Rendimiento diRendimiento diagnóstico de un algoritmo basado en ecografía clínica para el diagnóstico de insuficiencia cardiaca aguda en pacientes que consultan en urgencias por disnea / Diagnostic performance of a clinical ultrasound-based algorithm for acute heart failure in patients presenting to the emergency department with dyspnea

Objetivos. Analizar el rendimiento diagnóstico de un algoritmo ecográfico que incluye el tiempo de desaceleración precoz del flujo mitral (TD) para establecer el diagnóstico de insuficiencia cardiaca aguda (ICA) en pacientes que consultan en un servicio de urgencias hospitalario (SUH) por disnea. Métodos. Análisis prospectivo de una muestra de conveniencia de pacientes que consultan por disnea aguda en un SUH. El algoritmo ecográfico incluyó la ecografía pulmonar y cuatro parámetros ecocardiográficos, se midió MAPSE (desplazamiento sistólico del plano del anillo mitral), medidas doppler de flujo mitral, medidas doppler tisular en el anillo mitral lateral y TD. El diagnóstico final fue asignado por 2 médicos ciegos entre sí y a los hallazgos ecográficos. Resultados. Se incluyeron 166 pacientes adultos, la edad media fue de 76 años (DE 13) y 79 eran mujeres (48%). Hubo 62 pacientes (37%) con un diagnóstico final de ICA. La concordancia entre asignadores fue buena para el diagnóstico de ICA (κ = 0,71). El algoritmo clasificó a todos los pacientes, no hubo ningún diagnóstico indeterminado. El rendimiento diagnóstico del algoritmo mostró un área bajo la curva de 0,91 (IC 95%: 0,86-0,96), sensibilidad del 87% (IC 95%: 76%-94%), especificidad del 95% (IC 95%: 89%-98%), razón de verosimilitud positiva del 18,1 (IC 95%: 7,7-42,8), razón de verosimilitud negativa del 0,14 (IC 95%: 0,07-0,26). Conclusiones. Un algoritmo ecográfico que incluye el TD tiene un buen rendimiento para el diagnóstico de ICA en pacientes que acuden a SUH por disnea. Además, el uso de TD permite clasificar a todos los pacientes. (AU)

Objective. To study the diagnostic performance of an ultrasound-based algorithm that includes the deceleration time (DT) of early mitral filling to establish a diagnosis of acute heart failure (AHF) in patients who come to an emergency department because of dyspnea. Methods. Prospective analysis in a convenience sample of patients who came to a hospital emergency department with acute dyspnea. The algorithm included ultrasound findings and 4 echocardiographic findings as follows: mitral annular plane systolic excursion, Doppler mitral flow velocity, tissue Doppler imaging measure of the lateral annulus, and the DT of early mitral filling. The definitive diagnosis was made by 2 physicians blinded to each other’s diagnosis and the ultrasound findings. Results. A total of 166 adult patients with a mean (SD) age of 76 (13) years were included; 79 (48%) were women. AHF was the definitive diagnosis in 62 patients (37%). Diagnostic agreement was good between the 2 physicians (κ = 0.71). The algorithm classified all the patients, and there were no undetermined diagnoses. Diagnostic performance indicators for the ultrasound-based algorithm integrating early DT findings were as follows: area under the receiver operating characteristic curve, 0.91 (95% CI, 0.86-0.96); sensitivity, 87% (95% CI, 76%-94%); specificity, 95% (95% CI, 89%-98%); positive likelihood ratio, 18.1 (95% CI, 7.7-42.8); and negative likelihood ratio, 0.14 (95% CI, 0.07-0.26). Conclusions. The ultrasound-based algorithm integrating the DT of early mitral filling performs well for diagnosing AHF in emergency patients with dyspnea. The inclusion of early DT allows all patients to be diagnosed. (AU)

Diagnostic performance of a clinical ultrasound-based algorithm for acute heart failure in patients presenting to the emergency department with dyspnea. / Rendimiento diagnóstico de un algoritmo basado en ecografía clínica para el diagnóstico de insuficiencia cardiaca aguda en pacientes que consultan en urgencias por disnea.

