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1. Elevated plasma Galectin-3 is associated with major adverse kidney events and death after ICU admission

Author

Boutin, L, Legrand, M, Sadoune, M, Mebazaa, A, Gayat, E, Chadjichristos, CE, and Dépret, F

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Kidney Disease, Prevention, Renal and urogenital, Good Health and Well Being, Acute Kidney Injury, Biomarkers, Critical Illness, Female, Galectin 3, Humans, Intensive Care Units, Kidney, Middle Aged, Prospective Studies, Acute kidney injury, Galectin-3, Major Adverse Kidney Event, Renal biomarker, Medical and Health Sciences, Emergency & Critical Care Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundGalectin-3 (Gal-3) is a proinflammatory and profibrotic protein especially overexpressed after Acute Kidney Injury (AKI). The early renal prognostic value of Gal-3 after AKI in critically ill patients remains unexplored. The objective was to evaluate the prognostic value of plasma level of Gal-3 for Major Adverse Kidney Events (MAKE) and mortality 30 days after ICU admission across AKI stages.MethodsThis is an ancillary study of a prospective, observational, multicenter cohort (FROG-ICU). AKI was defined using KDIGO definition.ResultsTwo thousand and seventy-six patients had a Gal-3 plasma level measurement at ICU admission. Seven hundred and twenty-three (34.8%) were females and the median age was 63 [51, 74] years. Eight hundred and seven (38.9%) patients developed MAKE, 774 (37.3%) had AKI and mortality rate at 30 days was 22.4% (N = 465). Patients who developed MAKE had higher Gal-3 level at admission compared to patients without (30.2 [20.8, 49.2] ng/ml versus 16.9 [12.7, 24.3] ng/ml, p

Published
2022

2. Monitoring circulating dipeptidyl peptidase 3 (DPP3) predicts improvement of organ failure and survival in sepsis: a prospective observational multinational study

Author

Blet, Alice, Deniau, Benjamin, Santos, Karine, van Lier, Dirk PT, Azibani, Feriel, Wittebole, Xavier, Chousterman, Benjamin G, Gayat, Etienne, Hartmann, Oliver, Struck, Joachim, Bergmann, Andreas, Antonelli, Massimo, Beishuizen, Albertus, Constantin, Jean-Michel, Damoisel, Charles, Deye, Nicolas, Di Somma, Salvatore, Dugernier, Thierry, François, Bruno, Gaudry, Stephane, Huberlant, Vincent, Lascarrou, Jean-Baptiste, Marx, Gernot, Mercier, Emmanuelle, Oueslati, Haikel, Pickkers, Peter, Sonneville, Romain, Legrand, Matthieu, Laterre, Pierre-François, and Mebazaa, Alexandre

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Kidney Disease, Infectious Diseases, Hematology, Clinical Research, Sepsis, Infection, Inflammatory and immune system, Good Health and Well Being, Aged, Biomarkers, Chi-Square Distribution, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Female, Humans, Intensive Care Units, Male, Middle Aged, Mortality, Multiple Organ Failure, Organ Dysfunction Scores, Proportional Hazards Models, Prospective Studies, Statistics, Nonparametric, DPP3, Biomarker, Outcome, Septic shock, Organ dysfunction, AdrenOSS-1 Study Investigators, Medical and Health Sciences, Emergency & Critical Care Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundDipeptidyl peptidase 3 (DPP3) is a cytosolic enzyme involved in the degradation of various cardiovascular and endorphin mediators. High levels of circulating DPP3 (cDPP3) indicate a high risk of organ dysfunction and mortality in cardiogenic shock patients.MethodsThe aim was to assess relationships between cDPP3 during the initial intensive care unit (ICU) stay and short-term outcome in the AdrenOSS-1, a prospective observational multinational study in twenty-four ICU centers in five countries. AdrenOSS-1 included 585 patients admitted to the ICU with severe sepsis or septic shock. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by the Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use and need for renal replacement therapy. cDPP3 levels were measured upon admission and 24 h later.ResultsMedian [IQR] cDPP3 concentration upon admission was 26.5 [16.2-40.4] ng/mL. Initial SOFA score was 7 [5-10], and 28-day mortality was 22%. We found marked associations between cDPP3 upon ICU admission and 28-day mortality (unadjusted standardized HR 1.8 [CI 1.6-2.1]; adjusted HR 1.5 [CI 1.3-1.8]) and between cDPP3 levels and change in renal and liver SOFA score (p = 0.0077 and 0.0009, respectively). The higher the initial cDPP3 was, the greater the need for organ support and vasopressors upon admission; the longer the need for vasopressor(s), mechanical ventilation or RRT and the higher the need for fluid load (all p  40.4 ng/mL upon admission, a decrease in cDPP3 below 40.4 ng/mL after 24 h was associated with an improvement of organ function at 48 h and better 28-day outcome. By contrast, persistently elevated cDPP3 at 24 h was associated with worsening organ function and high 28-day mortality.ConclusionsAdmission levels and rapid changes in cDPP3 predict outcome during sepsis. Trial Registration ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015.

Published
2021

3. Circulating dipeptidyl peptidase-3 at admission is associated with circulatory failure, acute kidney injury and death in severely ill burn patients

Author

Dépret, François, Amzallag, Juliette, Pollina, Adrien, Fayolle-Pivot, Laure, Coutrot, Maxime, Chaussard, Maïté, Santos, Karine, Hartmann, Oliver, Jully, Marion, Fratani, Alexandre, Oueslati, Haikel, Cupaciu, Alexandru, Benyamina, Mourad, Guillemet, Lucie, Deniau, Benjamin, Mebazaa, Alexandre, Gayat, Etienne, Farny, Boris, Textoris, Julien, and Legrand, Matthieu

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Kidney Disease, Physical Injury - Accidents and Adverse Effects, Good Health and Well Being, Acute Kidney Injury, Aged, Burns, Cohort Studies, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Female, Humans, Male, Middle Aged, Patient Admission, Prognosis, Prospective Studies, Risk Factors, Severity of Illness Index, Shock, Dipeptidyl peptidase-3, Burn patients, Mortality, Acute kidney injury, Biomarkers, PRONOBURN group, Medical and Health Sciences, Emergency & Critical Care Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundDipeptidyl peptidase-3 (DPP3) is a metallopeptidase which cleaves bioactive peptides, notably angiotensin II, and is involved in inflammation regulation. DPP3 has been proposed to be a myocardial depressant factor and to be involved in circulatory failure in acute illnesses, possibly due to angiotensin II cleavage. In this study, we evaluated the association between plasmatic DPP3 level and outcome (mortality and hemodynamic failure) in severely ill burn patients.MethodsIn this biomarker analysis of a prospective cohort study, we included severely ill adult burn patients in two tertiary burn intensive care units. DPP3 was measured at admission (DPP3admin) and 3 days after. The primary endpoint was 90-day mortality. Secondary endpoints were hemodynamic failure and acute kidney injury (AKI).ResultsOne hundred and eleven consecutive patients were enrolled. The median age was 48 (32.5-63) years, with a median total body surface area burned of 35% (25-53.5) and Abbreviated Burn Severity Index (ABSI) of 8 (7-11). Ninety-day mortality was 32%. The median DPP3admin was significantly higher in non-survivors versus survivors (53.3 ng/mL [IQR 28.8-103.5] versus 27.1 ng/mL [IQR 19.4-38.9]; p

Published
2020

4. Accuracy of a multiparametric score based on pulse wave analysis for prediction of fluid responsiveness: ancillary analysis of an observational study

Author

Neuschwander, Arthur, Barthélémy, Romain, Ditchi, David, Dramé, Fatou, Redouté, Maximilien, Stern, Jules, Cholley, Bernard, Mebazaa, Alexandre, Chousterman, Benjamin Glenn, and Pirracchio, Romain

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Cardiovascular, Clinical Research, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Aged, Blood Pressure, Cardiac Output, Female, Fluid Therapy, Hemodynamics, Humans, Male, Middle Aged, Prospective Studies, Pulse Wave Analysis, Respiration, Artificial, Stroke Volume, pressure recording analytical method, pulse contour, fluid responsiveness, cardiac output, Anesthesiology, Clinical sciences
Abstract

PurposeThe pressure recording analytical method (PRAM) monitor is a non-invasive pulse contour cardiac output (CO) device that cannot be considered interchangeable with the gold standard for CO estimation. It, however, generates additional hemodynamic indices that need to be evaluated. Our objective was to investigate the performance of a multiparametric predictive score based on a combination of several parameters generated by the PRAM monitor to predict fluid responsiveness.MethodsSecondary analysis of a prospective observational study from April 2016 to December 2017 in two French teaching hospitals. We included critically ill patients who were monitored by esophageal Doppler monitoring and an invasive arterial line, and received a 250-500 mL crystalloid fluid challenge. The main outcome measure was the predictive score discrimination evaluated by the area under the receiver operating characteristics curve.ResultsThe three baseline PRAM-derived parameters associated with fluid responsiveness in univariate analysis were pulse pressure variation, cardiac cycle efficiency, and arterial elastance (P

Published
2020

5. Activation of the renin-angiotensin-aldosterone system is associated with Acute Kidney Injury in COVID-19.

Author

Dudoignon, Emmanuel, Moreno, Nabila, Deniau, Benjamin, Coutrot, Maxime, Longer, Romain, Amiot, Quentin, Mebazaa, Alexandre, Pirracchio, Romain, Depret, François, and Legrand, Matthieu

Subjects
Humans, Pneumonia, Viral, Coronavirus Infections, Critical Illness, Creatinine, Aldosterone, Renin-Angiotensin System, Aged, Middle Aged, Intensive Care Units, Female, Male, Acute Kidney Injury, Pandemics, Betacoronavirus, COVID-19, SARS-CoV-2, Renin-angiotensin-aldosterone system, Pneumonia, Viral
Abstract

The pathophysiology of acute kidney injury (AKI) in COVID-19 patients is still poorly understood. SARS-CoV-2 has been suggested to modulate the renin-angiotensin-aldosterone system (RAAS). In this series of COVID-19 critically ill patients, we report evidence of activation of the RAAS in COVID-19 patients with AKI.

Published
2020

6. Impact of renin-angiotensin system inhibitors continuation versus discontinuation on outcome after major surgery: protocol of a multicenter randomized, controlled trial (STOP-or-NOT trial)

Author

Legrand, Matthieu, Futier, Emmanuel, Leone, Marc, Deniau, Benjamin, Mebazaa, Alexandre, Plaud, Benoît, Coriat, Pierre, Rossignol, Patrick, Vicaut, Eric, and Gayat, Etienne

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Trials and Supportive Activities, Patient Safety, Cardiovascular, Comparative Effectiveness Research, Clinical Research, Hypertension, Heart Disease, 5.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Development of treatments and therapeutic interventions, 6.4 Surgery, 6.1 Pharmaceuticals, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Drug Administration Schedule, France, Heart Failure, Humans, Multicenter Studies as Topic, Perioperative Care, Postoperative Complications, Randomized Controlled Trials as Topic, Renin-Angiotensin System, Risk Factors, Time Factors, Treatment Outcome, STOP-OR-NOT study investigators, ACE inhibitors, ARB, Acute kidney injury, Complications, Mortality, Outcome, Strategy, Surgery, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, General & Internal Medicine, Clinical sciences, Epidemiology, Health services and systems
Abstract

BackgroundChronic treatment of hypertension or heart failure very often includes an angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) as renin-angiotensin system inhibitors (RASi) treatments. To stop or not to stop these medications before major surgery remains an unresolved issue. The lack of evidence leads to conflicting guidelines with respect to RASi management before major surgery. The purpose of this study is to evaluate the impact of a strategy of RASi continuation or discontinuation on perioperative complications in patients undergoing major non-cardiac surgery.MethodsThis is a multicenter, open-labeled randomized controlled trial in > 30 French centers. In the experimental group, RASi will be continued while the treatment will be stopped 48 h before the surgery in the control arm. The primary endpoint is a composite endpoint of major complications after surgery. An endpoint adjudication committee will review clinical data and adjudicate efficacy endpoints while blinded to the assigned study drug group. Main analysis will be by intention-to-treat comparing the composite outcome measure at 28 days in the two groups. A total of 2222 patients are planned to detect an absolute complications difference of 5%.DiscussionThe results of the trial should provide robust evidence to anesthesiologists and surgeons regarding management of RASi before major non-cardiac surgery.Trial registrationClinicalTrials.gov, NCT03374449 . Registered on 11 December 2017.

Published
2019

7. Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study.

Author

Mebazaa, Alexandre, Geven, Christopher, Hollinger, Alexa, Wittebole, Xavier, Chousterman, Benjamin Glen, Blet, Alice, Gayat, Etienne, Hartmann, Oliver, Scigalla, Paul, Struck, Joachim, Bergmann, Andreas, Antonelli, Massimo, Beishuizen, Albertus, Constantin, Jean-Michel, Damoisel, Charles, Deye, Nicolas, Di Somma, Salvatore, Dugernier, Thierry, François, Bruno, Gaudry, Stephane, Huberlant, Vincent, Lascarrou, Jean-Baptiste, Marx, Gernot, Mercier, Emmanuelle, Oueslati, Haikel, Pickkers, Peter, Sonneville, Romain, Legrand, Matthieu, Laterre, Pierre-François, and AdrenOSS-1 study investigators

Subjects
AdrenOSS-1 study investigators, Humans, Sepsis, Multiple Organ Failure, Hospitalization, Length of Stay, Hospital Mortality, Proportional Hazards Models, Chi-Square Distribution, Survival Analysis, Prospective Studies, Aged, Middle Aged, Intensive Care Units, Belgium, France, Germany, Italy, Netherlands, Female, Male, Adrenomedullin, Patient Outcome Assessment, Biomarkers, Biomarker, Outcome, Sepsis-2, Sepsis-3, Emergency & Critical Care Medicine, Medical and Health Sciences
Abstract

BackgroundAdrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial.MethodsAdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock.ResultsCirculating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8).ConclusionsAdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial.Trial registrationClinicalTrials.gov, NCT02393781 . Registered on March 19, 2015.

Published
2018

8. Determinants of long-term outcome in ICU survivors: results from the FROG-ICU study

Author

Gayat, Etienne, Cariou, Alain, Deye, Nicolas, Vieillard-Baron, Antoine, Jaber, Samir, Damoisel, Charles, Lu, Qin, Monnet, Xavier, Rennuit, Isabelle, Azoulay, Elie, Léone, Marc, Oueslati, Heikel, Guidet, Bertrand, Friedman, Diane, Tesnière, Antoine, Sonneville, Romain, Montravers, Philippe, Pili-Floury, Sébastien, Lefrant, Jean-Yves, Duranteau, Jacques, Laterre, Pierre-François, Brechot, Nicolas, Chevreul, Karine, Michel, Morgane, Cholley, Bernard, Legrand, Matthieu, Launay, Jean-Marie, Vicaut, Eric, Singer, Mervyn, Resche-Rigon, Matthieu, and Mebazaa, Alexandre

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Clinical Research, Patient Safety, Cardiovascular, Heart Disease, Good Health and Well Being, Aged, Belgium, Cohort Studies, Critical Illness, Female, France, Hospital Mortality, Hospitalization, Humans, Intensive Care Units, Length of Stay, Male, Middle Aged, Odds Ratio, Outcome Assessment, Health Care, Prospective Studies, Respiration, Artificial, Survivors, Time Factors, Vasoconstrictor Agents, Biomarkers, Discharge, Long-term survival, Post-intensive care syndrome, Score, Medical and Health Sciences, Emergency & Critical Care Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundIntensive care unit (ICU) survivors have reduced long-term survival compared to the general population. Identifying parameters at ICU discharge that are associated with poor long-term outcomes may prove useful in targeting an at-risk population. The main objective of the study was to identify clinical and biological determinants of death in the year following ICU discharge.MethodsFROG-ICU was a prospective, observational, multicenter cohort study of ICU survivors followed 1 year after discharge, including 21 medical, surgical or mixed ICUs in France and Belgium. All consecutive patients admitted to intensive care with a requirement for invasive mechanical ventilation and/or vasoactive drug support for more than 24 h following ICU admission and discharged from ICU were included. The main outcome measure was all-cause mortality at 1 year after ICU discharge. Clinical and biological parameters on ICU discharge were measured, including the circulating cardiovascular biomarkers N-terminal pro-B type natriuretic peptide, high-sensitive troponin I, bioactive-adrenomedullin and soluble-ST2. Socioeconomic status was assessed using a validated deprivation index (FDep).ResultsOf 1570 patients discharged alive from the ICU, 333 (21%) died over the following year. Multivariable analysis identified age, comorbidity, red blood cell transfusion, ICU length of stay and abnormalities in common clinical factors at the time of ICU discharge (low systolic blood pressure, temperature, total protein, platelet and white cell count) as independent factors associated with 1-year mortality. Elevated biomarkers of cardiac and vascular failure independently associated with 1-year death when they are added to multivariable model, with an almost 3-fold increase in the risk of death when combined (adjusted odds ratio 2.84 (95% confidence interval 1.73-4.65), p

Published
2018

9. Outbreak of Invasive Wound Mucormycosis in a Burn Unit Due to Multiple Strains of Mucor circinelloides f. circinelloides Resolved by Whole-Genome Sequencing

Author

Garcia-Hermoso, Dea, Criscuolo, Alexis, Lee, Soo Chan, Legrand, Matthieu, Chaouat, Marc, Denis, Blandine, Lafaurie, Matthieu, Rouveau, Martine, Soler, Charles, Schaal, Jean-Vivien, Mimoun, Maurice, Mebazaa, Alexandre, Heitman, Joseph, Dromer, Françoise, Brisse, Sylvain, Bretagne, Stéphane, Alanio, Alexandre, Lockhart, Shawn, and Voigt, Kerstin

Subjects
Infectious Diseases, Emerging Infectious Diseases, Biotechnology, Aetiology, 2.2 Factors relating to the physical environment, Infection, Burn Units, Burns, Cluster Analysis, Cross Infection, Disease Outbreaks, France, Genetic Variation, Genotype, Humans, Molecular Epidemiology, Molecular Typing, Mucor, Mucormycosis, Phylogeny, Whole Genome Sequencing, Wound Infection, Wounds and Injuries, Mucor circinelloides, Mucorales, burn, clade, genome, genotype, mixed infection, mucormycosis, outbreak, strains, whole-genome sequencing, wound, Microbiology
Abstract

Mucorales are ubiquitous environmental molds responsible for mucormycosis in diabetic, immunocompromised, and severely burned patients. Small outbreaks of invasive wound mucormycosis (IWM) have already been reported in burn units without extensive microbiological investigations. We faced an outbreak of IWM in our center and investigated the clinical isolates with whole-genome sequencing (WGS) analysis. We analyzed M. circinelloides isolates from patients in our burn unit (BU1, Hôpital Saint-Louis, Paris, France) together with nonoutbreak isolates from Burn Unit 2 (BU2, Paris area) and from France over a 2-year period (2013 to 2015). A total of 21 isolates, including 14 isolates from six BU1 patients, were analyzed by whole-genome sequencing (WGS). Phylogenetic classification based on de novo assembly and assembly free approaches showed that the clinical isolates clustered in four highly divergent clades. Clade 1 contained at least one of the strains from the six epidemiologically linked BU1 patients. The clinical isolates were specific to each patient. Two patients were infected with more than two strains from different clades, suggesting that an environmental reservoir of clonally unrelated isolates was the source of contamination. Only two patients from BU1 shared one strain, which could correspond to direct transmission or contamination with the same environmental source. In conclusion, WGS of several isolates per patients coupled with precise epidemiological data revealed a complex situation combining potential cross-transmission between patients and multiple contaminations with a heterogeneous pool of strains from a cryptic environmental reservoir.IMPORTANCE Invasive wound mucormycosis (IWM) is a severe infection due to environmental molds belonging to the order Mucorales. Severely burned patients are particularly at risk for IWM. Here, we used whole-genome sequencing (WGS) analysis to resolve an outbreak of IWM due to Mucor circinelloides that occurred in our hospital (BU1). We sequenced 21 clinical isolates, including 14 from BU1 and 7 unrelated isolates, and compared them to the reference genome (1006PhL). This analysis revealed that the outbreak was mainly due to multiple strains that seemed patient specific, suggesting that the patients were more likely infected from a pool of diverse strains from the environment rather than from direct transmission among them. This study revealed the complexity of a Mucorales outbreak in the settings of IWM in burn patients, which has been highlighted based on WGS combined with careful sampling.

Published
2018

10. Undetectable haptoglobin is associated with major adverse kidney events in critically ill burn patients.

Author

Dépret, François, Dunyach, Chloé, De Tymowski, Christian, Chaussard, Maïté, Bataille, Aurélien, Ferry, Axelle, Moreno, Nabila, Cupaciu, Alexandru, Soussi, Sabri, Benyamina, Mourad, Mebazaa, Alexandre, Serror, Kevin, Chaouat, Marc, Garnier, Jean-Pierre, Pirracchio, Romain, Legrand, Matthieu, and PRONOBURN group

Subjects
PRONOBURN group, Humans, Burns, Creatinine, Haptoglobins, Respiration, Artificial, Risk Factors, Statistics, Nonparametric, Retrospective Studies, Cohort Studies, Adult, Middle Aged, Intensive Care Units, Paris, Female, Male, Acute Kidney Injury, Acute kidney injury, Burn patients, Haptoglobin, Intravascular haemolysis, Major adverse kidney event, Kidney Disease, Clinical Research, Injury (total) Accidents/Adverse Effects, Renal and urogenital, Emergency & Critical Care Medicine, Medical and Health Sciences
Abstract

BackgroundIntravascular haemolysis has been associated with acute kidney injury (AKI) in different clinical settings (cardiac surgery, sickle cell disease). Haemolysis occurs frequently in critically ill burn patients. The aim of this study was to assess the predictive value of haptoglobin at admission to predict major adverse kidney events (MAKE) and AKI in critically ill burn patients.MethodsWe conducted a retrospective, single-centre cohort study in a burn critical care unit in a tertiary centre, including all consecutive severely burned patients (total burned body surface > 20% and/or shock and/or mechanical ventilation at admission) from January 2012 to April 2017 with a plasmatic haptoglobin dosage at admission.ResultsA total of 130 patients were included in the analysis. Their mean age was 49 (34-62) years, their median total body surface area burned was 29% (15-51%) and the intensive care unit (ICU) mortality was 25%. Early haemolysis was defined as an undetectable plasmatic haptoglobin at admission. We used logistic regression to identify MAKE and AKI risk factors. In multivariate analysis, undetectable haptoglobin was associated with MAKE and AKI (respectively, OR 6.33, 95% CI 2.34-16.45, p

Published
2017

11. Organ dysfunction, injury and failure in acute heart failure: from pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

Author

Harjola, Veli-Pekka, Mullens, Wilfried, Banaszewski, Marek, Bauersachs, Johann, Brunner-La Rocca, Hans-Peter, Chioncel, Ovidiu, Collins, Sean, Doehner, Wolfram, Filippatos, Gerasimos, Flammer, Andreas, Fuhrmann, Valentin, Lainscak, Mitja, Lassus, Johan, Legrand, Matthieu, Masip, Josep, Mueller, Christian, Papp, Zoltán, Parissis, John, Platz, Elke, Rudiger, Alain, Ruschitzka, Frank, Schäfer, Andreas, Seferovic, Petar, Skouri, Hadi, Yilmaz, Mehmet, and Mebazaa, Alexandre

Subjects
Heart failure, Multiple organ failure, Venous congestion, Acute Disease, Cardiology, Diagnostic Imaging, Disease Management, Europe, Heart Failure, Humans, Multiple Organ Failure, Societies, Medical
Abstract

Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post-discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient-centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field.

Published
2017

12. Infectious Complications and Immune/Inflammatory Response in Cardiogenic Shock Patients

Author

Parenica, Jiri, Jarkovsky, Jiri, Malaska, Jan, Mebazaa, Alexandre, Gottwaldova, Jana, Helanova, Katerina, Litzman, Jiri, Dastych, Milan, Tomandl, Josef, Spinar, Jindrich, Dostalova, Ludmila, Lokaj, Petr, Tomandlova, Marie, Pavkova, Monika Goldergova, Sevcik, Pavel, and Legrand, Matthieu

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Heart Disease, Hematology, Sepsis, Heart Disease - Coronary Heart Disease, Cardiovascular, Infectious Diseases, Clinical Research, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Inflammatory and immune system, Infection, Good Health and Well Being, Aged, Aged, 80 and over, Biomarkers, C-Reactive Protein, Calcitonin, Female, Hospital Mortality, Humans, Lipopolysaccharide Receptors, Male, Middle Aged, Myocardial Infarction, Peptide Fragments, Prognosis, Prospective Studies, ROC Curve, Risk Factors, Serum Amyloid P-Component, Shock, Cardiogenic, Shock, Septic, GREAT Network, Emergency & Critical Care Medicine, Clinical sciences
Abstract

IntroductionPatients with cardiogenic shock (CS) are at a high risk of developing infectious complications; however, their early detection is difficult, mainly due to a frequently occurring noninfectious inflammatory response, which accompanies an extensive myocardial infarction (MI) or a postcardiac arrest syndrome. The goal of our prospective study was to describe infectious complications in CS and the immune/inflammatory response based on a serial measurement of several blood-based inflammatory biomarkers.MethodsEighty patients with CS were evaluated and their infections were monitored. Inflammatory markers (C-reactive protein, procalcitonin, pentraxin 3, presepsin) were measured seven times per week. The control groups consisted of 11 patients with ST segment elevation myocardial infarction without CS and without infection, and 22 patients in septic shock.ResultsInfection was diagnosed in 46.3% of patients with CS; 16 patients developed an infection within 48 h. Respiratory infection was most common, occurring in 33 out of 37 patients. Infection was a significant or even the main reason of death only in 3.8% of all patients with CS, and we did not find statistically significant difference in 3-month mortality between group of patients with CS with and without infection. There was no statistically significant prolongation of the duration of mechanical ventilation associated with infection. Strong inflammatory response is often in patients with CS due to MI, but we found no significant difference in the course of the inflammatory response expressed by evaluated biomarkers in patients with CS with and without infection. We found a strong relationship between the elevated inflammatory markers (sampled at 12 h) and the 3-month mortality: the area under the curve of receiver operating characteristic ranged between 0.683 and 0.875.ConclusionThe prevalence of infection in patients with CS was 46.3%, and respiratory tract infections were the most common type. Infections did not prolong statistically significantly the duration of mechanical ventilation and did not increase the prevalence of hospital mortality in this high-risk CS population. CS due to acute myocardial infarction was accompanied by a strong and highly variable inflammatory response, but it did not reach the intensity of the inflammatory response observed in patients with septic shock. An extensive immune/inflammatory response in patients with CS is linked to a poor prognosis.

