Risk factors for post-ICU red blood cell transfusion: a prospective study

INTRODUCTION: Factors predictive of the need for red blood cell (RBC) transfusion in the intensive care unit (ICU) have been identified, but risk factors for transfusion after ICU discharge are unknown. This study aims identifies risk factors for RBC transfusion after discharge from the ICU. METHODS: A prospective, monocentric observational study was conducted over a 6-month period in a 24-bed medical ICU in a French university hospital. Between June and December 2003, 550 critically ill patients were consecutively enrolled in the study. RESULTS: A total of 428 patients survived after treatment in the ICU; 47 (11% of the survivors, 8.5% of the whole population) required RBC transfusion within 7 days after ICU discharge. Admission for sepsis (odds ratio [OR] 341.60, 95% confidence interval [CI] 20.35–5734.51), presence of an underlying malignancy (OR 32.6, 95%CI 3.8–280.1), female sex (OR 5.4, 95% CI 1.2–24.9), Logistic Organ Dysfunction score at ICU discharge (OR 1.45, 95% CI 1.1–1.9) and age (OR 1.06, 95% CI 1.02–1.12) were independently associated with RBC transfusion after ICU stay. Haemoglobin level at discharge predicted the need for delayed RBC transfusion. Use of vasopressors (OR 0.01, 95%CI 0.001–0.17) and haemoglobin level at discharge from the ICU (OR 0.02, 95% CI 0.007–0.09; P < 0.001) were strong independent predictors of transfusion of RBC 1 week after ICU discharge. CONCLUSION: Sepsis, underlying conditions, unresolved organ failures and haemoglobin level at discharge were related to an increased risk for RBC transfusion after ICU stay. We suggest that strategies to prevent transfusion should focus on homogeneous subgroups of patients and take into account post-ICU needs for RBC transfusion

Microangiopathies thrombotiques en réanimation (étude rétrospective multicentrique)

PARIS5-BU Méd.Cochin (751142101) / SudocPARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Caractérisation fonctionnelle des cellules dentritiques au cours de l'immunodépression induite par le sepsis

Le sepsis est caractérisé par une dysrégulation de la réaction inflammatoire suivie d'une immunodépression complexe associée à la survenue d'infections nosocomiales. Les mécanismes de régulation de la phase d'immunodépression post-infectieuse sont actuellement méconnus, mais pourraient impliquer les cellules dendritiques (CD). Lors d'une infection, les récepteurs de type Toll (TLR) déterminent l'amplitude de la réponse inflammatoire initiale et sont impliqués dans la maturation des CDs, mais leur contribution dans le développement ultérieur d'une immunodépression est mal compris. L'objectif de ce projet de recherche était d'investiguer le rôle des CDs et des voies de signalisation dépendantes des TLRs dans l'immunodépression induite par le sepsis. Nous avons établi un modèle murin de double agression infectieuse séquentielle sous la forme d'un sepsis polymicrobien sublétal suivi d'une pneumonie secondaire tardive à Pseudomonas aeruginosa. Nous avons évalué le rôle des CDs dans la modulation des défenses pulmonaires des souris post-septiques envers une agression infectieuse secondaire. A l'aide de souris knockout TLR2-/- , TLR4-/-, TLR2x4-/- et MyD88-/-, nous avons analysé l'importance relative des TLRs dans l'homéostasie des CDs et dans la réponse de l'hôte à une infection pulmonaire secondaire. Enfin, dans une approche translationnelle, nous avons évalué les taux circulants de CDs chez des patients porteurs de choc septique et la relation avec la survenue d'infections nosocomiales. Ce travail introduit des perspectives nouvelles dans la physiopathologie de l'immunodépression post-infectieuse et suggère des applications thérapeutiques potentielles.Sepsis is characterized by a dysregulated inflammatory response followed by a complex immunosuppressive state that can favor the emergence of nosocomial infections. Mechanisms that regulate post-infective immunosuppression are largely unknown but may involve dendritic cells (DC) that link innate and adaptive immunity. Toll-like receptors (TLR) are critical determinants of the magnitude of the inflammatory response and are involved in the maturation process of DCs, but their contribution to the development of sepsis-induced immune dysfunction are poorly understood. The aim of this research project was to investigate the role of DCs and TLR-dependent signalling pathways in the regulation of sepsis-induced immunosuppression. For this purpose, we established a "double-hit" murine model through a sublethal polymicrobial sepsis followed by late-onset Pseudomonas aeruginosa pneumonia. In this model, we assessed the role of DCs in the modulation of lung defence towards a secondary infectious insult in post-septic mice. Using knockout mice TLR2-/- , TLR4-/-, TLR2x4-/- et MyD88-/-, we analyzed the relative contribution of TLRs to sepsis-induced defects of DCs and to the host response towards secondary pulmonary infection. In a translational approach, we assessed DC blood counts in septic shock patients and their relations with the development of nosocomial infections. Our results provide new insights in the pathophysiology of post-infective immunosuppression and suggest potential therapeutic applications.PARIS5-BU Méd.Cochin (751142101) / SudocSudocFranceF

