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Article ; Online: Vascular and valvular calcification biomarkers.

Clemente, Alberto / Traghella, Irene / Mazzone, Annamaria / Sbrana, Silverio / Vassalle, Cristina

2019 Volume 95, Page(s) 73–103

Abstract: Vascular and valvular calcification constitutes a major health problem with serious clinical consequences. It is important for medical laboratorians to improve their knowledge on this topic and to know which biological markers may have a potential ... ...

Abstract	Vascular and valvular calcification constitutes a major health problem with serious clinical consequences. It is important for medical laboratorians to improve their knowledge on this topic and to know which biological markers may have a potential interest and might be useful for diagnosis and for management of ectopic calcifications. This review focuses on the pathophysiological mechanisms of vascular and valvular calcification, with emphasis on the mechanisms that are different for the two types of events, which underscore the need for differentiated healthcare, and explain different response to therapy. Available imaging and scoring tools used to assess both vascular and valvular calcification, together with the more studied and reliable biological markers emerging in this field (e.g., Fetuin A and matrix Gla protein), are discussed. Recently proposed functional assays, measuring the propensity of human serum to calcify, appear promising for vascular calcification assessment and are described. Further advancement through omic technologies and statistical tools is also reported. Clinical chemistry and laboratory medicine practitioners overlook this new era that will engage them in the near future, where a close cooperation of professionals with different competencies, including laboratorists, is required. This innovative approach may truly revolutionize practice of laboratory and of whole medicine attitude, making progression in knowledge of pathways relevant to health, as the complex calcification-related pathways, and adding value to patient care, through a precision medicine strategy.
MeSH term(s)	Animals ; Biomarkers/metabolism ; Humans ; Vascular Calcification/metabolism ; Vascular Calcification/physiopathology
Chemical Substances	Biomarkers
Language	English
Publishing date	2019-10-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	210505-6
ISSN	2162-9471 ; 0065-2423
ISSN (online)	2162-9471
ISSN	0065-2423
DOI	10.1016/bs.acc.2019.08.002
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Article: Association of Circulating Neutrophils with Relative Volume of Lipid-Rich Necrotic Core of Coronary Plaques in Stable Patients: A Substudy of SMARTool European Project.

Sbrana, Silverio / Cecchettini, Antonella / Bastiani, Luca / Mazzone, Annamaria / Vozzi, Federico / Caselli, Chiara / Neglia, Danilo / Clemente, Alberto / Scholte, Arthur J H A / Parodi, Oberdan / Pelosi, Gualtiero / Rocchiccioli, Silvia

Life (Basel, Switzerland)

2023 Volume 13, Issue 2

Abstract: Background and aims: Coronary atherosclerosis is a chronic non-resolving inflammatory process wherein the interaction of innate immune cells and platelets plays a major role. Circulating neutrophils, in particular, adhere to the activated endothelium ... ...

Abstract	Background and aims: Coronary atherosclerosis is a chronic non-resolving inflammatory process wherein the interaction of innate immune cells and platelets plays a major role. Circulating neutrophils, in particular, adhere to the activated endothelium and migrate into the vascular wall, promoting monocyte recruitment and influencing plaque phenotype and stability at all stages of its evolution. We aimed to evaluate, by flow cytometry, if blood neutrophil number and phenotype-including their phenotypic relationships with platelets, monocytes and lymphocytes-have an association with lipid-rich necrotic core volume (LRNCV), a generic index of coronary plaque vulnerability, in a group of stable patients with chronic coronary syndrome (CCS). Methods: In 55 patients, (68.53 ± 1.07 years of age, mean ± SEM; 71% male), the total LRNCV in each subject was assessed by a quantitative analysis of all coronary plaques detected by computed tomography coronary angiography (CTCA) and was normalized to the total plaque volume. The expression of CD14, CD16, CD18, CD11b, HLA-DR, CD163, CCR2, CCR5, CX3CR1, CXCR4 and CD41a cell surface markers was quantified by flow cytometry. Adhesion molecules, cytokines and chemokines, as well as MMP9 plasma levels, were measured by ELISA. Results: On a per-patient basis, LRNCV values were positively associated, by a multiple regression analysis, with the neutrophil count ( Conclusions: These preliminary findings suggest that a sustained increase in circulating neutrophils, together with the up-regulation of the integrin/activation membrane neutrophil marker CD11b may contribute, through the progressive intra-plaque accumulation of necrotic/apoptotic cells exceeding the efferocytosis/anti-inflammatory capacity of infiltrating macrophages and lymphocytes, to the relative enlargement of the lipid-rich necrotic core volume of coronary plaques in stable CAD patients, thus increasing their individual risk of acute complication.
Language	English
Publishing date	2023-02-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life13020428
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Article ; Online: The Positive Impact of Early Frailty Levels on Mortality in Elderly Patients with Severe Aortic Stenosis Undergoing Transcatheter/Surgical Aortic Valve Replacement.