Published
2017

13. Prevalence and Prognosis of Hyperkalemia in Patients with Acute Myocardial Infarction

Author

Grodzinsky, Anna, Goyal, Abhinav, Gosch, Kensey, McCullough, Peter A, Fonarow, Gregg C, Mebazaa, Alexandre, Masoudi, Frederick A, Spertus, John A, Palmer, Biff F, and Kosiborod, Mikhail

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Patient Safety, Heart Disease - Coronary Heart Disease, Cardiovascular, Heart Disease, Good Health and Well Being, Aged, Female, Hospital Mortality, Humans, Hyperkalemia, Male, Myocardial Infarction, Prevalence, Prognosis, Registries, Renal Dialysis, Risk Factors, United States, Acute myocardial infarction, Dialysis, Hyperkalemia prevalence, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundHyperkalemia is common and potentially dangerous in hospitalized patients; its contemporary prevalence and prognostic importance after acute myocardial infarction are not well described.MethodsIn 38,689 consecutive patients with acute myocardial infarction from the Cerner Health Facts database, we evaluated the association between maximum in-hospital potassium levels and in-hospital mortality. Patients were stratified by dialysis status and grouped by maximum potassium as follows:

Published
2016

14. Evidence of Uncoupling between Renal Dysfunction and Injury in Cardiorenal Syndrome: Insights from the BIONICS Study

Author

Legrand, Matthieu, De Berardinis, Benedetta, Gaggin, Hanna K, Magrini, Laura, Belcher, Arianna, Zancla, Benedetta, Femia, Alexandra, Simon, Mandy, Motiwala, Shweta, Sambhare, Rasika, Di Somma, Salvatore, Mebazaa, Alexandre, Vaidya, Vishal S, Januzzi, James L, and Team, from the Global Research on Acute Conditions

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Cardiovascular, Kidney Disease, Clinical Research, Heart Disease, Patient Safety, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Renal and urogenital, Good Health and Well Being, Acetylglucosaminidase, Acute Kidney Injury, Acute-Phase Proteins, Aged, Aged, 80 and over, Biomarkers, Cardio-Renal Syndrome, Cystatin C, Female, Fibrinogen, Hepatitis A Virus Cellular Receptor 1, Humans, Kidney Diseases, Kidney Function Tests, Lipocalin-2, Lipocalins, Male, Membrane Glycoproteins, Middle Aged, Prospective Studies, Proto-Oncogene Proteins, Receptors, Virus, Global Research on Acute Conditions Team, General Science & Technology
Abstract

ObjectiveThe objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF).MethodsIn a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF.Results26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF.ConclusionsIn ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153).

Published
2014

15. The elusive task of biomarkers of renal injury.

Author

Legrand, Matthieu, Mari, Arnaud, and Mebazaa, Alexandre

Subjects
Humans, Proto-Oncogene Proteins, Hospital Mortality, Judgment, Emergency Service, Hospital, Female, Male, Lipocalins, Acute Kidney Injury, Emergency & Critical Care Medicine, Medical and Health Sciences
Abstract

Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most promising candidate biomarkers of renal injury, with expression in renal tissue increasing dramatically after ischemia-reperfusion injury but not in the case of pure pre-renal failure. In a recent issue of Critical Care, Di Somma and colleagues reported that NGAL could improve the classification of acute kidney injury compared with clinical assessment and showed that NGAL was associated with poor prognosis. NGAL may therefore carry different information than biomarkers of renal function. This study finally provides additional evidence for the highly complex relationship between renal function and renal injury.

Published
2013

16. The Effectiveness of Inodilators in Reducing Short Term Mortality among Patient with Severe Cardiogenic Shock: A Propensity-Based Analysis

Author

Pirracchio, Romain, Parenica, Jiri, Resche Rigon, Matthieu, Chevret, Sylvie, Spinar, Jindrich, Jarkovsky, Jiri, Zannad, Faiez, Alla, François, and Mebazaa, Alexandre

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Cardiovascular, Clinical Trials and Supportive Activities, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Aged, Aged, 80 and over, Cardiotonic Agents, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Propensity Score, Shock, Cardiogenic, Treatment Outcome, Vasodilator Agents, GREAT network, General Science & Technology
Abstract

BackgroundThe best catecholamine regimen for cardiogenic shock has been poorly evaluated. When a vasopressor is required to treat patients with the most severe form of cardiogenic shock, whether inodilators should be added or whether inopressors can be used alone has not been established. The purpose of this study was to compare the impact of these two strategies on short-term mortality in patients with severe cardiogenic shocks.Methods and resultsThree observational cohorts of patients with decompensated heart failure were pooled to comprise a total of 1,272 patients with cardiogenic shocks. Of these 1,272 patients, 988 were considered to be severe because they required a vasopressor during the first 24 hours. We developed a propensity-score (PS) model to predict the individual probability of receiving one of the two regimens (inopressors alone or a combination) conditionally on baseline-measured covariates. The benefit of the treatment regimen on the mortality rate was estimated by fitting a weighted Cox regression model. A total of 643 patients (65.1%) died within the first 30 days (inopressors alone: 293 (72.0%); inopressors and inodilators: 350 (60.0%)). After PS weighting, we observed that the use of an inopressor plus an inodilator was associated with an improved short-term mortality (HR: 0.66 [0.55-0.80]) compared to inopressors alone.ConclusionsIn the most severe forms of cardiogenic shock where a vasopressor is immediately required, adding an inodilator may improve short-term mortality. This result should be confirmed in a randomized, controlled trial.

Published
2013

17. The Intersection Between Heart Failure and Critical Care Cardiology: An International Perspective on Structure, Staffing, and Design Considerations

Author

SHASHANK S. Sinha, ERIN A. BOHULA, SEAN VAN DIEPEN, SERGIO LEONARDI, Alexandre Mebazaa, Alastair G. Proudfoot, ALESSANDRO SIONIS, YEW WOON CHIA, FERNANDO G. ZAMPIERI, RENATO D. LOPES, and JASON N. KATZ

Subjects
Heart Failure, Internationality, Critical Care, Critical Illness, Cardiology, Workforce, Humans, Cardiology and Cardiovascular Medicine
Abstract

The overall patient population in contemporary cardiac intensive care units (CICUs) has only increased with respect to patient acuity, complexity, and illness severity. The current population has more cardiac and noncardiac comorbidities, a higher prevalence of multiorgan injury, and consumes more critical care resources than previously. Patients with heart failure (HF) now occupy a large portion of contemporary tertiary or quaternary care CICU beds around the world. In this review, we discuss the core issues that relate to the care of critically ill patients with HF, including global perspectives on the organization, designation, and collaboration of CICUs regionally and across institutions, as well as unique models for provisioning care for patients with HF within a health care setting. The latter includes a discussion of traditional and emerging models, specialized HF units, the makeup and implementation of multidisciplinary team-based decision-making, and cardiac critical care admission and triage practices. This article illustrates the ways in which critically ill patients with HF have helped to shape contemporary CICUs throughout the world and explores how these very patients will similarly help to inform the future maturation of these specialized critical care units. Finally, we will critically examine broad, contemporary, international models of HF and cardiac critical care delivery in North America, Europe, South America, and Asia, and conclude with opportunities for the further investigation and generation of evidence for care delivery.

Published
2022

18. Cardiac troponin and skeletal muscle oxygenation in severe post-partum haemorrhage

Author

Heyer, Laurent, Mebazaa, Alexandre, Gayat, Etienne, Resche-Rigon, Matthieu, Rabuel, Christophe, Rezlan, Eva, Lukascewicz, Anne-Claire, Madadaki, Catharina, Pirracchio, Romain, Schurando, Patrick, Morel, Olivier, Fargeaudou, Yann, and Payen, Didier

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Heart Disease, Cardiovascular, Clinical Research, Adult, Female, Humans, Muscle, Skeletal, Oxygen Consumption, Postpartum Hemorrhage, Pregnancy, Spectroscopy, Near-Infrared, Troponin I, Medical and Health Sciences, Emergency & Critical Care Medicine, Biomedical and clinical sciences, Health sciences
Abstract

IntroductionCardiac troponin has been shown to be elevated in one-half of the parturients admitted for post-partum haemorrhage. The purpose of the study was to assess whether increased cardiac troponin was associated with a simultaneous alteration in haemoglobin tissue oxygen saturation in peripheral muscles in post-partum haemorrhage.MethodsTissue haemoglobin oxygen saturation of thenar eminence muscle (StO2) was measured via near-infrared spectroscopy technology. Two sets of StO2 parameters (both isolated baseline and during forearm ischaemia-reperfusion tests) were collected at two time points: upon intensive care unit admission and prior to intensive care unit discharge. Comparisons were performed using Wilcoxon paired tests, and univariate associations were assessed using logistic regression model and Wald tests.ResultsThe 42 studied parturients, admitted for post-partum haemorrhage, had clinical and biological signs of severe blood loss. Initial cardiac troponin I was increased in 24/42 parturients (0.43 +/- 0.60 microrg/l). All measured parameters of muscular haemoglobin oxygen saturation, including Srecovery, were also altered at admission and improved together with improved haemodynamics, when bleeding was controlled. Multivariate analysis showed that muscular Srecovery

Published
2009

19. Performance of Early Capillary Refill Time Measurement on Outcomes in Cardiogenic Shock: An Observational, Prospective Multicentric Study

Author

Hamid Merdji, Anais Curtiaud, Antoine Aheto, Antoine Studer, Veli-Pekka Harjola, Alexandra Monnier, Kevin Duarte, Nicolas Girerd, Marion Kibler, Hafid Ait-Oufella, Julie Helms, Alexandre Mebazaa, Bruno Levy, Antoine Kimmoun, Ferhat Meziani, BOZEC, Erwan, Service de Médecine Intensive et Réanimation [Strasbourg], CHU Strasbourg, Les Hôpitaux Universitaires de Strasbourg (HUS), Université de Strasbourg (UNISTRA), Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsinki University Hospital [Finland] (HUS), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Clinical Research in Intensive Care and Sepsis - TRIal Group for Global Evaluation and Research in SEPsis (Réseau CRICS-TRIGGERSEP)

Subjects
Pulmonary and Respiratory Medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Microcirculation, Shock, Cardiogenic, Hemodynamics, Humans, Stroke Volume, Prospective Studies, Critical Care and Intensive Care Medicine, Ventricular Function, Left, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Retrospective Studies
Abstract

International audience; Background: Identification of cardiogenic shock severity is a critical step to adapt the management level upon admission. Peripheral tissue perfusion signs, simple and reliable markers of tissue hypoperfusion have never been extensively assessed during cardiogenic shock.Methods: All consecutive patients admitted in ICU for cardiogenic shock of two tertiary teaching hospitals were included in a prospective observational study. Macro-hemodynamic parameters (such as heart rate, blood pressure, left ventricular ejection fraction and cardiac index) and peripheral tissue perfusion signs such as capillary refill time on the index fingertip, mottling and Pv-aCO2 (the difference between partial pressure of CO2 in venous blood and arterial blood) were recorded at inclusion (H0), H6, H12, H24 and H48. The composite primary endpoint was the association between 90-day mortality or the need for venoarterial-ECMO support.Results: 61 patients were included; at inclusion, simplified acute physiology score II was 64 (52-77) points. The primary endpoint was met by 42% of patients. Capillary refill time values were significantly higher at all time-points in non survivors or patients needing venoarterial-ECMO support. In univariate analysis, capillary refill time > 3 sec at inclusion was associated with 90-day all-cause mortality or venoarterial-ECMO support (Hazard Ratio of 12.38; 95% CI 2.91 to 52.71). Capillary refill time at inclusion was poorly associated with macrocirculatory parameters but significantly correlated with microcirculatory parameters. Further, capillary refill time added incremental value to Cardshock score, with an AUC combination at 0.93.Conclusion: In patients admitted in ICU for cardiogenic shock, our preliminary data suggest that a prolonged capillary refill time > 3 sec was associated with an early prediction of 90-day mortality or the need for venoarterial-ECMO support

Published
2022

20. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

Author

Theresa A, McDonagh, Marco, Metra, Marianna, Adamo, Roy S, Gardner, Andreas, Baumbach, Michael, Böhm, Haran, Burri, Javed, Butler, Jelena, Čelutkienė, Ovidiu, Chioncel, John G F, Cleland, Andrew J S, Coats, Maria G, Crespo-Leiro, Dimitrios, Farmakis, Martine, Gilard, Stephane, Heymans, Arno W, Hoes, Tiny, Jaarsma, Ewa A, Jankowska, Mitja, Lainscak, Carolyn S P, Lam, Alexander R, Lyon, John J V, McMurray, Alexandre, Mebazaa, Richard, Mindham, Claudio, Muneretto, Massimo, Francesco Piepoli, Susanna, Price, Giuseppe M C, Rosano, Frank, Ruschitzka, Anne, Kathrine Skibelund, Johannes, Waltenberger, Mcdonagh, Theresa A, Metra, Marco, Adamo, Marianna, Gardner, Roy S, Baumbach, Andrea, Böhm, Michael, Burri, Haran, Butler, Javed, Čelutkienė, Jelena, Chioncel, Ovidiu, Cleland, John G F, Coats, Andrew J S, Crespo-Leiro, Maria G, Farmakis, Dimitrio, Gilard, Martine, Heymans, Stephane, Hoes, Arno W, Jaarsma, Tiny, Jankowska, Ewa A, Lainscak, Mitja, Lam, Carolyn S P, Lyon, Alexander R, Mcmurray, John J V, Mebazaa, Alexandre, Mindham, Richard, Muneretto, Claudio, Francesco Piepoli, Massimo, Price, Susanna, Rosano, Giuseppe M C, Ruschitzka, Frank, Kathrine Skibelund, Anne, University of Zurich, Cardiology, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H02 Cardiomyopathy, and McDonagh, Theresa A

Subjects
diagnosis, cardiac resynchronization therapy, heart failure, 2700 General Medicine, Guideline, Cardiovascular System, neuro-hormonal antagonist, pharmacotherapy, VENTRICULAR ASSIST DEVICE, QUALITY-OF-LIFE, Germany, multidisciplinary management, neuro, ejection fraction, CARDIAC-RESYNCHRONIZATION THERAPY, General Medicine, Guidelines, acute heart failure, advanced heart failure, arrhythmias, comorbidities, hospitalization, mechanical circulatory support, natriuretic peptides, neuro-hormonal antagonists, transplantation, Bayes Theorem, Chronic Disease, Europe, France, Humans, Italy, United Kingdom, United States, Cardiology, Heart Failure, diagnosi, PRESERVED EJECTION FRACTION, BRAIN NATRIURETIC PEPTIDE, 10209 Clinic for Cardiology, CORONARY-ARTERY-DISEASE, Cardiology and Cardiovascular Medicine, ACUTE MYOCARDIAL-INFARCTION, comorbiditie, IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR, 610 Medicine & health, arrhythmia, 2705 Cardiology and Cardiovascular Medicine, natriuretic peptide, WORSENING RENAL-FUNCTION, hormonal antagonists, AORTIC-VALVE-REPLACEMENT
Abstract

Document Reviewers: Rudolf A. de Boer (CPG Review Coordinator) (Netherlands), P. Christian Schulze (CPG Review Coordinator) (Germany), Magdy Abdelhamid (Egypt), Victor Aboyans (France), Stamatis Adamopoulos (Greece), Stefan D. Anker (Germany), Elena Arbelo (Spain), Riccardo Asteggiano (Italy), Johann Bauersachs (Germany), Antoni Bayes-Genis (Spain), Michael A. Borger (Germany), Werner Budts (Belgium), Maja Cikes (Croatia), Kevin Damman (Netherlands), Victoria Delgado (Netherlands), Paul Dendale (Belgium), Polychronis Dilaveris (Greece), Heinz Drexel (Austria), Justin Ezekowitz (Canada), Volkmar Falk (Germany), Laurent Fauchier (France), Gerasimos Filippatos (Greece), Alan Fraser (United Kingdom), Norbert Frey (Germany), Chris P. Gale (United Kingdom), Finn Gustafsson (Denmark), Julie Harris (United Kingdom), Bernard Iung (France), Stefan Janssens (Belgium), Mariell Jessup (United States of America), Aleksandra Konradi (Russia), Dipak Kotecha (United Kingdom), Ekaterini Lambrinou (Cyprus), Patrizio Lancellotti (Belgium), Ulf Landmesser (Germany), Christophe Leclercq (France), Basil S. Lewis (Israel), Francisco Leyva (United Kingdom), AleVs Linhart (Czech Republic), Maja-Lisa Løchen (Norway), Lars H. Lund (Sweden), Donna Mancini (United States of America), Josep Masip (Spain), Davor Milicic (Croatia), Christian Mueller (Switzerland), Holger Nef (Germany), Jens-Cosedis Nielsen (Denmark), Lis Neubeck (United Kingdom), Michel Noutsias (Germany), Steffen E. Petersen (United Kingdom), Anna Sonia Petronio (Italy), Piotr Ponikowski (Poland), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Dimitrios J. Richter (Greece), Evgeny Schlyakhto (Russia), Petar Seferovic (Serbia), Michele Senni (Italy), Marta Sitges (Spain), Miguel Sousa-Uva (Portugal), Carlo G. Tocchetti (Italy), Rhian M. Touyz (United Kingdom), Carsten Tschoepe (Germany), Johannes Waltenberger (Germany/Switzerland) All experts involved in the development of these guidelines have submitted declarations of interest. These have been compiled in a report and published in a supplementary document simultaneously to the guidelines. The report is also available on the ESC website www.escardio.org/guidelines For the Supplementary Data which include background information and detailed discussion of the data that have provided the basis for the guidelines see European Heart Journal online.

Published
2022

21. Safety and efficacy of istaroxime in patients with acute heart failure‐related pre‐cardiogenic shock – a multicentre, randomized, double‐blind, placebo‐controlled, parallel group study ( <scp>SEISMiC</scp> )

Author

Marco Metra, Ovidiu Chioncel, Gad Cotter, Beth Davison, Gerasimos Filippatos, Alexandre Mebazaa, Maria Novosadova, Piotr Ponikowski, Phillip Simmons, Joseph Soffer, and Steven Simonson

Subjects
Heart Failure, Cardiotonic Agents, Shock, Cardiogenic, Acute heart failure, Blood pressure, Cardiogenic shock, Istaroxime, SERCA2a, Therapeutics, Double-Blind Method, Etiocholanolone, Humans, Cardiology and Cardiovascular Medicine
Abstract

We examined the effects of istaroxime in patients hospitalized for acute heart failure (AHF) related Society for Cardiovascular Angiography and Interventions (SCAI) stage B pre-cardiogenic shock (CS).Sixty patients with AHF without acute myocardial infarction with pre-CS, defined as systolic blood pressure (SBP)90 mmHg without hypoperfusion, venous lactate ≥2 mmol/L and/or mechanical or inotropic support, were randomized to istaroxime 1.0-1.5 μg/kg/min or placebo for 24 h. The primary endpoint, the adjusted area under the curve (AUC) change in SBP from time of treatment to 6 h, was 53.1 (standard error [SE] 6.88) mmHg × hour versus 30.9 (SE 6.76) mmHg × hour with istaroxime versus placebo (p = 0.017). Adjusted SBP AUC at 24 h was 291.2 (SE 27.5) versus 208.7 (SE 27.0) mmHg × hour (p = 0.025). At 24 h, some echocardiographic measurements improved with istaroxime versus placebo including cardiac index (+0.21 L/min/mIn a phase 2a study of patients with AHF related pre-CS, istaroxime improved blood pressure and some echocardiography measures related to heart failure and was well tolerated.

Published
2022

22. Characteristics and prognosis of Herpesviridae-related pneumonia in critically ill burn patients

Author

Charline Riaud, Alexandre Fratani, Kevin Serror, Maïté Chaussard, Matthieu Lafaurie, Haikel Oueslati, Alexandru Cupaciu, Lucie Guillemet, Maxime Coutrot, François Dépret, Jil Rouaux, Maud Salmona, Marc Chaouat, Matthieu Legrand, Jérôme LeGoff, Mourad Benyamina, and Alexandre Mebazaa

Subjects
medicine.medical_specialty, Critical Illness, Smoke inhalation, Critical Care and Intensive Care Medicine, law.invention, Cohort Studies, law, Smoke, Internal medicine, medicine, Humans, Herpesviridae, Retrospective Studies, medicine.diagnostic_test, business.industry, Ventilator-associated pneumonia, Pneumonia, General Medicine, Middle Aged, Smoke Inhalation Injury, Prognosis, medicine.disease, Intensive care unit, Intensive Care Units, Bronchoalveolar lavage, Emergency Medicine, Surgery, SOFA score, Burns, business, Total body surface area, Cohort study
Abstract

The aim of this study was to describe the prevalence, characteristics and outcome of critically burn patients with pulmonary HSV reactivation.Retrospective, single-center cohort study in a burn critical care unit in a tertiary center, including all consecutive severely burn patients with bronchoalveolar lavage performed for pneumoniae suspicion and screened for HSV from January 2013 and April 2017. We used logistic regression to identify factors associated with HSV reactivation and outcomes.94 patients were included, mean age was 51 (39-64) years; median total body surface area burned was 36 (25-54)% and ICU mortality 38%. Fifty-five patients (59%) had pulmonary HSV reactivation and 30 (55%) were treated with acyclovir. Patients with HSV reactivation were more severely ill with higher SOFA score at admission compared to patient without HSV reactivation (6 [3-8] vs. 2 [1-4], p0.0001 respectively). In multivariate analysis, sex, SOFA score at admission and smoke inhalation were significantly associated with HSV reactivation. Only septic shock was associated with 90-day mortality when HSV reactivation was not.Pulmonary HSV reactivation is frequent among severely ill burn patients. Initial severity and smoke inhalation are risk factors. Antiviral treatment was not associated with outcome.

Published
2022

23. Use of pragmatic and explanatory trial designs in acute care research: lessons from COVID-19

Author

Jonathan D Casey, Laura M Beskow, Jeremy Brown, Samuel M Brown, Étienne Gayat, Michelle Ng Gong, Michael O Harhay, Samir Jaber, Jacob C Jentzer, Pierre-François Laterre, John C Marshall, Michael A Matthay, Todd W Rice, Yves Rosenberg, Alison E Turnbull, Lorraine B Ware, Wesley H Self, Alexandre Mebazaa, Sean P Collins, Vanderbilt University [Nashville], National Institute of Neurological Disorders and Stroke [Bethesda] (NINDS), National Institutes of Health [Bethesda] (NIH), University of Utah, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Albert Einstein College of Medicine [New York], University of Pennsylvania, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Mayo Clinic [Rochester], Université Catholique de Louvain = Catholic University of Louvain (UCL), St. Michael's Hospital, University of California [San Francisco] (UC San Francisco), University of California (UC), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Johns Hopkins University (JHU), and MORNET, Dominique

Subjects
[SDV] Life Sciences [q-bio], Pulmonary and Respiratory Medicine, Research Design, [SDV]Life Sciences [q-bio], COVID-19, Humans, Hydroxychloroquine
Abstract

International audience; Unique challenges arise when conducting trials to evaluate therapies already in common clinical use, including difficulty enrolling patients owing to widespread open-label use of trial therapies and the need for large sample sizes to detect small but clinically meaningful treatment effects. Despite numerous successes in trials evaluating novel interventions such as vaccines, traditional explanatory trials have struggled to provide definitive answers to time-sensitive questions for acutely ill patients with COVID-19. Pragmatic trials, which can increase efficiency by allowing some or all trial procedures to be embedded into clinical care, are increasingly proposed as a means to evaluate therapies that are in common clinical use. In this Personal View, we use two concurrently conducted COVID-19 trials of hydroxychloroquine (the US ORCHID trial and the UK RECOVERY trial) to contrast the effects of explanatory and pragmatic trial designs on trial conduct, trial results, and the care of patients managed outside of clinical trials. In view of the potential advantages and disadvantages of explanatory and pragmatic trial designs, we make recommendations for their optimal use in the evaluation of therapies in the acute care setting.

Published
2022

24. Biologically Active Adrenomedullin (bio-ADM) is of potential value in identifying congestion and selecting patients for neurohormonal blockade in acute dyspnea

Author

Justas Simonavičius, Aurimas Mikalauskas, Kamilė Čerlinskaitė, Etienne Gayat, Vytautas Juknevičius, Eglė Palevičiūtė, Irina Alitoit-Marrote, Denis Kablučko, Loreta Bagdonaitė, Mindaugas Balčiūnas, Dovilė Vaičiulienė, Ieva Jonauskienė, Justina Motiejūnaitė, Kęstutis Stašaitis, Audrys Kukulskis, Šarūnas Damalakas, Toma Šimbelytė, Neringa Taparauskaitė, Gintarė Pukanasienė, Aleksandras Laucevičius, Aušra Kavoliūnienė, Alexandre Mebazaa, Jelena Čelutkienė, RS: Carim - Heart, and Cardiologie

Subjects
Adrenomedullin, Dyspnea, Patient Selection, Humans, General Medicine, Biomarkers, Respiratory Sounds
Abstract

This study was designed to evaluate the role of biologically active adrenomedullin (bio-ADM) in congestion assessment and risk stratification in acute dyspnea.This is a sub-analysis of the Lithuanian Echocardiography Study of Dyspnea in Acute Settings. Congestion was assessed by means of clinical (peripheral edema, rales) and sonographic (estimated right atrial pressure) parameters. Ninety-day mortality was chosen for outcome analysis.There were 1188 patients included. Bio-ADM concentration was higher in patients with peripheral edema at admission (48.2 [28.2-92.6] vs 35.4 [20.9-59.2] ng/L, P.001). There was a stepwise increase in bio-ADM concentration with increasing prevalence of rales: 29.8 [18.8-51.1], 38.5 [27.5-67.1], and 51.1 [33.1-103.2] ng/L in patients with no rales, rales covering less than one-half, and greater than or equal to one-half of the pulmonary area, respectively (P0.001). Bio-ADM concentration demonstrated gradual elevation in patients with normal, moderately, and severely increased estimated right atrial pressure: 25.1 [17.6-42.4] ng/L, 36.1 [23.1-50.2], and 47.1 [30.7-86.7] ng/L, respectively (P.05). Patients with bio-ADM concentration35.5 ng/L were at more than twofold increased risk of dying (P.001). Survival in those with high bio-ADM was significantly modified by neurohormonal blockade at admission (P.05), especially if NT-proBNP levels were lower than the median (P = .002 for interaction).Bio-ADM reflects the presence and the degree of pulmonary, peripheral, and intravascular volume overload and is strongly related to 90-day mortality in acute dyspnea. Patients with high bio-ADM levels demonstrated survival benefit from neurohormonal blockade.

