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Health care systems worldwide have been battling the ongoing COVID-19 pandemic. Since the beginning of the COVID-19 pandemic, Lymphocytes and CRP have been reported as markers of interest. We chose to investigate the prognostic value of the LCR ratio as a marker of severity and mortality in COVID-19 infection. Between 1 March and 30 April 2020, we conducted a multicenter, retrospective cohort study of patients with moderate and severe coronavirus disease 19 (COVID-19), all of whom were hospitalized after being admitted to the Emergency Department (ED). We conducted our study in six major hospitals of northeast France, one of the outbreak’s epicenters in Europe. A total of 1035 patients with COVID-19 were included in our study. Around three-quarters of them (76.2%) presented a moderate form of the disease, while the remaining quarter (23.8%) presented a severe form requiring admission to the ICU. At ED admission, the median LCR was significantly lower in the group presenting severe disease compared to that with moderate disease (versus 6.24 (3.24–12) versus 12.63 ((6.05–31.67)), p < 0.001). However, LCR was neither associated with disease severity (OR: 0.99, CI 95% (0.99–1)), p = 0.476) nor mortality (OR: 0.99, CI 95% (0.99–1)). In the ED, LCR, although modest, with a threshold of 12.63, was a predictive marker for severe forms of COVID-19.

Summary Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov , NCT04324073 . Findings 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival. Funding Assistance publique—Hopitaux de Paris

Anaphylaxis is the most severe of the allergic hypersensitivity reactions. It is caused by the release of mediators from blood components such as mast cells and basophils into the bloodstream. Anaphylaxis is a common disease, its diagnosis is clinical and, given its pathophysiology, the treatment of choice is adrenaline.

We have previously surveyed a panel of 508 physicians from around the world about which biomarkers would be relevant if obtained in a very short time frame, corresponding to emergency situations (life-threatening or not). The biomarkers that emerged from this study were markers of cardiovascular disease: troponin, D-dimers, and brain natriuretic peptide (BNP). Cardiovascular disease is a group of disorders affecting the heart and blood vessels. At the intersection of medicine, basic research and engineering, biosensors that address the need for rapid biological analysis could find a place of choice in the hospital or primary care ecosystem. Rapid, reliable, and inexpensive analysis with a multi-marker approach, including machine learning analysis for patient risk analysis, could meet the demand of medical teams. The objective of this opinion review, proposed by a multidisciplinary team of experts (physicians, biologists, market access experts, and engineers), is to present cases where a rapid biological response is indeed valuable, to provide a short overview of current biosensor technologies for cardiac biomarkers designed for a short result time, and to discuss existing market access issues.

Introduction: Understanding hypoxemia, with and without the clinical signs of acute respiratory failure (ARF) in COVID-19, is key for management. Hence, from a population of critical patients admitted to the emergency department (ED), we aimed to study silent hypoxemia (Phenotype I) in comparison to symptomatic hypoxemia with clinical signs of ARF (Phenotype II). Methods: This multicenter study was conducted between 1 March and 30 April 2020. Adult patients who were presented to the EDs of nine Great-Eastern French hospitals for confirmed severe or critical COVID-19, who were then directly admitted to the intensive care unit (ICU), were retrospectively included. Results: A total of 423 critical COVID-19 patients were included, out of whom 56.1% presented symptomatic hypoxemia with clinical signs of ARF, whereas 43.9% presented silent hypoxemia. Patients with clinical phenotype II were primarily intubated, initially, in the ED (46%, p < 0.001), whereas those with silent hypoxemia (56.5%, p < 0.001) were primarily intubated in the ICU. Initial univariate analysis revealed higher ICU mortality (29.2% versus 18.8%, p < 0.014) and in-hospital mortality (32.5% versus 18.8%, p < 0.002) in phenotype II. However, multivariate analysis showed no significant differences between the two phenotypes regarding mortality and hospital or ICU length of stay. Conclusions: Silent hypoxemia is explained by various mechanisms, most physiological and unspecific to COVID-19. Survival was found to be comparable in both phenotypes, with decreased survival in favor of Phenotype II. However, the spectrum of silent to symptomatic hypoxemia appears to include a continuum of disease progression, which can brutally evolve into fatal ARF.

Background: Non-ST elevation acute coronary syndrome (NSTE-ACS) is one of the most frequent manifestations of coronary artery disease. The occurrence of serious heart rhythm disorders (SHRDs) in NSTE-ACS is not well documented. However, continuous heart rhythm monitoring is recommended during the initial management of NSTE-ACS. The targeted monitoring of patients at greater risk for SHRDs could facilitate patients’ care in emergency departments (EDs) where the flow of patients is continuously increasing. Methods: This retrospective single-center study included 480 patients from emergency and cardiology departments within the Strasbourg University Hospital between 1 January 2019 and 31 December 2020. The objective was to estimate the frequency of the occurrence of SHRDs among patients with NSTE-ACS. The secondary objective was to highlight the factors associated with a higher risk of SHRDs. Results: The proportion of SHRDs during the first 48 h of hospital care was 2.3% (CI95%: 1.2–4.1%, n = 11). Two time periods were considered: before coronary angiography (1.0%), and during, or after coronary angiography (1.3%). In the first group, two patients required immediate treatment (0.4% of the patients) and no death occurred. In the univariate analysis, the variables significantly associated with SHRDs were age, anticoagulant medication, a decrease in glomerular filtration rate, plasmatic hemoglobin, and left ventricle ejection fraction (LVEF), and an increase in plasmatic troponin, BNP, and CRP levels. In the multivariable analysis, plasmatic hemoglobin > 12 g/dL seemed to be a protective factor for SHRDs. Conclusions: In this study, SHRDs were rare and, most often, spontaneously resolved. These data challenge the relevance of systematic rhythm monitoring during the initial management of patients with NSTE-ACS.

