Search

Heart failure (HF) is a rising global cardiovascular epidemic driven by aging and chronic inflammation. As elderly populations continue to increase, precision treatments for age-related cardiac decline are urgently needed. Here we report that cardiac and blood expression of IGFBP7 is robustly increased in patients with chronic HF and in an HF mouse model. In a pressure overload mouse HF model, Igfbp7 deficiency attenuated cardiac dysfunction by reducing cardiac inflammatory injury, tissue fibrosis and cellular senescence. IGFBP7 promoted cardiac senescence by stimulating IGF-1R/IRS/AKT-dependent suppression of FOXO3a, preventing DNA repair and reactive oxygen species (ROS) detoxification, thereby accelerating the progression of HF. In vivo, AAV9-shRNA-mediated cardiac myocyte Igfbp7 knockdown indicated that myocardial IGFBP7 directly regulates pathological cardiac remodeling. Moreover, antibody-mediated IGFBP7 neutralization in vivo reversed IGFBP7-induced suppression of FOXO3a, restored DNA repair and ROS detoxification signals and attenuated pressure-overload-induced HF in mice. Consequently, selectively targeting IGFBP7-regulated senescence pathways may have broad therapeutic potential for HF.

Resume Pour une revue medicale, la diffusion a grande echelle de chacun de ses articles est aujourd’hui indispensable pour toucher un large public scientifique. Dans ce contexte, l’utilisation du reseau social Twitter permet a chaque nouvelle publication d’etre diffusee tres rapidement, a faible cout, pour des lecteurs precis et partout dans le monde. C’est de loin le reseau social le plus utilise pour partager les publications en 2021. Les reflexions autour de ce sujet ont ainsi abouti a la creation en novembre 2020 de la Social Media Team (SoMe Team) d’Anaesthesia Critical Care and Pain Medicine, le journal anglophone international de la Societe francaise d’anesthesie et de reanimation (SFAR). Cette equipe est coordonnee par un editeur en charge des reseaux sociaux, en lien direct avec le redacteur en chef du journal. Il elabore le planning des tweets en fonction du programme de publication du journal, il fleche le type de contenu qui y sera associe et sollicite les auteurs pour l’obtention d’images ou de courtes videos de presentation de leur publication. Le contenu graphique et la diffusion sur Twitter sont assures par les membres de l’equipe dediee aux reseaux sociaux.

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

The coronavirus disease 2019 (COVID-19) pandemic has affected health and economy worldwide on an unprecedented scale. Patients have diverse clinical outcomes, but those with preexisting cardiovascular disease, hypertension, and related conditions incur disproportionately worse outcome. The high infectivity of severe acute respiratory syndrome coronavirus 2 is in part related to new mutations in the receptor binding domain, and acquisition of a furin cleavage site in the S-spike protein. The continued viral shedding in the asymptomatic and presymptomatic individuals enhances its community transmission. The virus uses the angiotensin converting enzyme 2 receptor for internalization, aided by transmembrane protease serine 2 protease. The tissue localization of the receptors correlates with COVID-19 presenting symptoms and organ dysfunction. Virus-induced angiotensin converting enzyme 2 downregulation may attenuate its function, diminish its anti-inflammatory role, and heighten angiotensin II effects in the predisposed patients. Lymphopenia occurs early and is prognostic, potentially associated with reduction of the CD4+ and some CD8+ T cells. This leads to imbalance of the innate/acquired immune response, delayed viral clearance, and hyperstimulated macrophages and neutrophils. Appropriate type I interferon pathway activation is critical for virus attenuation and balanced immune response. Persistent immune activation in predisposed patients, such as elderly adults and those with cardiovascular risk, can lead to hemophagocytosis-like syndrome, with uncontrolled amplification of cytokine production, leading to multiorgan failure and death. In addition to the airways and lungs, the cardiovascular system is often involved in COVID-19 early, reflected in the release of highly sensitive troponin and natriuretic peptides, which are all extremely prognostic, in particular, in those showing continued rise, along with cytokines such as interleukin-6. Inflammation in the vascular system can result in diffuse microangiopathy with thrombosis. Inflammation in the myocardium can result in myocarditis, heart failure, cardiac arrhythmias, acute coronary syndrome, rapid deterioration, and sudden death. Aggressive support based on early prognostic indicators with expectant management can potentially improve recovery. Appropriate treatment for heart failure, arrhythmias, acute coronary syndrome, and thrombosis remain important. Specific evidence-based treatment strategies for COVID-19 will emerge with ongoing global collaboration on multiple approaches being evaluated. To protect the wider population, antibody testing and effective vaccine will be needed to make COVID-19 history.

