A locally optimised machine learning approach to early prognostication of long-term neurological outcomes after out-of-hospital cardiac arrest.

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.

Postoperative outcomes after total sevoflurane inhalation sedation using a disposable delivery system (Sedaconda-ACD) in cardiac surgery.

Introduction: The COVID-19 pandemic prompted our team to develop new solutions for performing cardiac surgery without intravenous anesthetics due to a shortage of these drugs. We utilized an anesthetic conserving device (Sedaconda-ACD) to administer total inhaled anesthesia because specific vaporizers were unavailable for administering inhaled agents during cardiopulmonary bypass (CPB) in our center. We documented our experience and postoperative cardiovascular outcomes. The primary outcome was the peak level of troponin, with secondary outcomes encompassing other cardiovascular complications. Material and methods: A single-center retrospective study was conducted. We performed a multivariate analysis with a propensity score. This investigation took place at a large university referral center. Participants: Adult patients (age ≥ 18) who underwent elective cardiac surgery with CPB between June 2020 to March 2021. Intervention: During the inclusion period, two anesthesia protocols for the maintenance of anesthesia coexisted-total inhaled anesthesia with Sedaconda-ACD and our classic protocol with intravenous drugs during and after CPB. Primary endpoint: Troponin peak level recorded after surgery (highest level recorded within 48 h following the surgery). Results: Out of the 654 included patients, 454 were analyzed after matching (intravenous group = 297 and inhaled group = 157). No significant difference was found between the groups in postoperative troponin peak levels (723 ng/l vs. 993 ng/l-p = 0.2). Total inhaled anesthesia was associated with a decreased requirement for inotropic medications (OR = 0.53, 95% CI 0.29-0.99, p = 0.04). Conclusion: In our cohort, the Sedaconda-ACD device enabled us to achieve anesthesia without intravenous agents, and we did not observe any increase in postoperative complications. Total inhaled anesthesia with sevoflurane was not associated with a lower incidence of myocardial injury assessed by the postoperative troponin peak level. However, in our cohort, the use of inotropic drugs was lower.

Comparing COVID-19 and influenza: Epidemiology, clinical characteristics, outcomes and mortality in the ICU.

RATIONALE: Several authors have compared COVID-19 infection with influenza in the ICU. OBJECTIVE: This study aimed to compare the baseline clinical profiles, care procedures, and mortality outcomes of patients admitted to the intensive care unit, categorized by infection status (Influenza vs. COVID-19). METHODS: Retrospective observational study. Data were extracted from the Toulouse University Hospital from March 2014 to March 2021. To compare survival curves, we plotted the survival at Day-90 using the Kaplan-Meier curve and conducted a log-rank test. Additionally, we performed propensity score matching to adjust for confounding factors between the COVID-19 and influenza groups. Furthermore, we use the CART model for multivariate analysis. RESULTS: The study included 363 patients admitted to the ICU due to severe viral pneumonia: 152 patients (41.9 %) with influenza and 211 patients (58.1 %) with COVID-19. COVID-19 patients exhibited a higher prevalence of cardiovascular risk factors, whereas influenza patients had significantly higher severity scores (SOFA: 10 [6-12] vs. 6 [3-9], p<0.01 and SAPS II: 51 [35-67] vs. 37 [29-50], p<0.001). Overall mortality rates were comparable between the two groups (27.6 % (n = 42) in the influenza group vs. 21.8 % (n = 46) in the COVID-19 group, p=NS). Mechanical ventilation was more commonly employed in the influenza group (76.3 % (n = 116) vs. 59.7 % (n = 126), p<0.001); however, COVID-19 patients required longer durations of mechanical ventilation (18 [9-29] days vs. 13 [5-24] days, p<0.006) and longer hospital stays (23 [13-34] days vs. 18.5 [9-34.5] days, p = 0.009). The CART analysis revealed that the use of extra renal replacement therapy was the most influential prognostic factor in the influenza group, while the PaO2/FiO2-PEEP ratio played a significant role in the COVID-19 group. CONCLUSIONS: Despite differences in clinical presentation and prognostic factors, the mortality rates at 90 days, after adjusting for confounding factors, were similar between COVID-19 and influenza patients.