OBJECTIVES: To study the diagnostic performance of an ultrasound-based algorithm that includes the deceleration time (DT) of early mitral filling to establish a diagnosis of acute heart failure (AHF) in patients who come to an emergency department because of dyspnea. MATERIAL AND METHODS: Prospective analysis in a convenience sample of patients who came to a hospital emergency department with acute dyspnea. The algorithm included ultrasound findings and 4 echocardiographic findings as follows: mitral annular plane systolic excursion, Doppler mitral flow velocity, tissue Doppler imaging measure of the lateral annulus, and the DT of early mitral filling. The definitive diagnosis was made by 2 physicians blinded to each other's diagnosis and the ultrasound findings. RESULTS: A total of 166 adult patients with a mean (SD) age of 76 (13) years were included; 79 (48%) were women. AHF was the definitive diagnosis in 62 patients (37%). Diagnostic agreement was good between the 2 physicians (κ = 0.71). The algorithm classified all the patients, and there were no undetermined diagnoses. Diagnostic performance indicators for the ultrasound-based algorithm integrating early DT findings were as follows: area under the receiver operating characteristic curve, 0.91 (95% CI, 0.86-0.96); sensitivity, 87% (95% CI, 76%-94%); specificity, 95% (95% CI, 89%-98%); positive likelihood ratio, 18.1 (95% CI, 7.7-42.8); and negative likelihood ratio, 0.14 (95% CI, 0.07-0.26). CONCLUSION: The ultrasound-based algorithm integrating the DT of early mitral filling performs well for diagnosing AHF in emergency patients with dyspnea. The inclusion of early DT allows all patients to be diagnosed.

OBJETIVO: Analizar el rendimiento diagnóstico de un algoritmo ecográfico que incluye el tiempo de desaceleración precoz del flujo mitral (TD) para establecer el diagnóstico de insuficiencia cardiaca aguda (ICA) en pacientes que consultan en un servicio de urgencias hospitalario (SUH) por disnea. METODO: Análisis prospectivo de una muestra de conveniencia de pacientes que consultan por disnea aguda en un SUH. El algoritmo ecográfico incluyó la ecografía pulmonar y cuatro parámetros ecocardiográficos, se midió MAPSE (desplazamiento sistólico del plano del anillo mitral), medidas doppler de flujo mitral, medidas doppler tisular en el anillo mitral lateral y TD. El diagnóstico final fue asignado por 2 médicos ciegos entre sí y a los hallazgos ecográficos. RESULTADOS: Se incluyeron 166 pacientes adultos, la edad media fue de 76 años (DE 13) y 79 eran mujeres (48%). Hubo 62 pacientes (37%) con un diagnóstico final de ICA. La concordancia entre asignadores fue buena para el diagnóstico de ICA (κ = 0,71). El algoritmo clasificó a todos los pacientes, no hubo ningún diagnóstico indeterminado. El rendimiento diagnóstico del algoritmo mostró un área bajo la curva de 0,91 (IC 95%: 0,86-0,96), sensibilidad del 87% (IC 95%: 76%-94%), especificidad del 95% (IC 95%: 89%-98%), razón de verosimilitud positiva del 18,1 (IC 95%: 7,7-42,8), razón de verosimilitud negativa del 0,14 (IC 95%: 0,07-0,26). CONCLUSIONES: Un algoritmo ecográfico que incluye el TD tiene un buen rendimiento para el diagnóstico de ICA en pacientes que acuden a SUH por disnea. Además, el uso de TD permite clasificar a todos los pacientes.

Low Percentage of Perforin-Expressing NK Cells during Severe SARS-CoV-2 Infection: Consumption Rather than Primary Deficiency.

Genetic defects in the ability to deliver effective perforin have been reported in patients with hemophagocytic lymphohistiocytosis. We tested the hypothesis that a primary perforin deficiency might also be causal in severe SARS-CoV-2 infection. We recruited 54 volunteers confirmed as being SARS-CoV-2-infected by RT-PCR and admitted to intensive care units or non-intensive care units and age- and sex-matched healthy controls. Compared with healthy controls, the percentage of perforin-expressing CD3-CD56+ NK cells quantified by flow cytometry was low in COVID-19 patients (69.9 ± 17.7 versus 78.6 ± 14.6%, p = 0.026). There was no correlation between the proportions of perforin-positive NK cells and T8 lymphocytes. Moreover, the frequency of NK cells producing perforin was neither linked to disease severity nor predictive of death. Although IL-6 is known to downregulate perforin production in NK cells, we did not find any link between perforin expression and IL-6 plasma level. However, we unveiled a negative correlation between the degranulation marker CD107a and perforin expression in NK cells (r = -0.488, p = 10-4). PRF1 gene expression and the frequency of NK cells harboring perforin were normal in patients 1 y after acute SARS-CoV-2 infection. A primary perforin defect does not seem to be a driver of COVID-19 because NK perforin expression is 1) linked neither to T8 perforin expression nor to disease severity, 2) inversely correlated with NK degranulation, and 3) normalized at distance from acute infection. Thus, the cause of low frequency of perforin-positive NK cells appears, rather, to be consumption.

