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.

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)

Consistency of data reporting in fluid responsiveness studies in the critically ill setting: the CODEFIRE consensus from the Cardiovascular Dynamic section of the European Society of Intensive Care Medicine.

PURPOSE: To provide consensus recommendations regarding hemodynamic data reporting in studies investigating fluid responsiveness and fluid challenge (FC) use in the intensive care unit (ICU). METHODS: The Executive Committee of the European Society of Intensive Care Medicine (ESICM) commissioned and supervised the project. A panel of 18 international experts and a methodologist identified main domains and items from a systematic literature, plus 2 ancillary domains. A three-step Delphi process based on an iterative approach was used to obtain the final consensus. In the Delphi 1 and 2, the items were selected with strong (≥ 80% of votes) or week agreement (70-80% of votes), while the Delphi 3 generated recommended (≥ 90% of votes) or suggested (80-90% of votes) items (RI and SI, respectively). RESULTS: We identified 5 main domains initially including 117 items and the consensus finally resulted in 52 recommendations or suggestions: 18 RIs and 2 SIs statements were obtained for the domain "ICU admission", 11 RIs and 1 SI for the domain "mechanical ventilation", 5 RIs for the domain "reason for giving a FC", 8 RIs for the domain pre- and post-FC "hemodynamic data", and 7 RIs for the domain "pre-FC infused drugs". We had no consensus on the use of echocardiography, strong agreement regarding the volume (4 ml/kg) and the reference variable (cardiac output), while weak on administration rate (within 10 min) of FC in this setting. CONCLUSION: This consensus found 5 main domains and provided 52 recommendations for data reporting in studies investigating fluid responsiveness in ICU patients.

The proteome of bacterial membrane vesicles in Escherichia coli-a time course comparison study in two different media.

Introduction: Bacteria inhabit the in- and outside of the human body, such as skin, gut or the oral cavity where they play an innoxious, beneficial or even pathogenic role. It is well known that bacteria can secrete membrane vesicles (MVs) like eukaryotic cells with extracellular vesicles (EVs). Several studies indicate that bacterial membrane vesicles (bMVs) play a crucial role in microbiome-host interactions. However, the composition of such bMVs and their functionality under different culture conditions are still largely unknown. Methods: To gain a better insight into bMVs, we investigated the composition and functionality of E. coli (DSM 105380) bMVs from the culture media Lysogeny broth (LB) and RPMI 1640 throughout the different phases of growth (lag-, log- and stationary-phase). bMVs from three time points (8 h, 54 h, and 168 h) and two media (LB and RPMI 1640) were isolated by ultracentrifugation and analyzed using nanoparticle tracking analysis (NTA), cryogenic electron microscopy (Cryo-EM), conventional transmission electron microscopy (TEM) and mass spectrometry-based proteomics (LC-MS/MS). Furthermore, we examined pro-inflammatory cytokines IL-1ß and IL-8 in the human monocyte cell line THP-1 upon bMV treatment. Results: Particle numbers increased with inoculation periods. The bMV morphologies in Cryo-EM/TEM were similar at each time point and condition. Using proteomics, we identified 140 proteins, such as the common bMV markers OmpA and GroEL, present in bMVs isolated from both media and at all time points. Additionally, we were able to detect growth-condition-specific proteins. Treatment of THP-1 cells with bMVs of all six groups lead to significantly high IL-1ß and IL-8 expressions. Conclusion: Our study showed that the choice of medium and the duration of culturing significantly influence both E. coli bMV numbers and protein composition. Our TEM/Cryo-EM results demonstrated the presence of intact E. coli bMVs. Common E. coli proteins, including OmpA, GroEL, and ribosome proteins, can consistently be identified across all six tested growth conditions. Furthermore, our functional assays imply that bMVs isolated from the six groups retain their function and result in comparable cytokine induction.

Impact of adjuvant radiochemotherapy on free flap volume in head and neck reconstruction: A systematic review and meta-analysis.

