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Sepsis is associated with thrombocytopenia and microvascular thrombosis. Studies have described platelets implication in this pathology but their kinetics of activation and behavior remain poorly known. We show in a mouse model of peritonitis, the appearance of platelet-rich thrombi in organ microvessels and organ damage. Complementary methods are necessary to characterize platelet activation during sepsis as circulating soluble markers and platelet-monocyte aggregates revealed early platelet activation, while surface activation markers were detected at later stage. A microfluidic based ex-vivo thrombosis assay demonstrated that platelets from septic mice have a prothrombotic behavior at shear rate encountered in microvessels. Interestingly, we found that even though phosphoinositide-3-kinase β−deficient platelet mice formed less thrombi in liver microcirculation, peritoneal sepsis activates a platelet alternative pathway to compensate the otherwise mandatory role of this lipid-kinase to form stable thrombi at high shear rate. Platelets are rapidly activated during sepsis. Thrombocytopenia can be attributed in part to platelet-rich thrombi formation in capillaries and platelet-leukocytes interactions. Platelets from septic mice have a prothrombotic phenotype at a shear rate encountered in arterioles. Further studies are necessary to unravel molecular mechanisms leading to this prothrombotic state of platelets in order to guide the development of future treatments of polymicrobial sepsis.

Imbalance in the redox equilibrium is common in any type of aggression. Cardiopulmonary bypass (CPB) initiation induces metabolic perturbations, and reliable biological monitoring tools for this condition are currently limited (e.g., lactate/pyruvate ratio). The measurement of arterial whole blood redox potential (Eredox) provides a systemic assessment of the redox state and may serve as a valuable marker for detecting metabolic perturbations during CPB. In this prospective exploratory study involving patients undergoing cardiac surgery, we investigated variations in Eredox and lactate/pyruvate ratio during CPB initiation. Using a prospective exploratory study design, we assessed the changes in Eredox and relevant variables during the initiation of CPB in 16 cardiac surgery patients. Upon initiation of CPB we observed a significant decrease in arterial whole blood redox potential (101.90 mV + /- 11.52 vs. 41.80 mV + /- 10,26; p < 0.0001). Concomitantly, the lactate/pyruvate ratio significantly increased (12.81 + /- 0.90 vs 67.1 + /- 7.94; p < 0.0001) while the acetoacetate/β-hydroxybutyrate ratio significantly decreased (1.11 + /- 0.19 vs. 0.54 + /- 0.05 at 0 min; p = 0.0055). The circulatory failure indicated by changes in the lactate/pyruvate ratio and ketone bodies at the initiation of CPB correlated with a significant reduction in Eredox. Arterial Eredox is a novel variable that holds promise in the detection and monitoring of metabolic aggression during CPB. Its assessment during CPB initiation could provide valuable insights into the patient's circulatory status, as the Eredox appears to be more sensitive than lactate for monitoring circulatory insufficiency.

Host defense against infection is based on two crucial mechanisms: the inflammatory response and the activation of coagulation. Platelets are involved in both hemostasis and immune response. These mechanisms work together in a complex and synchronous manner making the contribution of platelets of major importance in sepsis. This is a summary of the pathophysiology of sepsis-induced thrombocytopenia, microvascular consequences, platelet-endothelial cells and platelet–pathogens interactions. The critical role of platelets during sepsis and the therapeutic implications are also reviewed.

Background Prolonged weaning is a major issue in intensive care patients and tracheostomy is one of the last resort options. Optimized patient-ventilator interaction is essential to weaning. The purpose of this study was to compare patient-ventilator synchrony between pressure support ventilation (PSV) and neurally adjusted ventilatory assist (NAVA) in a selected population of tracheostomised patients. Methods We performed a prospective, sequential, non-randomized and single-centre study. Two recording periods of 60 min of airway pressure, flow, and electrical activity of the diaphragm during PSV and NAVA were recorded in a random assignment and eight periods of 1 min were analysed for each mode. We searched for macro-asynchronies (ineffective, double, and auto-triggering) and micro-asynchronies (inspiratory trigger delay, premature, and late cycling). The number and type of asynchrony events per minute and asynchrony index (AI) were determined. The two respiratory phases were compared using the non-parametric Wilcoxon test after testing the equality of the two variances (F-Test). Results Among the 61 patients analysed, the total AI was lower in NAVA than in PSV mode: 2.1% vs 14% ( p  < 0.0001). This was mainly due to a decrease in the micro-asynchronies index: 0.35% vs 9.8% ( p  < 0.0001). The occurrence of macro-asynchronies was similar in both ventilator modes except for double triggering, which increased in NAVA. The tidal volume (ml/kg) was lower in NAVA than in PSV (5.8 vs 6.2, p  < 0.001), and the respiratory rate was higher in NAVA than in PSV (28 vs 26, p  < 0.05). Conclusion NAVA appears to be a promising ventilator mode in tracheotomised patients, especially for those requiring prolonged weaning due to the decrease in asynchronies.