(1) Introduction: In the present study, we investigate the prognostic value of platelet-to-lymphocyte ratio (PLR) as a marker of severity and mortality in COVID-19 infection. (2) Methods: Between 1 March and 30 April 2020, we conducted a multicenter, retrospective cohort study of patients with moderate to severe coronavirus 19 (COVID-19), all of whom were hospitalized after being admitted to the emergency department (ED). (3) Results: A total of 1035 patients were included in our study. Neither lymphocytes, platelets or PLR were associated with disease severity. Lymphocyte count was significantly lower and PLR values were significantly higher in the group of patients who died, and both were associated with mortality in the univariate analysis (OR: 0.524, 95% CI: (0.336–0.815), p = 0.004) and (OR: 1.001, 95% CI: (1.000–1.001), p = 0.042), respectively. However, the only biological parameter significantly associated with mortality in the multivariate analysis was platelet count (OR: 0.996, 95% CI: (0.996–1.000), p = 0.027). The best PLR value for predicting mortality in COVID-19 was 356.6 (OR: 3.793, 95% CI: (1.946–7.394), p < 0.001). (4) Conclusion: A high PLR value is however associated with excess mortality.

International audience; Background: There have been reports of procoagulant activity in patients with COVID-19. Whether there is an association between pulmonary embolism (PE) and COVID-19 in the emergency department (ED) is unknown. The aim of this study was to assess whether COVID-19 is associated with PE in ED patients who underwent a computed tomographic pulmonary angiogram (CTPA).Methods: A retrospective study in 26 EDs from six countries. ED patients in whom a CTPA was performed for suspected PE during a 2-month period covering the pandemic peak. The primary endpoint was the occurrence of a PE on CTPA. COVID-19 was diagnosed in the ED either on CT or reverse transcriptase-polymerase chain reaction. A multivariable binary logistic regression was built to adjust with other variables known to be associated with PE. A sensitivity analysis was performed in patients included during the pandemic period.Results: A total of 3,358 patients were included, of whom 105 were excluded because COVID-19 status was unknown, leaving 3,253 for analysis. Among them, 974 (30%) were diagnosed with COVID-19. Mean (±SD) age was 61 (±19) years and 52% were women. A PE was diagnosed on CTPA in 500 patients (15%). The risk of PE was similar between COVID-19 patients and others (15% in both groups). In the multivariable binary logistic regression model, COVID-19 was not associated with higher risk of PE (adjusted odds ratio = 0.98, 95% confidence interval = 0.76 to 1.26). There was no association when limited to patients in the pandemic period.Conclusion: In ED patients who underwent CTPA for suspected PE, COVID-19 was not associated with an increased probability of PE diagnosis. These results were also valid when limited to the pandemic period. However, these results may not apply to patients with suspected COVID-19 in general.

International audience; (1) Context: The management of acute coronary syndrome (ACS) is based on a rapid diagnosis. The aim of this study was to focus on the ACS symptoms differences according to gender, in order to contribute to the improvement of knowledge regarding the clinical presentation in women. (2) Methods: We searched for relevant literature in two electronic databases, and analyzed the symptom presentation for patients with suspected ACS. Fifteen prospective studies were included, with a total sample size of 10,730. (3) Results: During a suspected ACS, women present more dyspnea, arm pain, nausea and vomiting, fatigue, palpitations and pain at the shoulder than men, with RR (95%CI) of 1.13 [1.10; 1.17], 1.30 [1.05; 1.59], 1,40 [1.26; 1.56], 1.08 [1.01; 1.16], 1.67 [1.49; 1.86], 1.78 [1.02; 3.13], respectively. They are older by (95%CI) 4.15 [2.28; 6.03] years compared to men. The results are consistent in the analysis of the ACS confirmed subgroup. (4) Conclusions: We have shown that there is a gender-based symptomatic difference and a female presentation for ACS. The "typical" or "atypical" semiology of ACS symptoms should no longer be used.

(1) Introduction: Multiple studies have demonstrated that lymphocyte count monitoring is a valuable prognostic tool for clinicians during inflammation. The aim of our study was to determine the prognostic value of delta lymphocyte H24 from admission from the emergency department for mortality and severity of SARS-CoV-2 infection. (2) Methods: We have made a retrospective and multicentric study in six major hospitals of northeastern France. The patients were hospitalized and had a confirmed diagnosis of SARS-CoV-2 infection. (3): Results: A total of 1035 patients were included in this study. Factors associated with infection severity were CRP > 100 mg/L (OR: 2.51, CI 95%: (1.40–3.71), p < 0.001) and lymphopenia < 800/mm3 (OR: 2.15, CI 95%: (1.42–3.27), p < 0.001). In multivariate analysis, delta lymphocytes H24 (i.e., the difference between lymphocytes values at H24 and upon admission to the ED) < 135 was one of the most significant biochemical factors associated with mortality (OR: 2.23, CI 95%: (1.23–4.05), p = 0.009). The most accurate threshold for delta lymphocytes H24 was 75 to predict severity and 135 for mortality. (4) Conclusion: Delta lymphocytes H24 could be a helpful early screening prognostic biomarker to predict severity and mortality associated with COVID-19.

