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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

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.

(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.

IntroductionNeuroendocrine cells release Catestatin (CST) from Chromogranin A (CgA) to regulate stress responses. As regards COVID-19 patients (COVID+) requiring oxygen supply, to date nobody has studied CST as a potential mediator in the regulation of immunity.Patients & MethodsAdmission plasma CST and CgA - its precursor - concentrations were measured (ELISA test) in 73 COVID+ and 27 controls. Relationships with demographics, comorbidities, disease severity and outcomes were analysed (Mann-Whitney, Spearman correlation tests, ROC curves).ResultsAmong COVID+, 49 required ICU-admission (COVID+ICU+) and 24 standard hospitalization (COVID+ICU-). Controls were either healthy staff (COVID-ICU-, n=11) or (COVID-ICU+, patients n=16). Median plasma CST were higher in COVID+ than in controls (1.6 [1.02; 3.79] vs 0.87 [0.59; 2.21] ng/mL, pppppConclusionRespiratory COVID patients release significant amounts of CST in the plasma making this protein widely available for the neural regulation of immunity. If confirmed prospectively, plasma CST will reliably help in predicting in-hospital mortality, whereas CgA will facilitate the detection of patients prone to care-related infections.

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.

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: 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.

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.

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.

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

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 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 are evolutionary conserved proteins 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 during centriole duplication on the external surface of the procentriole. Functional analysis performed both in Paramecium and mammalian cells demonstrate the requirement of these proteins for distal appendage assembly and basal body docking. Finally, we show that mammalian centrioles require another component, Moonraker (MNR), to recruit OFD1, FOPNL, and CEP90, which will then recruit the distal appendage proteins CEP83, CEP89, and CEP164. Altogether, we propose that this OFD1, FOPNL, and CEP90 functional module is required to determine in mammalian cells the future position of distal appendage proteins.

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.

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.

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.

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: 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.

Introduction: For the past two years, healthcare systems worldwide have been battling the ongoing COVID-19 pandemic. Several studies tried to find predictive factors of mortality in COVID-19 patients. We aimed to research age as a predictive factor associated with in-hospital mortality in severe and critical SARS-CoV-2 infection. Methods: Between 1 March and 20 April 2020, we conducted a multicenter and retrospective study on a cohort of severe COVID-19 patients who were all hospitalized in the Intensive Care Unit (ICU). We led our study in nine hospitals of northeast France, one of the pandemic’s epicenters in Europe. Results: The median age of our study population was 66 years (58–72 years). Mortality was 24.6% (CI 95%: 20.6–29%) in the ICU and 26.5% (CI 95%: 22.3–31%) in the hospital. Non-survivors were significantly older (69 versus 64 years, p < 0.001) than the survivors. Although a history of cardio-vascular diseases was more frequent in the non-survivor group (p = 0.015), other underlying conditions and prior level of autonomy did not differ between the two groups. On multivariable analysis, age appeared to be an interesting predictive factor of in-hospital mortality. Thus, age ranges of 65 to 74 years (OR = 2.962, CI 95%: 1.231–7.132, p = 0.015) were predictive of mortality, whereas the group of patients aged over 75 years was not (OR = 3.084, CI 95%: 0.952–9.992, p = 0.06). Similarly, all comorbidities except for immunodeficiency (OR = 4.207, CI 95%: 1.006–17.586, p = 0.049) were not predictive of mortality. Finally, survival follow-up was obtained for the study population. Conclusion: Age appears to be a relevant predictive factor of in-hospital mortality in cases of severe or critical SARS-CoV-2 infection.

Introduction : Internet est un outil utile aux medecins pour completer leurs connaissances. Le but de cette etude etait d’identifier les pratiques de recherche sur Internet des etudiants en medecine et d’evaluer leur amelioration par une action de sensibilisation. Methodes : Quatre-vingt-dix etudiants de la faculte de medecine de Strasbourg ont ete randomises en deux groupes. Le groupe A a repondu a des questions annexees a un cas clinique, puis a un questionnaire declaratif concernant leurs pratiques habituelles de recherche d’informations medicales sur Internet. Le groupe B a d’abord ete sensibilise a ces pratiques grâce au questionnaire avant de repondre au cas clinique. Notre analyse a porte sur l’historique de leurs recherches, les scores obtenus par les etudiants et sur l’auto-evaluation de leurs pratiques. Resultats : Les etudiants declarent consulter indifferemment des sites medicaux de reference et des sites de vulgarisation medicale, resultats retrouves experimentalement avec le cas clinique. Une action de sensibilisation prealable favorise l’utilisation de Google.fr et la consultation de sites de reference comme celui de la Haute Autorite de sante, et reduit la consultation de sites de vulgarisation. La sensibilisation incite les etudiants a multiplier leurs sources d’information. Les etudiants ayant utilise Internet ont obtenu de meilleures notes que ceux ayant repondu a l’aide de leurs seules connaissances. Conclusion : Internet permet de completer efficacement les connaissances medicales. Les etudiants sensibilises a leurs pratiques de recherche sur Internet consultent des sites de meilleure qualite tout en multipliant leurs sources d’information. Il est necessaire de developper de meilleures formations a l’utilisation de cet outil.

