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Thrombosis is a hallmark of severe COVID-19. Alpha-1-antitrypsin (AAT), an inflammation-inducible serpin with anti-inflammatory, tissue protective and anticoagulant properties may be involved in severe COVID-19 pathophysiology including thrombosis onset. In this study, we examined AAT ability to predict occurrence of thrombosis and in-hospital mortality during COVID-19. To do so, we performed a monocentric cross-sectional study of 137 hospitalized patients with COVID-19 of whom 56 (41%) were critically ill and 33 (22.4%) suffered from thrombosis during hospitalization. We measured AAT and IL-6 plasma levels in all patients and phenotyped AAT in a subset of patients with or without thrombosis paired for age, sex and COVID-19 severity. We observed that AAT levels at admission were higher in both non-survivors and thrombosis patients than in survivors and non-thrombosis patients. AAT: IL-6 ratio was lower in non-survivors and thrombosis patients. In a logistic regression multivariable analysis model adjusted on age, BMI and D-dimer levels, a higher AAT: IL-6 was a protective factor of both in-hospital mortality (Odds ratio, OR: 0.07 95%CI [0.02-0.25], p 0.001) and thrombosis (OR 0.36 95%CI [0.14-0.82], p = 0.02). AAT phenotyping did not show a higher proportion of AAT abnormal variants in thrombosis patients.Our findings suggest an insufficient production of AAT regarding inflammation intensity during severe COVID-19. AAT appeared as a powerful predictive marker of severity, mortality and thrombosis mirroring the imbalance between harmful inflammation and protective counter-balancing mechanism in COVID-19. Restoring the balance between AAT and inflammation could offer therapeutic opportunities in severe COVID-19.

The Aeson total artificial heart (A-TAH) has been developed for patients at risk of death from biventricular failure. We aimed to assess the inflammatory status in nine subjects implanted with the A-TAH in kinetics over one year. Laboratory assessment of leukocyte counts, inflammatory cytokines assay, and peripheral blood mononuclear cell collection before and after A-TAH implantation. Leukocyte counts were not significantly modulated according to time after A-TAH implantation (coefficient of the linear mixed effect model with 95% CI, -0.05 (-0.71 to -0.61); p = 0.44). We explored inflammatory cytokine after A-TAH and did not observe, at any time, a modified profile compared to pre-implantation values (all p -values0.05). Finally, we compared the distribution of circulating immune cell subpopulations identified based on sequential expression patterns for multiple clusters of differentiation. None of the population explored had significant modulation during the 12-month follow-up (all p -values0.05). In conclusion, using a cytokine multiplex assay combined with a flow cytometry approach, we demonstrated the absence of inflammatory signals in peripheral blood over a period of 12 months following A-TAH implantation.