Is the shock index correlated with blood loss? An experimental study on a controlled hemorrhagic shock model in piglets.

INTRODUCTION: The quantification of blood loss in a severe trauma patient allows prognostic quantification and the engagement of adapted therapeutic means. The Advanced Trauma Life Support classification of hemorrhagic shock, based in part on hemodynamic parameters, could be improved. The search for reproducible and non-invasive parameters closely correlated with blood depletion is a necessity. An experimental model of controlled hemorrhagic shock allowed us to obtain hemodynamic and echocardiographic measurements during controlled blood spoliation. The primary aim was to demonstrate the correlation between the Shock Index (SI) and blood depletion volume (BDV) during the hemorrhagic phase of an experimental model of controlled hemorrhagic shock in piglets. The secondary aim was to study the correlations between blood pressure (BP) values and BDV, SI and cardiac output (CO), and pulse pressure (PP) and stroke volume during the same phase. METHODS: We analyzed data from 66 anesthetized and ventilated piglets that underwent blood spoliation at 2 mL.kg-1.min-1 until a mean arterial pressure (MAP) of 40 mmHg was achieved. During this bleeding phase, hemodynamic and echocardiographic measurements were performed regularly. RESULTS: The correlation coefficient between the SI and BDV was 0.70 (CI 95%, [0.64; 0.75]; p < 0.01), whereas between MAP and BDV, the correlation coefficient was -0.47 (CI 95%, [-0.55; -0.38]; p < 0.01). Correlation coefficient between SI and CO and between PP and stroke volume were - 0.45 (CI 95%, [-0.53; -0.37], p < 0.01) and 0.62 (CI 95%, [0.56; 0.67]; p < 0.01), respectively. CONCLUSIONS: In a controlled hemorrhagic shock model in piglets, the correlation between SI and BDV seemed strong.

Repetitive mRNA vaccination is required to improve the quality of broad-spectrum anti-SARS-CoV-2 antibodies in the absence of CXCL13.

Since the initial spread of severe acute respiratory syndrome coronavirus 2 infection, several viral variants have emerged and represent a major challenge for immune control, particularly in the context of vaccination. We evaluated the quantity, quality, and persistence of immunoglobulin G (IgG) and IgA in individuals who received two or three doses of messenger RNA (mRNA) vaccines, compared with previously infected vaccinated individuals. We show that three doses of mRNA vaccine were required to match the humoral responses of preinfected vaccinees. Given the importance of antibody-dependent cell-mediated immunity against viral infections, we also measured the capacity of IgG to recognize spike variants expressed on the cell surface and found that cross-reactivity was also strongly improved by repeated vaccination. Last, we report low levels of CXCL13, a surrogate marker of germinal center activation and formation, in vaccinees both after two and three doses compared with preinfected individuals, providing a potential explanation for the short duration and low quality of Ig induced.

Management of patients suffering from mild traumatic brain injury 2023.

OBJECTIVE: To develop a multidisciplinary French reference that addresses initial pre- and in-hospital management of a mild traumatic brain injury patient. DESIGN: A panel of 22 experts was formed on request from the French Society of Emergency Medicine (SFMU) and the French Society of Anaesthesiology and Critical Care Medicine (SFAR). A policy of declaration and monitoring of links of interest was applied and respected throughout the process of producing the guidelines. Similarly, no funding was received from any company marketing a health product (drug or medical device). The expert panel had to respect and follow the Grade® (Grading of Recommendations Assessment, Development and Evaluation) methodology to evaluate the quality of the evidence on which the recommendations were based. Given the impossibility of obtaining a high level of evidence for most of the recommendations, it was decided to adopt a "Recommendations for Professional Practice" (RPP) format, rather than a Formalized Expert Recommendation (FER) format, and to formulate the recommendations using the terminology of the SFMU and SFAR Guidelines. METHODS: Three fields were defined: 1) pre-hospital assessment, 2) emergency room management, and 3) emergency room discharge modalities. The group assessed 11 questions related to mild traumatic brain injury. Each question was formulated using a PICO (Patients Intervention Comparison Outcome) format. RESULTS: The experts' synthesis work and the application of the GRADE® method resulted in the formulation of 14 recommendations. After two rounds of rating, strong agreement was obtained for all recommendations. For one question, no recommendation could be made. CONCLUSION: There was strong agreement among the experts on important, transdisciplinary recommendations, the purpose of which is to improve management practices for patients with mild head injury.