Ventilator-associated pneumonia (VAP) is the most common infection in severely injured patients requiring mechanical ventilation. Chest trauma has been identified as a significant risk factor for VAP. This study aimed to describe the risk factors for early VAP in patients with severe blunt thoracic trauma admitted to the intensive care unit (ICU) and receiving mechanical ventilation. A retrospective cohort study was conducted using data from a national registry including data from 17 French trauma centers during a period of seven years. The study included patients with severe blunt thoracic trauma requiring invasive mechanical ventilation. Data analysis focused on identifying independent risk factors for early suspected VAP (occurring within 48 hours to 5 days after ICU admission) using two models of logistic regression. From 31700 patients screened 712 patients were analyzed. Early suspected VAP occurred in 192 (27%) patients. The study identified several independent risk factors associated with early suspected VAP in patients with severe blunt thoracic trauma: male gender (OR= 2.77, 95%CI: 1.68-4.77, p < 0.001), ASA score >1 (OR= 1.64, 95%CI: 1.08-2.50, p = 0.019), injury severity score (ISS) >15 (OR=3.15, 95%CI: 1.13-11.99, p = 0.025), initial Glasgow Coma Scale (GCS) score <9 (OR=2.71, 95%CI: 1.88-3.96, p < 0.001), absolute thoracic abbreviated injury scale (AIS) (OR=1.51, 95%CI: 1.14-1.99, p = 0.003), and the number of packed red blood cells (PRBCs) transfused within the first 24 hours (OR=1.04, 95%CI: 1.00-1.08, p = 0.027). Prehospital antibiotic administration was identified as a protective factor (OR=0.54, 95%CI: 0.29-0.94, p = 0.028). In patients with severe blunt chest trauma receiving invasive mechanical ventilation, male gender, ASA score, ISS > 15, GCS < 9, thoracic AIS and number of PRBCs transfused were independent risk factors for early suspected VAP. Prehospital antibiotic therapy was a protective factor, suggesting potential strategies for VAP prevention.

In the intensive care unit, patients are subject to discomforts and pain. Their management is essentially based on pharmacologic approaches. Immersive virtual reality could represent an adjunctive non-invasive and non-pharmacological pain control technique. It is based on real-time interaction with an artificial 360° immersive world using interfaces that enable physical and emotional perceptions to make the user feel better trying to reduce pain perception and to limit anxiety. Evaluation of virtual reality in intensive care unit is lacking and further studies are necessary before to introduce this alternative method for critical patients.

Linezolid is an antibiotic used against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Its primary adverse effect is haematotoxicity. The objective of this study was to analyse the risk factors for onset of thrombocytopenia in critically ill patients treated with linezolid. This was a retrospective, single-centre study of 72 patients. Platelets were measured from D0 to D20 after the start of treatment. The risk factors for thrombocytopenia were identified using a multivariate logistic regression analysis following a Monte Carlo simulation. Following ROC curve analysis, a baseline platelet count lower than 108 × 109/L and a Cmin higher than 4 mg/L, with respective odds ratios of 117 (95% CI [97–206]) and 3 (95% CI [1.5–6.2]) in the simulated population, were identified as risk factors. Among the source population patients combining these 2 factors, a significantly higher number developed thrombocytopenia (66.7% vs. 33.3%, p = 0.0042). A baseline platelet count lower than 108 × 109/L and a Cmin higher than 4 mg/L are risk factors for the onset of thrombocytopenia in critically ill patients treated with linezolid.