Therapie - In Press.Proof corrected by the author Available online since dimanche 19 mars 2017

Acute renal infarction is an uncommon and often under diagnosed condition mostly because of misleading symptoms. Accurate data regarding clinical presentation, laboratory tests, diagnostic and treatment are lacking. Detection is often delayed or missed because of non-specific clinical presentation. The mechanisms of acute renal infarction are various, mainly embolic or thrombotic. Abdominal CT scan remains the most valuable exam to confirm the diagnosis. Therapeutic guidelines for the treatment of renal embolism have not been well established. The standard treatment strategy includes anticoagulation with or without thrombolysis. Despite the uncertainty regarding management, the renal outcome remains favorable. Some patients do develop some degree of renal insufficiency during the acute episode. We report here the case of a 73-year-old woman with bilateral acute renal infarction after discontinuation of anticoagulant therapy.

INTRODUCTION In septic shock patients, postseptic immunosuppression state after the systemic inflammatory response syndrome is responsible for nosocomial infections, with subsequent increased mortality. The aim of the present study was to assess the underlying cellular mechanisms of the postseptic immunosuppression state, by investigating mitochondrial functions of peripheral blood mononuclear cells (PBMCs) from septic shock patients over 7 days. MATERIALS AND METHODS Eighteen patients admitted to a French intensive care unit for septic shock were included. At days 1 and 7, PBMCs were isolated by Ficoll density gradient centrifugation. Mitochondrial respiration of intact septic PBMCs was assessed versus control group PBMCs, by measuring O2 consumption in plasma, using high-resolution respirometry. Mitochondrial respiration was then compared between septic plasmas and control plasmas for control PBMCs, septic PBMCs, and lymphoid cell-line (CEM). To investigate the role of plasma, we measured several plasma cytokines, among them High-Mobility Group Box 1 (HMGB1), by enzyme-linked immunosorbent assays. RESULTS Basal O2 consumption of septic shock PBMCs was of 8.27 ± 3.39 and 10.48 ± 3.99 pmol/s/10 cells at days 1 and 7, respectively, significantly higher than in control PBMCs (5.37 ± 1.46 pmol/s/10 cells, P

Background Septic shock-induced disseminated intravascular coagulation is responsible for increased occurrence of multiple organ dysfunction and mortality. Immunothrombosis-induced coagulopathy may contribute to hypercoagulability. We aimed at determining whether recombinant human thrombomodulin (rhTM) could control exaggerated immunothrombosis by studying procoagulant responses, fibrinolysis activity borne by microvesicles (MVs) and NETosis in septic shock. Methods In a septic shock model after a cecal ligation and puncture-induced peritonitis (H0), rats were treated with rhTM or a placebo at H18, resuscitated and monitored during 4 h. At H22, blood was sampled to perform coagulation tests, to characterize MVs and to detect neutrophils extracellular traps (NETs). Lungs were stained with hematoxylin–eosin for inflammatory injury assessment. Results Coagulopathy was attenuated in rhTM-treated septic rats compared to placebo-treated rats, as attested by a significant decrease in procoagulant annexin A5+-MVs and plasma procoagulant activity of phospholipids and by a significant increase in antithrombin levels (84 ± 8 vs. 64 ± 6%, p