S100B serum level: A relevant biomarker for the management of non-traumatic headaches in emergency care?

BACKGROUND: The diagnostic of primary or secondary headaches in emergency units is mostly based on brain imaging, which is expensive and sometimes hardly accessible. An increase in serum S100B protein has already been found in several neurological conditions inducing brain damage. The objective of this study was to assess the diagnostic performance of S100B serum assay to distinguish primary and secondary headaches among patients with non-traumatic headaches in the emergency department. METHODS: This was a phase 2, prospective, monocentric diagnostic study. Eighty-one adult patients with non-traumatic headaches in the emergency department were included. In addition to the usual management, a blood assay of the S100B protein was performed in the emergency department, as well as a brain MRI between 48 and 96 h if not performed during the initial management. The primary or secondary headache diagnosis was made at one month by an expert committee, blindly of the results of the S100B assay. The primary outcome was the blood assay of the S100B protein. RESULTS: There was 63 patients for analysis in the primary headache group and 17 in the secondary headache group. The S100B protein assay was significantly higher in secondary headaches than primary headaches, with an AUC of the ROC curve of 0.67. The optimal threshold of 0.06 µg.L-1 allowed to obtain those diagnostic characteristics: sensitivity 75% [48; 93], specificity 62% [48; 74], PPV 35% [20; 54] and NPV 90% [76; 97]. The association between the S100B protein level and the onset of pain was significantly higher for patients with headaches <3 h. CONCLUSION: The assay of the S100B protein could be useful in the management of this pathology in emergencies. Future studies taking into account dosing time and etiologies could be conducted in order to refine its use in practice.

Effect of Tocilizumab on Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta or Omicron Variants: A Propensity-Matched Analysis in Nimes University Hospital, France.

We aimed to assess the factors associated with mortality in patients treated with tocilizumab for a SARS-CoV-2 pneumonia due to the delta or omicron variants of concern (VOC) and detect an effect of tocilizumab on mortality. We conducted a prospective cohort study in a tertiary hospital from 1 August 2021 to 31 March 2022 including patients with severe COVID-19, treated with tocilizumab. Factors associated with mortality were assessed in a Cox model; then, the 60-day mortality rates of COVID-19 patients treated with standard of care (SoC) +/- tocilizumab were compared after 1:1 propensity score matching. The mortality rate was 22% (N = 26/118) and was similar between delta and omicron cases (p = 0.6). The factors independently associated with mortality were age (HR 1.06; 95% CI (1.02-1.11), p = 0.002), Charlson index (HR 1.33; 95% CI (1.11-1.6), p = 0.002), WHO-CPS (HR 2.56; 95% CI (1.07-6.22) p = 0.03), and tocilizumab infusion within the first 48 h following hospital admission (HR 0.37, 95% CI (0.14-0.97), p = 0.04). No significant differences in mortality between the tocilizumab plus SoC and SoC alone groups (p = 0.5) were highlighted. However, the patients treated with tocilizumab within the 48 h following hospital admission had better survival (p = 0.04). In conclusion, our results suggested a protective effect on mortality of the early administration of tocilizumab in patients with severe COVID-19 regardless of the VOC involved.

ARTERIAL DIAMETER VARIATIONS AS A NEW INDEX FOR STROKE VOLUME ASSESSMENT: AN EXPERIMENTAL STUDY ON A CONTROLLED HEMORRHAGIC SHOCK MODEL IN PIGLETS.