Objective: To compare the severity of pulmonary embolism (PE) between patients with and without COVID, and to assess the association between severity and in-hospital-mortality. Methods: We performed an analysis of 549 COVID (71.3% PCR-confirmed) and 439 non-COVID patients with PE consecutively included by 62 Spanish and 16 French emergency departments. PE-severity was assessed by size, the presence of right ventricular dysfunction (RVD), and the sPESI. The association of PE-severity and in-hospital-mortality was assessed both in COVID and non-COVID patients, and the interaction of COVID status and PE severity/outcome associations was also evaluated. Results: COVID patients had PEs of smaller size (43% vs 56% lobar or larger, 42% vs. 35% segmental and 13% vs. 9% subsegmental, respectively; p = 0.01 for trend), less RVD (22% vs. 16%, p=0.02) and lower sPESI (p=0.03 for trend). Risk of in-hospital death was higher in COVID patients (12.8% vs. 5.3%, p < 0.001). PE-severity assessed by RVD and sPESI was independently associated with in-hospital-mortality in COVID patients, while PE size and sPESI were significantly associated with in-hospital-mortality in non-COVID. COVID status showed a significant interaction in the association of PE size and outcome (p=0.01), with OR for in-hospital mortality in COVID and non-COVID patients with lobar or larger PE of 0.92 (95%CI=0.19-4.47) and 4.47 (95% CI=1.60-12.5), respectively. Sensitivity analyses using only PCR-confirmed COVID cases confirmed these results. Conclusion: COVID patients present a differential clinical picture, with PE of less severity than in non-COVID patients. An increased sPESI was associated with the risk of mortality in both groups but, PE size did not seem to be associated with in-hospital mortality in COVID patients.

International audience; (1) Backround: Technological advances should foster gains in physicians’ efficiency. For example, a reduction of the medical decision time can be enabled by faster biological tests. The main objective of this study was to collect responses from an international panel of physicians on their needs for biomarkers and also to convey the improvement in the outcome to be made possible by the potential development of fast diagnostic tests for these biomarkers. (2) Methods: we distributed a questionnaire on the Internet to physicians. (3) Results: 508 physicians participated in this survey. The mean age was 38 years. General practice and emergency medicine were heavily represented, with 95% CIs of 44% (39.78, 48.41) and 32% (27.84, 35.94)), respectively. The two most represented countries were France (95% CI: 74% (70.20, 77.83)) and the USA (95% CI: 11% (8.65, 14.18)). Ninety-eight percentages of the physicians thought that obtaining cited biomarkers more quickly would be beneficial to their practice and to patient’s care. The main biomarkers of interest identified by our panel were troponin (95% CI: 51% (46.24, 54.94)), C-reactive protein (95% CI: 42% (38.03, 46.62)), D-dimer (95% CI: 29% (24.80, 32.68)), and brain natriuretic peptide (95% CI: 13% (10.25, 16.13)). (4) Conclusions: Our study highlights the real technological need for fast biomarker results, which could be provided by biosensors. The relevance of some answers such as troponin is questionable.

IMPORTANCE Uncontrolled studies suggest that pulmonary embolism (PE) can be safely ruled out using the YEARS rule, a diagnostic strategy that uses varying D-dimer thresholds. OBJECTIVE To prospectively validate the safety of a strategy that combines the YEARS rule with the pulmonary embolism rule-out criteria (PERC) rule and an age-adjusted D-dimer threshold. DESIGN, SETTINGS, AND PARTICIPANTS A cluster-randomized, crossover, noninferiority trial in 18 emergency departments (EDs) in France and Spain. Patients (N = 1414) who had a low clinical risk of PE not excluded by the PERC rule or a subjective clinical intermediate risk of PE were included from October 2019 to June 2020, and followed up until October 2020. INTERVENTIONS Each center was randomized for the sequence of intervention periods. In the intervention period (726 patients), PE was excluded without chest imaging in patients with no YEARS criteria and a D-dimer level less than 1000 ng/mL and in patients with 1 or more YEARS criteria and a D-dimer level less than the age-adjusted threshold (500 ng/mL if age = 50 years). In the control period (688 patients), PE was excluded without chest imaging if the D-dimer level was less than the age-adjusted threshold. MAIN OUTCOMES AND MEASURES The primary end point was venous thromboembolism (VTE) at 3 months. The noninferiority margin was set at 1.35%. There were 8 secondary end points, including chest imaging, ED length of stay, hospital admission. nonindicated anticoagulation treatment, all-cause death, and all-cause readmission at 3 months. RESULTS Of the 1414 included patients (mean age, 55 years; 58% female), 1217 (86%) were analyzed in the per-protocol analysis. PE was diagnosed in the ED in 100 patients (7.1%). At 3 months, VTE was diagnosed in 1 patient in the intervention group (0.15% [95% CI, 0.0% to 0.86%]) vs 5 patients in the control group (0.80% [95% CI, 0.26% to 1.86%]) (adjusted difference, -0.64% [1-sided 97.5% CI, -infinity to 0.21%), within the noninferiority margin). Of the 6 analyzed secondary end points, only 2 showed a statistically significant difference in the intervention group compared with the control group: chest imaging (30.4% vs 40.0%; adjusted difference, -8.7% [95% CI, -13.8% to -3.5%]) and ED median length of stay (6 hours [IQR, 4 to 8 hours] vs 6 hours [IQR, 5 to 9 hours]; adjusted difference, -1.6 hours [95% CI, -2.3 to -0.9]). CONCLUSIONS AND RELEVANCE Among ED patients with suspected PE, the use of the YEARS rule combined with the age-adjusted D-dimer threshold in PERC-positive patients, compared with a conventional diagnostic strategy, did not result in an inferior rate of thromboembolic events.