SARS-CoV-2 Omicron variant infection affects blood platelets, a comparative analysis with Delta variant.

Introduction: In 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. Methods: Clinical 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. Results: Severe 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. Discussion: Although 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.

Influence of arterial blood gases on the renal arterial resistive index in intensive care unit.

BACKGROUND: Renal artery Doppler sonography with resistive index (RI) determination is a noninvasive, fast, and reliable diagnostic tool increasingly used in the intensive care unit (ICU) to predict and assess the reversibility of acute kidney injury (AKI). However, interpreting the RI can be challenging due to numerous influencing factors. While some studies have explored various confounding factors, arterial blood gases have received limited attention. Therefore, our study aims to evaluate the impact of arterial blood gases on the RI in the ICU setting. METHODS: This prospective observational study enrolled ICU patients who required blood gas analysis and had not experienced significant hemodynamic changes recently. The RI was measured using standardized Doppler ultrasound within an hour of the arterial blood gases sampling and analysis. RESULTS: A total of sixty-four patients were included in the analysis. Univariate analysis revealed a correlation between the RI and several variables, including PaCO2 (R = 0.270, p = 0.03), age (R = 0.574, p < 0.0001), diastolic arterial pressure (DAP) (R = - 0.368, p = 0.0028), and SaO2 (R = - 0.284, p = 0.0231). Multivariate analysis confirmed that age > 58 years and PaCO2 were significant factors influencing the RI, with respective odds ratios of 18.67 (p = 0.0003) and 1.132 (p = 0.0267). CONCLUSION: The interpretation of renal arterial RI should take into account thresholds for PaCO2, age, and diastolic arterial pressure. Further studies are needed to develop a comprehensive scoring system that incorporates all these cofactors for a reliable analysis of RI levels. Trial registration This observational study, registered under number 70-0914, received approval from local Ethical Committee of Toulouse University Hospital.

Prevalence and risk factors of significant persistent pain symptoms after critical care illness: a prospective multicentric study.

BACKGROUND: Prevalence, risk factors and medical management of persistent pain symptoms after critical care illness have not been thoroughly investigated. METHODS: We performed a prospective multicentric study in patients with an intensive care unit (ICU) length of stay ≥ 48 h. The primary outcome was the prevalence of significant persistent pain, defined as a numeric rating scale (NRS) ≥ 3, 3 months after admission. Secondary outcomes were the prevalence of symptoms compatible with neuropathic pain (ID-pain score > 3) and the risk factors of persistent pain. RESULTS: Eight hundred fourteen patients were included over a 10-month period in 26 centers. Patients had a mean age of 57 (± 17) years with a SAPS 2 score of 32 (± 16) (mean ± SD). The median ICU length of stay was 6 [4-12] days (median [interquartile]). At 3 months, the median intensity of pain symptoms was 2 [1-5] in the entire population, and 388 (47.7%) patients had significant pain. In this group, 34 (8.7%) patients had symptoms compatible with neuropathic pain. Female (Odds Ratio 1.5 95% CI [1.1-2.1]), prior use of anti-depressive agents (OR 2.2 95% CI [1.3-4]), prone positioning (OR 3 95% CI [1.4-6.4]) and the presence of pain symptoms on ICU discharge (NRS ≥ 3) (OR 2.4 95% CI [1.7-3.4]) were risk factors of persistent pain. Compared with sepsis, patients admitted for trauma (non neuro) (OR 3.5 95% CI [2.1-6]) were particularly at risk of persistent pain. Only 35 (11.3%) patients had specialist pain management by 3 months. CONCLUSIONS: Persistent pain symptoms were frequent in critical illness survivors and specialized management remained infrequent. Innovative approaches must be developed in the ICU to minimize the consequences of pain. TRIAL REGISTRATION: NCT04817696. Registered March 26, 2021.

Comprehensive analysis of coagulation factor delivery strategies in a cohort of trauma patients.