Mazzone, Annamaria / Del Turco, Serena / Trianni, Giuseppe / Quadrelli, Paola / Marotta, Marco / Bastiani, Luca / Gasbarri, Tommaso / D'Agostino, Andreina / Mariani, Massimiliano / Basta, Giuseppina / Foffa, Ilenia / Sbrana, Silverio / Vassalle, Cristina / Ravani, Marcello / Solinas, Marco / Berti, Sergio

Journal of cardiovascular development and disease

2023 Volume 10, Issue 5

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2023-05-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2777082-5
ISSN	2308-3425 ; 2308-3425
ISSN (online)	2308-3425
ISSN	2308-3425
DOI	10.3390/jcdd10050212
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Article: Blood M2-like Monocyte Polarization Is Associated with Calcific Plaque Phenotype in Stable Coronary Artery Disease: A Sub-Study of SMARTool Clinical Trial.

Sbrana, Silverio / Cecchettini, Antonella / Bastiani, Luca / Di Giorgi, Nicoletta / Mazzone, Annamaria / Ceccherini, Elisa / Vozzi, Federico / Caselli, Chiara / Neglia, Danilo / Clemente, Alberto / Scholte, Arthur J H A / Parodi, Oberdan / Pelosi, Gualtiero / Rocchiccioli, Silvia

Biomedicines

2022 Volume 10, Issue 3

Abstract: Background: Atherosclerosis is a chronic inflammatory disease. The balance between pro- and anti-inflammatory factors, acting on the arterial wall, promotes less or more coronary plaque macro-calcification, respectively. We investigated the association ... ...

Abstract	Background: Atherosclerosis is a chronic inflammatory disease. The balance between pro- and anti-inflammatory factors, acting on the arterial wall, promotes less or more coronary plaque macro-calcification, respectively. We investigated the association between monocyte phenotypic polarization and CTCA-assessed plaque dense-calcium volume (DCV) in patients with stable coronary artery disease (CAD). Methods: In 55 patients, individual DCV component was assessed by quantitative CTCA and normalized to total plaque volume. Flow cytometry expression of CD14, CD16, CD18, CD11b, HLA-DR, CD163, CCR2, CCR5, CX3CR1 and CXCR4 was quantified. Adhesion molecules and cytokines were measured by ELISA. Results: DCV values were significantly associated, by multiple regression analysis, with the expression (RFI) of CCR5 ( Conclusions: The association between DCV and M2-like phenotypic polarization of circulating monocytes indicates that plaque macro-calcification in stable CAD may be partly modulated by an anti-inflammatory monocyte functional state, as evidenced by cell membrane receptor patterns.
Language	English
Publishing date	2022-02-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10030565
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Article ; Online: Statins association with calcification in coronary plaque and heart valves: a possible different clinical significance: Montignoso HEart and Lung Project (MHELP) study preliminary data in primary cardiovascular prevention.

Mazzone, Annamaria / Clemente, Alberto / Sbrana, Silverio / Latta, Daniele Della / Chiappino, Sara / Berti, Sergio / Chiappino, Dante / Vassalle, Cristina

European journal of preventive cardiology

2020 Volume 28, Issue 8, Page(s) e15–e17

MeSH term(s)	Calcinosis ; Cardiovascular Diseases/drug therapy ; Heart Valves ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Lung ; Plaque, Atherosclerotic/drug therapy ; Preliminary Data ; Vascular Calcification/diagnostic imaging ; Vascular Calcification/drug therapy ; Vascular Calcification/prevention & control
Chemical Substances	Hydroxymethylglutaryl-CoA Reductase Inhibitors
Language	English
Publishing date	2020-06-10
Publishing country	England
Document type	Letter
ZDB-ID	2626011-6
ISSN	2047-4881 ; 2047-4873
ISSN (online)	2047-4881
ISSN	2047-4873
DOI	10.1177/2047487320932330
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Article: Primary and Memory Response of Human Monocytes to Vaccines: Role of Nanoparticulate Antigens in Inducing Innate Memory.

Barbosa, Mayra M Ferrari / Kanno, Alex Issamu / Farias, Leonardo Paiva / Madej, Mariusz / Sipos, Gergö / Sbrana, Silverio / Romani, Luigina / Boraschi, Diana / Leite, Luciana C C / Italiani, Paola

Nanomaterials (Basel, Switzerland)

2021 Volume 11, Issue 4

Abstract: Innate immune cells such as monocytes and macrophages are activated in response to microbial and other challenges and mount an inflammatory defensive response. Exposed cells develop the so-called innate memory, which allows them to react differently to a ...