Published
2022

25. Biomarkers for the prediction of heart failure and cardiovascular events in patients with type 2 diabetes

Author

Peter Seferović, Dimitrios Farmakis, Antoni Bayes‐Genis, Tuvia Ben Gal, Michael Böhm, Ovidiu Chioncel, Roberto Ferrari, Gerasimos Filippatos, Loreena Hill, Ewa Jankowska, Mitja Lainscak, Yuri Lopatin, Lars H. Lund, Alexandre Mebazaa, Marco Metra, Brenda Moura, Giuseppe Rosano, Thomas Thum, Adriaan Voors, Andrew J.S. Coats, Publica, and Cardiovascular Centre (CVC)

Subjects
Cardiovascular prevention, Diabetes mellitus, Diabetes Mellitus, Type 2, Cardiology, Biomarkers, Cardiovascular risk, Heart failure, Humans, Heart Failure, Cardiology and Cardiovascular Medicine, Type 2
Abstract

Knowledge on risk predictors of incident heart failure (HF) in patients with type 2 diabetes (T2D) is crucial given the frequent coexistence of the two conditions and the fact that T2D doubles the risk of incident HF. In addition, HF is increasingly being recognized as an important endpoint in trials in T2D. On the other hand, the diagnostic and prognostic performance of established cardiovascular biomarkers may be modified by the presence of T2D. The present position paper, derived by an expert panel workshop organized by the Heart Failure Association of the European Society of Cardiology, summarizes the current knowledge and gaps in evidence regarding the use of a series of different biomarkers, reflecting various pathogenic pathways, for the prediction of incident HF and cardiovascular events in patients with T2D and in those with established HF and T2D.

Published
2022

26. Protein Biomarkers of New-Onset Heart Failure: Insights From the Heart Omics and Ageing Cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study

Author

Nicolas Girerd, Daniel Levy, Kevin Duarte, Joao Pedro Ferreira, Christie Ballantyne, Timothy Collier, Anne Pizard, Jens Björkman, Javed Butler, Andrew Clark, John G. Cleland, Christian Delles, Javier Diez, Arantxa González, Mark Hazebroek, Jennifer Ho, Anne-Cécile Huby, Shih-Jen Hwang, Roberto Latini, Beatrice Mariottoni, Alexandre Mebazaa, Pierpaolo Pellicori, Naveed Sattar, Peter Sever, Jan A. Staessen, Job Verdonschot, Stephane Heymans, Patrick Rossignol, and Faiez Zannad

Subjects
Heart Failure, Aging, proteomics, Risk Factors, Natriuretic Peptide, Brain, protein interaction maps, Humans, biomarkers, Longitudinal Studies, Atherosclerosis, Cardiology and Cardiovascular Medicine, Peptide Fragments, cardiovascular diseases
Abstract

Background: We sought to identify protein biomarkers of new-onset heart failure (HF) in 3 independent cohorts (HOMAGE cohort [Heart Omics and Ageing], ARIC study [Atherosclerosis Risk in Communities], and FHS [Framingham Heart Study]) and assess if and to what extent they improve HF risk prediction compared to clinical risk factors alone. Methods: A nested case-control design was used with cases (incident HF) and controls (without HF) matched on age and sex within each cohort. Plasma concentrations of 276 proteins were measured at baseline in ARIC (250 cases/250 controls), FHS (191/191), and HOMAGE cohort (562/871). Results: In single protein analysis, after adjusting for matching variables and clinical risk factors (and correcting for multiple testing), 62 proteins were associated with incident HF in ARIC, 16 in FHS, and 116 in HOMAGE cohort. Proteins associated with incident HF in all cohorts were BNP (brain natriuretic peptide), NT-proBNP (N-terminal pro-B-type natriuretic peptide), eukaryotic translation initiation factor 4E-BP1 (4E-binding protein 1), hepatocyte growth factor (HGF), Gal-9 (galectin-9), TGF-alpha (transforming growth factor alpha), THBS2 (thrombospondin-2), and U-PAR (urokinase plasminogen activator surface receptor). The increment in C -index for incident HF based on a multiprotein biomarker approach, in addition to clinical risk factors and NT-proBNP, was 11.1% (7.5%–14.7%) in ARIC, 5.9% (2.6%–9.2%) in FHS, and 7.5% (5.4%–9.5%) in HOMAGE cohort, all P Conclusions: A multiprotein biomarker approach improves prediction of incident HF when added to natriuretic peptides and clinical risk factors.

Published
2023

27. A case-control, multicentre study of consecutive patients with COVID-19 and acute (myo)pericarditis: incidence, risk factors, clinical characteristics and outcomes

Author

Òscar, Mirò, Manel, Sabaté, Sònia, Jiménez, Alexandre, Mebazaa, Gemma, Martínez-Nadal, Pascual, Piñera, Guillermo, Burillo-Putze, Alfonso, Martín, Francisco Javier, Martín-Sánchez, Javier, Jacob, Aitor, Alquézar-Arbé, Eric Jorge, García-Lamberechts, Pere, Llorens, and Juan, González Del Castillo

Subjects
Risk Factors, Case-Control Studies, Incidence, Natriuretic Peptide, Brain, Emergency Medicine, COVID-19, Humans, Pericarditis, General Medicine, Critical Care and Intensive Care Medicine, Adenosine Monophosphate, Biomarkers, Peptide Fragments
Abstract

ObjectiveTo estimate incidence, risk factors, clinical characteristics and outcomes of acute (myo)pericarditis (AMP) in patients with COVID-19.MethodsCase-control, retrospective review, consecutive case inclusion performed in 62 Spanish EDs. All COVID-19 patients with AMP (cases) were compared in clinical characteristics and outcomes with COVID-19 without AMP (control group A) and non-COVID patients with AMP (control group B). We estimated unadjusted standardised incidence (SI, not adjusted by population’s age/sex) of AMP in COVID-19 and non-COVID populations (per 100 000/year).ResultsWe identified 67 AMP in COVID-19 patients (SI=56.5, OR with respect to non-COVID patients=4.43, 95% CI=3.98 to 4.94). Remarkably, COVID-19 cases presented with chest pain less frequently than non-COVID patients and had less typical ECG changes, higher NT-proBNP (N-terminal prohormone of brain natriuretic peptide), more left and right ventricular dysfunction in echocardiography and more need of inotropic/vasopressor drugs. Admission to intensive care was higher than control group A (OR=3.22, 95% CI=1.43 to 7.23), and in-hospital mortality was higher than control group B (OR=7.75, 95% CI=2.77 to 21.7).ConclusionAMP is unusual as a form of COVID-19 presentation (about 1‰ cases), but SI is more than fourfold higher than non-COVID population, and it is less symptomatic, more severe and has higher in-hospital mortality; therefore, rapid recognition, echocardiographic assessment of myopericardial inflammation/dysfunction and treatment with vasoactive drugs when needed are recommended in AMP in patients with COVID-19.

Published
2022

28. Acute Heart Failure in the 2021 ESC Heart Failure Guidelines: a scientific statement from the Association for Acute CardioVascular Care (ACVC) of the European Society of Cardiology

Author

Josep, Masip, W, Frank Peacok, Mattia, Arrigo, Xavier, Rossello, Elke, Platz, Louise, Cullen, Alexandre, Mebazaa, Susanna, Price, Héctor, Bueno, Salvatore, Di Somma, Mucio, Tavares, Martin R, Cowie, Alan, Maisel, Christian, Mueller, Òsar, Miró, and National Institutes of Health (Estados Unidos)

Subjects
Heart Failure, Educational Paper, Critical Care, Cardiology, Shock, Cardiogenic, Humans, General Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Abstract

The current European Society of Cardiology (ESC) Heart Failure Guidelines are the most comprehensive ESC document covering heart failure to date; however, the section focused on acute heart failure remains relatively too concise. Although several topics are more extensively covered than in previous versions, including some specific therapies, monitoring and disposition in the hospital, and the management of cardiogenic shock, the lack of high-quality evidence in acute, emergency, and critical care scenarios, poses a challenge for providing evidence-based recommendations, in particular when by comparison the data for chronic heart failure is so extensive. The paucity of evidence and specific recommendations for the general approach and management of acute heart failure in the emergency department is particularly relevant, because this is the setting where most acute heart failure patients are initially diagnosed and stabilized. The clinical phenotypes proposed are comprehensive, clinically relevant and with minimal overlap, whilst providing additional opportunity for discussion around respiratory failure and hypoperfusion. F.P. has received research grants from Abbott, Becton Dickenson, Brainbox, Calcimedica, CSL Behring, Cue, Ortho Clinical Diagnostics, Relypsa, Roche, Salix, Siemens. Consultant: Abbott, Astra-Zeneca, Beckman, Bosch, Fast Biomedical, Forrest Devices, Ischemia Care, Dx, Instrument Labs, Janssen, Nabriva, Ortho Clinical Diagnostics, Osler, Relypsa, Roche, Quidel, Salix, Siemens, Upstream and has stock/ownership interests in AseptiScope Inc, Brainbox Inc, Braincheck Inc, Coagulo Inc, Comprehensive Research Associates LLC, Comprehensive Research Management Inc, Emergencies in Medicine LLC, Fast Inc, Forrest Devices, Ischemia DX LLC, Lucia Inc, Prevencio Inc, ScPharma, Trivirum Inc, Upstream Inc. E.P.’ employer has received support from Novartis for consulting work and she has consulted for scPharmaceuticals outside of the submitted work. She has received research support from the NIH (R01HL148439). Sí

Published
2022

29. Changes in inferior vena cava area represent a more sensitive metric than changes in filling pressures during experimental manipulation of intravascular volume and tone

Author

Marat Fudim, Javed Butler, Kenneth McDonald, Juan Betuel Ivey-Miranda, Robert Gaul, Devin Mahoney, Stephen Sheridan, Barry A. Borlaug, Jeffrey M. Testani, Alastair P Gray, Kevin Damman, Daniel Burkhoff, Christopher Maulion, Alexandre Mebazaa, Jennifer L. Asher, Veena S. Rao, Martin R. Cowie, Friedrich Wetterling, Zachary L. Cox, and Cardiovascular Centre (CVC)

Subjects
Cardiac function curve, Cardiac Catheterization, medicine.medical_specialty, Central Venous Pressure, Heart Diseases, Vena Cava, Inferior, Vasodilation, Volume loading, Inferior vena cava, medicine.artery, Internal medicine, medicine, Intravascular volume status, Animals, Humans, Heart Failure, Sheep, business.industry, medicine.disease, Additional research, medicine.vein, Heart failure, Pulmonary artery, cardiovascular system, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract

AIMS: Remote monitoring of pulmonary artery pressure has reduced heart failure (HF) hospitalizations in chronic HF as elevation of pulmonary artery pressure provides information that can guide treatment. The venous system is characterized by high capacitance, thus substantial increases in intravascular volume can occur before filling pressures increase. The inferior vena cava (IVC) is a highly compliant venous conduit and thus a candidate for early detection of change in intravascular volume. We aimed to compare IVC cross-sectional area using a novel sensor with cardiac filling pressures during experimental manipulation of volume status, vascular tone, and cardiac function.METHODS AND RESULTS: Experiments were conducted in sheep to manipulate volume status (colloid infusion), vascular tone (nitroglycerin infusion) and cardiac function (rapid cardiac pacing). A wireless implantable IVC sensor was validated ex-vivo and in-vivo, and then used to measure the cross-sectional area of the IVC. Right- and left-sided cardiac filling pressures were obtained via right heart catheterization. The IVC sensor provided highly accurate and precise measurements of cross-sectional area in ex-vivo and in-vivo validation. IVC area changes were more sensitive than the corresponding changes in cardiac filling pressures during colloid infusion (p CONCLUSIONS: Inferior vena cava area can be remotely and accurately measured in real time with a wireless implantable sensor. Changes in IVC area are more sensitive than corresponding changes in filling pressures following experimental volume loading and fluid redistribution. Additional research is warranted to understand if remote monitoring of the IVC may have advantages over pressure-based monitors in HF.

Published
2022

30. A comprehensive characterization of acute heart failure with preserved versus mildly reduced versus reduced ejection fraction – insights from the <scp>ESC‐HFA EORP</scp> Heart Failure Long‐Term Registry

Author

Kapłon-Cieślicka, Agnieszka, Benson, Lina, Chioncel, Ovidiu, Crespo-Leiro, Maria G, Coats, Andrew J S, Anker, Stefan D, Filippatos, Gerasimos, Ruschitzka, Frank, Hage, Camilla, Drożdż, Jarosław, Seferovic, Petar, Rosano, Giuseppe M C, Piepoli, Massimo, Mebazaa, Alexandre, McDonagh, Theresa, Lainscak, Mitja, Savarese, Gianluigi, Ferrari, Roberto, Maggioni, Aldo P, Lund, Lars H, University of Zurich, and Lund, Lars H

Subjects
Heart failure with mildly reduced ejection fraction, Heart Failure, Heart failure with mid-range ejection fraction, Aftercare, 610 Medicine & health, Stroke Volume, Prognosis, 2705 Cardiology and Cardiovascular Medicine, Patient Discharge, Hospitalization, Treatment, Heart failure with preserved ejection fraction, 10209 Clinic for Cardiology, Humans, Registries, Cardiology and Cardiovascular Medicine
Abstract

[Abstract] Aims: To perform a comprehensive characterization of acute heart failure (AHF) with preserved (HFpEF), versus mildly reduced (HFmrEF) versus reduced ejection fraction (HFrEF). Methods and results: Of 5951 participants in the ESC HF Long-Term Registry hospitalized for AHF (acute coronary syndromes excluded), 29% had HFpEF, 18% HFmrEF, and 53% HFrEF. Hospitalization reasons were most commonly atrial fibrillation (more in HFmrEF and HFpEF), followed by ischaemia (HFmrEF), infection (HFmrEF and HFpEF), worsening renal function (HFrEF), and uncontrolled hypertension (HFmrEF and HFpEF). Hospitalization characteristics included lower blood pressure, more oedema and higher natriuretic peptides with lower ejection fraction, similar pulmonary congestion, more mitral regurgitation in HFrEF and HFmrEF and more tricuspid regurgitation in HFrEF. In-hospital mortality was 3.4% in HFrEF, 2.1% in HFmrEF and 2.2% in HFpEF. Intravenous diuretic (∼80%) and nitrate (∼15%) use was similar but inotrope use greater in HFrEF (16%, vs. HFmrEF 7.4% vs. HFpEF 5.3%). Weight loss and estimated glomerular filtration rate improvement were greater in HFrEF, whereas reduction in natriuretic peptides was similar. Over 1 year post-discharge, events per 100 patient-years (95% confidence interval) in HFrEF versus HFmrEF versus HFpEF were: all-cause death 22 (20-24) versus 17 (14-20) versus 17 (15-20); cardiovascular (CV) death 12 (10-13) versus 8.6 (6.6-11) versus 8.4 (6.9-10); non-CV death 2.4 (1.8-3.1) versus 3.3 (2.1-4.8) versus 4.5 (3.5-5.9); all-cause hospitalization 48 (45-51) versus 35 (31-40) versus 42 (39-46); HF hospitalization 29 (27-32) versus 19 (16-22) versus 17 (15-20); and non-CV hospitalization 7.7 (6.6-8.9) versus 9.6 (7.5-12) versus 15 (13-17). Conclusion: In AHF, HFrEF is more severe and has greater in-hospital mortality. Post-discharge, HFrEF has greater CV risk, HFpEF greater non-CV risk, and HFmrEF lower overall risk.

Published
2022

31. The association of biological sex and long-term outcomes in patients with acute dyspnea at the emergency department

Author

Prabakar Vaittinada Ayar, Justina Motiejūnaitė, Kamilė Čerlinskaitė, Benjamin Deniau, Alice Blet, Aušra Kavoliūnienė, Alexandre Mebazaa, Jelena Čelutkienė, and Feriel Azibani

Subjects
Adult, Hospitalization, Male, Dyspnea, Acute Disease, Emergency Medicine, Humans, Female, Registries, Emergency Service, Hospital, Aged
Abstract

Marked differences have been described between women and men in disease prevalence, clinical presentation, response to treatment and outcomes. However, such data are scarce in the acutely ill. An awareness of differences related to biological sex is essential for the success of clinical care and outcomes in patients presenting with acute dyspnea, the most frequent cause of emergency department (ED) admission.The aim of the present study was to assess the effect of biological sex on 1-year all-cause mortality in patients presenting with acute dyspnea to the ED.Consecutive adult patients presenting with acute dyspnea in two Lithuanian EDs were included. Clinical characteristics, laboratory data and medication use at discharge were collected. Follow-up at 1 year was performed via national data registries.The primary outcome of the study was 1-year all-cause mortality. Hazard ratios (HRs) for 1-year mortality according to biological sex were calculated using a Cox proportional hazards regression model, with and without adjustment for the following confounders: age, systolic blood pressure, creatinine, sodium and hemoglobin.A total of 1455 patients were included. Women represented 43% of the study population. Compared to men, women were older [median (interquartile range [IQR]) age 74 (65-80) vs. 68 (59-77) years, P0.0001]. The duration of clinical signs before admission was shorter for women [median (IQR) duration 4 (1-14) vs. 7(2-14) days, P = 0.006]. Unadjusted 1-year all-cause mortality was significantly lower in women (21 vs. 28%, P = 0.001). Adjusted HR of 1-year all-cause mortality was lower in women when compared to men [HR 0.68 (0.53-0.88), P = 0.0028]. Additional sensitivity analyses confirmed the survival benefit for women in subgroups including age greater and lower than 75 years, the presence of comorbidities and causes of dyspnea (cardiac or noncardiac).Women have better 1-year survival than men after the initial ED presentation for acute dyspnea. Understanding the biological sex-related differences should lead toward precision medicine, and improve clinical decision-making to promote gender equality in health.

Published
2021

32. Immunity and inflammation: the neglected key players in congenital heart disease?

Author

Johann Bauersachs, Alexandre Mebazaa, Benjamin G. Chousterman, Sarah Cohen, and Laura M. Wienecke

Subjects
Adult, Heart Defects, Congenital, Heart disease, Population, Heart failure, Inflammation, Context (language use), Disease, Bioinformatics, Article, Immune system, Immunity, medicine, Humans, Child, education, Pandemics, Congenital heart disease, education.field_of_study, SARS-CoV-2, business.industry, COVID-19, Infant, Thymectomy, medicine.disease, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract

Although more than 90% of children born with congenital heart disease (CHD) survive into adulthood, patients face significantly higher and premature morbidity and mortality. Heart failure as well as non-cardiac comorbidities represent a striking and life-limiting problem with need for new treatment options. Systemic chronic inflammation and immune activation have been identified as crucial drivers of disease causes and progression in various cardiovascular disorders and are promising therapeutic targets. Accumulating evidence indicates an inflammatory state and immune alterations in children and adults with CHD. In this review, we highlight the implications of chronic inflammation, immunity, and immune senescence in CHD. In this context, we summarize the impact of infant open-heart surgery with subsequent thymectomy on the immune system later in life and discuss the potential role of comorbidities and underlying genetic alterations. How an altered immunity and chronic inflammation in CHD influence patient outcomes facing SARS-CoV-2 infection is unclear, but requires special attention, as CHD could represent a population particularly at risk during the COVID-19 pandemic. Concluding remarks address possible clinical implications of immune changes in CHD and consider future immunomodulatory therapies.

Published
2021

33. Soluble CD146 in the detection and grading of intravascular and tissue congestion in patients with acute dyspnoea: analysis of the prospective observational Lithuanian Echocardiography Study of Dyspnoea in Acute Settings (LEDA) cohort

Author

Renata Juknevičienė, Justas Simonavičius, Aurimas Mikalauskas, Kamilė Čerlinskaitė-Bajorė, Mattia Arrigo, Vytautas Juknevičius, Irina Alitoit-Marrote, Denis Kablučko, Loreta Bagdonaitė, Dalius Vitkus, Mindaugas Balčiūnas, Gitana Zuozienė, Jūratė Barysienė, Diana Žaliaduonytė, Kęstutis Stašaitis, Aušra Kavoliūnienė, Alexandre Mebazaa, Jelena Čelutkienė, RS: Carim - Heart, and Cardiologie

Subjects
EUROPEAN ASSOCIATION, Adult, Heart Failure, NATRIURETIC PEPTIDE, MORTALITY, PULMONARY CONGESTION, Adult cardiology, adult cardiology, echocardiography, heart failure, ultrasound, vascular medicine, Lithuania, ADULTS, General Medicine, CD146 Antigen, DIAGNOSIS, Peptide Fragments, Dyspnea, Echocardiography, Ultrasound, Natriuretic Peptide, Brain, HEART-FAILURE, Humans, Prospective Studies, VASCULAR MEDICINE, AMERICAN SOCIETY, Biomarkers
Abstract

ObjectivesTo evaluate the potential of soluble cluster of differentiation 146 (sCD146) in the detection and grading of congestion in patients with acute dyspnoea.DesignSubanalysis of the prospective observational Lithuanian Echocardiography Study of Dyspnoea in Acute Settings (LEDA) cohort.SettingTwo Lithuanian university centres.ParticipantsAdult patients with acute dyspnoea admitted to the emergency department.MethodsCongestion was assessed using clinical and sonographic parameters. All patients underwent sCD146 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing.ResultsThe median value of sCD146 concentration in the study cohort (n=437) was 405 (IQR 315–509) ng/mL. sCD146 was higher in patients with peripheral oedema than in those without (median (IQR) 472 (373–535) vs 400 (304–501) ng/mL, p=0.009) and with pulmonary rales than in those without (439 (335–528) vs 394 (296–484) ng/mL, p=0.001). We found a parallel increase of estimated right atrial pressure (eRAP) and sCD146 concentration: sCD146 was 337 (300–425), 404 (290–489) and 477 (363–572) ng/mL in patients with normal, moderately elevated and high eRAP, respectively (p=0.001). In patients with low NT-proBNP, high sCD146 distinguished a subgroup with a higher prevalence of oedema as compared with patients with low levels of both biomarkers (76.0% vs 41.0%, p=0.010). Moreover, high sCD146 indicated a higher prevalence of elevated eRAP, irrespective of NT-proBNP concentration (pConclusionsCD146 concentration reflects the degree of intravascular and tissue congestion assessed by clinical and echocardiographic indices, with this association maintained in patients with low NT-proBNP. Our data support the notion that NT-proBNP might represent heart stretch while sCD146 rather represents peripheral venous congestion.

Published
2022

35. Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial

Author

Laterre, Pierre-François, Pickkers, Peter, Marx, Gernot, Wittebole, Xavier, Meziani, Ferhat, Dugernier, Thierry, Huberlant, Vincent, Schuerholz, Tobias, François, Bruno, Lascarrou, Jean-Baptiste, Beishuizen, Albertus, Oueslati, Haikel, Contou, Damien, Hoiting, Oscar, Lacherade, Jean-Claude, Chousterman, Benjamin, Pottecher, Julien, Bauer, Michael, Godet, Thomas, Karakas, Mahir, Helms, Julie, Bergmann, Andreas, Zimmermann, Jens, Richter, Kathleen, Hartmann, Oliver, Pars, Melanie, Mebazaa, Alexandre, AdrenOSS-2 study participants, Castanares Zapatero, Diego, Collienne, Christine, Gérard, Ludovic, Hantson, Philippe, Montiel, Virginie, Berghe, Caroline, Dujardin, Marie-France, Gielens, Leslie, Renard, Suzanne, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, and UCL - (SLuc) Service de soins intensifs

Subjects
medicine.medical_specialty, Randomization, Original, Adrecizumab (HAM8101), lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Critical Care and Intensive Care Medicine, Placebo, Antibodies, Monoclonal, Humanized, law.invention, Adrenomedullin, Randomized controlled trial, Double-Blind Method, law, Internal medicine, Septic shock, medicine, Humans, Enibarcimab, business.industry, Hazard ratio, Endothelial function, medicine.disease, Shock, Septic, Treatment Outcome, Tolerability, SOFA score, business, Biomarkers
Abstract

Purpose Investigate safety and tolerability of adrecizumab, a humanized monoclonal adrenomedullin antibody, in septic shock patients with high adrenomedullin. Methods Phase-2a, double-blind, randomized, placebo-controlled biomarker-guided trial with a single infusion of adrecizumab (2 or 4 mg/kg b.w.) compared to placebo. Patients with adrenomedullin above 70 pg/mL

Published
2021

36. Regional variation of effects of new antidiabetic medications in cardiovascular outcome trials

Author

Olav W. Nielsen, Aldo P. Maggioni, Christopher L. Edwards, Marco Metra, Naoki Sato, Barry H. Greenberg, Faiez Zannad, Gad Cotter, Alexandre Mebazaa, Georg Ertl, Beth A. Davison, Alain Cohen-Solal, Ovidiu Chioncel, Stefanie Senger, John R. Teerlink, Momentum Research Inc. [Durham, NC, USA] (MRI), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, University of California [San Francisco] (UC San Francisco), University of California (UC), Veterans Affairs Medical Center, San Francisco, California, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), IT University of Copenhagen (ITU), Università degli Studi di Brescia = University of Brescia (UniBs), Civic Hospital of Brescia, Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), University of California [San Diego] (UC San Diego), Associazione Nazionale Medici Cardiologi Ospedalieri [Firenze] (ANMCO), University of Würzburg = Universität Würzburg, Nippon Medical School [Tokyo, Japon], Hôpital Lariboisière-Fernand-Widal [APHP], and leboeuf, Christophe

Subjects
medicine.medical_specialty, 030204 cardiovascular system & hematology, Glucagon-Like Peptide-1 Receptor, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Heart Failure, Humans, Hypoglycemic Agents, Regression Analysis, Sodium-Glucose Transporter 2 Inhibitors, Treatment Outcome, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Diabetes Mellitus, medicine, Treatment effect, 030212 general & internal medicine, business.industry, medicine.disease, Random effects model, Differential effects, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Heart failure, Cardiology and Cardiovascular Medicine, business, Type 2, Mace
Abstract

International audience; Background In international trials, glucagon-like protein-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2Is) were effective in improving cardiovascular (CV) outcomes. Methods We assessed the effect of GLP-1RAs and SGLT2Is treatment effect on CV endpoints by geographical region in multiple international trials using random effects weighted least squares meta-regressions. Results The estimated effects of both SGLT2Is and GLP-1RAs on major adverse CV events (MACE) in North America (SGLT2Is n = 12,399, HR 0.90, 95% CI 0.81-1.01; GLP-1RAs n = 12,515, HR 0.95, 95% CI 0.83-1.09) and in Europe (SGLT2Is n = 19,435, HR 0.93, 95% CI 0.85-1.02; GLP-1RAs n = 22,812, HR 0.88, 95% CI 0.79-0.99) were numerically lower but not statistically different to the rest of the world (ROW) (SGLT2Is n = 15,127, HR 0.83, 95% CI 0.75-0.92, p-value for interaction 0.26; GLP-1RAs n = 17,494, HR 0.82, 95% CI 0.73-0.92, p-value for interaction 0.28). Effects of SGLT2Is on heart failure readmission or CV death varied significantly by region (P = 0.0094). The effect of SGLT2Is was significantly smaller in Europe (n = 18,653, HR 0.86, 95% CI 0.78-0.95) than in the ROW (n = 12,463, HR 0.68, 95% CI 0.61-0.76, P = 0.0024). The smaller effect in North America (n = 9776, HR 0.76, 95% CI 0.66-0.87) did not differ significantly from that in the ROW (P = 0.2370). Conclusion The effects of SGLT2Is on HF events are larger in the ROW. Further analyses and studies are needed to better elucidate the differential effects of SGLTIs and GLP-1RAs by geographical regions.