Background: Carmat bioprosthetic total artificial heart (Aeson; A-TAH) is a pulsatile and autoregulated device. The aim of this study is to evaluate level of hemolysis potential acquired von Willebrand syndrome after A-TAH implantation. Methods: We examined the presence of hemolysis and acquired von Willebrand syndrome in adult patients receiving A-TAH support (n=10) during their whole clinical follow-up in comparison with control subjects and adult patients receiving Heartmate II or Heartmate III support. We also performed a fluid structure interaction model coupled with computational fluid dynamics simulation to evaluate the A-TAH resulting shear stress and its distribution in the blood volume. Results: The cumulative duration of A-TAH support was 2087 days. A-TAH implantation did not affect plasma free hemoglobin over time, and there was no association between plasma free hemoglobin and cardiac output or beat rate. For VWF (von Willebrand factor) evaluation, A-TAH implantation did not modify multimers profile of VWF in contrast to Heartmate II and Heartmate III. Furthermore, fluid structure interaction coupled with computational fluid dynamics showed a gradually increase of blood damage according to increase of cardiac output ( P Conclusions: We demonstrated that A-TAH does not cause hemolysis or AWVS. However, relationship between HMWM and cardiac output depending flow confirms relevance of VWF as a biological sensor of blood flow, even in normal range.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is presenting as a systemic disease associated with vascular inflammation and endothelial injury. Severe forms of SARS-CoV-2 infection induce acute respiratory distress syndrome (ARDS) and there is still an ongoing debate on whether COVID-19 ARDS and its perfusion defect differs from ARDS induced by other causes. Beside pro-inflammatory cytokines (such as interleukin-1 β [IL-1β] or IL-6), several main pathological phenomena have been seen because of endothelial cell (EC) dysfunction: hypercoagulation reflected by fibrin degradation products called D-dimers, micro- and macrothrombosis and pathological angiogenesis. Direct endothelial infection by SARS-CoV-2 is not likely to occur and ACE-2 expression by EC is a matter of debate. Indeed, endothelial damage reported in severely ill patients with COVID-19 could be more likely secondary to infection of neighboring cells and/or a consequence of inflammation. Endotheliopathy could give rise to hypercoagulation by alteration in the levels of different factors such as von Willebrand factor. Other than thrombotic events, pathological angiogenesis is among the recent findings. Overexpression of different proangiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) or placental growth factors (PlGF) have been found in plasma or lung biopsies of COVID-19 patients. Finally, SARS-CoV-2 infection induces an emergency myelopoiesis associated to deregulated immunity and mobilization of endothelial progenitor cells, leading to features of acquired hematological malignancies or cardiovascular disease, which are discussed in this review. Altogether, this review will try to elucidate the pathophysiology of thrombotic complications, pathological angiogenesis and EC dysfunction, allowing better insight in new targets and antithrombotic protocols to better address vascular system dysfunction. Since treating SARS-CoV-2 infection and its potential long-term effects involves targeting the vascular compartment and/or mobilization of immature immune cells, we propose to define COVID-19 and its complications as a systemic vascular acquired hemopathy.

International audience; BackgroundThe outbreak of chilblain-like lesions (CLL) during the COVID-19 pandemic has been reported extensively, potentially related to SARS-CoV-2 infection, yet its underlying pathophysiology is unclear.ObjectivesTo study skin and blood endothelial and immune system activation in CLL in comparison with healthy controls and seasonal chilblains (SC), defined as cold-induced sporadic chilblains occurring during 2015 and 2019 with exclusion of chilblain lupus.MethodsThis observational study was conducted during 9–16 April 2020 at Saint-Louis Hospital, Paris, France. All patients referred with CLL seen during this period of the COVID-19 pandemic were included in this study. We excluded patients with a history of chilblains or chilblain lupus. Fifty patients were included.ResultsHistological patterns were similar and transcriptomic signatures overlapped in both the CLL and SC groups, with type I interferon polarization and a cytotoxic–natural killer gene signature. CLL were characterized by higher IgA tissue deposition and more significant transcriptomic activation of complement and angiogenesis factors compared with SC. We observed in CLL a systemic immune response associated with IgA antineutrophil cytoplasmic antibodies in 73% of patients, and elevated type I interferon blood signature in comparison with healthy controls. Finally, using blood biomarkers related to endothelial dysfunction and activation, and to angiogenesis or endothelial progenitor cell mobilization, we confirmed endothelial dysfunction in CLL.ConclusionsOur findings support an activation loop in the skin in CLL associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells leading to clinical manifestations.

