumare, R., Politi, A., Gritti, S., Poletti, F., Mafrici, A., Fusco, R., Bongo, A. S., Bacchini, S., Gasparetto, V., Ferraiuolo, G., De Luca, M., Campana, C., Bonatti, R., Gaita, F., Bergerone, S., Bonmassari, R., Zeni, P., Langialonga, T., Scarcia, A., Caravita, L., Musacchio, E., Augello, G., Usmiani, T., Stomaci, B., Cirino, D., Pierini, S., Bottiglieri, G., Liso, A., Mussardo, M., Tosi, P., Sala, R., Belloni, A., Blengino, S., Lisi, E., Delfino, P., Auguadro, C., Brunazzi, M. C., Pacchioni, E., Fattore, L., Bosco, B., Blandizzi, S., Pajes, G., Patruno, N., Perna, G. P., Francioni, M., Favale, S., Vestito, D., Lombardi, A., Capecchi, A., Ferrero, P., De Vincenzo, C., Magri, G., Indolfi, C., De Rosa, S., Rossi, M., Collarini, L., Agnelli, D., Conti, G., Tonelli, C., Spadaro, C., Negroni, S., DI Noto, G., Lanari, A., Casolo, G., Del Meglio, J., Negrini, M., Celentano, A., Sifola, C., Rellini, G., Mattia, A. D., Molero, U., Piovaccari, G., Grosseto, D., Callegarin, L., Fiasconaro, G., Crivello, R., Thiebat, B., Leone, G., Tamburino, C., Caruso, G., Cassadonte, F., Sassone, B., Fuca, G., Sormani, L., Percoco, G. F., Mazzucco, R., Cazzani, E., Gianni, M., Limido, A., Luvini, M., Guglielmi, R., Mannarini, A., Moruzzi, P., Pastori, P., Golia, B., Marzano, A., Orazi, S., Marchese, I., Anselmi, M., Girardi, P., Nassiacos, D., Meloni, S., Busacca, P., Generali, C. A., Corda, S., Costanza, G., Montalto, S., Argenziano, L., Tommasini, P., Emdin, M., Pasanisi, E. M., Colivicchi, F., Tubaro, M., Azzolini, P., Luciani, C., Doronzo, B., Coppolino, A., Dellavesa, P., Zenone, F., DI Marco, A., De Conti, F., Piccinni, G. C., Gualtieri, M. R., Bisignani, G., Leone, A., Arcuri, G. M., Marinacci, L., Rossi, P., Perotti, S., Cometti, V. C., Arcidiacono, S., Tramontana, M., Bazzucchi, M., Mezzetti, P., Romano, M., Villani, R., DI Giovambattista, R., Volpe, B., Tedesco, L., Carini, M., Vinci, S., Paolini, E. A., Busoni, F., Piergentili, C., Navazio, A., Manca, F., Cocco, F., Pennetta, C. A., Maggiolini, S., Galbiati, R., Bruna, C., Ferrero, L., Brigido, S., Barducci, E., Musacchio, D., Manduca, B., Marchese, D., Patrassi, L. A., Pattarino, F. A., Rocchi, M., Briglia, S., Fanelli, R., Villella, M., Gronda, E., Massa, D., Lenti, V., DI Gregorio, L., Bottero, M., Bazzanini, F., Braggion, G., Antoniceli, R., Caraceni, D., Guzzo, V., DI Giovanni, P., Scarpini, S., Severgnini, B., Musolino, M. F., Casa, S. D., Gobbi, M., Arena, G., Bonizzato, S., Agnoletto, V., Sansoni, S., Pes, R. A. M., Denti, S., Polizzi, G. M., Pino, R., Commisso, B., Merlino, A., DI Lorenzo, L., Porchetta, I., Del Furia, F., Colombi, E., Covini, D., Cavalieri, F., Antonaci, S., Rubino, G., Ciulla, A., Bui, F., Casorelli, E., Caliendo, L., Laezza, A., Americo, L., Schillaci, A. M., Cordoni, M., Barsotti, L., Gaudio, C., Barilla, F., Cannone, M., Memeo, R., Truncellito, L., Andriani, A., Salituri, S., Verrina, F., Pafi, M., Sebastiani, M. L., Amico, A. F., Scolozzi, D., Lupi, G., D'Alea, A., Catanzariti, D., Angheben, C., Ottaviano, A., Levantesi, G., de Luca, Leonardo, Musumeci, Giuseppe, Leonardi, Sergio, Gonzini, Lucio, Cavallini, Claudio, Calabrò, Paolo, Mauro, Ciro, Cacciavillani, Luisa, Savonitto, Stefano, de Servi, Stefano, Caporale, Roberto, Ceravolo, Roberto, Formigli, Dario, Lupi, Alessandro, Rakar, Sadir, Smecca, Ivan, Maggioni, Aldo Pietro, Lucci, Donata, Lorimer, Andrea, Orsini, Giampietro, Fabbri, Gianna, Bianchini, Elisa, Abrignani, Maurizio Giuseppe, Bonura, Francesc, Trimarco, Bruno, Galasso, Gennaro, Misuraca, Gianfranco, Manes, Maria Teresa, Tuccillo, Bernardino, and Irace, Luigi.