Published
2021

37. Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Author

Labeau, Sonia O, Afonso, Elsa, Benbenishty, Julie, Blackwood, Bronagh, Boulanger, Carole, Brett, Stephen J, Calvino-Gunther, Silvia, Chaboyer, Wendy, Coyer, Fiona, Deschepper, Mieke, François, Guy, Honore, Patrick M, Jankovic, Radmilo, Khanna, Ashish K, Llaurado-Serra, Mireia, Lin, Frances, Rose, Louise, Rubulotta, Francesca, Saager, Leif, Williams, Ged, Blot, Stijn I, Dritan, Muzha, Antoni Margarit Ribas, Fernando, Lipovesty, Cecilia, Loudet, Fiona, Coyer, Philipp, Eller, Nafseen, Mostafa, Patrick, M Honoré, Vanesa Mercado Telleria, Jasmina, Smajic, Paula Cristina Nogueira, Khalid Mahmood Khan Nafees, Romuald, Hentchoya, Louise, Rose, Javiera, Soledad, Frances, Lin, Yenny, Cardenas, Amylkar Garay Reyes, Alan, Sustic, Meropi, Mpouzika, Tamas, Vymazal, Hanne Irene Jensen, Hernan, Aguirre-Bermeo, Liivi, Maddison, Maija, Valta, Silvia, Calvino-Gunther, Frank, Bloos, Faustina Excel Adipa, Vasilios, Koulouras, Judy, Enamorado, Zsuzsann, Ágoston, Hrönn, Birgisdóttir, Amit, Gupta, Mohan, Gurjar, Bram, Kilapong, Seyed Mohammadreza Hashemian, Ignacio, Martin-Loeches, Julie, Benbenishty, Andrea, Cortegiani, Kelly, Fletcher, Yoshiro, Hayashi, Wangari, Waweru-Siika, Khalid, Abidi, Sang-Min, Lee, Burhan, Hadri, Mihails, Dolgusevs, Fayez François Abillama, Tomas, Jovaisa, Cyril, Thix, Muhammed, Elhadi, Basri Mat Nor, Shanti, Ratnam, Mohd Zulfakar Mazlan, Sundaresan, Maiyalagan, Luis, Sánchez-Hurtado, Adrian, Belii, Mendsaikhan, Naranpurev, Prabha, Gautam, Dylan De Lange, Rachael, Parke, Rose Ekama Ilesanmi, Mirjana, Shosholcheva, Antonija, Petosic, Ranveig, Lind, Madiha Hashmi Ffarcsi, Javier, Bogarin, Aaron Mark Hernandez, Malgorzata, Mikaszewska-Sokolewicz, Bruno, Sousa, Dana, Tomescu, Dorel, Sandesc, Theogene, Twagirumugabe, Vitaly, Gusarov, Maie, Ebaid, Radmilo, Jankovic, Gari, Slobodianiuk, Andrea, Martonova, Rihard, Knafelj, Mervyn, Mer, Emilio, Maseda, Bernardo, Panka, Joerg, C Schefold, Eva, Joelsson-Alm, Konlawij, Trongtrakul, Lorna, Merritt-Charles, Lamia Ouanes Besbes, Yalım, Dikmen, Lesia, Zgrzheblovska, Mark, Fielding, Francesca, Rubulotta, Ashish, K Khanna, Leif, Saager, Ingrid von der Osten, Alban, Greca, Alma, Cani, Nordian, Xhindi, Genci, Hyska, Antonio Margarit Ribas, Susana, Pinto, Paulo, Alves, Romina, Esposito, Emanuel, Valgolio, John Thomas Sanchez Minope, Antonio, Abdala, Maria, Ayala, Silvina, Bravo, Ana, Bantar, Patricia, Delgado, Gustavo, Badariotti, Fernando, Lipovestky, Ana, Diaz, Pablo, Saul, Mariano, Setten, Alejandra, Aucapina, Ysica, Acosta, Victor, Gonzalez, Luis, Camputaro, Fernando, Baccaro, Robert, Villa, Marcela, Mastantuono, Emiliano, Dean, Oscar Fernández Rostello, Patricia, Brizuela, Julio Ricardo Bartoli, Matias, Guereschi, Cristian, Quiroga, Sofia, Putruele, Paula, Villegas, Veronica, Curilen, Ruben, Fernandez, Mariangeles Gabriela Nocheretti, Rosana Gabriela Escalante, Cecilia Inés Loudet, Silvia, Fernandez, Ana Laura Gonzalez, Gustavo Andres Alvarez, Federico, Iglesias, Silvia, Chaparro, Graciela, Zakalik, Gonzalo, Pagella, Matías, Baini, Pierina Arias Campos, Ignacio, Sabbag, Armando, Schmukler, Imelda Perdomo Fonseca, Gonzalo Martín Alvarez, Mario, Ramirez, Fernando, Tapia, Carlos Alejandro Bascary, Graciela Del Valle Gimenez, Fernando Pablo Bertoletti, Esteban, Milioto, Pablo Julio Maldonaldo Bonsignore, Maria Alejandra Fernandez, Julie, Smith, Tim, Chimunda, Lorraine, Thompson, Teena, Maguire, Wendy, Chaboyer, Stacey, Watts, Marion, Mitchell, Madeleine, Powell, India, Lye, Leanne, Parsons, Nerilee, Baker, Claire, Reynolds, Amy, Thompson, Kristy, Masters, Kellie, Sosnowski, Lynette, Morrison, Gavin, D Leslie, Ramanathan, Lakshmanan, Alexis, Tabah, Wendy, Brown, Sharon, McDowell-Skaines, Andrea, Mclucas, Chris, Smith, Mandy, Tallot, Sarah, Jones, Michelle, Barakat-Johnson, Thomas, Leong, Rand, Butcher, Kerrie, Martin, Philipp, Douschan, Dirk von Lewinski, René, Schmutz, Uta, Kolussi, Fatema, Salman, Zainab, Ateya, Koen De Decker, Niels Van Regenmortel, Anita, Jans, Patricia, Wijnands, Stefano, Coremans, Patrick, M Honore, David De Bels, Tanja, Depuydt, Caroline, Paillet, Luc-Marie, Jacquet, Walter, Swinnen, Francis, Hannes, Matthia, Mergeay, Stijn Van de Velde, Silvie, Allaert, Pieter, Hoste, Christophe, Borin, Sandrine, Balon, Vincent, Fraipont, Patrick, Biston, Nicolas De Schryver, Thierry, Dugernier, Ilse Van Cotthem, Angelica Olivetto de Almeida, Silvia Angelica Jorge, Delmiro, Becker, Raysa Cristina Schmidt, Evellyn, Oliveira, Aline, Ramalho, Eliane, Mazocoli, Audrey, Fioretti, Elaine, Barros, Leticia, Serpa, Suzana, Bianchini, Ticiane, Campanili, Taís, Pantaleao, Paulo Carlos Garcia, Ana Lucia Vitti Ronchini, Rayanne, Santos, Nurulhuda Binti, A Manap, Sean, Bagshaw, Dominic, Carney, Jon, Davidow, Ella, Rokosh, Andréa Maria Laizner, Samantha, Smith, Megan, Mcquirter, Betty Star Kampayana, René, Favre, Martin, Sills, Julie, Dallaire, Cathy, Becker, Sherissa, Microys, Bonnie, Bowes, Jennifer, Lajeunesse, Rishi, Ghosh, Jacqueline, Baptiste-Savoie, Rose, Raizman, Gabriel, Suen, Noushin, Taghavi, Orla, Smith, Clare, Fielding, Julieta, Canales, Pia, Molina, Javiera, Chaparro, Maria Idalia Sepulveda, Matias Jesús Flamm Zamorano, Pamela, Rocha, Ximena, Villanueva, Paola, Araya, Meneses, Dayan, Fernando, Avalos, Xiaohan, Li, Liu, Yu, Xinxia, Li, Xiaoyan, Chen, Zhixia, Jiang, Jing, Yang, Jingfang, Chen, Lei, Yang, Kefang, Wang, Jie, Gao, Xiuhua, Fang, Ronghua, Zhao, Xinhua, Xia, Hongmei, Liu, Jing, Li, Haiyan, Wang, Gen, Meng, Yanhong, Di, Damei, Wang, Rong Hua Zhao, Li Ping Hu, Peipei, Xu, Qing Feng Jiao, Hai Yun Wang, Chun Jie Xia, Yan, Liu, Mei, Ye, Yan, Wan, Wenmei, Wang, Yajun, Ding, Aiua, Ren, Yan, Gao, Qi, Li, Guifang, Du, Yanling, Shen, Yanming, Ding, Ning, Li, Cui, Yuan, Lei, Tan, Qiang, Lin, Hailing, Guo, Howe, Yan, Xiao, Xu, Wei, Zhang, Jinxian, Liang, Libing, Zhang, Eryun, Tian, Qian, Zhao, Lin, Insu, Jingwen, Dong, Yanmei, Gu, Ying, Liu, Lina, Zhao, Wei, Wang, Hongmei, Qiao, Lili, Tuo, Mengmeng, Lv, Jin Yu Zhu, Jifen, Zhu, Ying, Wei, Man, Liu, Yin, He, Jiyin, Cheng, Jin, Liu, Jia, Na, Dongfang, Wei, Qing, Li, Xiaoying, Wu, Huan, Duan, Dongliang, Lin, Qiong, Liang, Xiaofang, Luo, Yunfeng, Xiong, Rong Fen Huang, Jing, Fu, Tao, Zan, Man, Ye, Zeya, Shi, Yanfei, Long, Yang, Lei, Xiaodi, Liu, Chen, Yumei, Lingling, Wang, Yali, Zhang, Yan, Xu, Cheng, Wang, Zhijuan, Chengxia, Sun, Jinhui, Song, Yingli, Wang, Xiumei, Liu, Yupeng, Liu, Yuxia, Yuan, Qingping, Huang, Fengling, Yang, Yun, Wu, Xianping, Luo, Xiaowu, Bai, Hong, Zheng, Min, Song, Yue, Sun, Zhangshuangzi, Li, Feifei, Luo, Miao, Liu, Li Chuntang Li, Xinjian, Li, Guiping, Zhang, Lina, Xiao, Tingting, Yu, Guangyuan, Gao, Wei, Wei, Fanglan, Wang, Ting, Han, Tingting, Li, Zeng, Qi, Jing Mei Zeng, Yan, Long, Fuqun, Pan, Jing, Wang, Guoxue, He, Haiyan, Chen, Feifei, Zhang, Chao, Yu, Gao, Chunhua, Xiuying, Yao, Dongmei, Bai, Liu, Lu, Xuelian, Xu, Yan, Wang, Xuejuan, Liang, Zhang, Na, Aizhi, Zhang, Xiaochun, Hu, Hui, Zhang, Ruixia, Wang, Poon Shing Tak, Sung Wai Ho, Qun Xia Jiang, Xinran, Ding, Liu, Hong, Limei, Miao, Zhaoxia, Feng, Liping, Huang, Juan, Wu, Yuping, Wang, Jiye, Guo, Baoke, Zhang, Chaoqun, Ma, Han, Yu, Congcong, Liu, Min, Ding, Linlin, Luan, Jing, Zheng, Shanshan, Lv, Shumin, Jiang, Wenzhen, Cao, Xiujuan, Xue, Guangyan, Liu, Xiyan, Wei, Youru, Jiang, Zhiru, Yao, Gao, Li, Jinhua, Li, Wenwen, Zhao, Mei, Jiang, Junping, Hao, Jing, Zhang, Caiju, Song, Feifei, Chen, Shuhui, Wang, Lili, Hu, Deyan, Cao, Jianhong, Wan, Xiaomin, Wang, Hongyan, Shao, Zhenxia, Zhang, Xia, Cui, Jingyu, Liu, Lijuan, Zhao, Xingguo, Li, Limei, Fan, Ling, Zhang, Min, Yu, Biyan, Li, Chunxia, Li, Ling, Liu, Xuelian, Liu, Wenmin, Chen, Yan, Li, Zhang, Zhigang, Yuchen, Wu, Chenghau, Mu, Guoyan, Zhu, Fan, Yang, Qi, Bo, Ling, Li, Meili, Chen, Jing Hua Jiang, Hai, Yin, Xuelian, Pang, Yue Ying Gong, Shunzhu, Yang, Xiaoli, Yan, Xianhong, Zheng, Dehong, Lei, Lei, Lei, Yinhua, Guo, Lihong, Liu, Jing, Yu, Wei, Sun, Aiping, Bi, Weiwei, Li, Yang, Wu, Ji, Li, Dongshu, Ni, Zijing, Wu, Bing, Song, Qin, Fei, Yang, Xiaoyan, Qiong, Ran, Xixi, Li, Xueping, Jiao, Hua, Ji, Sun, Zhiping, Hong, Ma, Jianhong, Mu, Yanhua, Hao, Yin, Li, Ying, Wang, Caihong, Hui, Wenjie, Ju, Yuxia, Huo, Yuxia, Wang, Lei, Chen, Yan, Yan, Qingli, Zhao, Hongjuan, Chen, Guijun, Bao, Ying, Cao, Hong, Li, Hong, Zhang, Ying, Zhang, Lina, Xu, Jia, Guixiang, Ying, Li, Hui Min Zhao, Xia, Huang, Zhaoxing, Dai, Yanman, Jian, Hongsu, Zhang, Zhixia, Tian, Zu Qing Cao, Miao, Li, Yang, Liu, Fei, Ouyang, Fuying, Ma, Wangyan, Jin, Liuyan, Ge, Shifen, Wu, Weilian, Yuan, Tianfei, Chen, Guanxiu, Shi, Zhihong, Chen, Kewei, Liu, Xue, Lin, Yuemen, Ly, Sun, Lijuan, Xiao Fang Tian, Shuo, Wang, Zhangxia, Feng, Xiaozhe, Liu, Yunchun, Dong, Jundi, Zhang, Nie, Bocui, Guoxian, Wang, Yingjuan, Zhao, Xiaojun, Wu, Qiao, Yang, Rongjun Ling Hu, Xue Qin Li, Zhu Jun Yu, Yanlan, Yao, Xiaoqiong, Deng, Yan, Xiao, Yan, Xie, Yanping, Yang, Huai, Yang, Yuming, Zhou, Zhuqing, Li, Min, Xiao, Yongxia, Yang, Yani, Tian, Luz Marina Silva Gama, Juan Sebastian Hernandez, Nestor, Caicedo, Jorge, Marin, Maria-Elena, Ochoa, Monica, Gomez, José, Rojas-Suarez, Jeniffer, Gonzalez, Amylkar José Garay Reyes, Edwin, Chapeta, Estefania, Orozco, Ina, Filipović-Grčić, Anita, Vuković, Suzana, Pečenković, Aleksandar, Šuput, Gordana, Zivanovic-Posilovic, Armanda, Bozena, Nikolina, Udiljak, Morena, Milic, Renata Curic Radivojevic, Slobodan, Mihaljevic, Marijana, Matas, Dinko, Tonkovic, Hemena, Čuljak, Ivana, Herceg, Gordana, Pavlisa, Milena, Dobric, Tatjana, Beker, Višnja Nesek Adam, Tanja, Goranovic, Chrysanthos, Markoulias, Mina, Mathaios, Maria, Mylordou, Eleni, Achilleos, Pavlina, Kleanthous, Veronika, Kotanidi, Maria, Foka, Iwy, Charalabous, Anna, Alexandrou, Marios, Georgiou, Artemis, Patsalos, Sofia, Zepoy, Constantina, Constantinou, Petr, Piza, Tomas, Vymazal, Elisabeth, Wiborg, Louise, Bruhn, Karin, Kaasby, Karin Rehnholt Pedersen, Sanne, Mikkelsen, Marie, Collet, Anne, Langvad, Hanne, Andresen, Susanne, Fischer, Inger Ebbesen Kjærgård, Britta, Jepsen, Birthe, Husted, Morten, Bestle, Anne Marie Kodal, Tina Charlotte Bitsch Hansen, Anne Sofie Bomholt Pedersen, Tina Damgaar Thomsen, Anisette, Hoegenhaven, Mette, From, Tine Melgaard Frandsen, Grit, Henning, Anja, Hansen, Inger Abildgaard Bliksted, Luis Mario Tamayo, Pedro, Mogrovejo, Carolina, Palaez, Diego Rolando Morocho Tutillo, Cintia Valencia Hurtado, Maria Fernanda García, Diana, Alvarez, Fausto, Guerrero, Alexandra, Vasquez, Martin, Kütimets, Kadri, Tamme, Eneli, Anvelt, Lomangisi, Dlamini-Sserumaga, Carita, Löfqvist, Virpi, Lusenius, Outi, Kauppi, Jenni-Katarina, Sakki, Tarja, Tervo-Heikkinen, Ulla, Kesti, Merja, Merilainen, Elina, Karjula, Minna, Peltomaa, Auli, Palmu, Maarit, Ahtiala, Maija Anniina Valta, Hervé, Mentec, Gaëtan, Plantefève, Guillaume, Besch, Sébastien, Pili-Floury, Stanislas, Ledochowski, Marc Danguy des Déserts, Christophe, Giacardi, Cédric, Daubin, Audrey, Massard, Yann Le Guen, Agnès, Blanc, Simon, Mandaroux, Silvia Calvino Günther, Prune, Avogadro, Anthony, Radavidson, Jean, Turc, Sébastien, Jochmans, Hervé, Quintard, Laetitia, Boyer, Cédric, Bruel, François, Philippart, Philippe, Montravers, Enora, Atchade, Nadine, Flessel, Benoît, Chinardet, Léa, Soulisse, Cindy, Pillard, Delphine, Ngo, Benjamin, Bongiorno, Nathalie, Heitzler, Virginie, Souppart, Nathalie, Gautheret, Jean-Francois, Timsit, Fatiha, Essardy, Muriel, Fartoukh, Daisy, Mehay, Fabienne, Etourneau, Jean-Christophe, Farkas, Pascal, Beuret, Gabriel, Preda, Etienne De Montmollin, Vincent, Castelain, Ulrich, Jaschinski, Monika, Rothenfusser, Detlef, Kindgen-Milles, Thomas, Dimski, Christine, Fiedler, Tobias, Heinicke, Patrick, Meybohm, Tobias, Schulze, Marc, Bota, Sabrina, Pelz, Tobias, Odenthal, Martin, Christ, Kathrin, Bösl, Achilleas, Chovas, Sebastian, Stehr, Philipp, Simon, Sarah, Grotheer, Sebastian, Schüppel, Stefan, Schaller, Lea, Albrecht, Andeas, Stübner, Stephan, Graeser, Nina, Kolbe, Martina, Lausch, Anja, Diers, Ulf, Guenther, Reimer, Riessen, Martin, Roller, Irene Pearl Osei, Anita-Chrysolyte, Kusi-Appiah, Yakubu, H Yakubu, Belinda, Guadi-Gosh, Christos, Dragoumanis, Christos, Christofis, Nikolaos, Kazakos, Styliani, Bastani, Charalampos, Martinos, Vasileios, Bekos, Metaxia, Papanikolaou, Theonymfi, Papavasilopoulou, Anna, Efthymiou, Vasiliki, Chantziara, Anna, Kyriakoudi, Nikolaos, Kakaras, Chrisi, Diakaki, Aikaterini, Flevari, Charikleia, Nikolaou, Kounougeri, Katerina, Lamprini, Avramopoulou, Kyriaki, Tsikritsaki, Georgios, Gkiokas, Eirini, Pantiora, Chrysostomos, Katsenos, Eirini-Chysovalanto, Patsiou, Paraskevi, Alexandropoulou, Ioannis, Koutsodimitropoulos, Epaminontas, Farmakis, Konstantina, Nestora, Marinos, Chatzis, Eumorfia, Kondili, Stella, Soundoulounaki, Ourania, Mousafiri, Dimitra, Lepida, Antonia, Liarmakopoulou, Georgios, Papathanakos, Mrina, Oikonomou, Panagiotis, Ioannides, Dimitrios, Papadopoulos, Ioannis, Staikos, Maria, Stafylaraki, Bogdan, Raitsiou, Konstantinos, Mandis, Ifigenia, Ravani, Styliani, Kourelea, Aikaterini, Efthimiou, Giannoula, Thoma, Apostolos, Bakas, Konstantinos, Psarulis, Souzana, Anisoglou, Eirini, Papageorgiou, Evangelia, Michailidou, Thomai, Tholioti, Athena, Lavrentieva, Evdokia, Sourla, Anastasia, Spyropoulou, Nikolaos, Pantelas, Kristina Mariana Matei Stalika, Ioannis, Georgakas, Antigoni, Karathanou, Syragoula, Tsikriki, Aikaterini, Dimoula, Sofia, Kanakaki, Aristeidis, Vakalos, Konstantinos, Pagioulas, Judy Enamorado Enamorado, Gabor, Nardai, Fatime, Hawchar, Asbjorn, Blondal, Brynja, Rygvadottir, Rannveig, J Jonasdottir, Hrönn, Birgisdottir, Bhagyesh, Shah, Shuchi, Kaushik, Swagata, Tripathy, Mukta, Singh, Sonika, Agarwal, Manish, Gupta, Meraj, Ahmad, Kishore, Mangal, Vaibhav, Bhargava, Vilas, Kushare, Simant, Jha, Lakshay, Bhakhtiani, Manoj, Kamal, Arvind, Baronia, Ade, Susanti, Mayang Indah Lestari, Zulkifli, Zulkifli, Windu, Baskoro, Farid, Zand, Fatemeh, Zarei, Ata, Mahmoodpoor, Farshad, Heidari, Fateme, Jafaraghaee, Aidan, O'Shea, Fiona, O'Shea, Caroline, O'Donnell, Geraldine, Craig, Gerry, Fitzpatrick, Lisa, Dunne, Jennifer, Hastings, Brian, Marsh, Caitriona, Cody, Elizabeth, Campbell, Deirdre, Doyle, Michelle, Pacturanan, Christine, Sheehan, Annette, Carey, Charlotte, Carter, Regina, Mulvey, Damien O'Connell Rosemary Finn, Catherine, Motherway, Amy, Walsh, Jennifer, Kehoe, Shella, Delossantos, Jennifer, Lalor, Siobhan, O'Nuallain, Helena, Behan, Sandra, Mcpherson, Ailesh, Corcoran, Patricia, Gordon, Glenda, Rooney, Dassy, Levy, Mazal, Azencot, Vladimir, Gurevich, Alinoy, Lavy, Valentina, Bendelari, Romina, Marconi, Antonio, Barone, Chiara, Gatti, Andrea, Giampaoletti, Cinzia, Borgognoni, Davide Massimo Ghioldi, Arena, Raimondo, Giacomo, Castiglione, Anna Vita Bruno, Giorgia, Rubulotta, Antonella, Mo, Amalia, Corso, Salvatore, Girianni, Andrea, Bruni, Eugenio, Garofalo, Salvatore Maurizio Maggiore, Alessandro Di Risio, Italo, Calamai, Rosario, Spina, Savino, Spadaro, Carlo Alberto Volta, Antonella, Cotoia, Lucia, Mirabella, Laura, Maulicino, Giancarlo, Abregal, Maria, Donvito, Paolo, D'Ambrosio, Filipo, Binda, Ileana, Adamina, Alessandro, Galazzi, Alessandra, Negro, Rosanna, Vaschetto, Fabio, Capuzzi, Margherita, Boschetto, Lucia, Stivanello, Luciano, Bonaccorso, Chiara, Megna, Pasquale, Iozzo, Antonino, Rizzo, Giovanni, Scire, Maria Rosa Taibi, Francesca Paola Tranello, Antonio, Manzo, Lidia, Traina, Beatrice, Pastore, Attilio, Quaini, Gian Domenico Giusti, Gloria, Montaldi, Federica, Piergentili, Federica, Mancini, Simona, Casaioli, Francesco, Uccelli, Fabio, Guarracino, Adriana, Onelli, Valentina Di Gravio, Maria, Cossu, Oliva, Matrona, Monica, Rocco, Daniela, Alampi, Federica, Dellafiore, Flavia, Ranalli, Matteo, Bossolasco, Elisabetta, Brizio, Pina, Migliorino, Paolo, Cortellazi, Moris, Rosati, Francesco, D'Ambrosio, Catia, Quagliotto, Erik, Roman-Pognuz, Alberto, Peratoner, De Rosa, Silvia, Marina Alessandra Martin, Francesca De Sanctis, Paolo, Ciorba, Patrick, Toppin, Hyacinth, Harding-Goldson, Shunsuke, Taito, Nobuaki, Shime, Ryohey, Yamamoto, Fumiya, Kanda, Akemi, Hirao, Moritoki, Egi, Ayako, Noguchi, Satoru, Hashimoto, Umeda, Aya, Hideaki, Sakuramoto, Akira, Ohuchi, Jun, Kataoka, Kumi, Maruyama, Izumi, Nakayama, Yoshimasa, Nishime, Koji, Fujimoto, Kenji, Takahashi, Mayumi, Tsujimoto, Masako, Shimizu, Eunice, Tole, Malcolm, C Correia, Je Hyeong Kim, Sunghoon, Park, Kyung Chan Kim, Jonghyun, Baek, Jung-Min, Bae, So Young Park, Tai Sun Park, Heung Bum Lee, Seung Yong Park, Jisoo, Park, Lee, Yeon-Joo, Cho, Young-Jae, Sang-Miin, Lee, Kyeongman, Jeon, Seok Chan Kim, Jongmin, Lee, Hyun Keun Chee, Jin Won Huh, Yun Su Sim, Junghyun, Kim, Youjin, Chang, Jong-Joon, Ahn, Byung Ju Kang, Won-Yeon, Lee, Seok Jeong Lee, Nehat, Baftiu, Ivasr, Krastins, Sonia, Stiban, Michel El Feghaly, Elie, Gharios, Marie, Merheb, Mohamed, Benlamin, Ala, Khaled, Wesal Ali Belkhair, Majd, Tabib, Firas, Ashour, Ahmed, Elhadi, Osama Wanees Emhemid Tababa, Taha, Khaled, Soad Imhmed, R Alkhumsi, Abdualhamid, I Alshrif, Ahmed Ali Aboufray, Aya, Alabuzidi, Ahmed Ramadan Triki, Mala, Elgammudi, Hajer Ben Zahra, Enas, Soula, Maram Milud Said Al-Alawi, Hazem, Ahmed, Mohamed Abdurazzag Ali Ghula, Saulius, Vosylius, Lucie, Mouton, Touraj, Rastegar, Claude, Sertznig, Gilles, Martin, Christian, Theisen, Christian, Ferretti, Fränk, Gils, Marc, Gallion, Asmah, Zainudin, Laila Kamaliah Kamalul Bahrin, Shanti Rudra Deva, Azmin Huda Abdul Rahim, Sherliza, Wahab, W Nazaruddin, W Hassan, Wan Nasrudin Wan Ismail, Mohd Nazri Ali, Tien Meng Khoo, Noryani Mohd Samat, Jenny May Geok Tong, Nik Azman Nik Adib, Mohd Basri Mat Nor, Shanthi, Ratnam, Nahla, Ismail, Siti Rohayah Sulaiman, Kit Weng Foong, Anita, Alias, Ngu Pei Hua, Jorge Macias Zermeno, Daniel, Blanco, Karely, Duran, Claudia Lizbeth Lopez Nava, San Juan Roman Nandyelly, Luis Alejandro Sanchez-Hurtado, Brigitte, Tejeda-Huezo, Mario Del Moral Armengol, Luis Pedro Ambriz Nava, Jorge Guerra Herrera, Gilberto Felipe Vazquez de Anda, Humberto, Gallegos-Perez, Nancy, Hernandez-Sanchez, Lucia, Hernandez-Ponce, Luis, Gorordo-Delsol, Marcos, Hernandez-Romero, Saira, Gomez, Fernando, Molinar, Silvio, A Ñamendys-Silva, Juan, P Romero-Gonzalez, Daira, Gonzalez, Antonio, Landaverde, Miguel Ángel Sosa, Berenice, Navarro, José Ivan Rodriguez de Molina Serrano, Sergio Reyes Iburrigarro, Alejandro, Ibarra, Joaquin, Aguirre, Mayra, Martinez-Gonzalez, Nayeli Rocio Cañas Padilla, Ana Alícia Velarde Pineda, Missael Vladimir Espinoza Villafuerte, María Ocotlan Gonzalez Herrera, Battsetseg, Baasanjav, Abdelhamid, Hachimi, Mina, Elkhayari, Tarek, Dendane, Nisha Bhandari Subedi, Sabina Dhakal Pathak, Meena, Manandhar, Laura Van Gulik, Mark Van Den Brink, Peter Van Vliet, Benjamin, Gerretsen, Lettie Van Den Berg, Marina De Haan, Binny, Tuinstra, Paul, Kuijpers, Jennifer, Reijntjens, Jan Wytze Vermeijden, Martin, Rinket, Margijske, Vanroest, Auke, Reidinga, Bert, Loef, Willem, Dieperink, Marisa, Onrust, Tom, Dormans, Laura, Bormans, Matty, Koopmans, Rik, T Gerritsen, Arlette Van Den Elst, Mirjam, Evers, Oscar, Oiting, Rob, Wilting, Bart, Ramaker, Mark van der Kuil, Jan-Willem, Fijen, Lenneke, Haas, Jasper, Haringman, Lynette, Newby, Eileen, Gilder, Danielle, Hacking, Rica, Dagooc, Rima, Song, Hansjoerg, Waibel, Frances, Dawn, Jackie, Rapley, Llesley, Chadwick, Carmel, Chapman, Petra, Crone, Jonathan, Albrett, Peter, Marko, Jennifer, Goodson, Troy, Browne, Richard, Whitticase, Cheryl, Davidson, Harriet, Judd, Daniel, Owens, Tonia, Onyeka, Innocent, Ugwu, Rose, Ilesanmi, Prisca Olabisi Adejumo, Afolabi, Owojuyigbe, Anthony, Adenekan, Stella, Uba, Christiana, Chime, Deborah, Jibrin, Babangida John Sankey, Oyebola, Adekola, Simeon, Olanipekun, Mirjana, Shosolcheva, Vanja, Gievski, Andrijan, Kartalov, Filip, Naumovski, Biljana, Kuzmanovska, Angela, Trposak, Zaneta, Bogoevska-Miteva, Rodney, Rosalia, Brita Fosser Olsen, Britt, Sjobo, Karianne Dale Jensen, Drammen, Sykehus, Birgitte Fosser Johansen, Esben, Straede, Edda, Johansen, Inger Johanne Finnstrom, Annette, Toellefsen, Hege, Ostenjo, Hege, Bjorgen, Bjorn, Bratsberg, Elin, Kristoffersen, Elin Mari Skorstad, Siri, Hansen, Sylvi, Vullum, Gro Anne Lunde, Wenche, Arntsen, Mette, Lund, Gro Ringstad Akselsen, Kristina Reinertsen Monstad, Ane, Stenset, Hanne, Haugom, Bjoern, Monsen, Lisa, Høgvall, Siw, Trudvang, Britt, Galaaen, Siv Karin Malmin, Marit Hildegunn Andersen, Rita Foss Hargott, Yvonne, Andersen, Elin, Steffenak, Marit, Nyhus, Barbro, Meland, Madiha, Hashmi, Noelia, Rivas, Elizabeth, Maidana, Alberto de Jesús Ortiz, Dolly Mabel Bordon Cabral, Marcelo, Simi, Cesar, Aponte, Juan Carlos Rivas, Sirley, Gill, Amilcar, Garcia, Gloria, Alvarenga, Laura, Cespedes, Hugo, Perez, Maria Liz Moreira, Fidelina, Canete, Roberto, Gonzalez, Natalia, Monges, Mary, Coman, Marcelo, Pederzani, Natalia, Franco, Ferdinand, Aganon, Regina, Martinez, Debbie, Noblezada-Uy, Chris Gerome Ellazar, Franklin Dean Cerezo, Jose Emmanuel Palo, Cristal April Jane Aperocho, Michael, Isanan, Marta, Tubacka, Przemyslaw, Jasiewicz, Miroslaw, Czuczwar, Michal, Borys, Aleksandra, Gutysz-Wojnicka, Lidia, Glinka, Ryszard, Gawda, Jan, Bilawicz, Paula, Cabrita, João, Vieira, Margarida