Too early initiation of renal replacement therapy may be harmful

In an observational multicenter study, Elseviers and colleagues report that renal replacement therapy (RRT) in acutely ill patients treated for acute kidney injury is an independent risk factor for death. This result may question the benefit of the current practice of early RRT initiation

094: Contribution of cardiac MRI to early evaluation and impact on the long term follow-up in myocarditis mimicking an acute coronary syndrome. A 43-cases prospective study

BackgroundAcute myocarditis (AM) diagnosis is a challenge to rule out an acute coronary syndrome (ACS). AM is thought to favour the evolution towards dilated cardiomyopathy (DCM) and the occurrence of severe arrhythmias. Three months after the acute episode, re-evaluation including cardiac MRI could help to identify patients at risk for unfavourable evolution. The use of MRI has rarely been investigated in AM prognosis stratification.Method and resultswe report a prospective series of 43 consecutive patients hospitalized for AM mimicking ACS: 36 men and 7 women, 32 years old on average, without sign of heart failure. All patients presented with troponine I elevation. Echocardiography showed moderate global left ventricular dysfunction in 6 cases and segmental wall motion abnormalities in 22. MRI performed early after admission never showed myocardial first-pass perfusion defect after gadolinium injection but subepicardial delayed-enhancement (DE) areas in 39 cases mainly located in lateral segments. Three months after the acute episode, no patient was symptomatic. Echocardiography, Holter monitoring and biological check-up were normal. MRI showed the persistence of DE in 23 cases without wall motion abnormality in the affected segments. The presence of these latter abnormalities led to effect an annually clinical examination with an ECG. One patient was lost at further follow-up. Among the other 22 patients, only one patient dysplayed heart failure revealing DCM with ventricular arrhythmias at 3 - year mean follow-up.Conclusionsat the time of admission, the absence of early perfusion defect at cardiac MRI after gadolinium injection and the subepicardial localization of the DE constitute reliable criteria in favour of AM diagnosis, allowing to rule out ACS. During the follow-up the persistence of a DE does not allow any prognosis stratification. In our series after a mean 3-year follow-up, it is not associated with any clinical and para-clinical disorder except in one case

Relationship between ventilator-associated pneumonia and mortality in COVID-19 patients: a planned ancillary analysis of the coVAPid cohort

Background Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. Methods Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox's regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. Findings Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 group (adjusted HR 1.65 (95% CI 1.11-2.46), p = 0.013), but not in influenza (1.74 (0.99-3.06), p = 0.052), or no viral infection groups (1.13 (0.68-1.86), p = 0.63). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. Interpretation VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality

a retrospective multicenter study

Funding This study was supported in part by a grant from the French government through the « Programme Investissement d’Avenir» (I-SITE ULNE) managed by the Agence Nationale de la Recherche (coVAPid project). Prof. Ignacio Martin-Loeches has been supported by SFI (Science Foundation Ireland), Grant number 20/COV/0038. The funders of the study had no role in the study design, data collection, analysis or interpretation, writing of the report or deci sion to submit for publication.BACKGROUND: Ventilator-associated pneumonia (VAP) is common in patients with severe SARS-CoV-2 pneumonia. The aim of this ancillary analysis of the coVAPid multicenter observational retrospective study is to assess the relationship between adjuvant corticosteroid use and the incidence of VAP. METHODS: Planned ancillary analysis of a multicenter retrospective European cohort in 36 ICUs. Adult patients receiving invasive mechanical ventilation for more than 48 h for SARS-CoV-2 pneumonia were consecutively included between February and May 2020. VAP diagnosis required strict definition with clinical, radiological and quantitative microbiological confirmation. We assessed the association of VAP with corticosteroid treatment using univariate and multivariate cause-specific Cox's proportional hazard models with adjustment on pre-specified confounders. RESULTS: Among the 545 included patients, 191 (35%) received corticosteroids. The proportional hazard assumption for the effect of corticosteroids on the incidence of VAP could not be accepted, indicating that this effect varied during ICU stay. We found a non-significant lower risk of VAP for corticosteroid-treated patients during the first days in the ICU and an increased risk for longer ICU stay. By modeling the effect of corticosteroids with time-dependent coefficients, the association between corticosteroids and the incidence of VAP was not significant (overall effect p = 0.082), with time-dependent hazard ratios (95% confidence interval) of 0.47 (0.17-1.31) at day 2, 0.95 (0.63-1.42) at day 7, 1.48 (1.01-2.16) at day 14 and 1.94 (1.09-3.46) at day 21. CONCLUSIONS: No significant association was found between adjuvant corticosteroid treatment and the incidence of VAP, although a time-varying effect of corticosteroids was identified along the 28-day follow-up.publishersversionpublishe