Subjects
Male, Prasugrel, medicine.medical_treatment, Myocardial Infarction, antithrombotic therapy, 030204 cardiovascular system & hematology, acute coronary syndromes, bivalirudin, heparins, percutaneous coronary intervention, prasugrel, ticagrelor, 0302 clinical medicine, Antithrombotic, 80 and over, Bivalirudin, 030212 general & internal medicine, Myocardial infarction, Prospective Studies, Registries, Aged, 80 and over, General Medicine, Hirudins, Middle Aged, Recombinant Proteins, Italy, Female, Cardiology and Cardiovascular Medicine, Ticagrelor, medicine.drug, medicine.medical_specialty, Platelet Glycoprotein GPIIb-IIIa Complex, NO, 03 medical and health sciences, Percutaneous Coronary Intervention, Internal medicine, medicine, Humans, Acute Coronary Syndrome, Aged, Aspirin, business.industry, Heparin, Percutaneous coronary intervention, Anticoagulants, medicine.disease, Peptide Fragments, Clinical trial, Cross-Sectional Studies, Logistic Models, Conventional PCI, Multivariate Analysis, business
Abstract

Aims In the last decades, several new therapies have emerged for the treatment of acute coronary syndromes (ACS). We sought to describe real-world patterns of use of antithrombotic treatments in the catheterization laboratory for ACS patients undergoing percutaneous coronary interventions (PCI). Methods EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units was a nationwide, prospective registry aimed to evaluate antithrombotic strategies employed in ACS patients in Italy. Results Over a 3-week period, a total of 2585 consecutive ACS patients have been enrolled in 203 cardiac care units across Italy. Among these patients, 1755 underwent PCI (923 with ST-elevation myocardial infarction and 832 with non-ST-elevation ACS). In the catheterization laboratory, unfractioned heparin was the most used antithrombotic drug in both ST-elevation myocardial infarction (64.7%) and non-ST-elevation ACS (77.5%) undergoing PCI and, as aspirin, bivalirudin and glycoprotein IIb/IIIa inhibitors (GPIs) more frequently employed before or during PCI compared with the postprocedural period. Any crossover of heparin therapy occurred in 36.0% of cases, whereas switching from one P2Y12 inhibitor to another occurred in 3.7% of patients. Multivariable analysis yielded several independent predictors of GPIs and of bivalirudin use in the catheterization laboratory, mainly related to clinical presentation, PCI complexity and presence of complications during the procedure. Conclusion In our contemporary, nationwide, all-comers cohort of ACS patients undergoing PCI, antithrombotic therapies were commonly initiated before the catheterization laboratory. In the periprocedural period, the most frequently employed drugs were unfractioned heparin, leading to a high rate of crossover, followed by GPIs and bivalirudin, mainly used during complex PCI. Clinical trial registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02015624.

Published
2017

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