Abstract	Innate immune cells such as monocytes and macrophages are activated in response to microbial and other challenges and mount an inflammatory defensive response. Exposed cells develop the so-called innate memory, which allows them to react differently to a subsequent challenge, aiming at better protection. In this study, using human primary monocytes in vitro, we have assessed the memory-inducing capacity of two antigenic molecules of
Language	English
Publishing date	2021-04-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662255-5
ISSN	2079-4991
ISSN	2079-4991
DOI	10.3390/nano11040931
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Article ; Online: Relationships Between Phenotype and Function of Blood CD4+ T-Cells and Ascending Thoracic Aortic Aneurysm: an Experimental Study.

Sbrana, Silverio / Tiwari, Kaushal Kishore / Bevilacqua, Stefano / Giungato, Paola / Kallushi, Enkel / Solinas, Marco / Mazzone, Anna Maria

Brazilian journal of cardiovascular surgery

2019 Volume 34, Issue 1, Page(s) 8–16

Abstract: Introduction: Non-familial ascending thoracic aorta dilation and aneurysms (TAAs) are silent diseases in elderly patients. Histopathology revealed that functionally polarized infiltrating CD4+ T-cells play a key role in aortic wall weakening.: ... ...

Abstract	Introduction: Non-familial ascending thoracic aorta dilation and aneurysms (TAAs) are silent diseases in elderly patients. Histopathology revealed that functionally polarized infiltrating CD4+ T-cells play a key role in aortic wall weakening. Objective: To evaluate the possible associations between phenotype and cytokine production of circulating CD4+ T-lymphocytes and the presence of TAA in patients with aortic valve disease (AVD). Methods: We studied blood samples from 10 patients with TAA and 10 patients with AVD. Flow cytometry was used to quantify: a) CD4+ T-lymphocytes surface expression of CD25, CD28, and chemokine receptors (CCR5, CXCR3, CX3CR1); b) fractions of in vitro stimulated CD4+ T-cells producing cytokines (interferon gamma [IFN-γ], interleukin [IL]-17A, IL-21, IL-10); c) CD4+CD25highFoxP3+ regulatory T-cells (Treg) fraction. Enzyme-linked immunosorbent assays (ELISA) were performed for cytokines (IFN-γ, IL-6, IL-10, IL-17A, IL-23, transforming growth factor beta [TGF-β]) and chemokines (RANTES, CX3CL1). Results: The total CD4+CD28±CD4+/CX3CR1+ T-cells fraction was higher (P=0.0323) in AVD (20.452±4.673) than in TAA patients (8.633±2.030). The frequency ratio of CD4+ T-lymphocytes producing IFN-γ vs. IL-17A+IL-21 cytokine-producing CD4+ T-cells was higher (P=0.0239) in AVD (2.102±0.272) than in TAA (1.365±0.123) patients. The sum of CD4+CD28±CD4+/CX3CR1+ T-cells correlated positively with values of the previous cytokine ratio (P=0.0002, R=0.732). The ratio of CD4+CD28±CD4+/CX3CR1+ T-cells vs. Treg was higher (P=0.0008) in AVD (20.859±3.393) than in TAA (6.367±1.277) patients. Conclusion: Our results show that the presence of TAA in subjects with AVD is associated with imbalance between phenotypic and cytokine-producing subsets of circulating CD4+ T-lymphocytes, prevalently oriented towards a pro-fibrotic and IFN-γ counteracting effect to functional polarization.
MeSH term(s)	Aged ; Analysis of Variance ; Aortic Aneurysm, Thoracic/blood ; Aortic Valve ; CD4-Positive T-Lymphocytes/physiology ; Cytokines/blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry/methods ; Heart Valve Diseases/blood ; Humans ; Male ; Phenotype ; Reference Values
Chemical Substances	Cytokines
Language	English
Publishing date	2019-02-21
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	2031026-2
ISSN	1678-9741 ; 0102-7638
ISSN (online)	1678-9741
ISSN	0102-7638
DOI	10.21470/1678-9741-2018-0310
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Article ; Online: Differential modulatory effects of Propofol and Sevoflurane anesthesia on blood monocyte HLA-DR and CD163 expression during and after cardiac surgery with cardiopulmonary bypass: a preliminary randomized flow cytometry study.