Primary ciliary dyskinesia (PCD) is a genetically and phenotypically heterogeneous disorder characterized by destructive respiratory disease and laterality abnormalities due to randomised left-right body asymmetry. PCD is mostly caused by mutations affecting components of the core axoneme structure of motile cilia that are essential for cilia movement. In addition, there is a growing group of PCD genes that encode proteins essential for the assembly of the ciliary dynein motors and the active transport process that delivers them from their cytoplasmic assembly site into the axoneme. We screened a cohort of affected individuals for disease-causing mutations using a targeted next generation sequencing panel and identified 2 unrelated families (3 affected children) with mutations in the uncharacterized C11orf70 gene. The affected children share a consistent PCD phenotype from early life with laterality defects and immotile respiratory cilia displaying combined loss of inner and outer dynein arms (IDA+ODA). Phylogenetic analysis shows C11orf70 is highly conserved, distributed across species similarly to proteins involved in the intraflagellar transport (IFT)-dependant assembly of axonemal dyneins. Paramecium C11orf70 RNAi knockdown led to combined loss of ciliary IDA+ODA with reduced cilia beating and swim velocity. Fluorescently tagged C11orf70 in Paramecium and Chlamydomonas localises mainly in the cytoplasm with a small amount in the ciliary component, its abundance in the axoneme being IFT-dependant. During ciliogenesis, C11orf70 accumulates at the ciliary tips in a similar distribution to the IFT-B protein IFT46. In summary, C11orf70 is essential for IFT-dependant assembly of dynein arms and C11orf70 mutations cause defective cilia motility and PCD.

A 61-year-old woman presented to the emergency department (ED) with a 1-week fever associated with progressive headache. She also reported weakness and paraesthesias in both legs. In the ED, the patient had normal vital parameters and reported no other medical history. Clinical examination showed a slight neck stiffness; the rest of the examination was normal. Laboratory findings showed a mild inflammatory syndrome. The patient had a lumbar punction; the cerebrospinal fluid (CSF) showed moderate pleocytosis (140 leucocytes/μL with a mononuclear …

Introduction Les progres therapeutiques et techniques modernes ont modifie le pronostic des patients admis en service de reanimation. Parallelement le vieillissement de la population a conduit a proposer en reanimation des patients de plus en plus âges. Neanmoins la disponibilite des lits varie selon les periodes de l’annee et les phenomenes climatiques. Ainsi le nombre de places disponibles en periode hivernale est moindre. L’objectif principal de cette etude etait l’analyse du pronostic vital et fonctionnel d’une population contemporaine de reanimation en periode d’activite maximale. Materiel et methodes Nous avons mene durant la periode du 1 er janvier au 31 mai 2013, une etude retrospective, monocentrique, dans un service de reanimation ou la disponibilite des lits est grande ( n = 30). Une analyse de survie a ete effectuee pour evaluer la mortalite intra-hospitaliere et a domicile. Pour apprecier la dependance des patients jusqu’a un an apres l’hospitalisation le Glasgow Outcome Scale (GOS) a ete utilise. Par ailleurs la presence d’une pathologie maligne et l’existence d’un projet therapeutique ont ete releves. Resultats Sur une periode de 5 mois, 388 patients ont ete admis avec un âge moyen de 62 ans (± 19 ans). La population de plus de 60 ans represente 61 % des admissions. L’origine des patients etait repartie equitablement entre services hospitaliers de medecine, services d’urgences et origine extra-hospitaliere (SAMU). L’IGS II moyen etait de 50 (± 21,7). Les motifs principaux d’admission etaient : detresse respiratoire (32 %), troubles neurologiques (20 %), infection (13 %). Un tiers des patients presentaient a leur admission ou avait un antecedent de pathologie maligne. La mortalite observee en reanimation a ete de 23 % (stable sur la derniere decennie) et la mortalite intra-hospitaliere de 31 %. La mortalite a un an etait de 44 %. Un âge superieur a 60 ans influence la mortalite de facon significative sans que l’on puisse mettre en evidence de difference entre les patients de plus de 80 ans et les patients de la tranche 60–79 ans ( Fig. 1 ). L’existence d’un cancer affecte significativement la survie a un an ( p = 0,0025) mais pas la survie a la sortie de reanimation ( p = 0,058). Le niveau de dependance des survivants est partiellement altere chez 21 % des patients sans lien avec l’âge et ce niveau est stable (GOS identique a la situation avant hospitalisation) chez 79 % des survivants. Discussion La mortalite a l’hopital predite par l’IGS n’atteint les 50 % prevus qu’a un an. La mortalite observee en reanimation n’est pas majoree au cours de la periode par rapport aux annees precedentes. Cette etude ne montre pas d’augmentation de la mortalite chez les patients actuels de reanimation. L’existence d’un cancer n’influence pas la survie des patients a un an apres l’âge de 70 ans des lors qu’il existe un projet therapeutique specifique. Ainsi, il ne semble pas exister de criteres objectifs pour limiter l’admission en reanimation des patients en fonction de l’âge ou de l’existence d’un cancer en cas de place disponible.