Ferreira Figueiredo, Cristiana Mota Pinheiro, Nelson, Antunes, Laura, Pedro, Fatima, Ferreira, Isabel, Parente, Maria, Varela, Fatima, Fernandes, Claudia, Martins, Abel, Viveiros, Raquel, Cavaco, Clara Santa Rita, Sofia, Dias, Ana Margarida Feranandes, Pedro, Silva, Catarina, Nunes, João, Cabral, Filpe, Pires, Hilaryano, Ferreira, Jacinta, Santos, Vitor Manuel Vaz Pinto, Bruno Miguel Bispo, Amelia, Ferreira, Elena, Molinos, Estevão, Lafuente, Ricardo, Gregorio, Humberto, Costa, Ângela, Lima, Susana, Ferreira, Vanda, Seromenho, Eulália, Luis, Idália, Valerio, Helena, Cesar, Ana, Tavares, Ahmed Subhy Alsheikhly, Saeed, Mahmood, Catalin Traian Guran, Alida, Moise, Daniela Carmen Filipescu, Mihail, Luchian, Mihai, Popescu, Monica Adriana Scutariu, Cristina, Petrisor, Natalia, Hagau, Ioana, Grigoras, Tatiana, Patrichi, Vitaly, Gusarev, Alexandra, Pivkina, Vladimir, Kulakov, Olga, Ignatenko, Julia, Kovaleva, Trina, Zhivotneva, Marina, Zhedaeva, Nikita, Matiushkov, Olga, Ershova, Natalya, Egorova, Victoria, Khoronenko, Danil, Baskakov, Dmitry, Sergeev, Michael, Piradov, Liudmila, Grishina, Marat, Magomedov, Evgeniy, Zuev, Uri, Gorokhovatsky, Anna, Leonova, Liudmila, Fadeeva, Vladislav, Belskiy, Dmitriy, Galishevskiy, Nadezhda, Zubareva, Maksim, Tribulev, Oksana, Zueva, Alexander, Kiselev, Nikolaj, Kamenshchikov, Ekaterina, Tokareva, Maxim, Petrushin, Irina, Starchenko, Isaac, Nshimyumuremyi, Jerome, Muhizi, Egide, Buregeya, Josue, Nzarora, Amer, Assiri, Maie Salem Ebaid, Ghaleb, Almekhlafi, Yasser, Mandourah, Jelena, Velickovic, Dejan, Veličković, Bojan, Jovanovic, Adi, Hadzibegovic, Branislava, Stefanovic, Vanja, Misic, Vesna, Bumbasirevic, Marija, Rajković, Milena, Stojanovic, Srđan, Gavrilovic, Maja, Stanojević, Aktham, Yaghi, Anton, Turčan, Peter, Firment, Garri, Slobodianiuk, Daria, Rabarova, Danca, Lančaričová, Janko, Vlaovic, Matjaž, Groznik, Milica, Lukic, Janja, Perme, Maja, Sostaric, Nejc, Umek, Tomislav, Mirkovic, Simon, Dolenc, Misa, Fister, Nika, Zorko, Andrej, Markota, Nomhle Princess Yeni, Phumele, Jali, Shelley, Schmollgruber, Muhommed Ridwaan Syed, Nivisha, Parag, Robert, Wise, Maria, Galiana, José Alejandro Navarro, Ana María De Pablo, Patricia, Albert, Pilar, Martinez, Yolanda, Mendiara, Barbara, Garcia, Ana Alabart Llinas, Marilyn, Riveiro, Elisabet, Gallart, Alba, Riera, Miquel, Sanz, Swagotika, Salo, Miguel Angel Gimenez Lajara, Montserrat Venturas Nieto, Rosa, Garcia, José Manuel Garcia Pena, Maria Carmen Gorgolas, Maria Aranzazu Isasi, Rafael, Sierra, Federico, Gordo, Isabel, Conejo, Vicent, Salvà-Costa, Carolina, Garzón-Tovar, Sara, Lospitao, Rafael, Gonzalez, Pedro, Gutierrez, Mercè, Girona, Jordi, Adamuz, Pablo Garcia Olivares, José Peral Gutierrez de Ceballos, Celia, Tirado, Irene De Wit, Ana Belén Curto Polo, Maria Del Mar Diaz Salcedo, Javier, Ripolles-Melchor, Eugenio, Martinez-Hurtado, Jorge Duerto Alvarez, María Luisa Bravo Arcas, Juan Ignacio Torres Gonzalez, Ana Belén Sánchez de la Ventana, Pablo Lopez-Arcas Calleja, Raquel Garcia Alvarez, Purificacion Sanchez Zamora, Alvaro Ortega Guerrero, Rosario, Cosano, Jonathan, Perez-Vacas, Margarita, Campos-Perez, Emma Moreno Barreiro, Losune Cano Sanchez, Monica Garcia Diaz, Raquel, Jimenez, Lorena Del Rio Cabajo, Daniel Sancho Muriel, Helena Fernandez Alonso, Ana Wensell Fernández, Isabel Santín Piñan, Guillermo Muñiz Albaiceta, Maria Cristina Iglesias Fernandez, Francisco Javier Saenz Abos, Pablo, Monedero, Ramon Molina Chueca, Lydia Gallego Aguirre, Silvia Call Manosa, Carmen Partera Luque, Neus, Calpe, Monica Recio Losilla, Meritxell Tapia Fores, Olga, Farre, Oscar, Fernandez, M Del Rosario Villar Redondo, Donaldo, S Arteta Arteta, Maria Angeles Hurtado Sanchez, Cristina Paños Espinosa, Laura Martinez Reyes, Laura Claramunt Domenech, Carmen Velasco Guillén, Josep Trenado Alvarez, Mercedes Del Cotillo, Jesus Emilio Barrueco-Francioni, Belen Burgos Conde, Maria Pilar Sogues Blanco, Maria Luisa Blasco, Ana Isabel Clement, Clara, Hurtado, Luz Coronado Sanz, David, Perez-Torres, Estefanía, Prol-Silva, Jorge, Pereira, Iván Areán González, Anastasio Espejo Cano, Cesar Rodriguez Nuñez, Inmaculada Lorenzo Fernadez, Alejandra Azahara Marguello Fernandez, Rosa Del Bosque Diez, Badiola, Hilario, Begoña, Zalba-Etayo, Ana, Pascual-Bielsa, Preveen, Banwarie, Dick, Nahar, Alisha van Axel, Naraindath, N Boedjawan, Erika Backlund Jansson, Ann-Sofie, Malvemyr, Lotta, Johansson, Ulla, Sandberg, Catarina, Tingsvik, Gunilla, Mattsson, Gun, Löf, Martin, Spångfors, Mona, Ringdal, Sebastian, Geijer, Lotti, Orvelius, Mia, Hylen, Caroline, Lagerhäll, Eva, Åkerman, Viveca Hamback Hellkvist, Ulrica, Mickelsson, Ewa, Wahlbom, Ing-Marie, Larsson, Ewa, Wallin, Filippo, Boroli, Solenne, Ory, Margaret Lynn Jong, Alexander, Dullenkopf, Martin, Lang, Yvan, Fleury, Marianne, Maus, Nawfel, Ben-Hamouda, Anne, Fishman, Mei Yu Hsu, Shu Chuan Chang, Konlawij, Trongtratul, Chaiwut, Sawawiboon, Sunthiti, Morakul, Bodin, Khwannimit, Keevan, Singh, Dale, Ventour, Dianne, Figaro-Barclay, Sasha, Sankar-Maharaj, Mhamed Sami Mebazaa, Salma, Kamoun, Souheil, Elatrous, Lamia, Besbes, Fekri, Abroug, Walid, Naija, Youssef Zied Elhechmi, Walid, Sellami, Zied, Hajjej, Takoua, Merhabene, Imen, Talik, Ozlem Ozkan Kuscu, Ozcengiz, Dilek, Avşar, Zerman, Hayriye Cankar Dal, Sema, Turan, Semih, Aydemir, Hakan, Yilmaz, Duygu Kayar Calili, Seval, İzdes, Melike, Cengiz, Ayça, Gümüş, Banu, Taşdemir, Ali, Kağnıcı, Mustafa, Ay, Serap Avcı Ay, Gulbahar, Caliskan, Turkay, Akbas, Abidin Oner Balbay, Serdar, Efe, Volkan, Inal, Gülseren, Elay, Pınar, Karabacak, Boğaç, Özserezli, Evren, Şentürk, Oktay, Demirkiran, Suha, Bozbay, Elif, Erdogan, Mustafa, Akker, Nebia, Peker, Asu, Ozgultekin, Sibel Ocak Serin, Can, Turan, Gulsah, Karaoren, Senay, Goksu, Sait, Karakurt, Huseyin, Arikan, Fethi, Gül, İsmail, Cinel, Iskender, Kara, Hasan Nabi Undar, Yesim Serife Bayraktar, Jale Bengi Çelik, Murat Emre Tokur, Demet Tok Aydin, İsmail, Yildiz, Beysim, Özcan, Başar, Erdivanli, Ahmet, Eroglu, Devrim, Akdağ, Nurdan, Ünlü, Adonis, Dungca, Ashwaq, Ali, Bindu, Thankamma, Paul Eric Reyes, Sini, John, Ajitha, Rajendran, Fatima Kasem El Ahmad, Kathleen Ann Smiley, Susanna, Hojden, Mia Thorning Miller, Vishnu Das Sasidharan Nair, Maria Gracia San Antonio, Khaled Al Qawasmeh, Sabah Abu Shawish, Hilary, Twiggs, Ines, Rosado, Volodymyr, Babych, Faye, Morren, Charlotte, Young, Nicola, Vaughan-Jones, Stephanie, Harris, Karen, Burns, Carmel, Georgiev, Rosina, Shayamano, Ian, Kerslake, Peter, Creber, Ana, Vochin, Catherine, O'Brien, Paul, Caddell, Samantha, Hagan, Mandy, Hughes, Tomasz, Torlinski, James, Sherwin, Santhana, Kannan, Amber, Markham, Richard, Lebon, Jason, Cupitt, Julius, Cranshaw, Nigel, White, Victoria, Marriott, Wendy, Milner, Casiano Barrera Groba, Joao, Azoia, Petra, Polgarova, Shaly, George, Ritoo, Kapoor, Ceri, Lynch, Nathalie, Fox, Karen, Cranmer, Natalie, Fox, Thomas, Llewellym, Kelly, Matthews, Louise, Maltby, Jowena, Ibao, Karen, Boulton, Rachel, Jarman, Karen, Baxter, Ashok Sundai Raj, Arif, Moghal, Joanne, White, Suzanne, Barrowcliffe, Mark, Pulletz, Vaarisan, Ganeshalingam, Rosaleen, Baruah, Carole, Boulanger, Helen, Baker, Justin, Woods, Poe Poe Ei, Vongayi, Ogbeide, Paul, Hayden, Jennifer, Hughes, Madhu, Balasubramanian, Armorel, Salberg, Rajnish, Saha, Dagmar, Holmquist, Claire, Derbyshire, Neil, Smith, Elizabeth, Stones, Jane, Ademokun, Monica, Popescu, Maria Schofield Legorburo, Samantha, North, Carole, Brett, Helen, Jaundoo, Jayne, Craig, Simon, Whiteley, Clare, Howcroft, Liz, Wilby, Peter, Delve, David, Shaw, Karen, Williams, Ingeborg, D Welters, Jane, Mcmullen, Stephen, Brett, Leah, Flores, Treiza, Trueman-Dawkins, Mae, Templeton, John, Adams, Catherine, Smith, John, Prowle, Heather, Byers, Andrea, Mcdonnell, Bernd Oliver Rose, Rosie, Reece-Anthony, Luis, Mendes, Marcela, Vizcaychipi, Rhian, Bull, Grace, Lacaden, Eleanor, Santiago, Carlos Castro Delgado, Sarah, Farnell-Ward, Elaine, Thorpe, Justine, Somerville, Anne, Williams, Donna, Cummings, Helen, Derrick, Sarah, Brumwell, Claire, Randell, Nicola, Mccann, Emma, Aves, Gillian, Berry, Tamas, Szakmany, Una, Gunter, Paul, Pulak, Nikki, Sarkar, Kerry, Wright, Vitor, Gomes, Jones, Jo, Ruth, Palfrey, Julie, Camsooksai, Abby, Lewis, Antony, Eneas, Ascanio, Tridente, Louise, Barr, Beverley, Thomas, Emma, Parkin, Daniel, Horner, Christian, Frey, Suzanne, Bench, Rachel, Baumber, Phil, Broadhurst, Matthew, Jackson, Lynne, Williams, Michele, Clark, Jonathan, Paddle, Sarah, Bean, Sarah, Buckley, Christopher, Palfreeman, Sophie, Liu, Nicola, Allison, Ben, Attwood, Penny, Parsons, Victoria, Houghton, Sarah Jane Turner, David, Higgins, Egidija, Bielskute, Nicola, Horrigan, Reni, Jacob, Karen, Habgood, Ahmed, Zaki, Amy, Collins, Jenny, Lord, Charalice, Ramiro, Agnieszka, 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European Society of Intensive Care Medicine (ESICM) Trials Group Collaborators, Muzha, D., Ribas, A.M., Lipovesty, F., Loudet, C., Coyer, F., Eller, P., Mostafa, N., Honoré, P.M., Telleria, V.M., Smajic, J., Nogueira, P.C., Nafees, KMK, Hentchoya, R., Rose, L., Soledad, J., Lin, F., Cardenas, Y., Reyes, A.G., Sustic, A., Mpouzika, M., Vymazal, T., Jensen, H.I., Aguirre-Bermeo, H., Maddison, L., Valta, M., Calvino-Gunther, S., Bloos, F., Adipa, F.E., Koulouras, V., Enamorado, J., Ágoston, Z., Birgisdóttir, H., Gupta, A., Gurjar, M., Kilapong, B., Hashemian, S.M., Martin-Loeches, I., Benbenishty, J., Cortegiani, A., Fletcher, K., Hayashi, Y., Waweru-Siika, W., Abidi, K., Lee, S.M., Hadri, B., Dolgusevs, M., Abillama, F.F., Jovaisa, T., Thix, C., Elhadi, M., Nor, B.M., Ratnam, S., Mazlan, M.Z., Maiyalagan, S., Sánchez-Hurtado, L., Belii, A., Naranpurev, M., Gautam, P., De Lange, D., Parke, R., Ilesanmi, R.E., Shosholcheva, M., Petosic, A., Lind, R., Ffarcsi, M.H., Bogarin, J., Hernandez, 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A.S., Goller, S., Afonso, E., Larina, E., Labeau, Sonia O. [0000-0003-3863-612X], Afonso, Elsa [0000-0003-0873-0852], Benbenishty, Julie [0000-0002-8488-9649], Blackwood, Bronagh [0000-0002-4583-5381], Boulanger, Carole [0000-0002-1392-6633], Brett, Stephen J. [0000-0003-4545-8413], Calvino-Gunther, Silvia [0000-0003-3586-7205], Chaboyer, Wendy [0000-0001-9528-7814], Coyer, Fiona [0000-0002-8467-0081], Deschepper, Mieke [0000-0001-6797-3147], Honore, Patrick M. [0000-0002-6697-4890], Jankovic, Radmilo [0000-0003-0742-8686], Khanna, Ashish K. [0000-0002-9083-891X], Llaurado-Serra, Mireia [0000-0002-5123-0581], Lin, Frances [0000-0001-8735-5469], Rose, Louise [0000-0003-1700-3972], Rubulotta, Francesca [0000-0001-8644-1728], Saager, Leif [0000-0003-3416-4727], Williams, Ged [0000-0002-7481-2445], Blot, Stijn I. [0000-0003-2145-0345], Apollo - University of Cambridge Repository, Critical Care, Labeau S.O., Afonso E., Benbenishty J., Blackwood B., Boulanger C., Brett S.J., Calvino-Gunther S., Chaboyer W., Coyer F., Deschepper M., Francois G., Honore P.M., Jankovic R., Khanna A.K., Llaurado-Serra M., Lin F., Rose L., Rubulotta F., Saager L., Williams G., Blot S.I., Muzha D., Ribas A.M., Lipovesty F., Loudet C., Eller P., Mostafa N., Telleria V.M., Smajic J., Nogueira P.C., Nafees K.M.K., Hentchoya R., Soledad J., Cardenas Y., Reyes A.G., Sustic A., Mpouzika M., Vymazal T., Jensen H.I., Aguirre-Bermeo H., Maddison L., Valta M., Bloos F., Adipa F.E., Koulouras V., Enamorado J., Agoston Z., Birgisdottir H., Gupta A., Gurjar M., Kilapong B., Hashemian S.M., Martin-Loeches I., Cortegiani A., Fletcher K., Hayashi Y., Waweru-Siika W., Abidi K., Lee S.-M., Hadri B., Dolgusevs M., Abillama F.F., Jovaisa T., Thix C., Elhadi M., Nor B.M., Ratnam S., Mazlan M.Z., Maiyalagan S., Sanchez-Hurtado L., Belii A., 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N.N., Jansson E.B., Malvemyr A.-S., Johansson L., Sandberg U., Tingsvik C., Mattsson G., Lof G., Spangfors M., Ringdal M., Geijer S., Orvelius L., Hylen M., Lagerhall C., Akerman E., Hellkvist V.H., Mickelsson U., Wahlbom E., Larsson I.-M., Wallin E., Boroli F., Ory S., Jong M.L., Dullenkopf A., Lang M., Fleury Y., Maus M., Ben-Hamouda N., Fishman A., Hsu M.Y., Chang S.C., Trongtratul K., Sawawiboon C., Morakul S., Khwannimit B., Singh K., Ventour D., Figaro-Barclay D., Sankar-Maharaj S., Mebazaa M.S., Kamoun S., Elatrous S., Besbes L., Abroug F., Naija W., Elhechmi Y.Z., Sellami W., Hajjej Z., Merhabene T., Talik I., Kuscu O.O., Dilek O., Zerman A., Dal H.C., Turan S., Aydemir S., Yilmaz H., Calili D.K., Izdes S., Cengiz M., Gumus A., Tasdemir B., Kagnici A., Ay M., Ay S.A., Caliskan G., Akbas T., Balbay A.O., Efe S., Inal V., Elay G., Karabacak P., Ozserezli B., Senturk E., Demirkiran O., Bozbay S., Erdogan E., Akker M., Peker N., Ozgultekin A., Serin S.O., Turan C., Karaoren G., Goksu S., Karakurt S., Arikan H., Gul F., Cinel I., Kara I., Undar H.N., Bayraktar Y.S., Celik J.B., Tokur M.E., Aydin D.T., Yildiz I., Ozcan B., Erdivanli B., Eroglu A., Akdag D., Unlu N., Dungca A., Ali A., Thankamma B., Reyes P.E., John S., Rajendran A., Ahmad F.K.E., Smiley K.A., Hojden S., Miller M.T., Das Sasidharan Nair V., Antonio M.G.S., Qawasmeh K.A., Shawish S.A., Twiggs H., Rosado I., Babych V., Morren F., Young C., Vaughan-Jones N., Harris S., Burns K., Georgiev C., Shayamano R., Kerslake I., Creber P., Vochin A., O'Brien C., Caddell P., Hagan S., Hughes M., Torlinski T., Sherwin J., Kannan S., Markham A., Lebon R., Cupitt J., Cranshaw J., White N., Marriott V., Milner W., Groba C.B., Azoia J., Polgarova P., George S., Kapoor R., Lynch C., Fox N., Cranmer K., Llewellym T., Matthews K., Maltby L., Ibao J., Boulton K., Jarman R., Baxter K., Raj A.S., Moghal A., White J., Barrowcliffe S., Pulletz M., Ganeshalingam V., Baruah R., Baker H., Woods J., Ei P.P., Ogbeide V., Hayden P., Hughes J., Balasubramanian M., Salberg A., Saha R., Holmquist D., Derbyshire C., Smith N., Stones E., Ademokun J., Legorburo M.S., North S., Brett C., Jaundoo H., Craig J., Whiteley S., Howcroft C., Wilby L., Delve P., Shaw D., Williams K., Welters I.D., McMullen J., Brett S., Flores L., Trueman-Dawkins T., Templeton M., Adams J., Prowle J., Byers H., McDonnell A., Rose B.O., Reece-Anthony R., Mendes L., Vizcaychipi M., Bull R., Lacaden G., Santiago E., Delgado C.C., Farnell-Ward S., Thorpe E., Somerville J., Williams A., Cummings D., Derrick H., Brumwell S., Randell C., McCann N., Aves E., Berry G., Szakmany T., Gunter U., Pulak P., Sarkar N., Wright K., Gomes V., Jones J., Palfrey R., Camsooksai J., Lewis A., Eneas A., Tridente A., Barr L., Thomas B., Parkin E., Horner D., Frey C., Bench S., Baumber R., Broadhurst P., Jackson M., Williams L., Clark M., Paddle J., Bean S., Buckley S., Palfreeman C., Liu S., Allison N., Attwood B., Parsons P., Houghton V., Turner S.J., Higgins D., Bielskute E., Horrigan N., Jacob R., Habgood K., Zaki A., Collins A., Lord J., Ramiro C., Kubisz-Pudelko A., Kotze M., Williams H., Iovenko I., Tsarev A., Briva A., Mendez G., Napolitano L., Teig M., Rodriguez G.E., Ben-Jacob T., Potestio C., Eng T., Mahanes D., Khanna A., Duggal A., Nananmori M., Lois M., Karamchandani K., Bealer C., Barefield C., Terry D., Fivecoat P., Idowu O., Cata J., Clesi T., Peterson J., Hatton K., Dhaliwal J., Mueller D., Tao J., Eltorai A.S., Pastores S.M., Remor N., Salazar J., Barkas D., Joffe A., Barnes C., Sona C., Schallom M., Short J., Lorenzo J., Von Der Osten I., Borkowska M., Demarre L., Pleitinckx V., Xing C., Debue A.-S., Goller S., Larina E., Labeau, S. O., Blackwood, B., Brett, S. J., Deschepper, M., Francois, G., Honore, P. M., Khanna, A. K., Williams, G., Blot, S. I., Ribas, A. M., Telleria, V. M., Nogueira, P. C., Nafees, K. M. K., Reyes, A. G., Jensen, H. I., Adipa, F. E., Agoston, Z., Hashemian, S. M., Lee, S. -M., Abillama, F. F., Nor, B. M., Mazlan, M. Z., Sanchez-Hurtado, L., De lange, D., Ilesanmi, R. E., Ffarcsi, M. H., Hernandez, A. M., Schefold, J. C., Besbes, L. O., Minope, J. T. S., Rostello, O. F., Bartoli, J. R., Nocheretti, M. G., Escalante, R. G., Loudet, C. I., Gonzalez, A. L., Alvarez, G. A., Campos, P. A., Fonseca, I. P., Alvarez, G. M., Bascary, C. A., del Valle Gimenez, G., Bertoletti, F. P., Bonsignore, P. J. M., Fernandez, M. A., Leslie, G. D., Mclucas, A., Jacquet, L. -M., de Almeida, A. O., Jorge, S. A., Schmidt, R. C., Garcia, P. C., Ronchini, A. L. V., Manap, N. B. A., Laizner, A. M., Mcquirter, M., Kampayana, B. S., Sepulveda, M. I., Zamorano, M. J. F., Zhao, R. H., Hu, L. P., Jiao, Q. F., Wang, H. Y., Xia, C. J., Insu, L., Zhu, J. Y., Zhu, J. F., Huang, R. F., Wang, L. L., Song, J. H., Liu, X. M., Li, Z. S., Li, L. C., Zeng, J. M., Hu, X. C., Wang, R. X., Tak, P. S., Ho, S. W., Jiang, Q. X., Huang, L. P., Liu, X. L., Jiang, J. H., Gong, Y. Y., Lei, D. H., Bi, A. P., Zhao, H. M., Cao, Z. Q., Wu, S. F., Tian, X. F., Feng, Z. X., Liu, X. Z., Jiang, Z. X., Wang, G. X., Hu, R. L., Li, X. Q., Yu, Z. J., Yang, Y. X., Gama, L. M. S., Hernandez, J. S., Ochoa, M. -E., Reyes, A. J. G., Filipovic-Grcic, I., Vukovic, A., Pecenkovic, S., Suput, A., Radivojevic, R. C., Culjak, H., Adam, V. N., Pedersen, K. R., Kjaergard, I. E., Kodal, A. M., Hansen, T. C. B., Pedersen, A. S. B., Thomsen, T. D., Frandsen, T. M., Bliksted, I. A., Tamayo, L. M., Tutillo, D. R. M., Hurtado, C. V., Garcia, M. F., Kutimets, M., Lofqvist, C., Sakki, J. -K., Valta, M. A., Plantefeve, G., Deserts, M. D., Gunther, S. C., Timsit, J. -F., Farkas, J. -C., Bosl, K., Schuppel, S., Stubner, A., Osei, I. P., Kusi-Appiah, A. -C., Yakubu, Y. H., Patsiou, E. -C., Stalika, K. M. M., Enamorado, J. E., Jonasdottir, R. J., Lestari, M. I., Finn, D. O. C. R., Mcpherson, S., Ghioldi, D. M., Bruno, A. V., Maggiore, S. M., Volta, C. A., Taibi, M. R., Tranello, F. P., Giusti, G. D., Martin, M. A., Correia, M. C., Kim, J. H., Kim, K. C., Bae, J. -M., Park, S. Y., Park, T. S., Lee, H. B., Kim, S. C., Chee, H. K., Huh, J. W., Sim, Y. S., Ahn, J. -J., Kang, B. J., Lee, W. -Y., Lee, S. J., Feghaly, M. E., Belkhair, W. A., Tababa, O. W. E., Alkhumsi, S. I. R., Alshrif, A. I., Aboufray, A. A., Triki, A. R., Zahra, H. B., Al-Alawi, M. M. S., Ghula, M. A. A., Bahrin, L. K. K., Deva, S. R., Rahim, A. H. A., Hassan, W. N. W., Ismail, W. N. W., Ali, M. N., Khoo, T. M., Samat, N. M., Tong, J. M. G., Adib, N. A. N., Nor, M. B. M., Sulaiman, S. R., Foong, K. W., Hua, N. P., Zermeno, J. M., Nava, C. L. L., Nandyelly, S. J. R., Sanchez-Hurtado, L. A., Nava, L. P. A., Herrera, J. G., de Anda, G. F. V., Namendys-Silva, S. A., Romero-Gonzalez, J. P., Sosa, M. A., de Molina Serrano, J. I. R., Iburrigarro, S. R., Padilla, N. R. C., Pineda, A. A. V., Villafuerte, M. V. E., Herrera, M. O. G., Subedi, N. B., Pathak, S. D., Vermeijden, J. W., Gerritsen, R. T., Fijen, J. -W., Adejumo, P. O., Sankey, B. J., Olsen, B. F., Jensen, K. D., Johansen, B. F., Finnstrom, I. J., Skorstad, E. M., Lunde, G. A., Akselsen, G. R., Monstad, K. R., Hogvall, L., Malmin, S. K., Andersen, M. H., Hargott, R. F., de Jesus Ortiz, A., Cabral, D. M. B., Rivas, J. C., Moreira, M. L., Ellazar, C. G., Cerezo, F. D., Palo, J. E., Aperocho, C. A. J., Figueiredo, M. F., Pinheiro, C. M., Rita, C. S., Feranandes, A. M., Pinto, V. M. V., Bispo, B. M., Lima, A., Alsheikhly, A. S., Guran, C. T., Filipescu, D. C., Scutariu, M. A., Ebaid, M. S., Velickovic, D., Rajkovic, M., Stanojevic, M., Turcan, A., Lancaricova, D., Yeni, N. P., Syed, M. R., Navarro, J. A., De Pablo, A. M., Llinas, A. A., Lajara, M. A. G., Nieto, M. V., Pena, J. M. G., Gorgolas, M. C., Isasi, M. A., Salva-Costa, V., Garzon-Tovar, C., Olivares, P. G., de Ceballos, J. P. G., Polo, A. B. C., del Mar Diaz Salcedo, M., Alvarez, J. D., Arcas, M. L. B., Gonzalez, J. I. T., de la Ventana, A. B. S., Calleja, P. L. -A., Alvarez, R. G., Zamora, P. S., Guerrero, A. O., Barreiro, E. M., Sanchez, L. C., Diaz, M. G., Muriel, D. S., Alonso, H. F., Fernandez, A. W., Pinan, I. S., Albaiceta, G. M., Fernandez, M. C. I., Abos, F. J. S., Chueca, R. M., Aguirre, L. G., Manosa, S. C., Luque, C. P., Losilla, M. R., Fores, M. T., del Rosario Villar Redondo, M., Arteta Arteta, D. S., Sanchez, M. A. H., Espinosa, C. P., Reyes, L. M., Domenech, L. C., Guillen, C. V., Alvarez, J. T., del Cotillo, M., Barrueco-Francioni, J. E., Conde, B. B., Blanco, M. P. S., Blasco, M. L., Clement, A. I., Sanz, L. C., Gonzalez, I. A., Cano, A. E., Nunez, C. R., Fernadez, I. L., Fernandez, A. A. M., Boedjawan, N. N., Jansson, E. B., Malvemyr, A. -S., Lof, G., Spangfors, M., Lagerhall, C., Akerman, E., Hellkvist, V. H., Larsson, I. -M., Jong, M. L., Hsu, M. Y., Chang, S. C., Mebazaa, M. S., Elhechmi, Y. Z., Kuscu, O. O., Dal, H. C., Calili, D. K., Izdes, S., Gumus, A., Tasdemir, B., Kagnici, A., Ay, S. A., Balbay, A. O., Ozserezli, B., Senturk, E., Serin, S. O., Gul, F., Cinel, I., Undar, H. N., Bayraktar, Y. S., Celik, J. B., Tokur, M. E., Aydin, D. T., Yildiz, I., Ozcan, B., Akdag, D., Unlu, N., Reyes, P. E., Ahmad, F. K. E., Smiley, K. A., Miller, M. T., Antonio, M. G. S., Qawasmeh, K. A., Shawish, S. A., Groba, C. B., Raj, A. S., Ei, P. P., Legorburo, M. S., Welters, I. D., Mcmullen, J., Mcdonnell, A., Rose, B. O., Delgado, C. C., Mccann, N., Turner, S. J., Rodriguez, G. E., Eltorai, A. S., Pastores, S. M., Demarre, L., and Debue, A. -S.