Objectives The world is currently facing an unprecedented healthcare crisis caused by the COVID-19 pandemic. The objective of these guidelines is to produce a framework to facilitate the partial and gradual resumption of intervention activity in the context of the COVID-19 pandemic. Methods The group has endeavoured to produce a minimum number of recommendations to highlight the strengths to be retained in the 7 predefined areas: (1) protection of staff and patients; (2) benefit/risk and patient information; (3) preoperative assessment and decision on intervention; (4) modalities of the preanaesthesia consultation; (5) specificity of anaesthesia and analgesia; (6) dedicated circuits and (7) containment exit type of interventions. Results The SFAR Guideline panel provides 51 statements on anaesthesia management in the context of COVID-19 pandemic. After one round of discussion and various amendments, a strong agreement was reached for 100% of the recommendations and algorithms. Conclusion We present suggestions for how the risk of transmission by and to anaesthetists can be minimised and how personal protective equipment policies relate to COVID-19 pandemic context.

Objectives To provide recommendations to facilitate the management of severe thermal burns during the acute phase in adults and children. Design A committee of 20 experts was asked to produce recommendations in six fields of burn management, namely, (1) assessment, admission to specialised burns centres, and telemedicine; (2) haemodynamic management; (3) airway management and smoke inhalation; (4) anaesthesia and analgesia; (5) burn wound treatments; and (6) other treatments. At the start of the recommendation-formulation process, a formal conflict-of-interest policy was developed and enforced throughout the process. The entire process was conducted independently of any industry funding. The experts drew up a list of questions that were formulated according to the PICO model (Population, Intervention, Comparison, and Outcomes). Two bibliography experts per field analysed the literature published from January 2000 onwards using predefined keywords according to PRISMA recommendations. The quality of data from the selected literature was assessed using GRADE® methodology. Due to the current paucity of sufficiently powered studies regarding hard outcomes (i.e. mortality), the recommendations are based on expert opinion. Results The SFAR guidelines panel generated 24 statements regarding the management of acute burn injuries in adults and children. After two scoring rounds and one amendment, strong agreement was reached for all recommendations. Conclusion Substantial agreement was reached among a large cohort of experts regarding numerous strong recommendations to optimise the management of acute burn injuries in adults and children.

Myocarditis and pericarditis may constitute adverse reactions of mRNA coronavirus disease 2019 (COVID-19) vaccines. This study aimed to document these reactions and to assess the association with patient sex and age. This is as an observational retrospective study using a case-non-case design (also called disproportionality study) on inflammatory heart reactions reported with mRNA COVID-19 vaccines within the World Health Organization (WHO) global safety database (VigiBase), up to June 30, 2021. Results are expressed using reporting odds ratios (RORs) and their 95% confidence interval (95% CI). Of 716,576 reports related to mRNA COVID-19 vaccines, 2,277 were cases of inflammatory heart reactions, including 1241 (55%) myocarditis and 851 (37%) pericarditis. The main age group was 18-29 years (704, 31%), and mostly male patients (1,555, 68%). Pericarditis onset was delayed compared with myocarditis with a median time to onset of 8 (3-21) vs. 3 (2-6) days, respectively (P = 0.001). Regarding myocarditis, an important disproportionate reporting was observed in adolescents (ROR, 22.3, 95% CI 19.2-25.9) and in 18-29 years old (ROR, 6.6, 95% CI 5.9-7.5) compared with older patients, as well as in male patients (ROR, 9.4, 95% CI 8.3-10.6). Reporting rate of myocarditis was increased in young adults and adolescents. Inflammatory heart reactions may rarely occur shortly following mRNA COVID-19 vaccination. Although an important disproportionate reporting of myocarditis was observed among adolescents and young adults, particularly in male patients, reporting rates support a very rare risk, that does not seem to compromise the largely positive benefit-risk balance of these vaccines. Furthermore, this study confirmed the value of disproportionality analyses for estimation of relative risks among subgroups of patients.