ABSTRACT: Background: The assessment of cardiac output (CO) is a major challenge during shock. The criterion standard for CO evaluation is transpulmonary thermodilution, which is an invasive technique. Speckle tracking is an automatized method of analyzing tissue motion using echography. This tool can be used to monitor pulsed arterial diameter variations with low interobserver variability. An experimental model of controlled hemorrhagic shock allows for multiple CO variations. The main aim of this study is to show the correlation between the femoral arterial diameter variations (fADVs) and the stroke volume (SV) measured by thermodilution during hemorrhagic shock management and the resuscitation of anesthetized piglets. The secondary objective is to explore the respective correlations between SV and subaortic time-velocity index, abdominal aorta ADV, carotid ADV, and subclavian ADV. Methods : Piglets were bled until mean arterial pressure reached 40 mm Hg. Controlled hemorrhage was maintained for 30 minutes before randomizing the piglets to three resuscitation groups-the fluid-filling group (reanimated with saline solution only), NEph group (norepinephrine + saline solution), and Eph group (epinephrin + saline solution). Speckle tracking, echocardiographic, and hemodynamic measures were performed at different stages of the protocol. Results : Thirteen piglets were recruited and included for statistical analysis. Of all the piglets, 164 fADV measures were attempted and 160 were successful (98%). The correlation coefficient between fADV and SV was 0.71 (95% confidence interval [CI], 0.62 to 0.78; P < 0.01). The correlation coefficient between SV and abdominal aorta ADV, subclavian ADV, and carotid ADV was 0.30 (95% CI, 0.13 to 0.46; P < 0.01), 0.56 (95% CI, 0.45 to 0.66, P < 0.01), and 0.15 (95% CI, -0.01 to 0.30, P = 0.06), respectively. Conclusions : In this hemorrhagic shock model using piglets, fADV was strongly correlated with SV.

Prescription errors by emergency physicians for inpatients are associated with emergency department length of stay.

OBJECTIVES: Adverse drug events are the sixth-leading cause of death in Western countries and are also more frequent in emergency departments (EDs). In some hospitals or on some occasions, ED physicians prescribe for patients who they have admitted. These prescriptions are then followed by the wards and can persist for several days. Our objectives were to determine the frequency of prescription errors for patients over 18years old hospitalized from ED to medical or surgical wards, and whether there exists a relationship between those prescription errors and ED LOS. METHODS: This was a single center retrospective study that was conduct in the ED of a university hospital with an annual census of 65 000 patients. The population studied consisted of patients over 18years old hospitalized from ED to medical or surgical wards between January 1st, 2012 and January 21st, 2012. RESULTS: Six hundred eight patients were included. One hundred fifty-four (25%) patients had prescription errors. Prescription errors were associated with increased ED length of stay (OR=2.47; 95% CIs [1.58; 3.92]) and polypharmacy (OR=1.78; 95% CIs [1.20; 2.66]). Fewer prescription errors were found when the patient was examined in the ED by a consultant (OR=0.61; 95% CIs [0.41; 0.91]) and when the medical history was known (OR=0.28; 95% CIs [0.10; 0.88]). CONCLUSION: Prescription errors occurred frequently in the ED. We assume that a clear communication and cooperation between EPs and consultants may help improve prescription accuracy.

T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID.

Background: As about 10% of patients with COVID-19 present sequelae, it is important to better understand the physiopathology of so-called long COVID. Method: To this aim, we recruited 29 patients hospitalized for SARS-CoV-2 infection and, by Luminex®, quantified 19 soluble factors in their plasma and in the supernatant of their peripheral blood mononuclear cells, including inflammatory and anti-inflammatory cytokines and chemokines, Th1/Th2/Th17 cytokines, and endothelium activation markers. We also measured their T4, T8 and NK differentiation, activation, exhaustion and senescence, T cell apoptosis, and monocyte subpopulations by flow cytometry. We compared these markers between participants who developed long COVID or not one year later. Results: None of these markers was predictive for sequelae, except programmed T4 cell death. T4 lymphocytes from participants who later presented long COVID were more apoptotic in culture than those of sequelae-free participants at Month 12 (36.9 ± 14.7 vs. 24.2 ± 9.0%, p = 0.016). Conclusions: Our observation raises the hypothesis that T4 cell death during the acute phase of SARS-CoV-2 infection might pave the way for long COVID. Mechanistically, T4 lymphopenia might favor phenomena that could cause sequelae, including SARS-CoV-2 persistence, reactivation of other viruses, autoimmunity and immune dysregulation. In this scenario, inhibiting T cell apoptosis, for instance, by caspase inhibitors, could prevent long COVID.

Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID.