Subjects
Male, Original, medicine.medical_treatment, artificial, Critical Care and Intensive Care Medicine, Medical and Health Sciences, Pressure ulcer, law.invention, Decubitus epidemiology, ICU, Morbidity, Mortality, Outcome, Pressure injury, Risk factors, Adult, Aged, Hospital Mortality, Humans, Patient Discharge, Prevalence, Risk Factors, Intensive Care Units, Respiration, Artificial, 0302 clinical medicine, decubitus epidemiology, pressure injury, pressure ulcer, outcome, risk factors, morbidity, mortality, law, Medicine and Health Sciences, adults, Medicine, Simplified Acute Physiology Score, icu, ziekenhuissterfte, Immunodeficiency, intensive care, European Society of Intensive Care Medicine (ESICM) Trials Group Collaborators, mannen, volwassenen, COST, Intensive care unit, STATE, ULCERS, Underweight, medicine.symptom, Life Sciences & Biomedicine, Human, medicine.medical_specialty, risicofactoren, Decubitus epidemiology, ICU, Pressure injury, Pressure ulcer, Outcome, Risk factors, Morbidity, Mortality, pressure injuries, Intensive Care Unit, prevalentie, NO, 1117 Public Health and Health Services, DecubICUs Study Team, 03 medical and health sciences, Critical Care Medicine, Anesthesiology, General & Internal Medicine, Health Sciences, ouderen, Mechanical ventilation, Science & Technology, business.industry, decubitus, Risk Factor, 030208 emergency & critical care medicine, 1103 Clinical Sciences, Odds ratio, medicine.disease, Emergency & Critical Care Medicine, Confidence interval, 030228 respiratory system, Emergency medicine, kunstmatige ademhaling, RISK-FACTORS, business, respiration
Abstract

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347, Funder: Flemish Society for Critical Care Nurses, Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score < 19, ICU stay > 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat.

Published
2021
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38. Association between in-ICU red blood cells transfusion and 1-year mortality in ICU survivors

Author

Alice Blet, Joel B. McNeil, Julie Josse, Bernard Cholley, Raphaël Cinotti, Gad Cotter, Agnès Dauvergne, Beth Davison, Kévin Duarte, Jacques Duranteau, Marie-Céline Fournier, Etienne Gayat, Samir Jaber, Sigismond Lasocki, Thomas Merkling, Katell Peoc’h, Imke Mayer, Malha Sadoune, Pierre-François Laterre, Romain Sonneville, Lorraine Ware, Alexandre Mebazaa, Antoine Kimmoun, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Vanderbilt University School of Medicine [Nashville], Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Médecine de précision par intégration de données et inférence causale (PREMEDICAL), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Momentum Research Inc., Durham, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers (UA), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpitaux Universitaires Paris Nord Val de Seine (HUPNVS), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Cliniques universitaires St Luc [Bruxelles], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord

Subjects
Intensive Care Units, Erythrocytes, Transfusion, [SDV]Life Sciences [q-bio], Critical care unit, Humans, Prospective Studies, Survivors, Mortality, Erythrocyte Transfusion, Critical Care and Intensive Care Medicine
Abstract

Background Impact of in-ICU transfusion on long-term outcomes remains unknown. The purpose of this study was to assess in critical-care survivors the association between in-ICU red blood cells transfusion and 1-year mortality. Methods FROG-ICU, a multicenter European study enrolling all-comers critical care patients was analyzed (n = 1551). Association between red blood cells transfusion administered in intensive care unit and 1-year mortality in critical care survivors was analyzed using an augmented inverse probability of treatment weighting-augmented inverse probability of censoring weighting method to control confounders. Results Among the 1551 ICU-survivors, 42% received at least one unit of red blood cells while in intensive care unit. Patients in the transfusion group had greater severity scores than those in the no-transfusion group. According to unweighted analysis, 1-year post-critical care mortality was greater in the transfusion group compared to the no-transfusion group (hazard ratio (HR) 1.78, 95% CI 1.45–2.16). Weighted analyses including 40 confounders, showed that transfusion remained associated with a higher risk of long-term mortality (HR 1.21, 95% CI 1.06–1.46). Conclusions Our results suggest a high incidence of in-ICU RBC transfusion and that in-ICU transfusion is associated with a higher 1-year mortality among in-ICU survivors. Trial registration (NCT01367093; Registered 6 June 2011). Graphic Abstract

Published
2022

39. Predictive performance and clinical application of COV50, a urinary proteomic biomarker in early COVID-19 infection: a prospective multicentre cohort study

Author

Jan A Staessen, Ralph Wendt, Yu-Ling Yu, Sven Kalbitz, Lutgarde Thijs, Justyna Siwy, Julia Raad, Jochen Metzger, Barbara Neuhaus, Armin Papkalla, Heiko von der Leyen, Alexandre Mebazaa, Emmanuel Dudoignon, Goce Spasovski, Mimoza Milenkova, Aleksandra Canevska-Taneska, Mercedes Salgueira Lazo, Mina Psichogiou, Marek W Rajzer, Łukasz Fuławka, Magdalena Dzitkowska-Zabielska, Guenter Weiss, Torsten Feldt, Miriam Stegemann, Johan Normark, Alexander Zoufaly, Stefan Schmiedel, Michael Seilmaier, Benedikt Rumpf, Mirosław Banasik, Magdalena Krajewska, Lorenzo Catanese, Harald D Rupprecht, Beata Czerwieńska, Björn Peters, Åsa Nilsson, Katja Rothfuss, Christoph Lübbert, Harald Mischak, Joachim Beige, Lukasz Fulawka, Harald Rupprecht, Beata Czerwienska, Jörg Ermisch, Nils Kellner, Lydia Peruth-Stutzmann, Stefanie Schroth, Jonathan Schmidt, Ulrike Schmidt, Daniel Breuer, Fariza Abeud, Marie-Celine Fournier, Badr Louadah, Rocio Molas, Fraile Loreto Rojas, Fabiola Alonso García, Isabel Garcia Sánchez, Ioana Cezara Hrom, Andrzej Więczek., Matthias Schwab, Kei K Asayama, Tine W Hansen, Gladys E Maestre, Dimitrios Basoulis, Georgios Karamanakos., Pawel Lis, Agnieszka Olszanecka, Rosa Bellmann-Weiler, Lucas Lanser, Alicia Edin, Matthias NE Forsell, Bernd Stegmayr, Björn-Erik Ole Jensen, Hans-Martin Orth, Sylke Borstel, Agata Mikolajewska, Manfred Hecking, Lukas Schmölz, Michał Hoffmann, Krzysztof Narkiewicz, Agnieszka Matera-Witkiewicz, Justyna Zachciał, Monika Litwin, and Patrycja Marciniak

Subjects
Adult, Proteomics, SARS-CoV-2, Medicine (miscellaneous), COVID-19, Public Health, Global Health, Social Medicine and Epidemiology, Health Informatics, Pilot Projects, Cohort Studies, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Health Information Management, Urologi och njurmedicin, Disease Progression, Urology and Nephrology, Humans, Decision Sciences (miscellaneous), Prospective Studies, Biomarkers
Abstract

BACKGROUND: The SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker. METHODS: CRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression and receiver operating characteristic curve analysis with a comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalisation costs adjusted for the gross per capita domestic product of each country. FINDINGS: From June 30 to Nov 19, 2020, 228 participants were recruited, and from April 30, 2020, to April 14, 2021, 784 participants were recruited, resulting in a total of 1012 participants. The entry WHO scores were 1-3 in 445 (44%) participants, 4-5 in 529 (52%) participants, and 6 in 38 (4%) participants; and of all participants, 119 died and 271 had disease progression. The odds ratio (OR) associated with COV50 in all 1012 participants for death was 2·44 (95% CI 2·05-2·92) unadjusted and 1·67 (1·34-2·07) when adjusted for sex, age, BMI, comorbidities, and baseline WHO score; and for disease progression, the OR was 1·79 (1·60-2·01) when unadjusted and 1·63 (1·41-1·91) when adjusted (p

Published
2022

40. 'A Delicate balance'—Perceptions and Experiences of ICU Physicians and Nurses Regarding Controlled Donation After Circulatory Death. A Qualitative Study

Author

Matthieu Le Dorze, Sara Martouzet, Etienne Cassiani-Ingoni, France Roussin, Alexandre Mebazaa, Lucas Morin, Nancy Kentish-Barnes, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Éducation Éthique Santé EA 7505 (EES), Université de Tours (UT), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hopital Saint-Louis [AP-HP] (AP-HP), Fondation de France, A source of funding was provided by the Fondation de France and was used for the transcription of the interviews. The funding source had no role in the design and conduct of the study., and HAL UVSQ, Équipe

Subjects
end of life, Transplantation, Terminal Care, Tissue and Organ Procurement, controlled donation after circulatory death, [SDV]Life Sciences [q-bio], Organ Transplantation, withdrawal of life-sustaining treatments, Death, [SDV] Life Sciences [q-bio], Intensive Care Units, organ donation, Physicians, Humans, qualitative research
Abstract

International audience; Controlled donation after circulatory death (cDCD) is considered by many as a potential response to the scarcity of donor organs. However, healthcare professionals may feel uncomfortable as end-of-life care and organ donation overlap in cDCD, creating a potential barrier to its development. The aim of this qualitative study was to gain insight on the perceptions and experiences of intensive care units (ICU) physicians and nurses regarding cDCD. We used thematic analysis of in-depth semi-structured interviews and 6-month field observation in a large teaching hospital. 17 staff members (8 physicians and 9 nurses) participated in the study. Analysis showed a gap between ethical principles and routine clinical practice, with a delicate balance between end-of-life care and organ donation. This tension arises at three critical moments: during the decision-making process leading to the withdrawal of life-sustaining treatments (LST), during the period between the decision to withdraw LST and its actual implementation, and during the dying and death process. Our findings shed light on the strategies developed by healthcare professionals to solve these ethical tensions and to cope with the emotional ambiguities. cDCD implementation in routine practice requires a shared understanding of the tradeoff between end-of-life care and organ donation within ICU. Copyright

Published
2022

41. Education and certification on heart failure of the Heart Failure Association of the European Society of Cardiology

Author

Mullens, Wilfried, Coats, Andrew J.S., Seferović, Petar M., Metra, Marco I., Mebazaa, Alexandre, Ruschitzka, Frank T., Filippatos, Gerasimos S., Volterrani, Maurizio, Ponikowski, Piotr P., Jankowska, Ewa Anita, Chioncel, Ovidiu, McDonagh, Theresa A., Piepoli, Massimo F., Milicic, Davor, Thum, Thomas, Hill, Loreena Michelle, Abdelhamid, Magdy, Adamopoulos, Stamatis, Belenkov, Yuri, Ben-Gal, Tuvia, Böhm, Michael, Cohen-Solal, Alain, Gustafsson, Finn, Jaarsma, Tiny, Moura, Brenda, Rakisheva, Amina, Ristic, Arsen D., Bayes-Genis, Antonio, Van Linthout, Sophia, Anker, Stefan D., Tocchetti, Carlo Gabriele, Lopatin, Yuri, Lund, Lars, Savarese, Gianluigi, Čelutkienė, Jelena, Cowie, Martin, Lambrinou, Ekaterini, Ray, Robin, Lainscak, Mitja, Skouri, Hadi, Wallner, Markus, Rosano, Giuseppe M C, Mullens, Wilfried, Coats, Andrew, Seferovic, Petar, Metra, Marco, Mebazaa, Alexandre, Ruschitzka, Frank, Filippatos, Gerasimo, Volterrani, Maurizio, Ponikowski, Piotr, Jankowska, Ewa A, Chioncel, Ovidiu, Mcdonagh, Theresa A, Piepoli, Massimo F, Milicic, Davor, Thum, Thoma, Hill, Loreena, Abdelhamid, Magdy, Adamopoulos, Stamati, Belenkov, Yuri, Gal, Tuvia Ben, Böhm, Michael, Cohen-Solal, Alain, Gustafsson, Finn, Jaarsma, Tiny, Moura, Brenda, Rakisheva, Amina, Ristic, Arsen, Bayes-Genis, Antonio, Van Linthout, Sophia, Anker, Stefan D, Tocchetti, Carlo Gabriele, Lopatin, Yury, Lund, Lar, Savarese, Gianluigi, Čelutkienė, Jelena, Cowie, Martin, Lambrinou, Ekaterini, Ray, Robin, Lainscak, Mitja, Skouri, Hadi, Wallner, Marku, and Rosano, Giuseppe M C

Subjects
Heart Failure, Certification, Europe, Humans, Societies, Medical, Cardiology, Quality of patient-centred, Heart failure, Medical and Health Sciences, Comprehensive educational programme, Medical, Quality of care centres, Clinical Medicine, Societies
Abstract

Heart failure (HF) is a devastating chronic and disabling disease with a wide variety of pharmaceutical and device treatment options which are becoming increasingly complex to implement. According to the Heart Failure Association (HFA) Atlas, a subspeciality resource aimed at sourcing contemporary data concerning the epidemiology and healthcare resources for HF, HF is prevalent in17.20 patients per1000 persons, accounting for 2671HFhospitalizations per million inhabitants annually in Europe.1HFpatients also suffer from a high prevalence of non-cardiac comorbidities, which adds complexity to their HF treatment and can negatively impact prognosis.2As a result, HF-related healthcare expenditure continues to rise, and healthcare organizations are becoming faced with the impossible challenge to provide the necessary financial and logistical support to this growing number of patients. In order to address these challenges, the HFA recently outlined the development of quality of care centres (QCC), in order to encourage multidisciplinary management of HF that will improve quality of care and survival.3However, there remains a significant unmet need to train sufficient multidisciplinary teams lead by HF specialists to take care of this expanding group of HF patients. In order to ensure that the next generation of medically-qualified HF specialists will receive high-quality training, this consensus statement of the HFA outlines the requirements for a European training and certification programme for such specialists. The primary goal of this comprehensive educational programme is to increase the quality of patient-centred care related to HF.