Introduction Overall survival of patients with out-of-hospital cardiac arrest (OHCA) remains low, even in those with return of spontaneous circulation (ROSC). In addition to usual prognostic characteristics, patients’ medical history may also influence their outcome. This study aimed to investigate the role of pre-arrest comorbidities on hospital survival, neurological outcome and mode of death in OHCA patients with successful ROSC. Methods From Jan 2012 to Sep 2017, all consecutive non-traumatic OHCA adults, admitted with a stable ROSC were included. Utstein characteristics, circumstances of arrest and interventions were prospectively recorded. Prior comorbidities were measured using the Charlson Comorbidity Index (CCI), and the population was divided into 3 groups (CCI 0, CCI 1–3 and CCI ≥ 4). The association of CCI with early and long-term mortality was assessed using logistic regression and association with withdrawal-of-life sustaining treatments (WLST) or another cause of death using multinomial regression. Results During the study period, 777 patients were analyzed and 483 (62%) died before hospital discharge, with death rate of 49%, 60% and 70% in CCI 0, CCI 1–3 and CCI ≥ 4 respectively. After adjustment, an increase CCI was significantly associated with in-hospital mortality (OR = 2.47 [1.35–4.52], p = 0.001 for CCI 1–3; OR = 2.82 [1.49–5.33], p = 0.003 for CCI ≥ 4; ref = CCI 0). Other independent predictors were non-shockable rhythm (OR = 3.23 [2.08–5]), lack of bystander CPR (OR = 1.96 [1.22–3.13]), epinephrine dose ≥ 2 mg (OR = 5.56 [3.70–8.33]), CA to CPR ≥ 5 min (OR = 1.96 [1.28–3.03]) and CPR to ROSC ≥ 20 min (OR = 2.13 [1.39–3.23]). Using multinomial regression, an increase in CCI was associated with all modes of in-hospital death, particularly with WLST-related death (RRadj = 2.48 [1.26–4.90], p = 0.01 for CCI = 1–3 and 3.75 [1.85−8.7.58], p Conclusion Alteration of chronic health status, as assessed by an elevated CCI, was associated with a higher mortality and a worse neurological outcome in OHCA patients. Presence and burden of comorbidities should be considered in the evaluation of the prognosis in patients admitted in hospital after cardiac arrest.

INTRODUCTION: Antiphospholipid antibodies (APA) clinical relevance in COVID-19 is controversial. We aimed to investigate the prevalence and prognostic value of conventional and non-conventional APA in COVID-19 patients. METHODS: This study was a multi-centric, prospective observational French cohort of patients hospitalized for COVID-19 suspicion. RESULTS: 249 patients were hospitalized for suspected COVID-19, including 154 with confirmed COVID-19 and 95 not confirmed. We found a significant increase in lupus anticoagulant (LA) positivity among COVID-19 positive patients (60.9% versus 23.7% in non-COVID19 patients, p

Background Mycobacterium genavense infection is rare and can occur in immunocompromised patients without human immunodeficiency virus (HIV). Methods We describe 2 cases of M genavense infection in solid organ transplant (SOT) recipients, and we performed a literature review of immunocompromised patients without HIV. Results Fifty-two cases are reported. Predisposing factors were receipt of SOT (40.4%) and autoimmune disease (36.5%). Infection was disseminated in 86.5% of cases. Organs involved were lymph nodes (72.3%), gastrointestinal tract (56.5%), lung (35.5%), and bone marrow (28.8%). Most patients were treated with at least 3 antimycobacterial agents (98%), with a clinical cure achieved in 54.9%. In multivariate analysis, lack for cure was associated with age of the time infection (odds ratio [OR], 15.81 [95% confidence interval {CI}, 2.92–152.93]; P = .011) and positive bone marrow culture (OR, 1.05 [95% CI, 1.01–1.12]; P = .042). Conclusions Mycobacterium genavense infection is a rare and generally disseminated disease with a poor prognosis. Optimal treatment regimen and its duration remain to be defined.

ImportanceEpinephrine improves return of spontaneous circulation after out-of-hospital cardiac arrest (OHCA). These beneficial cardiac effects do not directly translate to better neurologic outcomes, possibly because of epinephrine-induced microvascular effects that produce critical brain ischemia.ObjectiveTo examine whether targeted temperature management (TTM) modifies the adverse association between increasing prehospital epinephrine dose and neurologically favorable survival.Design, Setting, and ParticipantsThis retrospective cohort study assessed 14 612 adults from Seattle and King County, Washington, with nontraumatic OHCA between January 1, 2008, and December 31, 2018, and included those who achieved return of spontaneous circulation and were unconscious at hospital admission. Data analysis was performed from April 2021 to May 2022.ExposuresEpinephrine dose and TTM during prehospital resuscitation.Main Outcomes and MeasuresFavorable neurologic survival (Cerebral Performance Category [CPC] 1 or 2) and survival to hospital discharge.ResultsOf the 14 612 assessed adults, 5253 (median age, 63 years; IQR, 51-74 years; 3460 [65.8%] male) were eligible for the study. The median epinephrine dose was 2.0 mg (IQR, 1.0-3.0 mg); 3052 patients (58.1%) received TTM. In all, 1889 patients (36.0%) survived with CPC 1 to 2, and 2177 (41.4%) survived to discharge. Increasing doses of epinephrine were associated with a decreasing likelihood of CPC 1 to 2 (odds ratio [OR], 0.46; 95% CI 0.42-0.50 for each additional milligram of epinephrine) and survival (OR, 0.47; 95% CI, 0.43-0.51). The dose-dependent epinephrine association was modified by TTM. After adjusting for Utstein covariates, TTM was associated with a relative stepwise improvement in odds of CPC 1 to 2 (interaction OR, 1.36; 95% CI, 1.22-1.51) and survival (interaction OR, 1.37; 95% CI, 1.24-1.51). A significant interaction was also observed when the analysis was stratified according to initial rhythm among shockable OHCA and nonshockable OHCA (shockable interaction OR, 1.20; 95% CI, 1.04-1.39; and nonshockable interaction OR, 1.24, 95% CI, 1.07-1.45).Conclusions and RelevanceThis cohort study found an interaction between TTM and epinephrine dose such that the beneficial association of TTM increased with increasing epinephrine dose, suggesting that TTM may attenuate the adverse effects of higher-dose epinephrine.