Sbrana, Silverio / Nunziata, Anna / Storti, Simona / Haxhiademi, Dorela / Mazzone, Annamaria / Leone, Maria / Solinas, Marco / Del Sarto, Paolo

Perfusion

2019 Volume 35, Issue 1, Page(s) 48–56

Abstract: Introduction: The increase of the anti-inflammatory CD163: Methods: Blood from patients (Propofol = 11, Sevoflurane = 13) undergoing minimally invasive mitral valve surgery was drawn preoperatively (T1), before declamping (T2), at 6 (T3), 24 (T4), 48 ...

Abstract	Introduction: The increase of the anti-inflammatory CD163 Methods: Blood from patients (Propofol = 11, Sevoflurane = 13) undergoing minimally invasive mitral valve surgery was drawn preoperatively (T1), before declamping (T2), at 6 (T3), 24 (T4), 48 (T5), and 72 hours (T6) after declamping. C-reactive protein, haptoglobin, and lactate dehydrogenase were measured. A hemolytic index, as C-reactive protein/haptoglobin ratio, was introduced. Monocyte expression of HLA-DR, CD163, and the CD163 Results: Variations of hemolytic index and lactate dehydrogenase were higher with Propofol at T3 (p = 0.004 and p = 0.02, respectively) when compared with Sevoflurane. At T2, the down-modulation of CD163 was higher with Propofol (p = 0.005). Starting from T3, the up-regulatory trend of CD163 was basically higher with Propofol, although not significantly. Propofol induced higher increments of HLA-DR low fractions, at T2 (p = 0.04) and, to a lesser extent, at T4 (p = 0.06). Starting from T3, the CD163 Conclusion: Propofol seems to induce a higher postoperative fraction of the CD163
MeSH term(s)	Aged ; Anesthetics, Inhalation/administration & dosage ; Anesthetics, Inhalation/adverse effects ; Anesthetics, Intravenous/administration & dosage ; Anesthetics, Intravenous/adverse effects ; Antigens, CD/blood ; Antigens, Differentiation, Myelomonocytic/blood ; Biomarkers/blood ; Cardiac Surgical Procedures ; Cardiopulmonary Bypass ; Female ; Flow Cytometry ; HLA-DR Antigens/blood ; Hemolysis/drug effects ; Humans ; Male ; Middle Aged ; Monocytes/drug effects ; Monocytes/immunology ; Pilot Projects ; Propofol/administration & dosage ; Propofol/adverse effects ; Prospective Studies ; Random Allocation ; Receptors, Cell Surface/blood ; Sevoflurane/administration & dosage ; Sevoflurane/adverse effects ; Time Factors
Chemical Substances	Anesthetics, Inhalation ; Anesthetics, Intravenous ; Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; Biomarkers ; CD163 antigen ; HLA-DR Antigens ; Receptors, Cell Surface ; Sevoflurane (38LVP0K73A) ; Propofol (YI7VU623SF)
Language	English
Publishing date	2019-05-31
Publishing country	England
Document type	Comparative Study ; Journal Article ; Observational Study
ZDB-ID	645038-6
ISSN	1477-111X ; 0267-6591
ISSN (online)	1477-111X
ISSN	0267-6591
DOI	10.1177/0267659119848295
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Article ; Online: Blood Monocyte Phenotype Fingerprint of Stable Coronary Artery Disease: A Cross-Sectional Substudy of SMARTool Clinical Trial.

Sbrana, Silverio / Campolo, Jonica / Clemente, Alberto / Bastiani, Luca / Cecchettini, Antonella / Ceccherini, Elisa / Caselli, Chiara / Neglia, Danilo / Parodi, Oberdan / Chiappino, Dante / Smit, Jeff M / Scholte, Arthur J / Pelosi, Gualtiero / Rocchiccioli, Silvia

BioMed research international

2020 Volume 2020, Page(s) 8748934

Abstract: Background and aims: Atherosclerosis is an inflammatory disease with long-lasting activation of innate immunity and monocytes are the main blood cellular effectors. We aimed to investigate monocyte phenotype (subset fraction and marker expression) at ... ...