Published
2022

42. Sex‐ and age‐related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long‐Term Registry

Author

Lainscak, M., Milinkovic, I., Polovina, M., Crespo-Leiro, M. G., Lund, L. H., Anker, S. D., Laroche, C., Ferrari, R., Coats, A. J. S., Mcdonagh, T., Filippatos, G., Maggioni, A. P., Piepoli, M. F., Rosano, G. M. C., Ruschitzka, F., Simic, D., Asanin, M., Eicher, J. -C., Yilmaz, M. B., Seferovic, P. M., Gale, C. P., Chair, G. B., Branko Beleslin, R. S., Andrzej Budaj, P. L., Ovidiu Chioncel, R. O., Nikolaos Dagres, D. E., Nicolas Danchin, F. R., David Erlinge, S. E., Jonathan Emberson, G. B., Michael Glikson, I. L., Alastair Gray, G. B., Meral Kayikcioglu, T. R., Aldo Maggioni, I. T., Klaudia Vivien Nagy, H. U., Aleksandr Nedoshivin, R. U., Anna-Sonia Petronio, I. T., Jolien Roos-Hesselink, N. L., Lars Wallentin, S. E., Uwe Zeymer, D. E., Crespo-Leiro, M., Anker, S., Mebazaa, A., Coats, A., A. Goda A. L., M. Diez A. R., A. Fernandez A. R., F. Fruhwald A. T., Fazlibegovic, E., P. Gatzov B. G., A. Kurlianskaya B. Y., R. Hullin C. H., T. Christodoulides C. Y., J. Hradec C. Z., O. Wendelboe Nielsen D. K., R. Nedjar D. Z., T. Uuetoa E. E., M. Hassanein E. G., J. F. Delgado Jimenez E. S., P. Harjola F. I., V, D. Logeart F. R., V. Chumburidze G. E., D. Tousoulis G. R., D. Milicic H. R., B. Merkely H. U., O'Donoghue IE, E., O. Amir I. L., A. Shotan I. L., D. Shafie I. R., M. Metra I. T., A. Matsumori J. P., E. Mirrakhimov K. G., A. Kavoliuniene L. T., A. Erglis L. V., Vataman, E., M. Otljanska M. K., E. Srbinovska Kostovska M. K., D. Cassar DeMarco M. T., J. Drozdz P. L., Fonseca, C., O. Chioncel R. O., M. Dekleva R. S., E. Shkolnik R. U., U. Dahlstrom S. E., M. Lainscak S. I., E. Goncalvesova S. K., A. Temizhan T. R., V. Estrago U. Y., G. Bajraktari X. K., Auer, J., Ablasser, K., Fruhwald, F., Dolze, T., Brandner, K., Gstrein, S., Poelzl, G., Moertl, D., Reiter, S., Podczeck-Schweighofer, A., Muslibegovic, A., Vasilj, M., Cesko, M., Zelenika, D., Palic, B., Pravdic, D., Cuk, D., Vitlianova, K., Katova, T., Velikov, T., Kurteva, T., Gatzov, P., Kamenova, D., Antova, M., Sirakova, V., Krejci, J., Mikolaskova, M., Spinar, J., Krupicka, J., Malek, F., Hegarova, M., Lazarova, M., Monhart, Z., Hassanein, M., Sobhy, M., El Messiry, F., El Shazly, A. H., Elrakshy, Y., Youssef, A., Moneim, A. A., Noamany, M., Reda, A., Dayem, T. K. A., Farag, N., Halawa, S. I., Hamid, M. A., Said, K., Saleh, A., Ebeid, H., Hanna, R., Aziz, R., Louis, O., Enen, M. A., Ibrahim, B. S., Nasr, G., Elbahry, A., Sobhy, H., Ashmawy, M., Gouda, M., Aboleineen, W., Bernard, Y., Luporsi, P., Meneveau, N., Pillot, M., Morel, M., Seronde, M. -F., Schiele, F., Briand, F., Delahaye, F., Damy, T., de Groote, P., Fertin, M., Lamblin, N., Isnard, R., Lefol, C., Thevenin, S., Hagege, A., Jondeau, G., Logeart, D., Le Marcis, V., J. -F., Ly, Coisne, D., Lequeux, B., Le Moal, V., Mascle, S., Lotton, P., Behar, N., Donal, E., Thebault, C., Ridard, C., Reynaud, A., Basquin, A., Bauer, F., Codjia, R., Galinier, M., Tourikis, P., Stavroula, M., Tousoulis, D., Stefanadis, C., Chrysohoou, C., Kotrogiannis, I., Matzaraki, V., Dimitroula, T., Karavidas, A., Tsitsinakis, G., Kapelios, C., Nanas, J., Kampouri, H., Nana, E., Kaldara, E., Eugenidou, A., Vardas, P., Saloustros, I., Patrianakos, A., Tsaknakis, T., Evangelou, S., Nikoloulis, N., Tziourganou, H., Tsaroucha, A., Papadopoulou, A., Douras, A., Polgar, L., Merkely, B., Kosztin, A., Nyolczas, N., Nagy, A. C., Halmosi, R., Elber, J., Alony, I., Shotan, A., Fuhrmann, A. V., Amir, O., Romano, S., Marcon, S., Penco, M., Di Mauro, M., Lemme, E., Carubelli, V., Rovetta, R., Metra, M., Bulgari, M., Quinzani, F., Lombardi, C., Bosi, S., Schiavina, G., Squeri, A., Barbieri, A., Di Tano, G., Pirelli, S., Fucili, A., Passero, T., Musio, S., Di Biase, M., Correale, M., Salvemini, G., Brognoli, S., Zanelli, E., Giordano, A., Agostoni, P., Italiano, G., Salvioni, E., Copelli, S., Modena, M. G., Reggianini, L., Valenti, C., Olaru, A., Bandino, S., Deidda, M., Mercuro, G., Dessalvi, C. C., Marino, P. N., Di Ruocco, M. V., Sartori, C., Piccinino, C., Parrinello, G., Licata, G., Torres, D., Giambanco, S., Busalacchi, S., Arrotti, S., Novo, S., Inciardi, R. M., Pieri, P., Chirco, P. R., Galifi, M. A., Teresi, G., Buccheri, D., Minacapelli, A., Veniani, M., Frisinghelli, A., Priori, S. G., Cattaneo, S., Opasich, C., Gualco, A., Pagliaro, M., Mancone, M., Fedele, F., Cinque, A., Vellini, M., Scarfo, I., Romeo, F., Ferraiuolo, F., Sergi, D., Anselmi, M., Melandri, F., Leci, E., Iori, E., Bovolo, V., Pidello, S., Frea, S., Bergerone, S., Botta, M., Canavosio, F. G., Gaita, F., Merlo, M., Cinquetti, M., Sinagra, G., Ramani, F., Fabris, E., Stolfo, D., Artico, J., Miani, D., Fresco, C., Daneluzzi, C., Proclemer, A., Cicoira, M., Zanolla, L., Marchese, G., Torelli, F., Vassanelli, C., Voronina, N., Erglis, A., Tamakauskas, V., Smalinskas, V., Karaliute, R., Petraskiene, I., Kazakauskaite, E., Rumbinaite, E., Kavoliuniene, A., Vysniauskas, V., Brazyte-Ramanauskiene, R., Petraskiene, D., Stankala, S., Switala, P., Juszczyk, Z., Sinkiewicz, W., Gilewski, W., Pietrzak, J., Orzel, T., Kasztelowicz, P., Kardaszewicz, P., Lazorko-Piega, M., Gabryel, J., Mosakowska, K., Bellwon, J., Rynkiewicz, A., Raczak, G., Lewicka, E., Dabrowska-Kugacka, A., Bartkowiak, R., Sosnowska-Pasiarska, B., Wozakowska-Kaplon, B., Krzeminski, A., Zabojszcz, M., Mirek-Bryniarska, E., Grzegorzko, A., Bury, K., Nessler, J., Zalewski, J., Furman, A., Broncel, M., Poliwczak, A., Bala, A., Zycinski, P., Rudzinska, M., Jankowski, L., Kasprzak, J. D., Michalak, L., Soska, K. W., Drozdz, J., Huziuk, I., Retwinski, A., Flis, P., Weglarz, J., Bodys, A., Grajek, S., Kaluzna-Oleksy, M., Straburzynska-Migaj, E., Dankowski, R., Szymanowska, K., Grabia, J., Szyszka, A., Nowicka, A., Samcik, M., Wolniewicz, L., Baczynska, K., Komorowska, K., Poprawa, I., Komorowska, E., Sajnaga, D., Zolbach, A., Dudzik-Plocica, A., Abdulkarim, A. -F., Lauko-Rachocka, A., Kaminski, L., Kostka, A., Cichy, A., Ruszkowski, P., Splawski, M., Fitas, G., Szymczyk, A., Serwicka, A., Fiega, A., Zysko, D., Krysiak, W., Szabowski, S., Skorek, E., Pruszczyk, P., Bienias, P., Ciurzynski, M., Welnicki, M., Mamcarz, A., Folga, A., Zielinski, T., Rywik, T., Leszek, P., Sobieszczanska-Malek, M., Piotrowska, M., Kozar-Kaminska, K., Komuda, K., Wisniewska, J., Tarnowska, A., Balsam, P., Marchel, M., Opolski, G., Kaplon-Cieslicka, A., Gil, R. J., Mozenska, O., Byczkowska, K., Gil, K., Pawlak, A., Michalek, A., Krzesinski, P., Piotrowicz, K., Uzieblo-Zyczkowska, B., Stanczyk, A., Skrobowski, A., Ponikowski, P., Jankowska, E., Rozentryt, P., Polonski, L., Gadula-Gacek, E., Nowalany-Kozielska, E., Kuczaj, A., Kalarus, Z., Szulik, M., Przybylska, K., Klys, J., Prokop-Lewicka, G., Kleinrok, A., Aguiar, C. T., Ventosa, A., Pereira, S., Faria, R., Chin, J., De Jesus, I., Santos, R., Silva, P., Moreno, N., Queiros, C., Lourenco, C., Pereira, A., Castro, A., Andrade, A., Guimaraes, T. O., Martins, S., Placido, R., Lima, G., Brito, D., Francisco, A. R., Cardiga, R., Proenca, M., Araujo, I., Marques, F., Moura, B., Leite, S., Campelo, M., Silva-Cardoso, J., Rodrigues, J., Rangel, I., Martins, E., Correia, A. S., Peres, M., Marta, L., da Silva, G. F., Severino, D., Durao, D., Leao, S., Magalhaes, P., Moreira, I., Cordeiro, A. F., Ferreira, C., Araujo, C., Ferreira, A., Baptista, A., Radoi, M., Bicescu, G., Vinereanu, D., Sinescu, C. -J., Macarie, C., Popescu, R., Daha, I., Dan, G. -A., Stanescu, C., Dan, A., Craiu, E., Nechita, E., Aursulesei, V., Christodorescu, R., Otasevic, P., Simeunovic, D., Ristic, A. D., Celic, V., Pavlovic-Kleut, M., Lazic, J. S., Stojcevski, B., Pencic, B., Stevanovic, A., Andric, A., Iric-Cupic, V., Jovic, M., Davidovic, G., Milanov, S., Mitic, V., Atanaskovic, V., Antic, S., Pavlovic, M., Stanojevic, D., Stoickov, V., Ilic, S., Ilic, M. D., Petrovic, D., Stojsic, S., Kecojevic, S., Dodic, S., Adic, N. C., Cankovic, M., Stojiljkovic, J., Mihajlovic, B., Radin, A., Radovanovic, S., Krotin, M., Klabnik, A., Goncalvesova, E., Pernicky, M., Murin, J., Kovar, F., Kmec, J., Semjanova, H., Strasek, M., Iskra, M. S., Ravnikar, T., Suligoj, N. C., Komel, J., Fras, Z., Jug, B., Glavic, T., Losic, R., Bombek, M., Krajnc, I., Krunic, B., Horvat, S., Kovac, D., Rajtman, D., Cencic, V., Letonja, M., Winkler, R., Valentincic, M., Melihen-Bartolic, C., Bartolic, A., Vrckovnik, M. P., Kladnik, M., Pusnik, C. S., Marolt, A., Klen, J., Drnovsek, B., Leskovar, B., Anguita, M. J. F., Page, J. C. G., Martinez, F. M. S., Andres, J., Genis, A. B., Mirabet, S., Mendez, A., Garcia-Cosio, L., Roig, E., Leon, V., Gonzalez-Costello, J., Muntane, G., Garay, A., Alcade-Martinez, V., Fernandez, S. L., Rivera-Lopez, R., Puga-Martinez, M., Fernandez-Alvarez, M., Serrano-Martinez, J. L., Grille-Cancela, Z., Marzoa-Rivas, R., Blanco-Canosa, P., Paniagua-Martin, M. J., Barge-Caballero, E., Cerdena, I. L., Baldomero, I. F. H., Padron, A. L., Rosillo, S. O., Gonzalez-Gallarza, R. D., Montanes, O. S., Manjavacas, A. M. I., Conde, A. C., Araujo, A., Soria, T., Garcia-Pavia, P., Gomez-Bueno, M., Cobo-Marcos, M., Alonso-Pulpon, L., Cubero, J. S., Sayago, I., Gonzalez-Segovia, A., Briceno, A., Subias, P. E., Hernandez, M. V., Cano, M. J. R., Sanchez, M. A. G., Jimenez, J. F. D., Garrido-Lestache, E. B., Pinilla, J. M. G., de la Villa, B. G., Sahuquillo, A., Marques, R. B., Calvo, F. T., Perez-Martinez, M. T., Gracia-Rodenas, M. R., Garrido-Bravo, I. P., Pastor-Perez, F., Pascual-Figal, D. A., Molina, B. D., Orus, J., Gonzalo, F. E., Bertomeu, V., Valero, R., Martinez-Abellan, R., Quiles, J., Rodrigez-Ortega, J. A., Mateo, I., Elamrani, A., Fernandez-Vivancos, C., Valero, D. B., Almenar-Bonet, L., Sanchez-Lazaro, I. J., Marques-Sule, E., Facila-Rubio, L., Perez-Silvestre, J., Garcia-Gonzalez, P., Ridocci-Soriano, F., Garcia-Escriva, D., Pellicer-Cabo, A., de la Fuente Galan, L., Diaz, J. L., Platero, A. R., Arias, J. C., Blasco-Peiro, T., Julve, M. S., Sanchez-Insa, E., Aured-Guallar, C., Portoles-Ocampo, A., Melin, M., Hagglund, E., Stenberg, A., Lindahl, I. -M., Asserlund, B., Olsson, L., Dahlstrom, U., Afzelius, M., Karlstrom, P., Tengvall, L., Wiklund, P. -A., Olsson, B., Kalayci, S., Temizhan, A., Cavusoglu, Y., Gencer, E., Gunes, H., Lainscak, M., Milinkovic, I., Polovina, M., Crespo-Leiro, M. G., Lund, L. H., Anker, S. D., Laroche, C., Ferrari, R., Coats, A. J. S., Mcdonagh, T., Filippatos, G., Maggioni, A. P., Piepoli, M. F., Rosano, G. M. C., Ruschitzka, F., Simic, D., Asanin, M., Eicher, J. -C., Yilmaz, M. B., Seferovic, P. M., Gale, C. P., Chair, G. B., Branko Beleslin, R. S., Andrzej Budaj, P. L., Ovidiu Chioncel, R. O., Nikolaos Dagres, D. E., Nicolas Danchin, F. R., David Erlinge, S. E., Jonathan Emberson, G. B., Michael Glikson, I. L., Alastair Gray, G. B., Meral Kayikcioglu, T. R., Aldo Maggioni, I. T., Klaudia Vivien Nagy, H. U., Aleksandr Nedoshivin, R. U., Anna-Sonia Petronio, I. T., Jolien Roos-Hesselink, N. L., Lars Wallentin, S. E., Uwe Zeymer, D. E., Crespo-Leiro, M., Anker, S., Mebazaa, A., Coats, A., A. Goda A., L., M. Diez A., R., A. Fernandez A., R., F. Fruhwald A., T., Fazlibegovic, E., P. Gatzov B., G., A. Kurlianskaya B., Y., R. Hullin C., H., T. Christodoulides C., Y., J. Hradec C., Z., O. Wendelboe Nielsen D., K., R. Nedjar D., Z., T. Uuetoa E., E., M. Hassanein E., G., J. F. Delgado Jimenez E., S., V-, P. Harjola F. I., D. Logeart F., R., V. Chumburidze G., E., D. Tousoulis G., R., D. Milicic H., R., B. Merkely H., U., O'Donoghue IE, E., O. Amir I., L., A. Shotan I., L., D. Shafie I., R., M. Metra I., T., A. Matsumori J., P., E. Mirrakhimov K., G., A. Kavoliuniene L., T., A. Erglis L., V., Vataman, E., M. Otljanska M., K., E. Srbinovska Kostovska M., K., D. Cassar DeMarco M., T., J. Drozdz P., L., Fonseca, C., O. Chioncel R., O., M. Dekleva R., S., E. Shkolnik R., U., U. Dahlstrom S., E., M. Lainscak S., I., E. Goncalvesova S., K., A. Temizhan T., R., V. Estrago U., Y., G. Bajraktari X., K., Auer, J., Ablasser, K., Fruhwald, F., Dolze, T., Brandner, K., Gstrein, S., Poelzl, G., Moertl, D., Reiter, S., Podczeck-Schweighofer, A., Muslibegovic, A., Vasilj, M., Cesko, M., Zelenika, D., Palic, B., Pravdic, D., Cuk, D., Vitlianova, K., Katova, T., Velikov, T., Kurteva, T., Gatzov, P., Kamenova, D., Antova, M., Sirakova, V., Krejci, J., Mikolaskova, M., Spinar, J., Krupicka, J., Malek, F., Hegarova, M., Lazarova, M., Monhart, Z., Hassanein, M., Sobhy, M., El Messiry, F., El Shazly, A. H., Elrakshy, Y., Youssef, A., Moneim, A. A., Noamany, M., Reda, A., Dayem, T. K. A., Farag, N., Halawa, S. I., Hamid, M. A., Said, K., Saleh, A., Ebeid, H., Hanna, R., Aziz, R., Louis, O., Enen, M. A., Ibrahim, B. S., Nasr, G., Elbahry, A., Sobhy, H., Ashmawy, M., Gouda, M., Aboleineen, W., Bernard, Y., Luporsi, P., Meneveau, N., Pillot, M., Morel, M., Seronde, M. -F., Schiele, F., Briand, F., Delahaye, F., Damy, T., de Groote, P., Fertin, M., Lamblin, N., Isnard, R., Lefol, C., Thevenin, S., Hagege, A., Jondeau, G., Logeart, D., Le Marcis, V., Ly, J. -F., Coisne, D., Lequeux, B., Le Moal, V., Mascle, S., Lotton, P., Behar, N., Donal, E., Thebault, C., Ridard, C., Reynaud, A., Basquin, A., Bauer, F., Codjia, R., Galinier, M., Tourikis, P., Stavroula, M., Tousoulis, D., Stefanadis, C., Chrysohoou, C., Kotrogiannis, I., Matzaraki, V., Dimitroula, T., Karavidas, A., Tsitsinakis, G., Kapelios, C., Nanas, J., Kampouri, H., Nana, E., Kaldara, E., Eugenidou, A., Vardas, P., Saloustros, I., Patrianakos, A., Tsaknakis, T., Evangelou, S., Nikoloulis, N., Tziourganou, H., Tsaroucha, A., Papadopoulou, A., Douras, A., Polgar, L., Merkely, B., Kosztin, A., Nyolczas, N., Nagy, A. C., Halmosi, R., Elber, J., Alony, I., Shotan, A., Fuhrmann, A. V., Amir, O., Romano, S., Marcon, S., Penco, M., Di Mauro, M., Lemme, E., Carubelli, V., Rovetta, R., Metra, M., Bulgari, M., Quinzani, F., Lombardi, C., Bosi, S., Schiavina, G., Squeri, A., Barbieri, A., Di Tano, G., Pirelli, S., Fucili, A., Passero, T., Musio, S., Di Biase, M., Correale, M., Salvemini, G., Brognoli, S., Zanelli, E., Giordano, A., Agostoni, P., Italiano, G., Salvioni, E., Copelli, S., Modena, M. G., Reggianini, L., Valenti, C., Olaru, A., Bandino, S., Deidda, M., Mercuro, G., Dessalvi, C. C., Marino, P. N., Di Ruocco, M. V., Sartori, C., Piccinino, C., Parrinello, G., Licata, G., Torres, D., Giambanco, S., Busalacchi, S., Arrotti, S., Novo, S., Inciardi, R. M., Pieri, P., Chirco, P. R., Galifi, M. A., Teresi, G., Buccheri, D., Minacapelli, A., Veniani, M., Frisinghelli, A., Priori, S. G., Cattaneo, S., Opasich, C., Gualco, A., Pagliaro, M., Mancone, M., Fedele, F., Cinque, A., Vellini, M., Scarfo, I., Romeo, F., Ferraiuolo, F., Sergi, D., Anselmi, M., Melandri, F., Leci, E., Iori, E., Bovolo, V., Pidello, S., Frea, S., Bergerone, S., Botta, M., Canavosio, F. G., Gaita, F., Merlo, M., Cinquetti, M., Sinagra, G., Ramani, F., Fabris, E., Stolfo, D., Artico, J., Miani, D., Fresco, C., Daneluzzi, C., Proclemer, A., Cicoira, M., Zanolla, L., Marchese, G., Torelli, F., Vassanelli, C., Voronina, N., Erglis, A., Tamakauskas, V., Smalinskas, V., Karaliute, R., Petraskiene, I., Kazakauskaite, E., Rumbinaite, E., Kavoliuniene, A., Vysniauskas, V., Brazyte-Ramanauskiene, R., Petraskiene, D., Stankala, S., Switala, P., Juszczyk, Z., Sinkiewicz, W., Gilewski, W., Pietrzak, J., Orzel, T., Kasztelowicz, P., Kardaszewicz, P., Lazorko-Piega, M., Gabryel, J., Mosakowska, K., Bellwon, J., Rynkiewicz, A., Raczak, G., Lewicka, E., Dabrowska-Kugacka, A., Bartkowiak, R., Sosnowska-Pasiarska, B., Wozakowska-Kaplon, B., Krzeminski, A., Zabojszcz, M., Mirek-Bryniarska, E., Grzegorzko, A., Bury, K., Nessler, J., Zalewski, J., Furman, A., Broncel, M., Poliwczak, A., Bala, A., Zycinski, P., Rudzinska, M., Jankowski, L., Kasprzak, J. D., Michalak, L., Soska, K. W., Drozdz, J., Huziuk, I., Retwinski, A., Flis, P., Weglarz, J., Bodys, A., Grajek, S., Kaluzna-Oleksy, M., Straburzynska-Migaj, E., Dankowski, R., Szymanowska, K., Grabia, J., Szyszka, A., Nowicka, A., Samcik, M., Wolniewicz, L., Baczynska, K., Komorowska, K., Poprawa, I., Komorowska, E., Sajnaga, D., Zolbach, A., Dudzik-Plocica, A., Abdulkarim, A. -F., Lauko-Rachocka, A., Kaminski, L., Kostka, A., Cichy, A., Ruszkowski, P., Splawski, M., Fitas, G., Szymczyk, A., Serwicka, A., Fiega, A., Zysko, D., Krysiak, W., Szabowski, S., Skorek, E., Pruszczyk, P., Bienias, P., Ciurzynski, M., Welnicki, M., Mamcarz, A., Folga, A., Zielinski, T., Rywik, T., Leszek, P., Sobieszczanska-Malek, M., Piotrowska, M., Kozar-Kaminska, K., Komuda, K., Wisniewska, J., Tarnowska, A., Balsam, P., Marchel, M., Opolski, G., Kaplon-Cieslicka, A., Gil, R. J., Mozenska, O., Byczkowska, K., Gil, K., Pawlak, A., Michalek, A., Krzesinski, P., Piotrowicz, K., Uzieblo-Zyczkowska, B., Stanczyk, A., Skrobowski, A., Ponikowski, P., Jankowska, E., Rozentryt, P., Polonski, L., Gadula-Gacek, E., Nowalany-Kozielska, E., Kuczaj, A., Kalarus, Z., Szulik, M., Przybylska, K., Klys, J., Prokop-Lewicka, G., Kleinrok, A., Aguiar, C. T., Ventosa, A., Pereira, S., Faria, R., Chin, J., De Jesus, I., Santos, R., Silva, P., Moreno, N., Queiros, C., Lourenco, C., Pereira, A., Castro, A., Andrade, A., Guimaraes, T. O., Martins, S., Placido, R., Lima, G., Brito, D., Francisco, A. R., Cardiga, R., Proenca, M., Araujo, I., Marques, F., Moura, B., Leite, S., Campelo, M., Silva-Cardoso, J., Rodrigues, J., Rangel, I., Martins, E., Correia, A. S., Peres, M., Marta, L., da Silva, G. F., Severino, D., Durao, D., Leao, S., Magalhaes, P., Moreira, I., Cordeiro, A. F., Ferreira, C., Araujo, C., Ferreira, A., Baptista, A., Radoi, M., Bicescu, G., Vinereanu, D., Sinescu, C. -J., Macarie, C., Popescu, R., Daha, I., Dan, G. -A., Stanescu, C., Dan, A., Craiu, E., Nechita, E., Aursulesei, V., Christodorescu, R., Otasevic, P., Simeunovic, D., Ristic, A. D., Celic, V., Pavlovic-Kleut, M., Lazic, J. S., Stojcevski, B., Pencic, B., Stevanovic, A., Andric, A., Iric-Cupic, V., Jovic, M., Davidovic, G., Milanov, S., Mitic, V., Atanaskovic, V., Antic, S., Pavlovic, M., Stanojevic, D., Stoickov, V., Ilic, S., Ilic, M. D., Petrovic, D., Stojsic, S., Kecojevic, S., Dodic, S., Adic, N. C., Cankovic, M., Stojiljkovic, J., Mihajlovic, B., Radin, A., Radovanovic, S., Krotin, M., Klabnik, A., Goncalvesova, E., Pernicky, M., Murin, J., Kovar, F., Kmec, J., Semjanova, H., Strasek, M., Iskra, M. S., Ravnikar, T., Suligoj, N. C., Komel, J., Fras, Z., Jug, B., Glavic, T., Losic, R., Bombek, M., Krajnc, I., Krunic, B., Horvat, S., Kovac, D., Rajtman, D., Cencic, V., Letonja, M., Winkler, R., Valentincic, M., Melihen-Bartolic, C., Bartolic, A., Vrckovnik, M. P., Kladnik, M., Pusnik, C. S., Marolt, A., Klen, J., Drnovsek, B., Leskovar, B., Anguita, M. J. F., Page, J. C. G., Martinez, F. M. S., Andres, J., Genis, A. B., Mirabet, S., Mendez, A., Garcia-Cosio, L., Roig, E., Leon, V., Gonzalez-Costello, J., Muntane, G., Garay, A., Alcade-Martinez, V., Fernandez, S. L., Rivera-Lopez, R., Puga-Martinez, M., Fernandez-Alvarez, M., Serrano-Martinez, J. L., Grille-Cancela, Z., Marzoa-Rivas, R., Blanco-Canosa, P., Paniagua-Martin, M. J., Barge-Caballero, E., Cerdena, I. L., Baldomero, I. F. H., Padron, A. L., Rosillo, S. O., Gonzalez-Gallarza, R. D., Montanes, O. S., Manjavacas, A. M. I., Conde, A. C., Araujo, A., Soria, T., Garcia-Pavia, P., Gomez-Bueno, M., Cobo-Marcos, M., Alonso-Pulpon, L., Cubero, J. S., Sayago, I., Gonzalez-Segovia, A., Briceno, A., Subias, P. E., Hernandez, M. V., Cano, M. J. R., Sanchez, M. A. G., Jimenez, J. F. D., Garrido-Lestache, E. B., Pinilla, J. M. G., de la Villa, B. G., Sahuquillo, A., Marques, R. B., Calvo, F. T., Perez-Martinez, M. T., Gracia-Rodenas, M. R., Garrido-Bravo, I. P., Pastor-Perez, F., Pascual-Figal, D. A., Molina, B. D., Orus, J., Gonzalo, F. E., Bertomeu, V., Valero, R., Martinez-Abellan, R., Quiles, J., Rodrigez-Ortega, J. A., Mateo, I., Elamrani, A., Fernandez-Vivancos, C., Valero, D. B., Almenar-Bonet, L., Sanchez-Lazaro, I. J., Marques-Sule, E., Facila-Rubio, L., Perez-Silvestre, J., Garcia-Gonzalez, P., Ridocci-Soriano, F., Garcia-Escriva, D., Pellicer-Cabo, A., de la Fuente Galan, L., Diaz, J. L., Platero, A. R., Arias, J. C., Blasco-Peiro, T., Julve, M. S., Sanchez-Insa, E., Aured-Guallar, C., Portoles-Ocampo, A., Melin, M., Hagglund, E., Stenberg, A., Lindahl, I. -M., Asserlund, B., Olsson, L., Dahlstrom, U., Afzelius, M., Karlstrom, P., Tengvall, L., Wiklund, P. -A., Olsson, B., Kalayci, S., Temizhan, A., Cavusoglu, Y., Gencer, E., Gunes, H., University of Zurich, and Seferović, Petar M