BACKGROUND: Limited data exist regarding the effect of adjuvant radiochemotherapy on free flap volume in head and neck reconstruction. However, an adequate free flap volume is an important predictor of functional and patient-reported outcomes in head and neck reconstruction. METHODS: A systematic review of Medline, Embase, and the Cochrane Central Register of Controlled Trials was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. A total of 6710 abstracts were screened, and 36 full-text papers were reviewed. Nineteen studies met the inclusion criteria and were used to extract data for this analysis. RESULTS: A meta-analysis of 14 two-arm studies comparing the impact of adjuvant radiotherapy versus no adjuvant radiotherapy was performed. The main analysis revealed that 6 months postoperatively, irradiated flaps showed a significant reduction of volume (average, 9.4%) compared to nonirradiated flaps. The average interpolated pooled flap volumes 6 months postoperatively were 76.4% in irradiated flaps and 81.8% in nonirradiated flaps. After a median postoperative follow-up of 12 months, the total flap volume was 62.6% for irradiated flaps and 76% for nonirradiated flaps. Four studies reported that chemotherapy had no significant impact on free flap volume. CONCLUSIONS: Compared to nonirradiated flaps, irradiated flaps were significantly reduced in volume (range, 5% to 15.5%). Clinicians should take this into account when planning the surgical reconstruction of head and neck defects. Conducting large-scale prospective studies with standardized protocols and well-defined follow-up measurements could contribute to defining the ideal, personalized free flap volume for optimal function and patient-reported outcomes.

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.

Early temporary mechanical circulatory support for cardiogenic shock: Real-life data from a regional cardiac assistance network.

BACKGROUND: Temporary mechanical circulatory support as well as multidisciplinary team approach in a regional care organization might improve survival of cardiogenic shock. No study has evaluated the relative effect of each temporary mechanical circulatory support on mortality in the context of a regional network. METHODS: Prospective observational data were retrieved from patients consecutively admitted with cardiogenic shock to the intensive care units in 3 centers organized into a regional cardiac assistance network. Temporary mechanical circulatory support indication was decided by a heart team, based on the initial shock severity or if shock was refractory to medical treatment within 24 hours of admission. A propensity score for circulatory support use was used as an adjustment co-variable to emulate a target trial. The primary endpoint was in-hospital mortality. RESULTS: Two hundred and forty-six patients were included in the study (median age: 59.5 years, 71.9% male): 121 received early mechanical assistance. The main etiologies were acute myocardial infraction (46.8%) and decompensated heart failure (27.2%). Patients who received early mechanical assistance had more severe conditions than other patients. Their crude in-hospital mortality was 38% and 22.4% in other patients but adjusted in-hospital mortality was not different (hazard ratio 0.91, 95% CI:0.65-1.26). Patients with mechanical assistance had a higher rate of complications than others with longer Intensive Care Unit and hospital stays. CONCLUSIONS: In the conditions of a cardiac assistance regional network, in-hospital mortality was not improved by early mechanical assistance implantation. A high incidence of complications of temporary mechanical circulatory support may have jeopardized its potential benefit.

Towards a qualitative theory of the interruption of eating behavior change.

The poor maintenance of eating behavior change is one of the main obstacles to minimizing weight regain after weight loss during diets for non-surgical care of obese or overweight patients. We start with a known informal explanation of interruption in eating behavior change during severe restriction and formalize it as a causal network involving psychological variables, which we extend with energetic variables governed by principles of thermodynamics. The three core phenomena of dietary behavior change, i.e., non-initiation, initiation followed by discontinuation and initiation followed by non-discontinuation, are expressed in terms of the value of the key variable representing mood or psychological energy, the fluctuation of which is the result of three causal relationships. Based on our experimental knowledge of the time evolution profile of the three causal input variables, we then proceed to a qualitative analysis of the resulting theory, i.e., we consider an over-approximation of it which, after discretization, can be expressed in the form of a finite integer-based model. Using Answer Set Programming, we show that our formal model faithfully reproduces the three phenomena and, under a certain assumption, is minimal. We generalize this result by providing all the minimal models reproducing these phenomena when the possible causal relationships exerted on mood are extended to all the other variables (not just those assumed in the informal explanation), with arbitrary causality signs. Finally, by a direct analytical resolution of an under-approximation of our theory, obtained by assuming linear causalities, as a system of linear ODEs, we find exactly the same minimal models, proving that they are also equal to the actual minimal models of our theory since these are framed below and above by the models of the under-approximation and the over-approximation. We determine which parameters need to be person-specific and which can be considered invariant, i.e., we explain inter-individual variability. Our approach could pave the way for universally accepted theories in the field of behavior change and, more broadly, in other areas of psychology.

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.

Papillary and reticular fibroblasts generate distinct microenvironments that differentially impact angiogenesis.