Aims: Bioactive adrenomedullin (bio-ADM) was recently shown to be a prognostic marker in patients with acute circulatory failure. We investigate the association of bio-ADM with organ injury, functional impairment, and survival in cardiogenic shock (CS). Methods: OptimaCC was a multicenter and randomized trial in 57 patients with CS. In this post-hoc analysis, the primary endpoint was to assess the association between bio-ADM and 30-day all-cause mortality. Secondary endpoints included adverse events and parameters of organ injury or functional impairment. Results: Bio-ADM values were higher in 30-day non-survivors than 30-day survivors at inclusion (median (interquartile range) 67.0 (54.6–142.9) pg/mL vs. 38.7 (23.8–63.6) pg/mL, p = 0.010), at 24 h (p = 0.012), and up to 48 h (p = 0.027). Using a bio-ADM cutoff of 53.8 pg/mL, patients with increased bio-ADM had a HR of 3.90 (95% confidence interval 1.43–10.68, p = 0.008) for 30-day all-cause mortality, and similar results were observed even after adjustment for severity scores. Patients with the occurrence of refractory CS had higher bio-ADM value at inclusion (90.7 (59.9–147.7) pg/mL vs. 40.7 (23.0–64.7) pg/mL p = 0.005). Bio-ADM values at inclusion were correlated with pulmonary vascular resistance index, estimated glomerular filtration rate, and N-terminal pro-B-type natriuretic peptide (r = 0.49, r = –0.47, and r = 0.64, respectively, p &lt, 0.001). Conclusions: In CS patients, the values of bio-ADM are associated with some parameters of organ injury and functional impairment and are prognostic for the occurrence of refractory CS and 30-day mortality.

BackgroundTo counter the COVID-19 pandemic, mRNA vaccines, namely tozinameran and elasomeran, have been authorized in several countries. These next generation vaccines have shown high efficacy against COVID-19 and demonstrated a favorable safety profile. As widespread vaccinations efforts are taking place, incidents of myocarditis and pericarditis cases following vaccination have been reported. This safety signal has been recently confirmed by the European Medicine Agency and the U.S. Food and Drug Administration.This study aimed to investigate and analyze this safety signal using a dual pharmacovigilance database analysis.MethodsThis is as an observational study of reports of inflammatory heart reactions associated with mRNA COVID-19 vaccines reported in the World Health Organization’s global individual case safety report database (up to June 30th 2021), and in the U.S. Vaccine Adverse Event Reporting System (VAERS, up to May 21st 2021). Cases were described, and disproportionality analyses using reporting odds-ratios (ROR) and their 95% confidence interval (95%CI) were performed to assess relative risk of reporting according to patient sex and age.ResultsAt a global scale, the inflammatory heart reactions most frequently reported were myocarditis (1241, 55%) and pericarditis (851, 37%), the majority requiring hospitalization (n=796 (64%)). Overall, patients were young (median age 33 [21-54] years). The main age group was 18-29 years old (704, 31%), and mostly males (1555, 68%). Pericarditis onset was delayed compared to myocarditis with a median time to onset of 8 [3-21] vs. 3 [2-6] days, respectively (p=0.001). Regarding myocarditis, an important disproportionate reporting in males (ROR, 9.4 [8.3-10.6]) as well as in adolescents (ROR, 22.3 [19.2-25.9]) and 18-29 years old (ROR, 6.6 [5.9-7.5]) compared to older patients were observed.ConclusionsThe inflammatory heart reactions, namely myocarditis and pericarditis, have been reported world-wide shortly following COVID-19 mRNA vaccination. An important disproportionate reporting among adolescents and young adults, particularly in males, was observed especially for myocarditis. Guidelines must take this specific risk into account and to optimize vaccination protocols according to sex and age. While the substantial benefits of COVID-19 vaccination still prevail over risks, clinicians and the public should be aware of these reactions and seek appropriate medical attention.

Background Quantifying the activity of the adrenomedullin system might help to monitor and guide treatment in acute heart failure (AHF) patients. The aims were to (1) identify AHF patients with marked benefit or harm from specific treatments at hospital discharge and (2) predict mortality by quantifying the adrenomedullin system activity. Methods This was a prospective multicentre study. AHF diagnosis and phenotype were centrally adjudicated by two independent cardiologists among patients presenting to the emergency department with acute dyspnoea. Adrenomedullin system activity was quantified using the biologically active component, bioactive adrenomedullin (bio-ADM), and a prohormone fragment, midregional proadrenomedullin (MR-proADM). Bio-ADM and MR-proADM concentrations were measured in a blinded fashion at presentation and at discharge. Interaction with specific treatments at discharge and the utility of these biomarkers on predicting outcomes during 365-day follow-up were assessed. Results Among 1886 patients with adjudicated AHF, 514 patients (27.3%) died during 365-day follow-up. After adjusting for age, creatinine, and treatment at discharge, patients with bio-ADM plasma concentrations above the median (> 44.6 pg/mL) derived disproportional benefit if treated with diuretics (interaction p values n = 764) (interaction p values p p Conclusions Quantifying the adrenomedullin’s system activity may help to personalise post-discharge diuretic treatment and enable accurate risk-prediction in AHF.