PURPOSE: The 5th edition of The European recommendations for the management of major bleeding and coagulopathy following trauma leaves room for various coagulation factor administration strategies. The present study examines these strategies reporting prevalence and timing of administration, quantity dispensed, and transfusion ratios in French trauma centers and their compliance with recommendations alongside associated mortality data. METHODS: All adult patients, admitted directly to participating centers between 2011 and 2019, were extracted from a trauma registry. Two subpopulations were studied: severe hemorrhage (SH) and massive transfusion (MT) groups. RESULTS: A total of 19,396 patients were included, among whom 8.4% (1630) experienced SH and 3% (579) received MT. Within the first 24 hours, 10% received fresh frozen plasma (FFP), rising to 93% and 99% in the subgroups of patients experiencing SH and MT respectively. Only, 8% received fibrinogen concentrate (FC), increasing to 75% and 92% in subgroups SH and MT respectively. Co-administration of FFP and FC became the dominant strategy with 68% of patients at 6 h and 72% at 24 h in SH subgroup. In unadjusted data, mortality was systematically lower in groups that complied with recommendations, a lower mortality than expected was mostly observed in contrast to non-compliant subgroups. The per-patient compliance to studied recommendations was 21% and 22% in SH and MT subgroups. CONCLUSION: The main hemostatic strategy for major bleeding combined the administration of both FFP and FC, favoring an early additional supply of fibrinogen. Compliance with the recommendations was low in SH and MT subgroups.

Co-Infection and Ventilator-Associated Pneumonia in Critically Ill COVID-19 Patients Requiring Mechanical Ventilation: A Retrospective Cohort Study.

Considering virus-related and drug-induced immunocompromised status of critically ill COVID-19 patients, we hypothesize that these patients would more frequently develop ventilator-associated pneumonia (VAP) than patients with ARDS from other viral causes. We conducted a retrospective observational study in two intensive care units (ICUs) from France, between 2017 and 2020. We compared bacterial co-infection at ICU admission and throughout the disease course of two retrospective longitudinally sampled groups of critically ill patients, who were admitted to ICU for either H1N1 or SARS-CoV-2 respiratory infection and depicted moderate-to-severe ARDS criteria upon admission. Sixty patients in the H1N1 group and 65 in the COVID-19 group were included in the study. Bacterial co-infection at the endotracheal intubation time was diagnosed in 33% of H1N1 and 16% COVID-19 patients (p = 0.08). The VAP incidence per 100 days of mechanical ventilation was 3.4 (2.2−5.2) in the H1N1 group and 7.2 (5.3−9.6) in the COVID-19 group (p < 0.004). The HR to develop VAP was of 2.33 (1.34−4.04) higher in the COVID-19 group (p = 0.002). Ten percent of H1N1 patients and 30% of the COVID-19 patients had a second episode of VAP (p = 0.013). COVID-19 patients have fewer bacterial co-infections upon admission, but the incidence of secondary infections increased faster in this group compared to H1N1 patients.

Platelet activation and partial desensitization are associated with viral xenophagy in patients with severe COVID-19.

Mild thrombocytopenia, changes in platelet gene expression, enhanced platelet functionality, and presence of platelet-rich thrombi in the lung have been associated with thromboinflammatory complications of patients with COVID-19. However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gets internalized by platelets and directly alters their behavior and function in infected patients remains elusive. Here, we investigated platelet parameters and the presence of viral material in platelets from a prospective cohort of 29 patients with severe COVID-19 admitted to an intensive care unit. A combination of specific assays, tandem mass spectrometry, and flow cytometry indicated high levels of protein and lipid platelet activation markers in the plasma from patients with severe COVID-19 associated with an increase of proinflammatory cytokines and leukocyte-platelets interactions. Platelets were partly desensitized, as shown by a significant reduction of αIIbß3 activation and granule secretion in response to stimulation and a decrease of surface GPVI, whereas plasma from patients with severe COVID-19 potentiated washed healthy platelet aggregation response. Transmission electron microscopy indicated the presence of SARS-CoV-2 particles in a significant fraction of platelets as confirmed by immunogold labeling and immunofluorescence imaging of Spike and nucleocapsid proteins. Compared with platelets from healthy donors or patients with bacterial sepsis, platelets from patients with severe COVID-19 exhibited enlarged intracellular vesicles and autophagolysosomes. They had large LC3-positive structures and increased levels of LC3II with a co-localization of LC3 and Spike, suggesting that platelets can digest SARS-CoV-2 material by xenophagy in critically ill patients. Altogether, these data show that during severe COVID-19, platelets get activated, become partly desensitized, and develop a selective autophagy response.