a planned ancillary analysis of the coVAPid cohort

Funding: This study was supported in part by a grant from the French government through the «Programme Investissement d’Avenir» (I-SITE ULNE) managed by the Agence Nationale de la Recherche (coVAPid project). The funders of the study had no role in the study design, data collection, analysis, or interpreta tion, writing of the report, or decision to submit for publication.BACKGROUND: Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. METHODS: Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox's regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. FINDINGS: Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 (adjusted HR 1.70 (95% CI 1.16-2.47), p = 0.006), and influenza groups (1.75 (1.03-3.02), p = 0.045), but not in the no viral infection group (1.07 (0.64-1.78), p = 0.79). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. INTERPRETATION: VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov, number NCT04359693.publishersversionpublishe

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Insuffisance rénale aiguë obstructive : une lecture physiopathologique

International audienceObstructive acute renal failure is a heterogeneous entity as the pathophysiology of intratubular obstruction is quite different from upper tract obstruction. In the former case, tubules are dilated due to a high hydrostatic pressure whereas pressures are normal in urinary upper tract. In the latter case, a high pressure above the ureteral obstacle is responsible for dilated renal cavities leading to extrinsic compression with no or only few dilated tubules though high hydrostatic pressure are recorded within tubules. Obstruction within tubules may be related to crystal formation, exfoliated cells, cellular debris and/or protein gels altogether with cell proliferation, proliferating cells, and recruitment of inflammatory cells. Though fibrosis may develop, the occurrence of atubular glomeruli in several nephrons due to an initial loss of tubular patency highlights the critical importance of maintaining a fluid flow within tubules in order to avoid uncontrolled tubular cell proliferation. The onset of tubular obstruction in few tubules, especially in crystal nephropathy is underestimated especially in chronic kidney disease patients, thus suggesting that some macromolecular solubilizing factors may be potential relevant therapy to prevent (and/or reverse) chronic kidney disease progression or decrease acute renal failure sequelae.L’insuffisance rénale aiguë obstructive apparaît une entité hétérogène, la physiopathologie des obstructions intratubulaires étant différente des obstructions aiguës des voies excrétrices. En effet, dans un cas les tubules sont dilatés et le régime de pression dans les uretères, bassinets et calices est normal ; dans l’autre cas, les contraintes exercées sur les parois sont importantes et entraînent une déformation des cavités rénales conduisant rapidement à une compression extrinsèque du système tubulaire avec des tubules généralement pas ou peu dilatés, les pressions intratubulaires étant néanmoins élevées. L’insuffisance rénale aiguë obstructive est cependant dans tous les cas une insuffisance rénale aiguë organique, la présence de cristaux, de cellules desquamées, de débris cellulaires et/ou de gels protéiques intratubulaires entraînant une prolifération tubulaire de voisinage, un recrutement inflammatoire et dans les cas favorables, une résolution. La présence de séquelles à type de fibrose est une éventualité qui ne doit cependant pas faire sous-estimer la fréquence d’un défaut de reperméabilisation des lumières tubulaires avec constitution de nombreux néphrons non fonctionnels du fait de glomérules borgnes (sans tubule). Les phénomènes d’autorégulation de l’hémodynamique rénale ne sont donc pas nécessairement destinés uniquement à préserver un débit sanguin rénal constant mais aussi à maintenir un flux tubulaire afin d’éviter l’interruption définitive du flux par une prolifération anarchique des cellules tubulaires. La survenue d’une obstruction tubulaire focale et le diagnostic de néphropathies cristallines semble sous-estimés au cours de la maladie rénale chronique et suggère l’intérêt thérapeutique potentiel de certains solubilisateurs ou inhibiteurs macromoléculaires en situations aiguë et chronique

Cardiovascular disease in patients with spondyloarthropathies.

International audienceSpondyloarthropathies are associated with a greater cardiovascular risk than expected based on the cardiac lesions known to occur in these diseases. The prevalence of several conventional risk factors is high in spondyloarthropathy patients, and chronic inflammation also contributes to premature plaque formation. In addition, susceptibility genes for spondyloarthropathies may be associated with an increased risk of cardiovascular disease. Finally, several drugs used to treat spondyloarthropathies may contribute to the occurrence of cardiovascular events. A careful evaluation of the cardiovascular risk profile is a key component of the management of patients with spondyloarthropathies