Background Lumbar puncture (LP) is an invasive medical procedure that can be done by any doctor. Several simulation-based trainings have been built however the evaluations of the theoretical knowledge and the impact of the simulation-based training have never been performed in real life. The objective was to evaluate the impact of a LP training on the theoretical knowledge improvement and the performance of a LP in clinical practice. Methods Before and after medical students’ training, theoretical knowledge and confidence level were assessed. Over a 6 months period, the impact of simulation training was evaluated by the success rate of students’ first LP carried out in hospitalized patients and compared to the results of a no-training control. Results Students’ theoretical knowledge and confidence level showed significant improvement after simulation training on 115 students (p p = 0.0025). The technical assistance was also less frequently needed in the LP simulation group (19% vs 57%, respectively, p = 0.017). The rate of students who participated in this educational study was low. Discussion Simulation-based teaching was an effective way to improve students’ theoretical and practical knowledge. Whether this approach translates to other procedural skills in real clinical settings merits further study. The low participation rate in the study is due to the fact that students are not used to be included in educational studies and to the complexity of evaluation in routine clinical practice.

Supplemental Digital Content is available in the text., The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019, to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for high-sensitivity cardiac troponin I was 7.12 ([95% CI, 4.60–11.03] P

Sepsis is a global economic and health burden. Dipeptidyl peptidase 3 (DPP3) is elevated in the plasma of septic patients. The highest levels of circulating DPP3 (cDPP3) are found in non-survivor septic shock patients. The aim of this study was to evaluate the benefits of inhibiting cDPP3 by a specific antibody, Procizumab (PCZ), on cardiac function in an experimental model of sepsis, the caecal ligature and puncture (CLP) model. Rats were monitored by invasive blood pressure and echocardiography. Results are presented as mean ± SD, with p

Aims Adrenomedullin (ADM) is an important regulator of endothelial barrier function and vascular tone, and may represent a novel treatment target in sepsis. The non-neutralizing ADM antibody adrecizumab has shown promising results in preclinical sepsis models. In the present study, we investigated the safety, tolerability and pharmacokinetics (PK)/pharmacodynamics of adrecizumab in a first-in-man study and in a second study during experimental human endotoxaemia. Methods Forty-eight healthy male volunteers were enrolled in two randomized, double-blind, placebo-controlled phase I studies. In both studies, subjects received placebo or one of three doses of adrecizumab (n = 6 per group). In the second study, a bolus of 1 ng kg-1 endotoxin was followed by infusion of 1 ng kg-1 h-1 endotoxin for 3 h to induce systemic inflammation, and the study medication infusion started 1 h after endotoxin bolus administration. Results Adrecizumab showed an excellent safety profile in both studies. PK analyses showed proportional increases in the maximum plasma concentration of adrecizumab with increasing doses, a small volume of distribution, a low clearance rate and a terminal half-life of ~14 days. adrecizumab elicited a pronounced increase in plasma ADM levels, whereas levels of mid-regional pro-adrenomedullin remained unchanged, indicating that de novo synthesis of ADM was not influenced. In the second study, no effects of adrecizumab on cytokine clearance were observed, whereas endotoxin-induced flu-like symptoms resolved more rapidly. Conclusions Administration of adrecizumab is safe and well tolerated in humans, both in the absence and presence of systemic inflammation. These findings pave the way for further investigation of adrecizumab in sepsis patients.

Critical care clinicians are trained to analyze simultaneously multiple physiological parameters to predict critical conditions such as hemodynamic instability. We developed the Multi-task Learning Physiological Deep Learner (MTL-PDL), a deep learning algorithm that predicts simultaneously the mean arterial pressure (MAP) and the heart rate (HR). In an external validation dataset, our model exhibited very good calibration: R2 of 0.747 (95% confidence interval, 0.692 to 0.794) and 0.850 (0.815 to 0.879) for respectively, MAP and HR prediction 60-minutes ahead of time. For acute hypotensive episodes defined as a MAP below 65 mmHg for 5 min, our MTL-PDL reached a predictive value of 90% for patients at very high risk (predicted MAP ≤ 60 mmHg) and 2‰ for patients at low risk (predicted MAP >70 mmHg). Based on its excellent prediction performance, the Physiological Deep Learner has the potential to help the clinician proactively adjust the treatment in order to avoid hypotensive episodes and end-organ hypoperfusion.