Subjects
Male, Registry, medicine.medical_specialty, Adverse outcomes, 610 Medicine & health, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Independent predictor, 2705 Cardiology and Cardiovascular Medicine, Ventricular Function, Left, 03 medical and health sciences, Age, 0302 clinical medicine, Internal medicine, Age related, Hospitalization, Mortality, Sex, medicine, Humans, Registries, Medical prescription, Aged, Heart Failure, Ejection fraction, business.industry, Stroke Volume, medicine.disease, Ageing, Heart failure, 10209 Clinic for Cardiology, Female, Angiotensin Receptor Blockers, Cardiology and Cardiovascular Medicine, business
Abstract

[Abstract] Aims. This study aimed to assess age‐ and sex‐related differences in management and 1‐year risk for all‐cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results. Of 16 354 patients included in the European Society of Cardiology Heart Failure Long‐Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline‐directed medical therapy (GDMT) were high (angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, beta‐blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P ≤ 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1‐year follow‐up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all‐cause mortality were lower in women than in men (7.1% vs. 8.7%; P = 0.015), as were rates of all‐cause hospitalization (21.9% vs. 27.3%; P < 0.001) and there were no differences in causes of death. All‐cause mortality and all‐cause hospitalization increased with greater age in both sexes. Sex was not an independent predictor of 1‐year all‐cause mortality (restricted to patients with LVEF ≤45%). Mortality risk was significantly lower in patients of younger age, compared to patients aged >75 years. Conclusions. There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all‐cause mortality in patients with LVEF ≤45%.

Published
2019

43. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload

Author

Mullens, Wilfried, Dauw, Jeroen, Martens, Pieter, Verbrugge, Frederik H, Nijst, Petra, Meekers, Evelyne, Tartaglia, Katrien, Chenot, Fabien, Moubayed, Samer, Dierckx, Riet, Blouard, Philippe, Troisfontaines, Pierre, Derthoo, David, Smolders, Walter, Bruckers, Liesbeth, Droogne, Walter, Ter Maaten, Jozine M, Damman, Kevin, Lassus, Johan, Mebazaa, Alexandre, Filippatos, Gerasimos, Ruschitzka, Frank, Dupont, Matthias, ADVOR Study Group, Clinical sciences, Cardiology, Intensive Care, Cardiovascular Centre (CVC), University of Zurich, and Mullens, Wilfried

Subjects
Heart Failure, acute decompensated heart failure, Sodium, Water-Electrolyte Imbalance, 610 Medicine & health, Stroke Volume, 2700 General Medicine, General Medicine, Symptom Flare Up, Ventricular Function, Left, Acetazolamide, Treatment Outcome, Double-Blind Method, Sodium Potassium Chloride Symporter Inhibitors, Acute Disease, Natriuretic Peptide, Brain, 10209 Clinic for Cardiology, Humans, carbonic anhydrase inhibitor, Cardiology and Cardiovascular Medicine, Carbonic Anhydrase Inhibitors, Diuretics
Abstract

BACKGROUND: Whether acetazolamide, a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption, can improve the efficiency of loop diuretics, potentially leading to more and faster decongestion in patients with acute decompensated heart failure with volume overload, is unclear.METHODS: In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned patients with acute decompensated heart failure, clinical signs of volume overload (i.e., edema, pleural effusion, or ascites), and an N-terminal pro-B-type natriuretic peptide level of more than 1000 pg per milliliter or a B-type natriuretic peptide level of more than 250 pg per milliliter to receive either intravenous acetazolamide (500 mg once daily) or placebo added to standardized intravenous loop diuretics (at a dose equivalent to twice the oral maintenance dose). Randomization was stratified according to the left ventricular ejection fraction (≤40% or >40%). The primary end point was successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of decongestive therapy. Secondary end points included a composite of death from any cause or rehospitalization for heart failure during 3 months of follow-up. Safety was also assessed.RESULTS: A total of 519 patients underwent randomization. Successful decongestion occurred in 108 of 256 patients (42.2%) in the acetazolamide group and in 79 of 259 (30.5%) in the placebo group (risk ratio, 1.46; 95% confidence interval [CI], 1.17 to 1.82; PCONCLUSIONS: The addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure resulted in a greater incidence of successful decongestion. (Funded by the Belgian Health Care Knowledge Center; ADVOR ClinicalTrials.gov number, NCT03505788.).

Published
2022

44. A universal predictive and mechanistic urinary peptide signature in acute kidney injury

Author

Alexis, Piedrafita, Justyna, Siwy, Julie, Klein, Amal, Akkari, Ana, Amaya-Garrido, Alexandre, Mebazaa, Anna Belen, Sanz, Benjamin, Breuil, Laura, Montero Herrero, Bertrand, Marcheix, François, Depret, Lucie, Fernandez, Elsa, Tardif, Vincent, Minville, Melinda, Alves, Jochen, Metzger, Julia, Grossac, Harald, Mischak, Alberto, Ortiz, Stéphane, Gazut, Joost P, Schanstra, and François, Labaste

Subjects
Lipocalin-2, Predictive Value of Tests, Humans, Acute Kidney Injury, Peptides, Biomarkers
Abstract

The delayed diagnosis of acute kidney injury (AKI) episodes and the lack of specificity of current single AKI biomarkers hamper its management. Urinary peptidome analysis may help to identify early molecular changes in AKI and grasp its complexity to identify potential targetable molecular pathways.In derivation and validation cohorts totalizing 1170 major cardiac bypass surgery patients and in an external cohort of 1569 intensive care unit (ICU) patients, a peptide-based score predictive of AKI (7-day KDIGO classification) was developed, validated, and compared to the reference biomarker urinary NGAL and NephroCheck and clinical scores.A set of 204 urinary peptides derived from 48 proteins related to hemolysis, inflammation, immune cells trafficking, innate immunity, and cell growth and survival was identified and validated for the early discrimination (lt; 4 h) of patients according to their risk to develop AKI (OR 6.13 [3.96-9.59], p lt; 0.001) outperforming reference biomarkers (urinary NGAL and [IGFBP7].[TIMP2] product) and clinical scores. In an external cohort of 1569 ICU patients, performances of the signature were similar (OR 5.92 [4.73-7.45], p lt; 0.001), and it was also associated with the in-hospital mortality (OR 2.62 [2.05-3.38], p lt; 0.001).An overarching AKI physiopathology-driven urinary peptide signature shows significant promise for identifying, at an early stage, patients who will progress to AKI and thus to develop tailored treatments for this frequent and life-threatening condition. Performance of the urine peptide signature is as high as or higher than that of single biomarkers but adds mechanistic information that may help to discriminate sub-phenotypes of AKI offering new therapeutic avenues.

Published
2022

45. Comparison of Circulating Immune Cells Profiles and Kinetics Between Coronavirus Disease 2019 and Bacterial Sepsis*

Author

Etienne Gayat, Romain Barthélémy, Bruno Mégarbane, Caren Brumpt, Sehmi Mansouri, Sebastian Voicu, Candice Fontaine, Marie Neuwirth, Benjamin G. Chousterman, Alexandre Mebazaa, Charles de Roquetaillade, Matthieu Le Dorze, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre hospitalier Saint-Joseph [Paris], Hôpital Lariboisière-Fernand-Widal [APHP], and Mégarbane, Bruno

Subjects
Male, CD14, Receptor expression, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, sepsis, Sepsis, coronavirus disease 2019, Immunophenotyping, Immune system, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Humans, Immunologic Factors, Eosinophilia, Longitudinal Studies, Aged, Retrospective Studies, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, flow cytometry, Editorials, COVID-19, Middle Aged, immune endotypes, medicine.disease, Neutrophilia, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Intensive Care Units, Kinetics, Basophilia, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Female, France, medicine.symptom, business, severe acute respiratory syndrome coronavirus 2
Abstract

International audience; Objectives: Although clinical presentation of coronavirus disease 2019 has been extensively described, immune response to severe acute respiratory syndrome coronavirus 2 remains yet not fully understood. Similarities with bacterial sepsis were observed; however, few studies specifically addressed differences of immune response between both conditions. Here, we report a longitudinal analysis of the immune response in coronavirus disease 2019 patients, its correlation with outcome, and comparison between severe coronavirus disease 2019 patients and septic patients.Design: Longitudinal, retrospective observational study.Setting: Tertiary-care hospital during the first 2020 coronavirus disease 2019 outbreak in France.Patients: All successive patients with confirmed severe acute respiratory syndrome coronavirus 2 infection admitted to the emergency department, medical ward, and ICU with at least one available immunophenotyping performed during hospital stay.Measurements and main results: Between March and April 2020, 247 patients with coronavirus disease 2019 were included and compared with a historical cohort of 108 severe septic patients. Nonsevere coronavirus disease 2019 patients (n = 153) presented normal or slightly altered immune profiles. Severe coronavirus disease 2019 (n = 94) immune profile differed from sepsis. Coronavirus disease 2019 exhibited profound and prolonged lymphopenia (mostly on CD3, CD4, CD8, and NK cells), neutrophilia, and human leukocyte antigen D receptor expression on CD14+ monocytes down-regulation. Surprisingly, coronavirus disease 2019 patients presented a unique profile of B cells expansion, basophilia, and eosinophilia. Lymphopenia, human leukocyte antigen D receptor expression on CD14+ monocytes down-regulation, and neutrophilia were associated with a worsened outcome, whereas basophilia and eosinophilia were associated with survival. Circulating immune cell kinetics differed between severe coronavirus disease 2019 and sepsis, lack of correction of immune alterations in coronavirus disease 2019 patients during the first 2 weeks of ICU admission was associated with death and nosocomial infections.Conclusions: Circulating immune cells profile differs between mild and severe coronavirus disease 2019 patients. Severe coronavirus disease 2019 is associated with a unique immune profile as compared with sepsis. Several immune features are associated with outcome. Thus, immune monitoring of coronavirus disease 2019 might be of help for patient management.

Published
2021

46. Estimation of cardiac output variations induced by hemodynamic interventions using multi-beat analysis of arterial waveform: a comparative off-line study with transesophageal Doppler method during non-cardiac surgery

Author

Alex Hong, Jona Joachim, Joaquim Mateo, Etienne Gayat, Arthur Le Gall, Alexandre Mebazaa, and Fabrice Vallée

Subjects
medicine.medical_specialty, Accuracy and precision, Cardiac output, Concordance, Thermodilution, Hemodynamics, Health Informatics, Critical Care and Intensive Care Medicine, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, 030202 anesthesiology, Internal medicine, medicine, Humans, Waveform, Prospective Studies, Cardiac Output, Retrospective Studies, business.industry, Reproducibility of Results, 030208 emergency & critical care medicine, Anesthesiology and Pain Medicine, Blood pressure, Radial Artery, Cardiology, symbols, Bolus (digestion), business, Doppler effect
Abstract

Multi-beat analysis (MBA) of the radial arterial pressure (AP) waveform is a new method that may improve cardiac output (CO) estimation via modelling of the confounding arterial wave reflection. We evaluated the precision and accuracy using the trending ability of the MBA method to estimate absolute CO and variations (ΔCO) during hemodynamic challenges. We reviewed the hemodynamic challenges (fluid challenge or vasopressors) performed when intra-operative hypotension occurred during non-cardiac surgery. The CO was calculated offline using transesophageal Doppler (TED) waveform (COTED) or via application of the MBA algorithm onto the AP waveform (COMBA) before and after hemodynamic challenges. We evaluated the precision and the accuracy according to the Bland & Altman method. We also assessed the trending ability of the MBA by evaluating the percentage of concordance with 15% exclusion zone between ΔCOMBA and ΔCOTED. A non-inferiority margin was set at 87.5%. Among the 58 patients included, 23 (40%) received at least 1 fluid challenge, and 46 (81%) received at least 1 bolus of vasopressors. Before treatment, the COTED was 5.3 (IQR [4.1–8.1]) l min−1, and the COMBA was 4.1 (IQR [3–5.4]) l min−1. The agreement between COTED and COMBA was poor with a 70% percentage error. The bias and lower and upper limits of agreement between COTED and COMBA were 0.9 (CI95 = 0.82 to 1.07) l min−1, −2.8 (CI95 = −2.71 to−2.96) l min−1 and 4.7 (CI95 = 4.61 to 4.86) l min−1, respectively. After hemodynamic challenge, the percentage of concordance (PC) with 15% exclusion zone for ΔCO was 93 (CI97.5 = 90 to 97)%. In this retrospective offline analysis, the accuracy, limits of agreements and percentage error between TED and MBA for the absolute estimation of CO were poor, but the MBA could adequately track induced CO variations measured by TED. The MBA needs further evaluation in prospective studies to confirm those results in clinical practice conditions.

Published
2021

47. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

Author

John G F Cleland, A J S Coats, Marco Metra, John J.V. McMurray, Anne Kathrine Skibelund, Dimitrios Farmakis, Haran Burri, Tiny Jaarsma, Martine Gilard, Massimo F Piepoli, Roy S. Gardner, Frank Ruschitzka, Michael Böhm, Carolyn S.P. Lam, Javed Butler, Susanna Price, Andreas Baumbach, Ovidiu Chioncel, Alexander R. Lyon, Claudio Muneretto, Theresa McDonagh, Marianna Adamo, Jelena Čelutkienė, Ewa A. Jankowska, Alexandre Mebazaa, Giuseppe M.C. Rosano, Maria G Crespo-Leiro, Arno W. Hoes, Richard Mindham, Mitja Lainscak, Stephane Heymans, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Mcdonagh, Theresa A, Metra, Marco, Adamo, Marianna, Gardner, Roy S, Baumbach, Andrea, Böhm, Michael, Burri, Haran, Butler, Javed, Čelutkienė, Jelena, Chioncel, Ovidiu, Cleland, John G F, Coats, Andrew J S, Crespo-Leiro, Maria G, Farmakis, Dimitrio, Gilard, Martine, Heymans, Stephane, Hoes, Arno W, Jaarsma, Tiny, Jankowska, Ewa A, Lainscak, Mitja, Lam, Carolyn S P, Lyon, Alexander R, Mcmurray, John J V, Mebazaa, Alexandre, Mindham, Richard, Muneretto, Claudio, Francesco Piepoli, Massimo, Price, Susanna, Rosano, Giuseppe M C, Ruschitzka, Frank, and Kathrine Skibelund, Anne

Subjects
diagnosis, medicine.medical_treatment, heart failure, cardiac resynchronization therapy, Guideline, neuro-hormonal antagonist, pharmacotherapy, VENTRICULAR ASSIST DEVICE, QUALITY-OF-LIFE, multidisciplinary management, Medicine, ejection fraction, CARDIAC-RESYNCHRONIZATION THERAPY, Ejection fraction, advanced heart failure, transplantation, Guidelines, acute heart failure, arrhythmias, comorbidities, hospitalization, mechanical circulatory support, natriuretic peptides, neuro-hormonal antagonists, Chronic Disease, Humans, Stroke Volume, Cardiac Resynchronization Therapy, Heart Failure, diagnosi, PRESERVED EJECTION FRACTION, BRAIN NATRIURETIC PEPTIDE, Cardiology, CORONARY-ARTERY-DISEASE, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, comorbiditie, ACUTE MYOCARDIAL-INFARCTION, IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR, Cardiac resynchronization therapy, arrhythmia, Pharmacotherapy, Internal medicine, natriuretic peptide, business.industry, guidelines, medicine.disease, WORSENING RENAL-FUNCTION, Transplantation, Heart failure, AORTIC-VALVE-REPLACEMENT, business
Abstract

These are the clinical practice guidelines from the European Society of Cardiology for the diagnosis and treatment of acute and chronic heart failure, from 2021.

Published
2021

48. Monitoring circulating dipeptidyl peptidase 3 (DPP3) predicts improvement of organ failure and survival in sepsis: a prospective observational multinational study

Author

Etienne Gayat, Nicolas Deye, Xavier Wittebole, AdrenOSS study investigators, Pierre-François Laterre, Bruno François, Oliver Hartmann, Gernot Marx, Charles Damoisel, Vincent Huberlant, Emmanuelle Mercier, Thierry Dugernier, Alice Blet, Jean-Michel Constantin, Dirk van Lier, Karine Santos, Stéphane Gaudry, Benjamin G. Chousterman, Peter Pickkers, Jean-Baptiste Lascarrou, Salvatore Di Somma, Matthieu Legrand, Romain Sonneville, Feriel Azibani, Albertus Beishuizen, Andreas Bergmann, Alexandre Mebazaa, Benjamin Deniau, Joachim Struck, Massimo Antonelli, Haikel Oueslati, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, and UCL - (SLuc) Service de soins intensifs

Subjects
Male, Kidney Disease, Organ Dysfunction Scores, medicine.medical_treatment, Organ dysfunction, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Medical and Health Sciences, law.invention, 0302 clinical medicine, law, Septic shock, Prospective Studies, Outcome, Cardiogenic shock, Statistics, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Hematology, Middle Aged, Intensive care unit, Intensive Care Units, Infectious Diseases, AdrenOSS-1 Study Investigators, Female, SOFA score, medicine.symptom, Infection, medicine.medical_specialty, Multiple Organ Failure, DPP3, Statistics, Nonparametric, Sepsis, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Clinical Research, Internal medicine, medicine, Humans, Nonparametric, Renal replacement therapy, Mortality, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Aged, Proportional Hazards Models, Mechanical ventilation, Chi-Square Distribution, business.industry, Inflammatory and immune system, Research, 030208 emergency & critical care medicine, Biomarker, lcsh:RC86-88.9, medicine.disease, Emergency & Critical Care Medicine, Good Health and Well Being, business, Biomarkers
Abstract

Critical care 25(1), 61 (2021). doi:10.1186/s13054-021-03471-2, Published by BioMed Centra, London

Published
2021

49. Unusual arterial thrombotic events in Covid-19 patients

Author

P. Reiner, R. Bordier, C. de Roquetaillade, Marco Metra, Benjamin G. Chousterman, Gilles Montalescot, A. Guedon, Etienne Gayat, Michel Zeitouni, E. Houdart, D. Tomasoni, Alexandre Mebazaa, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Brescia, Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and CCSD, Accord Elsevier

Subjects
Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Short Communication, [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030204 cardiovascular system & hematology, Anticoagulation, 03 medical and health sciences, 0302 clinical medicine, Ischemia, Internal medicine, medicine, Humans, Splenic Infarction, 030212 general & internal medicine, Endothelial dysfunction, Stroke, Aorta, Aged, Retrospective Studies, SARS-CoV-2, business.industry, Acute coronary syndrom, Incidence (epidemiology), Arterial thrombosis, Anticoagulants, Extremities, Thrombosis, Middle Aged, Occlusive mesenteric ischemia, medicine.disease, Limb ischemia, 3. Good health, [SDV] Life Sciences [q-bio], Coronary Occlusion, Italy, Treatment dose, Mesenteric Ischemia, Cardiology, Female, France, Covid-19, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors
Abstract

Introduction COVID-19 infection is commonly complicated with pro-thrombotic state and endothelial dysfunction. While several studies reported a high incidence of venous thromboembolic events. The occurrence of arterial thromboses are yet rarely described and could be underestimated. Objectives To describe the clinical and biological characteristics of COVID-19 patients presenting with an associated arterial thromboembolic event. Material and methods We performed a retrospective multicentric study in 3 centers between France and Italy. All patients with a confirmed SARS-CoV-2 infection and arterial thromboembolic events were included in the analysis. Results From March 8th to April 25th 2020, we identified 20 patients (24 events) with arterial thromboembolic events over 209 admitted patients (9.6%) with severe COVID-19 infection. Arterial thrombotic events included acute coronary occlusions (n = 9), stroke (n = 6), limb ischemia (n = 3), splenic infarcts (n = 3), aortic thrombosis (n = 2) and occlusive mesenteric ischemia (n = 1). At the time of the event, 10/20 (50%) of patients received thromboprohylaxis, 2/20 (10%) were receiving treatment dose anticoagulation and 5/20 (25%) were receiving antiplatelet therapy. Conclusion Our observations suggest that serious arterial thrombotic events might occur in Covid-19 patients. However, the exact incidence of such events and the best way to prevent them yet remains to be investigated., Highlights • SARS-CoV-2 infection is commonly complicated with pro-thrombotic state and endothelial dysfunction. • High rate of venous thromboembolic events have been described among patients suffering from Covid-19. However, arterial thromboses are yet rarely described in this setting. • We report a total of 20 cases of COVID-19 patients suffering from arterial thromboses. • Our observations suggest that arterial thrombotic events might occur in Covid-19 patients and could be underestimated.

Published
2021

50. Kinetics of procalcitonin, C-reactive protein and interleukin-6 in cardiogenic shock – Insights from the CardShock study

Author

José Silva-Cardoso, Jindrich Spinar, Tuija Sabell, Heli Tolppanen, Valentina Carubelli, Monika Kasztura, Anu Kataja, Raija Jurkko, Veli-Pekka Harjola, Alexandre Mebazaa, John Parissis, Mari Hongisto, Ewa A. Jankowska, Kari Pulkki, Tuukka Tarvasmäki, Johan Lassus, Marek Banaszewski, Alessandro Sionis, and Toni Jäntti

Subjects
medicine.medical_specialty, Shock, Cardiogenic, Interleukin 6, Inflammation, 030204 cardiovascular system & hematology, Gastroenterology, Procalcitonin, C-reactive protein, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Cardiogenic shock, biology, Interleukin-6, business.industry, Prognosis, medicine.disease, Pathophysiology, 3. Good health, Kinetics, C-Reactive Protein, biology.protein, Population study, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Perfusion, Biomarkers
Abstract

Background: Inflammatory responses play an important role in the pathophysiology of cardiogenic shock (CS). The aim of this study was to investigate the kinetics of procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) in CS and to assess their relation to clinical presentation, other biochemical variables, and prognosis. Methods: Levels of PCT, CRP and IL-6 were analyzed in serial plasma samples (0-120h) from 183 patients in the CardShock study. The study population was dichotomized by PCTmax >= and < 0.5 mu g/L, and IL-6 and CRPmax above/below median. Results: PCT peaked already at 24 h [median PCTmax 0.71 mu g/L (IQR 0.24-3.4)], whereas CRP peaked later between 48 and 72 h [median CRPmax 137mg/L (59-247)]. PCT levels were significantly higher among non-survivors compared with survivors from 12 h on, as were CRP levels from 24 h on (p < 0.001). PCTmax >= 0.5 mu g/L (60% of patients) was associated with clinical signs of systemic hypoperfusion, cardiac and renal dysfunction, acidosis, and higher levels of blood lactate, IL-6, growth-differentiation factor 15 (GDF-15), and CRPmax. Similarly, IL-6 > median was associated with clinical signs and biochemical findings of systemic hypoperfusion. PCTmax >= 0.5 mu g/L and IL-6 > median were associated with increased 90-day mortality (50% vs. 30% and 57% vs. 22%, respectively; p < 0.01 for both), while CRPmax showed no prognostic significance. The association of inflammatory markers with clinical infections was modest. Conclusions: Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis. (C) 2020 Elsevier B.V. All rights reserved.

Published
2021

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