IntroductionIn November 2021, the SARS-CoV-2 Omicron variant of concern has emerged and is currently dominating the COVID-19 pandemic over the world. Omicron displays a number of mutations, particularly in the spike protein, leading to specific characteristics including a higher potential for transmission. Although Omicron has caused a significant number of deaths worldwide, it generally induces less severe clinical signs compared to earlier variants. As its impact on blood platelets remains unknown, we investigated platelet behavior in severe patients infected with Omicron in comparison to Delta.MethodsClinical and biological characteristics of severe COVID-19 patients infected with the Omicron (n=9) or Delta (n=11) variants were analyzed. Using complementary methods such as flow cytometry, confocal imaging and electron microscopy, we examined platelet activation, responsiveness and phenotype, presence of virus in platelets and induction of selective autophagy. We also explored the direct effect of spike proteins from the Omicron or Delta variants on healthy platelet signaling.ResultsSevere Omicron variant infection resulted in platelet activation and partial desensitization, presence of the virus in platelets and selective autophagy response. The intraplatelet processing of Omicron viral cargo was different from Delta as evidenced by the distribution of spike protein-positive structures near the plasma membrane and the colocalization of spike and Rab7. Moreover, spike proteins from the Omicron or Delta variants alone activated signaling pathways in healthy platelets including phosphorylation of AKT, p38MAPK, LIMK and SPL76 with different kinetics.DiscussionAlthough SARS-CoV-2 Omicron has different biological characteristics compared to prior variants, it leads to platelet activation and desensitization as previously observed with the Delta variant. Omicron is also found in platelets from severe patients where it induces selective autophagy, but the mechanisms of intraplatelet processing of Omicron cargo, as part of the innate response, differs from Delta, suggesting that mutations on spike protein modify virus to platelet interactions.

Background Out-of-hospital cardiac arrest (OHCA) represents a major burden for society and health care, with an average incidence in adults of 67 to 170 cases per 100,000 person-years in Europe and in-hospital survival rates of less than 10%. Patients and practitioners would benefit from a prognostication tool for long-term good neurological outcomes. Objective We aim to develop a machine learning (ML) pipeline on a local database to classify patients according to their neurological outcomes and identify prognostic features. Methods We collected clinical and biological data consecutively from 595 patients who presented OHCA and were routed to a single regional cardiac arrest centre in the south of France. We applied recursive feature elimination and ML analyses to identify the main features associated with a good neurological outcome, defined as a Cerebral Performance Category score less than or equal to 2 at six months post-OHCA. Results We identified 12 variables 24 h after admission, capable of predicting a six-month good neurological outcome. The best model (extreme gradient boosting) achieved an AUC of 0.96 and an accuracy of 0.92 in the test cohort. Conclusion We demonstrated that it is possible to build accurate, locally optimised prediction and prognostication scores using datasets of limited size and breadth. We proposed and shared a generic machine-learning pipeline which allows external teams to replicate the approach locally.

Biological cardiac injury related to the Severe Acute Respiratory Syndrome Coronavirus-2 infection has been associated with excess mortality. However, its functional impact remains unknown. The aim of our study was to explore the impact of biological cardiac injury on myocardial functions in patients with COVID-19. 31 patients with confirmed COVID-19 (CoV+) and 16 controls (CoV−) were prospectively included in this observational study. Demographic data, laboratory findings, comorbidities, treatments and myocardial function assessed by transthoracic echocardiography were collected and analysed in CoV+ with (TnT+) and without (TnT−) elevation of troponin T levels and compared with CoV−. Among CoV+, 13 (42%) exhibited myocardial injury. CoV+/TnT + patients were older, had lower diastolic arterial pressure and were more likely to have hypertension and chronic renal failure compared with CoV+/TnT−. The control group was comparable except for an absence of biological inflammatory syndrome. Left ventricular ejection fraction and global longitudinal strain were not different among the three groups. There was a trend of decreased myocardial work and increased peak systolic tricuspid annular velocity between the CoV− and CoV + patients, which became significant when comparing CoV− and CoV+/TnT+ (2167 ± 359 vs. 1774 ± 521%/mmHg, P = 0.047 and 14 ± 3 vs. 16 ± 3 cm/s, P = 0.037, respectively). There was a decrease of global work efficiency from CoV− (96 ± 2%) to CoV+/TnT− (94 ± 4%) and then CoV+/TnT+ (93 ± 3%, P = 0.042). In conclusion, biological myocardial injury in COVID 19 has low functional impact on left ventricular systolic function.