OBJECTIVES: Adrenomedullin has vascular properties and elevated plasma adrenomedullin levels were detected in sepsis. We assessed, in septic and nonseptic ICU patients, the relation between circulating adrenomedullin, the need for organ support and mortality, using an assay of bioactive adrenomedullin. DESIGN: Prospective multicenter observational cohort study. SETTING: Data from the French and euRopean Outcome reGistry in ICUs study. PATIENTS: Consecutive patients admitted to intensive care with a requirement for invasive mechanical ventilation and/or vasoactive drug support for more than 24 hours following ICU admission and discharged from ICU were included. INTERVENTIONS: Clinical and biological parameters were collected at baseline, including bioactive-adrenomedullin. Status of ICU survivors was assess until 1 year after discharge. The main outcome was the need for organ support, including renal replacement therapy and/or for inotrope(s) and/or vasopressor(s). Secondary endpoints were the ICU length of stay and the 28-day all-cause mortality. MEASUREMENTS AND MAIN RESULTS: Median plasma bioactive adrenomedullin (n = 2,003) was 66.6 pg/mL (34.6-136.4 pg/mL) and the median Simplified Acute Physiology Score II score 49 (36-63). Renal replacement therapy was needed in 23% and inotropes(s) and/or vasopressor(s) in 77% of studied patients. ICU length of stay was 13 days (7-21 d) and mortality at 28 days was 22 %. Elevated bioactive adrenomedullin independently predicted 1) the need for organ support (odds ratio, 4.02; 95% CI, 3.08-5.25) in ICU patients whether admitted for septic or nonseptic causes and 2) the need for renal replacement therapy (odds ratio, 4.89; 3.83-6.28), and for inotrope(s) and/or vasopressor(s) (odds ratio, 3.64; 2.84-4.69), even in patients who were not on those supports at baseline. Elevated bioactive adrenomedullin was also associated with a prolonged length of stay (odds ratio, 1.85; 1.49-2.29) and, after adjustment for Simplified Acute Physiology Score II, with mortality (odds ratio, 2.31; 1.83-2.92). CONCLUSIONS: Early measurement of bioactive adrenomedullin is a strong predictor of the need of organ support and of short-term mortality in critically ill patients

Aims Acute heart failure is a high mortality disease and its pathophysiology is not completely understood. Dipeptidyl peptidase 3 (DPP3) is a cytosolic enzyme involved in angiotensin II and enkephalins cleavage. The aim of this study was to investigate the association of circulating DPP3 (cDPP3) levels and mortality in cardiogenic shock patients and to determine the effects of high cDPP3 on organ function in a heart failure (HF) model in mice. Methods and results cDPP3 was measured in 174 patients in cardiogenic shock and high cDPP3 levels were associated with an increased short-term mortality risk (standardized hazard ratio: 1.4 (1.1-1.8)) and severe organ dysfunction. Additionally, a rapid decrease in cDPP3 in cardiogenic shock patients within 24 h of admission was associated with a favourable outcome. This study showed that injection of DPP3 induced myocardial depression (-10 ± 2% of shortening fraction) and impaired kidney haemodynamics (+0.30 ± 0.02 of renal resistive index) in healthy mice. cDPP3 inhibition by Procizumab, a specific antibody directed against cDPP3, promptly normalized cardiac function and kidney haemodynamics in an acute heart failure mouse model, with a marked reduction in oxidative stress and inflammatory signalling. Conclusion Our study demonstrated cDPP3 is a newly discovered myocardial depressant factor, the levels of which at admission are associated with mortality in severe HF patients. Furthermore, inhibition of cDPP3 by Procizumab improved haemodynamics in a mouse model of HF. Our results suggest that DPP3 could be a new biomarker and biotarget for severe HF.

BMJ open 9(2), e024475 (2019). doi:10.1136/bmjopen-2018-024475, Published by BMJ Publishing Group, London