Abstract	Background and aims: Atherosclerosis is an inflammatory disease with long-lasting activation of innate immunity and monocytes are the main blood cellular effectors. We aimed to investigate monocyte phenotype (subset fraction and marker expression) at different stages of coronary atherosclerosis in stable coronary artery disease (CAD) patients. Methods: 73 patients with chronic coronary syndrome were evaluated by CT coronary angiography (CTCA) and classified by maximal diameter stenosis of major vessels into three groups of CAD severity: CAD1 (no CAD/minimal CAD, Results: Total cell count and fraction of Mon2 were higher in CAD2 and CAD3 compared to CAD1. By multivariate regression analysis, Mon2 cell fraction and Mon2 expression of CX3CR1, CD18, and CD16 showed a statistically significant and independent increase, parallel to stenosis severity, from CAD1 to CAD2 and CAD3 groups. A similar trend was also present for CX3CR1 and HLA-DR expressions on total monocyte population. A less calcified plaque composition was associated to a higher Mon2 expression of CD16 and higher TNF- Conclusions: The results of this study suggest that a specific pattern of inflammation-correlated monocyte marker expression is associated to higher stenosis severity and less calcified lesions in stable CAD. The clinical trial Identifier is NCT04448691.
MeSH term(s)	Aged ; Antigens, CD/blood ; Coronary Angiography ; Coronary Artery Disease/blood ; Coronary Artery Disease/diagnostic imaging ; Cross-Sectional Studies ; Cytokines/blood ; Female ; Flow Cytometry ; HLA-DR Antigens/blood ; Humans ; Male ; Monocytes/metabolism ; Receptors, Chemokine/blood ; Severity of Illness Index
Chemical Substances	Antigens, CD ; Cytokines ; HLA-DR Antigens ; Receptors, Chemokine
Language	English
Publishing date	2020-07-27
Publishing country	United States
Document type	Clinical Trial ; Journal Article
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2020/8748934
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Article ; Online: Different inflammatory profile in young and elderly STEMI patients undergoing primary percutaneous coronary intervention (PPCI): Its influence on no-reflow and mortality.

Del Turco, Serena / Basta, Giuseppina / De Caterina, Alberto Ranieri / Sbrana, Silverio / Paradossi, Umberto / Taddei, Alessandro / Trianni, Giuseppe / Ravani, Marcello / Palmieri, Cataldo / Berti, Sergio / Mazzone, Annamaria

International journal of cardiology

2019 Volume 290, Page(s) 34–39

Abstract: Background: Coronary no-reflow phenomenon in ST-segment elevation myocardial infarction (STEMI) is associated with a poor clinical prognosis. Although its pathophysiology is not fully elucidated, a deregulated systemic inflammatory response plays an ... ...

Abstract	Background: Coronary no-reflow phenomenon in ST-segment elevation myocardial infarction (STEMI) is associated with a poor clinical prognosis. Although its pathophysiology is not fully elucidated, a deregulated systemic inflammatory response plays an important role. Specifically, the relationship between age-associated differences in inflammatory markers and either no-reflow or mortality in STEMI patients undergoing primary percutaneous coronary intervention (pPCI) has never been investigated. Methods and results: We retrospectively enrolled 625 consecutive STEMI patients undergoing pPCI for whom a complete laboratory inflammatory pattern was available. Routinely blood measured laboratory parameters were collected at the moment of admission. No reflow was defined as Thrombolysis in Myocardial Infarction (TIMI) flow-grade lower than 3. The population was divided into two groups using a cut-off centered at 65 years. Compared to younger patients, elderly patients had higher mean values of fibrinogen, brain natriuretic peptide (BNP), leukocytes, neutrophil-to-lymphocyte ratio (NLR), C reactive protein/albumin ratio (CAR). Conversely, lymphocyte count and albumin levels were higher in young patients. In elderly patients, the values of NLR, CAR as well as leukocytes, fibrinogen and neutrophils were associated with no-reflow, while in young patients only BNP value was associated. At multivariate Cox regression analysis, only BNP and NLR resulted as independent predictors of all-cause mortality in the whole population and in elderly patients. Conclusions: Elderly STEMI patients on admission had a higher acute pro-inflammatory profile than young patients, associated to coronary no-reflow and mortality outcome. These results suggest that a different therapeutic approach between elderly and young STEMI patients should be agreed.
MeSH term(s)	Age Factors ; Aged ; Aged, 80 and over ; Biomarkers/blood ; Coronary Circulation/physiology ; Female ; Humans ; Inflammation Mediators/blood ; Male ; Middle Aged ; Mortality/trends ; No-Reflow Phenomenon/blood ; No-Reflow Phenomenon/mortality ; No-Reflow Phenomenon/surgery ; Percutaneous Coronary Intervention/mortality ; Percutaneous Coronary Intervention/trends ; Retrospective Studies ; ST Elevation Myocardial Infarction/blood ; ST Elevation Myocardial Infarction/mortality ; ST Elevation Myocardial Infarction/surgery
Chemical Substances	Biomarkers ; Inflammation Mediators
Language	English
Publishing date	2019-05-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	779519-1
ISSN	1874-1754 ; 0167-5273
ISSN (online)	1874-1754
ISSN	0167-5273
DOI	10.1016/j.ijcard.2019.05.002
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