T cell cytotoxicity plays a major role in antiviral immunity. Anti-SARS-CoV-2 immunity may determine acute disease severity, but also the potential persistence of symptoms (long COVID). We therefore measured the expression of perforin, a cytotoxic mediator, in T cells of patients recently hospitalized for SARS-CoV-2 infection. We recruited 54 volunteers confirmed as being SARS-CoV-2-infected by RT-PCR and admitted to Intensive Care Units (ICUs) or non-ICU, and 29 age- and sex-matched healthy controls (HCs). Amounts of intracellular perforin and granzyme-B, as well as cell surface expression of the degranulation marker CD107A were determined by flow cytometry. The levels of 15 cytokines in plasma were measured by Luminex. The frequency of perforin-positive T4 cells and T8 cells was higher in patients than in HCs (9.9 ± 10.1% versus 4.6 ± 6.4%, p = 0.006 and 46.7 ± 20.6% vs 33.3 ± 18.8%, p = 0.004, respectively). Perforin expression was neither correlated with clinical and biological markers of disease severity nor predictive of death. By contrast, the percentage of perforin-positive T8 cells in the acute phase of the disease predicted the onset of long COVID one year later. A low T8 cytotoxicity in the first days of SARS-CoV-2 infection might favor virus replication and persistence, autoimmunity, and/or reactivation of other viruses such as Epstein-Barr virus or cytomegalovirus, paving the way for long COVID. Under this hypothesis, boosting T cell cytotoxicity during the acute phase of the infection could prevent delayed sequelae.

Evaluation of a New Echocardiographic Tool for Cardiac Output Monitoring: An Experimental Study on A Controlled Hemorrhagic Shock Model in Anesthetized Piglets.

BACKGROUND: Cardiac output (CO) monitoring is recommended in patients with shock. The search for a reliable, rapid, and noninvasive tool is necessary for clinical practice. A new echocardiographic CO flow index (COF) is the automatic calculation of the sub-aortic VTI multiplied by the automatic calculation of the heart rate (HR). The primary objective of this study was to show the correlation between COF and CO measured by thermodilution (COth) in a controlled hemorrhagic shock model in anesthetized piglets. Secondary objectives were to show the correlation between COth and CO calculated from left outflow tract (LVOT) measurement and manual VTI (COman), and CO measured by LVOT measurement and VTIauto (COauto). METHODS: Prospective interventional experimental study. In seventeen ventilated and anesthetized piglets, a state of hemorrhagic shock was induced, maintained, then resuscitated and stabilized. The gold standard for CO and stroke volume measurement was thermodilution (COth). RESULTS: 191 measurements were performed. The correlation coefficients (r) between COth and COF, COman, and COauto were 0.73 [0.62; 0.81], 0.66 [0.56; 0.74], and 0.73 [0.63; 0.81], respectively. CONCLUSIONS: In this study, the COF appears to have a strong correlation to the COth. This automatic index, which takes into account the HR and does not require the measurement of LVOT, could be a rapidly obtained index in clinical practice.

Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patients.

In addition to an inflammatory reaction, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-infected patients present lymphopenia, which we recently reported as being related to abnormal programmed cell death. As an efficient humoral response requires CD4 T-cell help, we hypothesized that the propensity of CD4 T cells to die may impact the quantity and quality of the humoral response in acutely infected individuals. In addition to specific immunoglobulins (Ig)A, IgM, and IgG against SARS-CoV-2 nucleocapsid (N), membrane (M), and spike (S1) proteins, we assessed the quality of IgG response by measuring the avidity index. Because the S protein represents the main target for neutralization and antibody-dependent cellular cytotoxicity responses, we also analyzed anti-S-specific IgG using S-transfected cells (S-Flow). Our results demonstrated that most COVID-19 patients have a predominant IgA anti-N humoral response during the early phase of infection. This specific humoral response preceded the anti-S1 in time and magnitude. The avidity index of anti-S1 IgG was low in acutely infected individuals compared to convalescent patients. We showed that the percentage of apoptotic CD4 T cells is inversely correlated with the levels of specific IgG antibodies. These lower levels were also correlated positively with plasma levels of CXCL10, a marker of disease severity, and soluble Fas ligand that contributes to T-cell death. Finally, we found lower S-Flow responses in patients with higher CD4 T-cell apoptosis. Altogether, these results demonstrate that individuals with high levels of CD4 T-cell apoptosis and CXCL10 have a poor ability to build an efficient anti-S response. Consequently, preventing CD4 T-cell death might be a strategy for improving humoral response during the acute phase, thereby reducing COVID-19 pathogenicity.

How traditional and digital analytics interventions can enhance lung-protective ventilation strategies during general anaesthesia: A two-year quality improvement project analysis.