Papillary and reticular dermis show distinct extracellular matrix (ECM) and vascularization corresponding to their specific functions. These characteristics are associated with gene expression patterns of fibroblasts freshly isolated from their native microenvironment. In order to assess the relevance of these fibroblast subpopulations in a tissue engineering context, we investigated their contribution to matrix production and vascularization using cell sheet culture conditions. We first performed RNA-seq differential expression analysis to determine whether several rounds of cell amplification and high-density culture affected their gene expression profile. Bioinformatics analysis revealed that expression of angiogenesis-related and matrisome gene signatures were maintained, resulting in papillary and reticular ECMs that differ in composition and structure. The impact of secreted or ECM-associated factors was then assessed using two independent 3D angiogenesis assays: -1/ a fibrin hydrogel-based assay allowing investigation of diffusible secreted factors, -2/ a scaffold-free cell-sheet based assay for investigation of fibroblast-produced microenvironment. These analyses revealed that papillary fibroblasts secrete highly angiogenic factors and produce a microenvironment characterised by ECM remodelling capacity and dense and branched microvascular network, whereas reticular fibroblasts produced more structural core components of the ECM associated with less branched and larger vessels. These features mimick the characteristics of both the ECM and the vasculature of dermis subcompartments. In addition to showing that skin fibroblast populations differentially regulate angiogenesis via both secreted and ECM factors, our work emphasizes the importance of papillary and reticular fibroblasts for engineering and modelling dermis microenvironment and vascularization. STATEMENT OF SIGNIFICANCE: Recent advances have brought to the forefront the central role of microenvironment and vascularization in tissue engineering for regenerative medicine and microtissue modelling. We have investigated the role of papillary and reticular fibroblast subpopulations using scaffold-free cell sheet culture. This approach provides differentiated cells conditions allowing the production of their own microenvironment. Analysis of gene expression profiles and characterisation of the matrix produced revealed strong and specific angiogenic properties that we functionally characterized using 3D angiogenesis models targeting the respective role of either secreted or matrix-bound factors. This study demonstrates the importance of cell-generated extracellular matrix and questions the importance of cell source and the relevance of hydrogels for developing physio-pathologically relevant tissue engineered substitutes.

Practical considerations for individualizing drug dosing in critically ill adults receiving renal replacement therapy.

Critically ill patients with sepsis admitted to the intensive care unit (ICU) often present with or develop renal dysfunction requiring renal replacement therapy (RRT) in addition to antimicrobial therapy. While early and appropriate antimicrobials for sepsis have been associated with an increased probability of survival, adequate dosing is also required in these patients. Adequate dosing of antimicrobials refers to dosing strategies that achieve serum drug levels at the site of infection that are able to provide a microbiological and/or clinical response while avoiding toxicity from excessive antibiotic exposure. Therapeutic drug monitoring (TDM) is the recommended strategy to achieve this goal, however, TDM is not routinely available in all ICUs and for all antimicrobials. In the absence of TDM, clinicians are therefore required to make dosing decisions based on the clinical condition of the patient, the causative organism, the characteristics of RRT, and an understanding of the physicochemical properties of the antimicrobial. Pharmacokinetics (PK) of antimicrobials can be highly variable between critically ill patients and also within the same patient over the course of their ICU stay. The initiation of RRT, which can be in the form of intermittent hemodialysis, continuous, or prolonged intermittent therapy, further complicates the predictability of drug disposition. This variability highlights the need for individualized dosing. This review highlights the practical considerations for the clinician for antimicrobial dosing in critically ill patients receiving RRT.

How to improve the efficiency and the safety of real-time ultrasound-guided central venous catheterization in 2023: a narrative review.

Central venous catheterization (CVC) is a frequent procedure, practiced by intensivists, anesthesiologists and advanced practice nurses in intensive care units and operative rooms. To reduce CVC-associated morbidity, it is essential to strive for best practices, based on the latest evidence. This narrative review aims to synthesize current knowledge on evidence-based best practices for CVC that improve the use and feasibility of real-time ultrasound-guided insertion procedures. Optimization of the vein puncture technique and the development of new technologies are discussed to reinforce the use of the subclavian vein catheterization as first choice. The search for alternative site of insertions, without increasing infectious and thrombotic risks, deserves further research.

Intensive Care Unit activity in France from the national database between 2013 and 2019: More critically ill patients, shorter stay and lower mortality rate.