(1) Introduction: According to recent studies, the ratio of C-reactive-protein to lymphocyte is more sensitive and specific than other biomarkers associated to systemic inflammatory processes. This study aimed to determine the prognostic value of CLR on COVID-19 severity and mortality at emergency department (ED) admission. (2) Methods: Between 1 March and 30 April 2020, we carried out a multicenter and retrospective study in six major hospitals of northeast France. The cohort was composed of patients hospitalized for a confirmed diagnosis of moderate to severe COVID-19. (3) Results: A total of 1,035 patients were included in this study. Factors associated with infection severity were the CLR (OR: 1.001, CI 95%: (1.000–1.002), p = 0.012), and the lymphocyte level (OR: 1.951, CI 95%: (1.024–3.717), p = 0.042). In multivariate analysis, the only biochemical factor significantly associated with mortality was lymphocyte rate (OR: 2.308, CI 95%: (1.286–4.141), p = 0.005). The best threshold of CLR to predict the severity of infection was 78.3 (sensitivity 79%; specificity 47%), and to predict mortality, was 159.5 (sensitivity 48%; specificity 70%). (4) Conclusion: The CLR at admission to the ED could be a helpful prognostic biomarker in the early screening and prediction of the severity and mortality associated with SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) is a serious public health issue that became rapidly pandemic. Liver injury and comorbidities, including metabolic syndrome, are associated with severe forms of the disease. This study sought to investigate liver injury, clinical features, and risk factors in patients with mild, moderate, and severe COVID-19. We retrospectively included all consecutive patients hospitalized with laboratory-confirmed COVID-19 between February, 22 and May 15, 2020 at the emergency rooms of a French tertiary hospital. Medical history, symptoms, biological and imaging data were collected. Among the 1381 hospitalizations for COVID-19, 719 patients underwent liver tests on admission and 496 (68.9%) patients displayed abnormal liver tests. Aspartate aminotransferase was most commonly abnormal in 57% of cases, followed by gamma-glutamyl transferase, alanine aminotransferase, albumin, alkaline phosphatase, and total bilirubin in 56.5%, 35.9%, 18.4%, 11.4%, and 5.8%. The presence of hepatocellular type more than 2xULN was associated with a higher risk of hospitalization and a worse course of severe disease (odd ratio [OR] 5.599; 95%CI: 1.27-23.86; p = 0.021; OR 3.404; 95% CI: 2.12-5.47; p < 0.001, respectively). A higher NAFLD fibrosis score was associated with a higher risk of hospitalization (OR 1.754; 95%CI: 1.27-2.43, p < 0.001). In multivariate analyses, patients with high fibrosis-4 index had a 3-fold greater risk of severe disease (p < 0.001). Abnormal liver tests are common in patients with COVID-19 and could predict the outcome. Patients with non-alcoholic fatty liver disease and liver fibrosis are at higher risk of progressing to severe COVID-19. journal article 2022 May 2022 02 25 imported

Emergency departments (EDs) were on the front line for the diagnostic workup of patients with COVID-19-like symptoms during the first wave. Chest imaging was the key to rapidly identifying COVID-19 before administering RT-PCR, which was time-consuming. The objective of our study was to compare the costs and organizational benefits of triage strategies in ED during the first wave of the COVID-19 pandemic.We conducted a retrospective study in five EDs in France, involving 3712 consecutive patients consulting with COVID-like symptoms between 9 March 2020 and 8 April 2020, to assess the cost effectiveness of imaging strategies (chest radiography, chest computed tomography (CT) scan in the presence of respiratory symptoms, systematic ultra-low-dose (ULD) chest CT, and no systematic imaging) on ED length of stay (LOS) in the ED and on hospital costs. The incremental cost-effectiveness ratio was calculated as the difference in costs divided by the difference in LOS.Compared with chest radiography, workup with systematic ULD chest CT was the more cost-effective strategy (average LOS of 6.89 hours; average cost of €3646), allowing for an almost 4-hour decrease in LOS in the ED at a cost increase of €98 per patient. Chest radiography (extendedly dominated) and RT-PCR with no systematic imaging were the least effective strategies, with an average LOS of 10.8 hours. The strategy of chest CT in the presence of respiratory symptoms was more effective than the systematic ULD chest CT strategy, with the former providing a gain of 37 minutes at an extra cost of €718.Systematic ULD chest CT for patients with COVID-like symptoms in the ED is a cost-effective strategy and should be considered to improve the management of patients in the ED during the pandemic, given the need to triage patients.

The purpose of this study was to compare the costs and organizational benefits of diagnostic workup without and with MRI dedicated to the ED.We conducted a prospective observational uncontrolled before-after study in one ED of a university hospital in France from July 1, 2018, and January 3, 2020. We included all consecutive patients presenting with dizziness or diplopia. The main outcomes were the clinical decision time of ED physicians and the total costs for each strategy. Outcomes were compared using propensity score with inverse probability weighting in the 2 arms and an incremental cost-effectiveness ratio (ICER) was calculated.Among the 199 patients during the "before" period (average age: 60.4 years ± 17.6): 112 men (57%), and 181 during the "after" period (average age, 54.8 years ± 18.5): 107 men (59%), the average costs were €2701 (95% CI 1918; 3704) and €2389 (95% CI: €1627; 3280) per patient, respectively. The average time to clinical decision was 9.8 h (95% CI: 8.9 10.7) in the group "before" and 7.7 h (95% CI: 7.1; 8.4) in the group "after" (ICER: €151 saved for a reduction of 1 h in clinical decision time). The probabilistic sensitivity analysis estimated a 71% chance that the MRI dedicated to ED was dominant (less costly and more effective).Easy access to MRI in the ED for posterior circulation stroke-like symptoms must be considered a relevant approach to help physicians for an appropriate and rapid diagnostic with reduction of costs.NCT03660852 KEY POINTS: • A dedicated MRI in the ED for diplopia or dizziness may be considered an efficient strategy improving diagnostic performance, reducing physicians' decision time, and decreasing hospital costs. • This strategy supports clinical decision-making with early treatment and management of patients with posterior circulation-like symptoms in the ED. • There is 71% chance that the MRI dedicated to ED was dominant (less costly and more effective) compared with a strategy without dedicated MRI.