COVID-19 and infectious diseases have been included in strategic development goals (SDG) of United Nations (UN). Severe form of COVID-19 has been described as an endothelial disease. In order to better evaluate Covid-19 endotheliopathy, we characterized several subsets of circulating endothelial extracellular vesicles (EVs) at hospital admission among a cohort of 60 patients whose severity of COVID-19 was classified at the time of inclusion. Degree of COVID-19 severity was determined upon inclusion and categorized as moderate to severe in 40 patients and critical in 20 patients. We measured citrated plasma EVs expressing endothelial membrane markers. Endothelial EVs were defined as harboring VE-cadherin (CD144+), PECAM-1 (CD31 + CD41-) or E-selectin (CD62E+). An increase in CD62E + EV levels on admission to the hospital was significantly associated with critical disease. Moreover, Kaplan-Meier survival curves for CD62E + EV level showed that level ≥ 88,053 EVs/μL at admission was a significant predictor of in hospital mortality (p = 0.004). Moreover, CD62E + EV level ≥ 88,053 EV/μL was significantly associated with higher in-hospital mortality (OR 6.98, 95% CI 2.1-26.4, p = 0.002) in a univariate logistic regression model, while after adjustment to BMI CD62E + EV level ≥ 88,053 EV/μL was always significantly associated with higher in-hospital mortality (OR 5.1, 95% CI 1.4-20.0, p = 0.01). The present findings highlight the potential interest of detecting EVs expressing E-selectin (CD62) to discriminate Covid-19 patients at the time of hospital admission and identify individuals with higher risk of fatal outcome.

Background Coronavirus disease 2019 (COVID‐19) is a respiratory disease associated with vascular inflammation and endothelial injury. Objectives To correlate circulating angiogenic markers vascular endothelial growth factor A (VEGF‐A), placental growth factor (PlGF), and fibroblast growth factor 2 (FGF‐2) to in‐hospital mortality in COVID‐19 adult patients. Methods Consecutive ambulatory and hospitalized patients with COVID‐19 infection were enrolled. VEGF‐A, PlGF, and FGF‐2 were measured in each patient ≤48 h following admission. Results The study enrolled 237 patients with suspected COVID‐19: 208 patients had a positive diagnostic for COVID‐19, of whom 23 were mild outpatients and 185 patients hospitalized after admission. Levels of VEGF‐A, PlGF, and FGF‐2 significantly increase with the severity of the disease (P