BACKGROUND: Knowledge of the occurrence and outcome of admissions to Intensive Care Units (ICU) over time is important to inform healthcare services planning. This observational study aims at describing the activity of French ICUs between 2013 and 2019. METHODS: Patient admission characteristics, organ dysfunction scores, therapies, ICU and hospital lengths of stay and case fatality were collected from the French National Hospital Database (population-based cohort). Logistic regression models were developed to investigate the association between age, sex, SAPS II, organ failure, and year of care on in-ICU case fatality. FINDINGS: Among 1,594,801 ICU admissions, the yearly ICU admission increased from 3.3 to 3.5 per year per 1000 inhabitants (bed occupancy rate between 83.4 and 84.3%). The mean admission SAPS II was 42 ± 22, with a gradual annual increase. The median lengths of stay in ICU and in hospital were 3 (interquartile range (IQR) = [1-7]) and 11 days (IQR = [6-21]), respectively, with a progressive decrease over time. The in-ICU and hospital mortality case fatalities decreased from 18.0% to 17.1% and from 21.1% to 19.9% between 2013 and 2019, respectively. Male sex, age, SAPS II score, and the occurrence of any organ failure were associated with a higher case fatality rate. After adjustment on age, sex, SAPS II and organ failure, in-ICU case fatality decreased in 2019 as compared to 2013 (adjusted Odds Ratio = 0.87 [95% confidence interval, 0.85-0.89]). INTERPRETATION: During the study, an increasing incidence of ICU admission was associated with higher severity of illness but lower in-ICU case fatality.

Early non-invasive ventilation and high-flow nasal oxygen therapy for preventing endotracheal intubation in hypoxemic blunt chest trauma patients: the OptiTHO randomized trial.

BACKGROUND: The benefit-risk ratio of prophylactic non-invasive ventilation (NIV) and high-flow nasal oxygen therapy (HFNC-O2) during the early stage of blunt chest trauma remains controversial because of limited data. The main objective of this study was to compare the rate of endotracheal intubation between two NIV strategies in high-risk blunt chest trauma patients. METHODS: The OptiTHO trial was a randomized, open-label, multicenter trial over a two-year period. Every adult patients admitted in intensive care unit within 48 h after a high-risk blunt chest trauma (Thoracic Trauma Severity Score ≥ 8), an estimated PaO2/FiO2 ratio < 300 and no evidence of acute respiratory failure were eligible for study enrollment (Clinical Trial Registration: NCT03943914). The primary objective was to compare the rate of endotracheal intubation for delayed respiratory failure between two NIV strategies: i) a prompt association of HFNC-O2 and "early" NIV in every patient for at least 48 h with vs. ii) the standard of care associating COT and "late" NIV, indicated in patients with respiratory deterioration and/or PaO2/FiO2 ratio ≤ 200 mmHg. Secondary outcomes were the occurrence of chest trauma-related complications (pulmonary infection, delayed hemothorax or moderate-to-severe ARDS). RESULTS: Study enrollment was stopped for futility after a 2-year study period and randomization of 141 patients. Overall, 11 patients (7.8%) required endotracheal intubation for delayed respiratory failure. The rate of endotracheal intubation was not significantly lower in patients treated with the experimental strategy (7% [5/71]) when compared to the control group (8.6% [6/70]), with an adjusted OR = 0.72 (95%IC: 0.20-2.43), p = 0.60. The occurrence of pulmonary infection, delayed hemothorax or delayed ARDS was not significantly lower in patients treated by the experimental strategy (adjusted OR = 1.99 [95%IC: 0.73-5.89], p = 0.18, 0.85 [95%IC: 0.33-2.20], p = 0.74 and 2.14 [95%IC: 0.36-20.77], p = 0.41, respectively). CONCLUSION: A prompt association of HFNC-O2 with preventive NIV did not reduce the rate of endotracheal intubation or secondary respiratory complications when compared to COT and late NIV in high-risk blunt chest trauma patients with non-severe hypoxemia and no sign of acute respiratory failure. CLINICAL TRIAL REGISTRATION: NCT03943914, Registered 7 May 2019.

Principles and Validations of an Artificial Intelligence-Based Recommender System Suggesting Acceptable Food Changes.

BACKGROUND: Along with the popularity of smartphones, artificial intelligence-based personalized suggestions can be seen as promising ways to change eating habits toward more desirable diets. OBJECTIVES: Two issues raised by such technologies were addressed in this study. The first hypothesis tested is a recommender system based on automatically learning simple association rules between dishes of the same meal that would make it possible to identify plausible substitutions for the consumer. The second hypothesis tested is that for an identical set of dietary-swaps suggestions, the more the user is-or thinks to be-involved in the process of identifying the suggestion, the higher is their probability of accepting the suggestion. METHODS: Three studies are presented in this article, first, we present the principles of an algorithm to mine plausible substitutions from a large food consumption database. Second, we evaluate the plausibility of these automatically mined suggestions through the results of online tests conducted for a group of 255 adult participants. Afterward, we investigated the persuasiveness of 3 suggestion methods of such recommendations in a population of 27 healthy adult volunteers through a custom designed smartphone application. RESULTS: The results firstly indicated that a method based on automatic learning of substitution rules between foods performed relatively well identifying plausible swaps suggestions. Regarding the form that should be used to suggest, we found that when users are involved in selecting the most appropriate recommendation for them, the resulting suggestions were more accepted (OR = 3.168; P < 0.0004). CONCLUSIONS: This work indicates that food recommendation algorithms can gain efficiency by taking into account the consumption context and user engagement in the recommendation process. Further research is warranted to identify nutritionally relevant suggestions.