Identifying an infection may be difficult in the ED. Neutrophilic leukocytosis is often used in the diagnosis of infection despite its lack of specificity in situations of stress. Our objective was to study the value of each parameter of the WBC count, in particular eosinopenia, to diagnose bacterial infections in the ED. We conducted a retrospective and observational study over a period of 6 months. All patients with one of the following diagnoses were eligible: pneumonia (9.9%), pyelonephritis (26.2%), prostatitis (8.4%), appendicitis (26.2%), cholecystitis (8.4%), and diverticular sigmoiditis (5%). A total of 466 infected patients were included for statistical analysis, and a control group of 466 uninfected patients was randomly selected in the same period of time. All leukocyte count parameters were significantly modified (p 0.001) in the infected group compared with the control group. Neutrophils and total leukocytes remain the two most suitable parameters for the diagnosis of infections in the ED. Eosinopenia represented the most efficient parameter of the WBC count for the diagnosis of urinary and biliary tract infections. Deep eosinopenia presented a specificity of 94% for the diagnosis of infection. Any modification of the WBC count associated with an elevation of CRP ( 40 mg/L) or fever ( 38.5 °C) showed a high specificity for the diagnosis of infection. A careful analysis of the WBC count remains a valuable tool for the diagnosis of infection in the ED.

In metazoa, cilia assembly is a cellular process that starts with centriole to basal body maturation, migration to the cell surface and docking to the plasma membrane. Basal body docking involves the interaction of both the distal end of the basal body and the transition fibers / distal appendages, with the plasma membrane. Mutations in numerous genes involved in basal body docking and transition zone assembly are associated with the most severe ciliopathies, highlighting the importance of these events in cilium biogenesis. In this context, the ciliate Paramecium has been widely used as a model system to study basal body and cilia assembly. However, despite the apparent evolutionary conservation of cilia assembly events across phyla, whether the same molecular players are functionally conserved, is not fully known. Here, we demonstrated that CEP90, FOPNL and OFD1 form an evolutionary conserved complex that is crucial for ciliogenesis. Using ultrastructure expansion microscopy, we unveiled that these proteins localize at the distal end of both centrioles/basal bodies in Paramecium and mammalian cells. Moreover, we found that these proteins are recruited early after centriole duplication on the external surface of the procentriole and define the future location of the distal appendages. Functional analysis performed both in Paramecium and mammalian cells demonstrate the requirement of this complex for distal appendage assembly and basal body docking. Finally, we show that mammals require another component, Moonraker (MNR), to recruit OFD1, FOPNL, and CEP90, which will then recruits the distal appendage protein CEP83. Altogether, we propose that this ternary complex is required to determine the future position of distal appendages.

The cilium is a cell extension forming a distinct compartment of eukaryotic cell body with a complex and dynamic structure. This structure is highly conserved across species and ensures various functions as sensory and motility. In humans, ciliary dysfunction results in diseases (ciliopathies) that can affect all organs. Thanks to its complex ciliary structure, the unicellular and ciliated microorganism, Paramecium, constitutes a model of choice not only to study the structure, assembly and function of cilia but also to validate the specific role of mutations of genes linked to the ciliopathies.La paramécie, un organisme modèle pour étudier la ciliogenèse et les maladies ciliaires.Le cil est une extension présente à la surface de la quasi-totalité des cellules eucaryotes. Conservé au cours de l’évolution, il assure des fonctions sensorielles et/ou motiles. Chez l’homme, le dysfonctionnement ciliaire est à l’origine de différentes maladies regroupées sous le nom de ciliopathies. Grâce à sa ciliature complexe, la paramécie constitue un modèle de choix pour étudier non seulement la structure, l’assemblage et les fonctions des cils, mais aussi pour valider les mutations de gènes associées à ces ciliopathies.

(1) Introduction: The neutrophil-to lymphocyte ratio is valued as a predictive marker in several inflammatory diseases. For example, an increasing NLR is a risk factor of mortality in sepsis. It also appears to be helpful in other settings such as cancer. The aim of our work was to study the prognostic value of NLR for disease severity and mortality in patients infected with SARS-CoV-2 upon their admission to the Emergency Department (ED) and its early variation (ΔNLR) in the first 24 h of management (H-24). (2) Methods: Between 1 March and 30 April 2020, we conducted a multicenter and retrospective cohort study of patients with moderate or severe coronavirus disease 19 (COVID-19), who were all hospitalized after presenting to the ED. (3) Results: A total of 1035 patients were included in our study. Factors associated with infection severity were C-reactive protein level (OR: 1.007, CI 95%: [1.005–1.010], p &lt, 0.001), NLR at H-24 (OR: 1.117, CI 95%: [1.060–1.176], p &lt, 0.001), and ΔNLR (OR: 1.877, CI 95%: [1.160–3.036], p: 0.01). The best threshold of ΔNLR to predict the severity of infection was 0.222 (sensitivity 56.1%, specificity 68.3%). In multivariate analysis, the only biochemical factor significantly associated with mortality was again ΔNLR (OR: 2.142, CI 95%: ([1.132–4.056], p: 0.019). The best threshold of ΔNLR to predict mortality was 0.411 (sensitivity 53.3%, specificity 67.3%). (4) Conclusion: The NLR and its early variation (ΔNLR) could help physicians predict both severity and mortality associated with SARS-CoV-2 infection, hence contributing to optimized patient management (accurate triage and treatment).