Background Sepsis still represents a major health issue, with persistent high morbidity and mortality rates. Cardiovascular dysfunction occurs frequently during sepsis. Adrenomedullin has been identified as a key mediator in vascular tone regulation. A non-neutralizing anti-adrenomedullin antibody, Adrecizumab, may improve haemodynamic dysfunction during caecal ligation and puncture-induced septic shock in a murine model. Our objective was to determine the role of Adrecizumab on haemodynamics in a rat model of sepsis. Methods For the induction of sepsis, caecal ligation and puncture were performed in Wistar male rats. Single blinded administration of Adrecizumab (2 mg/kg) or placebo was injected i.v. 24 h after the surgery, and norepinephrine was infused as the standard of care. There were > 7 animals per group. Invasive blood pressure and cardiac function (by echocardiography) were assessed until 3 h after Adrecizumab injection. Results A single therapeutic injection of Adrecizumab in septic rats induced rapid haemodynamic benefits with an increase in systolic blood pressure in septic-Adrecizumab rats versus untreated-septic rats (p = 0.049). The shortening fraction did not differ between the untreated-septic and septic-Adrecizumab groups. However, cardiac output increased during the 3 h after a single dose of Adrecizumab compared to untreated septic rats (p = 0.006). A single dose of Adrecizumab resulted in similar haemodynamics to the continuous administration of norepinephrine. Three hours after a single injection of Adrecizumab, there was no change in the inflammatory phenotype (TNFα, IL-10) in the hearts of the septic rats. By contrast, 3 h after a single Adrecizumab injection, free-radical production decreased in the hearts of septic-Adrecizumab vs untreated septic rats (p

International audience; Background: Acute hypotensive episodes (AHE), defined as a drop in the mean arterial pressure (MAP)

Introduction Heart failure (HF) affects more than 10% of people over the age of 651. Regardless the etiology, kidney injury is common during HF1. Correlation between the evolution, severity and mortality of HF and increase of renal resistance index (RRI) has been shown. The objective of this study is to describe the evolution of RRI in a mice acute heart failure (AHF) model. Methods The local ethics committee approved the study (S84/CNREEA#9). AHF was induced by subcutaneous injections of isoproterenol 3 and defined by a 10% decrease in the shortening fraction (SF) compared to baseline in C57Bl6 wild type male mice. The RRI was assessed by echography, after induction of AHF or in sham mice, as follow: RRI = (peak systolic velocity–end diastolic peak)/peak systolic velocity. RRI were compared by a Wilcoxon test (R software v3.4.4). A P value Results A total of 13 C57Bl6 mice were included (7 in sham group, 6 in AHF group). AHF mice had a lower SF and heart rate (HR) compared to sham mice (respectively 47 ± 1.7 vs. 62 ± 0.9, P Conclusion In our study, RRI increased in AHF mice and renal mean velocity decreased, suggesting a kidney injury induced by AHF. For the first time in a mice preclinical model, we showed the availability of a new tool in small animal to assess renal hemodynamic. Further studies are needed to confirm the validity of this marker during AHF, especially regarding kidney injury biomarkers.

Sepsis and septic shock still represent major health issues, with persisting high morbidity and mortality rates in critically ill patients. Cardiac dysfunction[1] occurs frequently during severe sepsis. Adrenomedullin (ADM) has been identified as a key mediator in vascular tone regulation[1]. A newly developed anti-ADM antibody Adrecizumab (ADZ) may improve hemodynamic dysfunction during resuscitated murine, cecal ligation and puncture (CLP)-induced septic shock[2].

Initial resuscitation, historically based on crystalloids fluids administration, is essential to burn patients' survival. However, hemodynamic targets have been poorly explored although avoidance of both hypovolemic status and too liberal fluid administration is the bottom line [1, 2].

International audience; The influenza H1N1 epidemics in 2009 led a substantial number of people to develop severe acute respiratory distress syndrome and refractory hypoxemia. In these patients, extracorporeal membrane oxygenation was used as rescue oxygenation therapy. Several randomized clinical trials and observational studies suggested that extracorporeal membrane oxygenation associated with protective mechanical ventilation could improve outcome, but its efficacy remains uncertain. Organized by the Societe de Reanimation de Langue Francaise (SRLF) in conjunction with the Societe Francaise d'Anesthesie et de Reanimation (SFAR), the Societe de Pneumologie de Langue Francaise (SPLF), the Groupe Francophone de Reanimation et d'Urgences Pediatriques (GFRUP), the Societe Francaise de Perfusion (SOFRAPERF), the Societe Francaise de Chirurgie Thoracique et Cardiovasculaire (SFCTV) et the Sociedad Espanola de Medecina Intensiva Critica y Unidades Coronarias (SEMICYUC), a Consensus Conference was held in December 2013 and a jury of 13 members wrote 65 recommendations to answer the five following questions regarding the place of extracorporeal life support for patients with acute respiratory distress syndrome: 1) What are the available techniques?; 2) Which patients could benefit from extracorporeal life support?; 3) How to perform extracorporeal life support?; 4) How and when to stop extracorporeal life support?; 5) Which organization should be recommended? To write the recommendations, evidence-based medicine (GRADE method), expert panel opinions, and shared decisions taken by all the thirteen members of the jury of the Consensus Conference were taken into account.