Implantation of engineered human microvasculature to study human infectious diseases in mouse models.

Animal models for studying human pathogens are crucially lacking. We describe the implantation in mice of engineered human mature microvasculature consisting of endothelial and perivascular cells embedded in collagen hydrogel that allows investigation of pathogen interactions with the endothelium, including in vivo functional studies. Using Neisseria meningitidis as a paradigm of human-restricted infection, we demonstrated the strength and opportunities associated with the use of this approach.

Echocardiographic hemodynamic assessment in decompensated cirrhosis: comparison between Intensivists and Gastroenterologists.

BACKGROUND & AIMS: Ascites is a frequent complication of cirrhosis. In intensive care units, initial hemodynamic assessment is frequently performed by echocardiography. This study evaluated the feasibility and usefulness of early hemodynamic assessment in the gastroenterology ward. METHODS: This observational cohort study prospectively included all patients admitted to a teaching hospital's gastroenterology unit for decompensated cirrhosis. A gastroenterologist with minimal training and an intensivist both performed an echocardiography exam. The primary outcome was inter-rater agreement and reliability for three echocardiography parameters: visual LVEF (Left Ventricular Ejection Fraction), subaortic VTI (velocity time integral) and E wave velocity. Secondary outcomes were agreement for presence of pleural effusion, description of 3 hemodynamics profiles (hypovolemic, hyperkinetic and intermediate), and 28-day mortality. RESULTS: From March 2018 to March 2020, 53 patients were included. The median age was 62 years and 81% were men. Patients presented mostly advanced liver disease, with 43% Child-Pugh C and median MELD score of 15.2. The limits of agreement between intensivists and gastroenterologists for subaortic VTI were - 6.6 to 7.2 cm, and ranged from - 0.6 to 0.37 m.s-1 for E wave velocity. Clinically significant differences between intensivists and gastroenterologists were found in 22% for subaortic VTI and 24.5% for E wave velocity. Reliability was good for subaortic VTI (ICC: 0.79, 95% CI [0.58; 0.9;]) and moderate for E wave velocity (0.53, 95% CI [0.19; 0.74]). The three hemodynamics profiles had different prognosis, with a 28-day mortality for Hypovolemic, Intermediate and Hyperkinetic group of 31, 18, and 4%, respectively. CONCLUSION: Reliability of hemodynamic assessment by gastroenterologists was good, while agreement was unsatisfactory, advocating for further training. Transthoracic echocardiography can differentiate hypovolemia from hyperkinetic states. The role of transthoracic echocardiography in managing decompensated cirrhosis requires further study. CLINICAL TRIAL NUMBER: NCT03650660.

Prognostic value of an automated thrombin generation assay in COVID-19 patients entering hospital: A multicentric, prospective observational study.

INTRODUCTION: The prognostic significance of the thrombin generation assay (TGA) with a thrombomodulin (TM) challenge in patients entering hospital with severe COVID-19 is uncertain. METHODS: We prospectively evaluated an automated TGA (aTGA) using the ST-ThromboScreen® assay and ST-Genesia® analyser in 179 patients with severe COVID-19 during their admission to 2 university hospitals. The primary outcome was early survival at Day 28 (D28). Secondary outcomes were late survival at Day 90 (D90), later transfer to an intensive care unit (ICU), and occurrence of any thrombotic complications during hospitalisation. RESULTS: Among the 174 patients, 50 were initially admitted to ICUs. Forty-two were transferred to ICUs before D28. Fourteen patients, all in ICUs, died before D28, and 20 before D90, all but 1 in ICUs. None of the aTGA-derived results were associated with vital status either at D28 or D90. Nine patients had a thrombotic event with no association with the aTGA results. Later transfer to the ICU was associated with higher velocity index, thrombin peak height and endogenous thrombin potential (ETP) values of the aTGA performed with TM, and mainly with a lower TM-induced decrease in ETP (odds ratio 15.5 (2.15-132), p = 0.009). CONCLUSIONS: aTGA, a global assay supposed to evidence coagulopathy, could predict neither early or late survival, nor thrombotic events, in hospitalised COVID-19 patients. Its clinical justification in that setting is thus unlikely. A relative resistance of the ETP to TM was associated with later transfer to the ICU and deserves further investigation.