A 54-year-old woman was admitted to the emergency department for an acute, fluctuating altered mental status and reduced perceptual awareness of her surroundings as well as disorganized thinking. Blood tests, including for drugs, were normal. A CT scan of the brain was normal. Magnetic resonance imaging and CT angiography of the supra-aortic vessels were both were consistent with moyamoya disease. The patient was hospitalized for further investigations. LEARNING POINTS: Moyamoya disease should be considered in the differential diagnosis of middle-aged patients presenting with an acute confusional state of unknown aetiology in the emergency department. The absence of focal examination findings does not exclude neurological disease as the cause of acute confusion, requiring further neuroimaging tests.

International audience; Background: Patients with COVID-19 pneumonia have an excess of inflammation and increased concentrations of cytokines including interleukin-1 (IL-1). We aimed to determine whether anakinra, a recombinant human IL-1 receptor antagonist, could improve outcomes in patients in hospital with mild-to-moderate COVID-19 pneumonia.Methods: In this multicentre, open-label, Bayesian randomised clinical trial (CORIMUNO-ANA-1), nested within the CORIMUNO-19 cohort, we recruited patients from 16 University hospitals in France with mild-to-moderate COVID-19 pneumonia, severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time RT-PCR, requiring at least 3 L/min of oxygen by mask or nasal cannula but without ventilation assistance, a score of 5 on the WHO Clinical Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the intensive care unit at admission to hospital. Eligible patients were randomly assigned (1:1) using a web-based secure centralised system, stratified by centre and blocked with varying block sizes (randomly of size two or four), to either usual care plus anakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) or usual care alone. Usual care was provided at the discretion of the site clinicians. The two coprimary outcomes were the proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 on the WHO-CPS) and survival without need for mechanical or non-invasive ventilation (including high-flow oxygen) at day 14. All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT04341584, and is now closed to accrual.Findings: Between April 8 and April 26, 2020, we screened 153 patients. The study was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: 59 were assigned to the anakinra group, and 57 were assigned to the usual care group. Two patients in the usual care group withdrew consent and were not analysed. In the analysable population, the median age was 66 years (IQR 59 to 76) and 80 (70%) participants were men. In the anakinra group, 21 (36%) of 59 patients had a WHO-CPS score of more than 5 at day 4 versus 21 (38%) of 55 in the usual care group (median posterior absolute risk difference [ARD] -2·5%, 90% credible interval [CrI] -17·1 to 12·0), with a posterior probability of ARD of less than 0 (ie, anakinra better than usual care) of 61·2%. At day 14, 28 (47%; 95% CI 33 to 59) patients in the anakinra group and 28 (51%; 95% CI 36 to 62) in the usual care group needed ventilation or died, with a posterior probability of any efficacy of anakinra (hazard ratio [HR] being less than 1) of 54·5% (median posterior HR 0·97; 90% CrI 0·62 to 1·52). At day 90, 16 (27%) patients in the anakinra group and 15 (27%) in the usual care group had died. Serious adverse events occurred in 27 (46%) patients in the anakinra group and 21 (38%) in the usual care group (p=0·45).Interpretation: Anakinra did not improve outcomes in patients with mild-to-moderate COVID-19 pneumonia. Further studies are needed to assess the efficacy of anakinra in other selected groups of patients with more severe COVID-19.Funding: The Ministry of Health, Programme Hospitalier de Recherche Clinique, Foundation for Medical Research, and AP-HP Foundation.

Introduction Seizures are one of the most common neurological reasons for emergency department (ED) visits. The benefit of ED-initiated, short-course outpatient benzodiazepine (BZD) treatment to prevent early recurrent seizure is unknown. This study assesses the risk of early seizure recurrence in patients who were or were not started with outpatient BZD in the ED. Methods This was a multicenter retrospective study conducted in eight French EDs between January 1 and December 31, 2019. All patients admitted for seizure were retrospectively screened and those discharged home from the ED were included. Patients with a history of chronic alcohol intoxication or chronic BZD therapy were excluded. Baseline characteristics, type of seizure, and 30-day outcome were retrospectively collected from the electronic health records. The primary endpoint was a return visit for seizure recurrence within 30 days. Independent factors associated with a seizure recurrence were identified using a multivariable binary logistic regression. Results A total of 2,218 patients were included and 1,820 were analyzed. The median age was 39 years and 60% were men. Among them 82% of patients had a generalized tonic-clonic seizure and 47% of seizures were idiopathic. BZD treatment was started in 773 (42%) patients. A total of 154 (8%) patients had an early recurrence at 30 days: 68 (9%) in patients who were treated with BZD versus 86 (8%) in patients who were not (odds ratio [OR] = 1.07, 95% confidence interval [CI] = 0.71 to 1.43). In multivariable analysis, two factors were independently associated with the primary endpoint: chronic epileptic treatment (adjusted OR = 2.58, 95% CI = 1.55 to 4.37) and having had a focal seizure (adjusted OR = 2.16, 95% CI = 1.56 to 4.37). Conclusion BZD therapy was started in 42% of patients who were discharged home after ED visit for a seizure. This treatment was not an independent factor associated with the risk of return visit for seizure recurrence at 30 days.