International audience; Corticosteroids have been shown to reduce short-term mortality during septic shock and therefore recommended in the most severe patients as adjuvant therapy. Until recently, recombinant human activated protein C (APC) was also considered in the management of more severe cases. As myocardial depression has long been recognized as a manifestation of organ dysfunction during septic shock, we examined whether corticosteroids (dexamethasone, 150 µg/kg per hour) and/or APC (33 µg/kg per hour) treatments improve sepsis-induced cardiac dysfunction during cecal ligature and puncture-induced septic shock in Wistar rats. All rats received intravenous saline resuscitation (10 mL/kg per hour) and antibiotics. Eighteen hours after surgery, anesthesia was performed (isoflurane), and myocardial function was assessed using a conductance catheter introduced into the left ventricle. Rats were then killed; blood and heart were harvested for biological analysis, including radical oxygen species determination. Cecal ligature and puncture induced hypotension, depression of myocardial systolic performance (demonstrated by significant decreases in dP/dtmax [first derivative of maximal developed pressure during isovolumetric contraction], end-systolic pressure-volume relationship, and preload recruitable stroke work) and alteration of diastolic function (dP/dtmin [first derivative of minimal developed pressure during isovolumetric relaxation]), whereas dexamethasone, APC, and their combination thereof allowed correction of hemodynamic disorders and improved myocardial mechanical efficiency. Cecal ligature and puncture was associated with higher levels of nitric oxide and superoxide anion (O2) in heart (electron paramagnetic resonance studies) and consequently peroxynitrite. Dexamethasone and APC also improved cardiac dysfunction by downregulating the inducible nitric oxide synthase pathway and reducing myocardial oxidative stress.

Background Impact of early systemic hemodynamic alterations and fluid resuscitation on outcome in the modern burn care remains controversial. We investigate the association between acute-phase systemic hemodynamics, timing of fluid resuscitation and outcome in critically ill burn patients. Methods Retrospective, single-center cohort study was conducted in a university hospital. Forty critically ill burn patients with total body surface area (TBSA) burn-injured >20 % with invasive blood pressure and cardiac output monitoring (transpulmonary thermodilution technique) within 8 h from trauma were included. We retrospectively examined hemodynamic variables during the first 24 h following admission, and their association with 90-day mortality. Results The median (interquartile range 25th–75th percentile) TBSA, Simplified Acute Physiology Score II (SAPS II) and Abbreviated Burn Severity Index of the study population were 41 (29–56), 31 (23–50) and 9 (7–11) %, respectively. 90-Day mortality was 42 %. There was no statistical difference between the median pre-hospital and 24-h administered fluid volume in survivors and non-survivors. On admission, stroke volume (SV), cardiac index (CI), oxygen delivery index and mean arterial pressure (MAP) were significantly lower in patients who died despite similar fluid resuscitation volume. ROC curves comparing the ability of initial SV, CI, MAP and lactate to discriminate 90-day mortality gave areas under curves of, respectively, 0.89 (CI 0.77–1), 0.77 (CI 0.58–0.95), 0.73 (CI 0.53–0.93) and 0.78 (CI 0.63–0.92); (p value