PURPOSE: This quality improvement project evaluated interventions implemented to enhance individual adherence to a lung-protective ventilation strategy and its triad: low tidal volume, PEEP ≥ 5, recruitment manoeuvres. METHODS: For two years, nine anaesthesia workstations were connected to an automated cloud-based analytics software tool, which automatically recorded ventilation parameters as soon as a new patient case was opened. Four quality improvement periods were determined over the first year: baseline, intervention, no intervention, intervention + digital. In the second year, the digital strategy was continued for nine months, followed by a final "overtime" period. Baseline and no intervention periods included no training. The intervention period included both conventional and educational programs. The digital period included pop-up messages, which automatically appeared on the screen of the anaesthesia data management system when patients were intubated. The primary endpoint was provider adherence to the recommended triad. RESULTS: From October 2018 to December 2020, 12,883 procedures were performed. Data were available for 8968 procedures: baseline (n = 2361), intervention (n = 2423), no intervention (n = 1064), intervention + digital (n = 1862), overtime (n = 1258). Age, Predicted Body Weight, ASA score, type of surgery and airway management were similar between periods. At baseline, 75.2% of procedures reported low tidal volume but only 6.9% involved the complete triad. At over time, Triad was 22% (p < 0.001). Over study period, each parameter of the Triad (RM, Vt and Peep) increased (p < 0.001 vs. baseline), driving pressure decreased although EtCO2 and plateau pressure had not changed. CONCLUSION: Training with the help of digital apps improved LPV adherence over time.

Early results of ultra-low-dose CT-scan for extremity traumas in emergency room.

Background: Ultra-low dose computed tomography (ULD-CT) was shown to be a good alternative to digital radiographs in various locations. This study aimed to assess the diagnostic sensitivity and specificity of ULD-CT versus digital radiographs in patients consulting for extremity traumas in emergency room. Methods: Digital radiography and ULD-CT scan were performed in patients consulting at the emergency department (February-August 2018) for extremity traumas. Fracture detection was evaluated retrospectively by two blinded independent radiologists. Sensitivity and specificity were evaluated using best value comparator (BVC) and a Bayesian latent class model (LCM) approaches and clinical follow-up. Image quality, quality diagnostic and diagnostic confidence level were evaluated (Likert scale). The effective dose received was calculated. Results: Seventy-six consecutive patients (41 men, mean age: 35.2±13.2 years), with 31 wrists/hands and 45 ankles/feet traumas were managed by emergency physicians. According to clinical data, radiography had 3 false positive and 10 false negative examinations, and ULD-CT, 2 of each. Radiography and ULD-CT specificities were similar; sensitivities were lower for radiography, with BVC and Bayesian. With Bayesian, ULD-CT and radiography sensitivities were 90% (95% CI: 87-93%) and 76% (95% CI: 71-81%, P<0.0001) and specificities 96% (95% CI: 93-98%) and 93% (95% CI: 87-97%, P=0.84). The inter-observer agreement was higher for ULD-CT for all subjective indexes. The effective dose for ULD-CT and radiography was 0.84±0.14 and 0.58±0.27 µSv (P=0.002) for hand/wrist, and 1.50±0.32 and 1.44±0.78 µSv (P=NS) for foot/ankle. Conclusions: With an effective dose level close to radiography, ULD-CT showed better detection of extremities fractures in the emergency room and may allow treatment adaptation. Further studies need to be performed to assess impact of such examination in everyday practice. Trial Registration: ClinicalTrials.gov Identifier: NCT04832490.

Analgesic efficacy of erector spinae plane blocks for lumbar spine surgery: a randomized double-blind controlled clinical trial.

INTRODUCTION: Erector spinae plane block has been proposed to reduce opioid use and improve pain relief with controversial results. This randomized clinical study aimed to assess the efficacy of erector spinae plane block in major spine surgery including multimodal and 'Enhance Recovery After Surgery' programs. METHOD: After institutional review board approval, adult patients undergoing elective lumbar spine surgery with standardized general anesthesia, rehabilitation and multimodal analgesia protocols were randomly allocated to receive bilateral ultrasound-guided block with saline versus ropivacaine (3.75 mg/mL). Before surgery, a bilateral erector spinae plane block was performed at lumbar level (third vertebrae) with 20 mL of solution for each side. The primary outcome was morphine consumption after 24 hours. Secondary outcomes included pain scores and side effects, from postanesthesia care unit to discharge, and questionnaires at 3 months on pain and quality of life (EQ-5D). RESULTS: From November 2019 to July 2021, 50 patients were enrolled with similar characteristics and surgery for each group. After the first 24 hours, there was no statistical difference regarding cumulative intravenous morphine consumption between ropivacaine and saline groups: 7.3 mg (3.7-19) vs 12.5 mg (3.5-26) (p=0.51). Over the five postoperative days, opioid sparing, pain scores and side effects were similar between groups. At 3 months, pain relief, incidence of chronic pain and EQ-5D were similar between groups. DISCUSSION: Erector spinae plane block used in conjunction with 'Enhance Recovery After Surgery' and multimodal analgesia protocols provides limited reduction in opioid consumption and no long-term benefits. TRIAL REGISTRATION NUMBER: EudraCT 2019-001678-26.