Plasma Endocan as a Biomarker of Thrombotic Events in COVID-19 Patients

(1) Background: Endocan is a marker of endothelial dysfunction that may be associated with thrombotic events. The aim of the study was to investigate the performance of endocan as a marker of thrombotic events in COVID-19 patients. (2) Methods: We measured endocan in plasma from 79 documented COVID-19 patients classified according to disease severity (from mild to critical). Thrombotic events were recorded. (3) Results: Endocan concentrations at admission were significantly increased according to COVID-19 severity. Levels of endocan were significantly increased in patients experiencing thrombotic events in comparison with those without (16.2 (5.5&ndash;26.7) vs. 1.81 (0.71&ndash;10.5) ng/mL, p &lt; 0.001). However, endocan concentrations were not different between pulmonary embolism and other thrombotic events. The Receiver Operating Characteristic (ROC) analysis for the identification of thrombotic events showed an area under the ROC curve (AUC) of 0.776 with an optimal threshold at 2.83 ng/mL (93.8% sensitivity and 54.7% specificity). When combining an endocan measurement with D-dimers, the AUC increased to 0.853. When considering both biomarkers, the Kaplan&ndash;Meier survival curves showed that the combination of endocan and D-dimers better discriminated patients with thrombotic events than those without. The combination of D-dimers and endocan was independently associated with thrombotic events. (4) Conclusions: Endocan might be a useful and informative biomarker to better identify thrombotic events in COVID-19 patients

Management of neutropenic patients in the intensive care unit (NEWBORNS EXCLUDED) recommendations from an expert panel from the French Intensive Care Society (SRLF) with the French Group for Pediatric Intensive Care Emergencies (GFRUP), the French Society of Anesthesia and Intensive Care (SFAR), the French Society of Hematology (SFH), the French Society for Hospital Hygiene (SF2H), and the French Infectious Diseases Society (SPILF).

Neutropenia is defined by either an absolute or functional defect (acute myeloid leukemia or myelodysplastic syndrome) of polymorphonuclear neutrophils and is associated with high risk of specific complications that may require intensive care unit (ICU) admission. Specificities in the management of critically ill neutropenic patients prompted the establishment of guidelines dedicated to intensivists. These recommendations were drawn up by a panel of experts brought together by the French Intensive Care Society in collaboration with the French Group for Pediatric Intensive Care Emergencies, the French Society of Anesthesia and Intensive Care, the French Society of Hematology, the French Society for Hospital Hygiene, and the French Infectious Diseases Society. Literature review and formulation of recommendations were performed using the Grading of Recommendations Assessment, Development and Evaluation system. Each recommendation was then evaluated and rated by each expert using a methodology derived from the RAND/UCLA Appropriateness Method. Six fields are covered by the provided recommendations: (1) ICU admission and prognosis, (2) protective isolation and prophylaxis, (3) management of acute respiratory failure, (4) organ failure and organ support, (5) antibiotic management and source control, and (6) hematological management. Most of the provided recommendations are obtained from low levels of evidence, however, suggesting a need for additional studies. Seven recommendations were, however, associated with high level of evidences and are related to protective isolation, diagnostic workup of acute respiratory failure, medical management, and timing surgery in patients with typhlitis

Critical Role of cRel Subunit of NF-κB in Sepsis Survival ▿ †

NF-κB is a critical regulator of gene expression during severe infections. NF-κB comprises homo- and heterodimers of proteins from the Rel family. Among them, p50 and p65 have been clearly implicated in the pathophysiology of sepsis. In contrast, the role of cRel in sepsis is still controversial and has been poorly studied in single-pathogen infections. We aimed to investigate the consequences of cRel deficiency in a cecal ligation and puncture (CLP) model of sepsis. We have approached the underlying mechanisms of host defense by analyzing bacterial clearance, systemic inflammation, and the distribution of spleen dendritic cell subsets. Moreover, by using a genome-wide technology, we have also analyzed the CLP-induced modifications in gene expression profiles both in wild-type (wt) and in rel−/− mice. The absence of cRel enhances mortality due to polymicrobial sepsis. Despite normal pathogen clearance, cRel deficiency leads to an altered systemic inflammatory response associated with a sustained loss of the spleen lymphoid dendritic cells. Furthermore, a whole-blood microarray study reveals that the differential outcome between wt and rel−/− mice during sepsis is preceded by remarkable changes in the expression of hundreds of genes involved in aspects of host-pathogen interaction, such as host survival and lipid metabolism. In conclusion, cRel is a key NF-κB member required for host antimicrobial defenses and a regulatory transcription subunit that controls the inflammatory and immune responses in severe infection

Remdesivir for Patients Hospitalized with COVID-19 Severe Pneumonia: A National Cohort Study (Remdeco-19)

International audienceBackground. Given the rapidly evolving pandemic of COVID-19 in 2020, authorities focused on the repurposing of available drugs to develop timely and cost-effective therapeutic strategies. Evidence suggested the potential utility of remdesivir in the framework of an early access program. REMDECO-19 is a multicenter national cohort study assessing the ability of remdesivir to improve the outcome of patients hospitalized with COVID-19. Methods. We conducted a retrospective real-life study that included all patients from the early access program of remdesivir in France. The primary endpoint was the clinical course evolution of critically ill and hospitalized COVID-19 patients treated with remdesivir. Secondary endpoints were the SOFA score evolution within 29 days following the admission and mortality at 29 and 90 days. Results. Eighty-five patients were enrolled in 22 sites from January to April 2020. The median WHO and SOFA scores were respectively reduced by two and six points between days 1 and 29. Improvement in the WHO-CPS and the SOFA score were observed in 83.5% and 79.3% of patients, respectively, from day 10. However, there was no effect of remdesivir on the 90-day survival based on the control cohort for hospitalized COVID-19 patients with invasive ventilation. Conclusions. SOFA score appeared to be an attractive approach to assess remdesivir efficacy and stratify its utilization or not in critically ill patients with COVID-19. This study brings a new clinical benchmark for therapeutic decision making and supports the use of remdesivir for some hospitalized COVID-19 patients