Acute heart failure (HF) is a multifactorial condition responsible for the death of several million people each year. Its pathophysiology is complex and not fully elucidated. Moreover, current treatments do not prevent the death of the most serious patients. Dipeptidyl peptidase 3 (DPP3) is a ubiquitous metalloproteinase involved in many biological processes, including blood pressure regulation (by cleaving angiotensin 2). The exact biological functions of DPP3 are unknown. The aims of this work were to determine the pathophysiological functions of DPP3 during catecholaminergic and septic induced acute HF. MethodsTwo models were used in this work: 1/Induced isoproterenol HF model (ISO, 300 mg/kg/12h) in 3-month-old male C57Bl6j mice and 2/ Induced septic HF model in 3-month-old male Wistar rats by ligation and caecal puncture (CLP). Cardiovascular (in both models) and renal (in the ISO model) parameters were evaluated by ultrasound. Myocardial oxidative stress was explored by DHE labeling on heart slices in both models. In vitro angiotensin assays in the presence of DPP3 were performed in mice (ISO model).ResultsInjection of the DPP3 protein in healthy mice was responsible for myocardial depression (10 ± 2% decrease in the shortening fraction) as well as altered renal hemodynamics (increase in renal resistance index of 0.30 ± 0.02). In addition, the addition of DPP3 to mouse plasma was associated with decreased levels of all angiotensins. 1/ In the ISO model, inhibition of DPP3 by Procizumab rapidly normalized cardiac function and renal hemodynamics with a marked reduction in oxidative stress and myocardial inflammation. 2/ In the sepsis model, Procizumab injection rapidly normalized the shortening fraction and cardiac output of septic animals. A reduction in oxidative stress was observed in the hearts of treated animals. In addition, mortality in septic animals treated with Procizumab was reduced.ConclusionDPP3 is a myocardial depressant factor involved in cardiogenic shock and septic cardiomyopathy. Inhibition of excessive levels of DPP3 by Procizumab, an antibody specific for DPP3, improved myocardial contraction, renal hemodynamics, and improved animal survival. This antibody positions itself as an interesting therapeutic option in the most severe cardiogenic and septic shock states. However, the mechanisms of action of Procizumab are not yet elucidated. A modulation of the circulating levels of the actors of the renin-angiotensin-aldosterone system and in particular of angiotensin-2 is the hypothesis currently adopted. It needs to be confirmed by experimental and clinical studies., L’insuffisance cardiaque (IC) aiguë est une pathologie multifactorielle responsable du décès de plusieurs millions de personnes chaque année. Sa physiopathologie est complexe et non entièrement élucidée. De plus, les traitements actuels ne permettent pas d’éviter le décès des patients les plus graves. La dipeptidyl peptidase 3 (DPP3) est une métalloprotéinase ubiquitaire impliquée dans de nombreux processus biologiques, notamment dans la régulation de la pression artérielle (en clivant l’angiotensine 2). Les fonctions biologiques exactes de la DPP3 sont inconnues à ce jour. Les objectifs de ce travail étaient de déterminer les fonctions physiopathologiques de la DPP3 au cours de l’IC aiguë d’origine catécholaminergique et septique. Méthodes Deux modèles ont été utilisés dans ce travail : 1/ le modèle d’IC aiguë à l’isoprotérénol (ISO, 300 mg/kg/12h) chez des souris mâles C57Bl6j de 3 mois et 2/ le modèle d’IC aiguë septique chez des rats mâles Wistar de 3 mois par ligature et ponction caecale (LPC). Les paramètres cardiovasculaires (dans les deux modèles) et rénaux (dans le modèle ISO) ont été évalués par échographie. Nous avons exploré le stress oxydant myocardique par marquage DHE sur des coupes de cœur dans les deux modèles. Des dosages d’angiotensines in vitro en présence DPP3 ont été réalisés chez la souris (modèle ISO) RésultatsL’injection de la protéine DPP3 chez la souris saine était responsable d’une dépression myocardique (baisse de 10 ± 2% de la fraction de raccourcissement) ainsi que d’une altération de l’hémodynamique rénale (augmentation de l’index de résistance rénale de 0.30 ± 0.02). De plus, l’adjonction de DPP3 avec le plasma de souris était associée à une baisse des taux de toutes les angiotensines. 1/ Dans le modèle d’IC aiguë à l’ISO, l’inhibition de la DPP3 par le Procizumab normalisait rapidement la fonction cardiaque ainsi que l’hémodynamique rénale avec une réduction marquée du stress oxydant et de l’inflammation myocardique. 2/ Dans le modèle de cardiomyopathie septique chez le rat, l’injection de Procizumab permettait de normaliser rapidement la fraction de raccourcissement et le débit cardiaque des animaux septiques. Une réduction du stress oxydant était observée dans le cœur des animaux traités. De plus, la mortalité des animaux septiques traités par le Procizumab était réduite.ConclusionLa DPP3 est un facteur dépresseur myocardique impliqué dans le choc cardiogénique et dans la cardiomyopathie septique. L’inhibition des taux excessifs de DPP3 par le Procizumab, un anticorps spécifique de la DPP3, permettait d’améliorer la contraction myocardique, l’hémodynamique rénale et d’améliorer la survie des animaux. Cet anticorps se positionne comme une option thérapeutique intéressante dans les états de chocs cardiogéniques et septiques les plus graves. Cependant, les mécanismes d’action du Procizumab ne sont encore élucidés. Une modulation des taux circulants des acteurs du système rénine angiotensine aldostérone et notamment de l’angiotensine 2 est l’hypothèse retenue actuellement. Elle doit être confirmée par des études expérimentales et cliniques.