Platelet Versus Megakaryocyte: Who Is the Real Bandleader of Thromboinflammation in Sepsis?

Platelets are mainly known for their key role in hemostasis and thrombosis. However, studies over the last two decades have shown their strong implication in mechanisms associated with inflammation, thrombosis, and the immune system in various neoplastic, inflammatory, autoimmune, and infectious diseases. During sepsis, platelets amplify the recruitment and activation of innate immune cells at the site of infection and contribute to the elimination of pathogens. In certain conditions, these mechanisms can lead to thromboinflammation resulting in severe organ dysfunction. Here, we discuss the interactions of platelets with leukocytes, neutrophil extracellular traps (NETs), and endothelial cells during sepsis. The intrinsic properties of platelets that generate an inflammatory signal through the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome are discussed. As an example of immunothrombosis, the implication of platelets in vaccine-induced immune thrombotic thrombocytopenia is documented. Finally, we discuss the role of megakaryocytes (MKs) in thromboinflammation and their adaptive responses.

Mass Training In Situ During COVID-19 Pandemic: Enhancing Efficiency and Minimizing Sick Leaves.

INTRODUCTION: Avoiding coronavirus disease 2019 (COVID-19) work-related infection in frontline healthcare workers is a major challenge. A massive training program was launched in our university hospital for anesthesia/intensive care unit and operating room staff, aiming at upskilling 2249 healthcare workers for COVID-19 patients' management. We hypothesized that such a massive training was feasible in a 2-week time frame and efficient in avoiding sick leaves. METHODS: We performed a retrospective observational study. Training focused on personal protective equipment donning/doffing and airway management in a COVID-19 simulated patient. The educational models used were in situ procedural and immersive simulation, peer-teaching, and rapid cycle deliberate practice. Self-learning organization principles were used for trainers' management. Ordinary disease quantity in full-time equivalent in March and April 2020 were compared with the same period in 2017, 2018, and 2019. RESULTS: A total of 1668 healthcare workers were trained (74.2% of the target population) in 99 training sessions over 11 days. The median number of learners per session was 16 (interquartile range = 9-25). In the first 5 days, the median number of people trained per weekday was 311 (interquartile range = 124-385). Sick leaves did not increase in March to April 2020 compared with the same period in the 3 preceding years. CONCLUSIONS: Massive training for COVID-19 patient management in frontline healthcare workers is feasible in a very short time and efficient in limiting the rate of sick leave. This experience could be used in the anticipation of new COVID-19 waves or for rapidly preparing hospital staff for an unexpected major health crisis.

Gunshot and stab wounds in France: descriptive study from a national trauma registry.

PURPOSE: Severe trauma is a major problem worldwide. In France, blunt trauma (BT) is predominant and few studies are available on penetrating trauma (PT). The purpose of this study was to perform a descriptive analysis of severe gunshot (GSW) and stab wounds (SW) in patients who were treated in French trauma centers. METHODS: Retrospective study on prospectively collected data in a national trauma registry. All adult (> 15 years) trauma patients primarily admitted in 1 of the 17 trauma centers members of the Traumabase between January 2015 to December 2018 were included. Data from patients who had a PT were compared with those who had suffered a BT over the same period. Due to the known differences between GSW and SW, sub-group analyses on data from GSW, SW and BT were also performed. RESULTS: 8128 patients were included. Twelve percent of the study group had a PT. The main mechanism of PT was SW (68.1%). Five hundred and eighty patients with PT (59.4%) required surgery within the first 24 h. Severe hemorrhage was more frequent in penetrating traumas (11.2% vs. 7.8% p < 0.001). Hospital mortality following PT was 8.9% vs 11% for blunt trauma (p = 0.047). Among PT the mortality after GSW was ten times higher than after SW (23.8% vs 2%). CONCLUSION: This work is the largest study to date that has specifically focused on GSW and SW in France, and will help improving knowledge in managing such patients in our country.