Introduction: Healthcare systems worldwide have been battling the ongoing COVID-19 pandemic. Eosinophils are multifunctional leukocytes implicated in the pathogenesis of several inflammatory processes including viral infections. We focus our study on the prognostic value of eosinopenia as a marker of disease severity and mortality in COVID-19 patients. Methods: Between 1 March and 30 April 2020, we conducted a multicenter and retrospective study on a cohort of COVID-19 patients (moderate or severe disease) who were hospitalized after presenting to the emergency department (ED). We led our study in six major hospitals of northeast France, one of the outbreak’s epicenters in Europe. Results: We have collected data from 1035 patients, with a confirmed diagnosis of COVID-19. More than three quarters of them (76.2%) presented a moderate form of the disease, while the remaining quarter (23.8%) presented a severe form requiring admission to the intensive care unit (ICU). Mean circulating eosinophils rate, at admission, varied according to disease severity (p < 0.001), yet it did not differ between survivors and non-survivors (p = 0.306). Extreme eosinopenia (=0/mm3) was predictive of severity (aOR = 1.77, p = 0.009); however, it was not predictive of mortality (aOR = 0.892, p = 0.696). The areas under the Receiver operating characteristics (ROC) curve were, respectively, 58.5% (CI95%: 55.3–61.7%) and 51.4% (CI95%: 46.8–56.1%) for the ability of circulating eosinophil rates to predict disease severity and mortality. Conclusion: Eosinopenia is very common and often profound in cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Eosinopenia was not a useful predictor of mortality; however, undetectable eosinophils (=0/mm3) were predictive of disease severity during the initial ED management.

International audience; Introduction The ongoing COVID-19 pandemic has led to devastating repercussions on health care systems worldwide. This viral infection has a broad clinical spectrum (ranging from influenza-like disease, viral pneumonia, and hypoxemia to acute respiratory distress syndrome requiring prolonged intensive care unit stays). The prognostic impact of measuring viral load on nasopharyngeal swab specimens (by reverse transcriptase polymerase chain reaction [RT-PCR]) is yet to be elucidated. Methods Between March 3 and April 5, 2020, we conducted a retrospective study on a cohort of COVID-19 patients (mild or severe disease) who were hospitalized after presenting to the emergency department (ED) and had at least one positive nasopharyngeal swab during their hospital stay. We led our study at the University Hospitals of Strasbourg in the Greater East region of France, one of the pandemic's epicenters in Europe. Results We have collected samples from a cohort of 287 patients with a confirmed diagnosis of COVID-19 who were included in our study. Nearly half of them (50.5%) presented a mild form of the disease, while the other half (49.5%) presented a severe form, requiring mechanical ventilation. Median (interquartile range) viral load on the initial upper respiratory swab at admission was 4.76 (3.29–6.06) log10 copies/reaction. When comparing survivors and nonsurvivors, this viral load measurement did not differ according to subgroups (p = 0.332). Additionally, we have found that respiratory viral load measurement was predictive of neither in-hospital mortality (adjusted odds ratio [AOR] = 1.05, 95% confidence interval [CI] = 0.85 to 1.31, p = 0.637) nor disease severity (AOR = 0.88, 95% CI = 0.73 to 1.06, p = 0.167). Conclusion Respiratory viral load measurement on the first nasopharyngeal swab (by RT-PCR) during initial ED management is neither a predictor of severity nor a predictor of mortality in SARS-CoV-2 infection. Host response to this viral infection along with the extent of preexisting comorbidities might be more foretelling of disease severity than the virus itself.

Introduction: Cancer patients are at high risk of developing septic shock (SSh) and are increasingly admitted to ICU given their improved long-term prognosis. We, therefore, compared the prognosis of cancer and non-cancer patients with SSh. Methods: We conducted a monocentric, retrospective cohort study (2013-2019) on patients admitted to ICU for SSh. We compared the clinical characteristics and management and studied short- and long-term mortality with ICU and in-hospital mortality and 1-year survival according to cancer status. Results: We analyzed 239 ICU stays in 210 patients, 59.5% of whom were men (n = 125), with a median age of 66.5 (IQR 56.3-77.0). Of the 121 cancer patients (57.6% of all patients), 70 had solid tumors (33.3%), and 51 had hematological malignancies (24.3%). When comparing ICU stays of patients with versus without cancer (n = 148 vs. n = 91 stays, respectively), mortality reached 30.4% (n = 45) vs. 30.0% (n = 27) in the ICU (p = 0.95), and 41.6% (n = 59) vs. 35.6% (n = 32) in hospital (p = 0.36), respectively. ICU length of stay (LOS) was 5.0 (2.0-11.3) vs. 6.0 (3.0-15.0) days (p = 0.27), whereas in-hospital LOS was 25.5 (13.8-42.0) vs. 19.5 (10.8-41.0) days (p = 0.33). Upon multivariate analysis, renal replacement therapy (OR = 2.29, CI95%: 1.06-4.93, p = 0.03), disseminated intravascular coagulation (OR = 5.89, CI95%: 2.49-13.92, p < 0.01), and mechanical ventilation (OR = 7.85, CI95%: 2.90-21.20, p < 0.01) were associated with ICU mortality, whereas malignancy, hematological, or solid tumors were not (OR = 1.41, CI95%: 0.65-3.04; p = 0.38). Similarly, overall cancer status was not associated with in-hospital mortality (OR = 1.99, CI95%: 0.98-4.03, p = 0.06); however, solid cancers were associated with increased in-hospital mortality (OR = 2.52, CI95%: 1.12-5.67, p = 0.03). Lastly, mortality was not significantly different at 365-day follow-up between patients with and without cancer. Conclusions: In-hospital and ICU mortality, as well as LOS, were not different in SSh patients with and without cancer, suggesting that malignancies should no longer be considered a barrier to ICU admission. Keywords: critical care; immunocompromised host; neoplasms; septic shock; treatment outcome.