Angiotensin II induces reactive oxygen species, DNA damage, and T-cell apoptosis in severe COVID-19.

BACKGROUND: Lymphopenia is predictive of survival in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: The aim of this study was to understand the cause of the lymphocyte count drop in severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Monocytic production of reactive oxygen species (ROSs) and T-cell apoptosis were measured by flow cytometry, DNA damage in PBMCs was measured by immunofluorescence, and angiotensin II (AngII) was measured by ELISA in patients infected with SARS-CoV-2 at admission to an intensive care unit (ICU) (n = 29) or not admitted to an ICU (n = 29) and in age- and sex-matched healthy controls. RESULTS: We showed that the monocytes of certain patients with COVID-19 spontaneously released ROSs able to induce DNA damage and apoptosis in neighboring cells. Of note, high ROS production was predictive of death in ICU patients. Accordingly, in most patients, we observed the presence of DNA damage in up to 50% of their PBMCs and T-cell apoptosis. Moreover, the intensity of this DNA damage was linked to lymphopenia. SARS-CoV-2 is known to induce the internalization of its receptor, angiotensin-converting enzyme 2, which is a protease capable of catabolizing AngII. Accordingly, in certain patients with COVID-19 we observed high plasma levels of AngII. When looking for the stimulus responsible for their monocytic ROS production, we revealed that AngII triggers ROS production by monocytes via angiotensin receptor I. ROSs released by AngII-activated monocytes induced DNA damage and apoptosis in neighboring lymphocytes. CONCLUSION: We conclude that T-cell apoptosis provoked via DNA damage due to the release of monocytic ROSs could play a major role in COVID-19 pathogenesis.

Taxonomical and functional changes in COVID-19 faecal microbiome could be related to SARS-CoV-2 faecal load.

Since the beginning of the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the gastrointestinal (GI) tract has emerged as an important organ influencing the propensity to and potentially the severity of the related COVID-19 disease. However, the contribution of the SARS-CoV-2 intestinal infection on COVID-19 pathogenesis remains to be clarified. In this exploratory study, we highlighted a possible link between alterations in the composition of the gut microbiota and the levels of SARS-CoV-2 RNA in the gastrointestinal tract, which could be more important than the presence of SARS-CoV-2 in the respiratory tract, COVID-19 severity and GI symptoms. As established by metaproteomics, altered molecular functions in the microbiota profiles of high SARS-CoV-2 RNA level faeces highlight mechanisms such as inflammation-induced enterocyte damage, increased intestinal permeability and activation of immune response that may contribute to vicious cycles. Uncovering the role of this gut microbiota dysbiosis could drive the investigation of alternative therapeutic strategies to favour the clearance of the virus and potentially mitigate the effect of the SARS-CoV-2 infection.

T cell apoptosis characterizes severe Covid-19 disease.

Severe SARS-CoV-2 infections are characterized by lymphopenia, but the mechanisms involved are still elusive. Based on our knowledge of HIV pathophysiology, we hypothesized that SARS-CoV-2 infection-mediated lymphopenia could also be related to T cell apoptosis. By comparing intensive care unit (ICU) and non-ICU COVID-19 patients with age-matched healthy donors, we found a strong positive correlation between plasma levels of soluble FasL (sFasL) and T cell surface expression of Fas/CD95 with the propensity of T cells to die and CD4 T cell counts. Plasma levels of sFasL and T cell death are correlated with CXCL10 which is part of the signature of 4 biomarkers of disease severity (ROC, 0.98). We also found that members of the Bcl-2 family had modulated in the T cells of COVID-19 patients. More importantly, we demonstrated that the pan-caspase inhibitor, Q-VD, prevents T cell death by apoptosis and enhances Th1 transcripts. Altogether, our results are compatible with a model in which T-cell apoptosis accounts for T lymphopenia in individuals with severe COVID-19. Therefore, a strategy aimed at blocking caspase activation could be beneficial for preventing immunodeficiency in COVID-19 patients.