COCARDE Study-Cardiac Imaging Phenotype in Patients With COVID-19: Protocol for a Prospective Observational Study.

BACKGROUND: The effects of SARS-CoV-2 (COVID-19) on the myocardium and their role in the clinical course of infected patients are still unknown. The severity of SARS-CoV-2 is driven by hyperinflammation, and the effects of SARS-CoV-2 on the myocardium may be significant. This study proposes to use bedside observations and biomarkers to characterize the association of COVID-19 with myocardial injury. OBJECTIVE: The aim of the study is to describe the myocardial function and its evolution over time in patients infected with SARS-CoV-2 and to investigate the link between inflammation and cardiac injury. METHODS: This prospective, monocentric, observational study enrolled 150 patients with suspected or confirmed SARS-CoV-2 infection at Toulouse University Hospital, Toulouse, France. Patients admitted to the intensive care unit (ICU), regular cardiologic ward, and geriatric ward of our tertiary university hospital were included during the pandemic period. Blood sampling, electrocardiography, echocardiography, and morphometric and demographic data were prospectively collected. RESULTS: A total of 100 patients were included. The final enrolment day was March 31, 2020, with first report of results at the end of the first quarter of 2021. The first echocardiographic results at admission of 31 patients of the COCARDE-ICU substudy population show that biological myocardial injury in COVID-19 has low functional impact on left ventricular systolic function. CONCLUSIONS: A better understanding of the effects of COVID-19 on myocardial function and its link with inflammation would improve patient follow-up and care. TRIAL REGISTRATION: Clinicaltrials.gov NCT04358952; https://clinicaltrials.gov/ct2/show/NCT04358952. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24931.

Evolution of platelet activation parameters during septic shock in intensive care unit.

During severe sepsis, platelet activation may induce disseminate microvascular thrombosis, which play a key role in critical organ failure. Crucially, most of the studies in this field have explored platelet-leukocyte interactions in animal models, or explored platelets under the spectrum of thrombocytopenia or disseminated intravascular coagulation and have not taken into account the complex interplay that might exist between platelets and leukocytes during human septic shock nor the kinetics of platelet activation. Here, we assessed platelet activation parameters at the admission of patients with sepsis to the intensive care unit (ICU) and 48 hours later. Twenty-two patients were enrolled in the study, thirteen (59.1%) of whom were thrombocytopenic. The control group was composed of twelve infection-free patients admitted during the study period. The activation parameters studied included platelet-leukocyte interactions, assessed by flow cytometry in whole blood, as well as membrane surface and soluble platelet activation markers measured by flow cytometry and dedicated ELISA kits. We also investigated platelet aggregation and secretion responses of patients with sepsis following stimulation, compared to controls. At admission, the level of circulating monocyte-platelet and neutrophil-platelet heterotypic aggregates was significantly higher in sepsis patients compared to controls and returned to a level comparable to controls or even below 48 hours later. Basal levels of CD62P and CD63 platelet membrane exposure at admission and 48 hours later were low and similar to controls. In contrast, plasma level of soluble GPVI and soluble CD40 ligand was significantly increased in septic patients, at the two times of analysis, reflecting previous platelet activation. Platelet aggregation and secretion responses induced by specific agonists were significantly decreased in septic conditions, particularly 48 hours after admission. Hence, we have observed for the first time that critically ill septic patients compared to controls have both an early and durable platelet activation while their circulating platelets are less responsive to different agonists.

What place for virtual reality in the intensive care unit during medical procedures?

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.