International audience; Overcrowding in Emergency Departments is often considered as an outcome of insufficient access to hospital beds or primary care, therefore a potential lack of health resources. We sought to describe the quantitative evolution of health resources in the French health care system, in comparison with demographic and epidemiologic parameters that reflect health needs. Overall, in the last decade, parameters of capacity and human resources stagnated while activity and spending increased jointly, stimulated by ageing of the population and chronic diseases mostly. Nevertheless, recent official previsions have again recommended to proceed with hospital bed reduction until 2030. This has led to a dangerous saturation of emergency care and to the ongoing systemic health crisis. This situation will require ambitious health resources reinforcement plans in both hospital and primary care. Furthermore, ageing of the population and chronic diseases must lead society to deliberate on the fundamental goals and funding of our health care system.

Introduction: The COVID-19 outbreak had a major impact on healthcare systems worldwide. Our study aims to describe the characteristics and therapeutic emergency mobile service (EMS) management of patients with vital distress due to COVID-19, their in-hospital care pathway and their in-hospital outcome. Methods: This retrospective and multicentric study was conducted in the six main centers of the French Greater East region, an area heavily impacted by the pandemic. All patients requiring EMS dispatch and who were admitted straight to the intensive care unit (ICU) were included. Clinical data from their pre-hospital and hospital management were retrieved. Results: We included a total of 103 patients (78.6% male, median age 68). In the initial stage, patients were in a critical condition (median oxygen saturation was 72% (60&ndash, 80%)). In the field, 77.7% (CI 95%: 71.8&ndash, 88.3%) were intubated. Almost half of our population (45.6%, CI 95%: 37.1&ndash, 56.9%) had clinical Phenotype 1 (silent hypoxemia), while the remaining half presented Phenotype 2 (acute respiratory failure). In the ICU, a great number had ARDS (77.7%, CI 95% 71.8&ndash, 88.3% with a PaO2/FiO2 &lt, 200). In-hospital mortality was 33% (CI 95%: 24.6&ndash, 43.3%). The two phenotypes showed clinical and radiological differences (respiratory rate, OR = 0.98, p = 0.02, CT scan lesion extension &gt, 50%, OR = 0.76, p &lt, 0.03). However, no difference was found in terms of overall in-hospital mortality (OR = 1.07, p = 0.74). Conclusion: The clinical phenotypes appear to be very distinguishable in the pre-hospital field, yet no difference was found in terms of mortality. This leads us to recommend an identical management in the initial phase, despite the two distinct presentations.

The sensitivity of reverse transcriptase polymerase chain reaction (RT-PCR) has been questioned due to negative results in some patients who were strongly suspected of having coronavirus disease 2019 (COVID-19). The aim of our study was to analyze the prognosis of infected patients with initial negative RT-PCR in the emergency department (ED) during the COVID-19 outbreak. This study included two cohorts of adult inpatients admitted into the ED. All patients who were suspected to be infected with SARS-CoV-2 and who underwent a typical chest CT imaging were included. Thus, we studied two distinct cohorts: patients with positive RT-PCR (PCR+) and those with negative initial RT-PCR (PCR&ndash, ). The data were analyzed using Bayesian methods. We included 66 patients in the PCR&ndash, group and 198 in the PCR+ group. The baseline characteristics did not differ except in terms of a proportion of lower chronic respiratory disease in the PCR&ndash, group. We noted a less severe clinical presentation in the PCR&ndash, group (lower respiratory rate, lower oxygen need and mechanical ventilation requirement). Hospital mortality (9.1% vs. 9.6%) did not differ between the two groups. Despite an initially less serious clinical presentation, the mortality of patients infected by SARS-CoV-2 with a negative RT-PCR did not differ from those with positive RT-PCR.

This article performed 2914 throat swabs for reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2 infection on which 1114 returned positive During this period of time, 200 patients were directly transferred in intensive care units (ICU) and 1002 patients were admitted to medical wards due to COVID-19 Gradually, during the first weeks of March, the growing flow of patients was no longer compatible with a classic ED's organisation Moreover, the need to protect the ED's staff and patients considerably reduced the total capacity of our department Before the outbreak, staff was used to receive and monitor patients in corridors or collective waiting areas Because of the risk of contaminating caregivers and other patients, this organisation was no longer possible Each patient needed to be confined to a closed examination room and the ED's capacity had then subsequently decreased by half A new organisation was prepared with the hospital's crisis cell and the entire ED's staff, and was gradually implemented Flows must be quick and the triage tools adapted to the situation In this COVID-19 outbreak, the chest CT scan, due to its high diagnostic performance in the case of typical images, appeared to be an efficient triage element In fact, it can be carried out as soon as the patient is admitted, allowing rapid referral to COVID-19 hospitalisation units in case of typical imaging The time saved is considerable because the patient is brought to medical imaging by ambulance drivers, reducing waiting times In case of respiratory failure, the diagnosis was quickly made for early referral to the ICU A detailed evaluation of the system remains to be done but we have noted a reduction in the time spent in the ED with this organisation while daily frequentation (around 100 visits) per day was similar to before the outbreak This shows the effectiveness of the strategic choices that have been made, i e to respond both to the increase in the number of visits and the reduction in ED's capacity