Supplemental Digital Content is available in the text., TRIAL REGISTRATION: NCT04420468. OBJECTIVES: Severe acute respiratory syndrome coronavirus 2–related multisystem inflammatory syndrome in children is frequently associated with shock; endothelial involvement may be one of the underlying mechanisms. We sought to describe endothelial dysfunction during multisystem inflammatory syndrome in children with shock and then assess the relationship between the degree of endothelial involvement and the severity of shock. DESIGN: Observational study. SETTING: A PICU in a tertiary hospital. PATIENTS: Patients aged under 18 (n = 28) with severe acute respiratory syndrome coronavirus 2–related multisystem inflammatory syndrome in children and shock, according to the Centers for Disease Control and Prevention criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between endothelial marker levels and shock severity were assessed using Spearman coefficient. The median (interquartile range) age was 9 years (7.5–11.2 yr). Sixteen children presented with cardiogenic and distributive shock, 10 presented with cardiogenic shock only, and two presented with distributive shock only. The median left ventricular ejection fraction, troponin level, and lactate level were, respectively, 40% (35–45%), 261 ng/mL (131–390 ng/mL), and 3.2 mmol/L (2–4.2 mmol/L). Twenty-five children received inotropes and/or vasopressors; the median Vasoactive and Inotropic Score was 8 (5–28). Plasma levels of angiopoietin-2 (6,426 pg/mL [2,814–11,836 pg/mL]), sE-selectin (130,405 pg/mL [92,987–192,499 pg/mL]), von Willebrand factor antigen (344% [288–378%]), and the angiopoietin-2/angiopoietin-1 ratio (1.111 [0.472–1.524]) were elevated and significantly correlated with the Vasoactive and Inotropic Score (r = 0.45, p = 0.016; r = 0.53, p = 0.04; r = 0.46, p = 0.013; and r = 0.46, p = 0.012, respectively). CONCLUSIONS: Endothelial dysfunction is associated with severe acute respiratory syndrome coronavirus 2–related multisystem inflammatory syndrome in children with shock and may constitute one of the underlying mechanisms.

Background Microthrombosis is a hallmark of COVID-19. We previously described von willebrand factor (VWF) and their high molecular weight multimers (HMWMs) as potential trigger of microthrombosis. Objectives Investigate VWF activity with collagen-binding assay and ADAMTS13 in COVID-19. Methods and results Our study enrolled 77 hospitalized COVID-19 patients including 37 suffering from a non-critical form and 40 with critical form. Plasma levels of VWF collagen-binding ability (VWF:CB) and ADAMTS13 activity (ADAMTS13:Act) were measured in the first 48 hours following admission. VWF:CB was increased in critical (631% IQR [460–704]) patients compared to non-critical patients (259% [235–330], p

Background The Utstein population is defined by non-traumatic, bystander-witnessed out-of-hospital cardiac arrest (OHCA) presenting with ventricular fibrillation (VF). It is used to compare resuscitation performance across emergency medical services (EMS) systems. We hypothesized a system-specific survival correlation between the current Utstein population and other VF populations defined by unwitnessed VF OHCA and VF OHCA after EMS arrival (EMS-witnessed). Expanding performance metrics to this more comprehensive population would make the Utstein definition more representative of the actual community burden and response to VF OHCA. Methods We performed a cohort investigation of all non-traumatic, VF OHCA in the Cardiac Arrest Registry to Enhance Survival from 1/1/2013-12/31/2018 among EMS agencies that treated > = 100 VF OHCA. We evaluated sample size and survival with the addition of the new VF populations. We used Pearson coefficient to assess whether there was a correlation of agency-specific survival outcomes between the current Utstein population and unwitnessed and EMS-witnessed VF OHCA. Results A total of 107 EMS agencies treated 38,836 VF arrests: 22,918 current Utstein, 11,297 unwitnessed VF, and 4621 EMS-witnessed VF OHCA. Overall, survival was 29.8% (11,567/38,836): 33.9% (7774/22,918) among current Utstein, 17.2% (1942/11,297) among unwitnessed VF, and 40.1% (1851/4621) among EMS-witnessed VF. For agency-specific survival outcome, the Pearson correlation was 0.52 between the current Utstein population versus combined unwitnessed and EMS-witnessed groups. For survival with Cerebral Performance Category 1–2, the Pearson correlation was 0.61. Conclusion Expanding the Utstein population to include unwitnessed and EMS-witnessed VF OHCA achieves a simpler, more inclusive case definition that minimizes variability in case determination and increases the number of survivors and eligible population by ∼50%, while still achieving a distinguishing metric of system-specific performance.

Objective D-dimer measurement is a safe tool to exclude pulmonary embolism (PE), but its specificity decreases in coronavirus disease 2019 (COVID-19) patients. Our aim was to derive a new algorithm with a specific D-dimer threshold for COVID-19 patients. Methods We conducted a French multicenter, retrospective cohort study among 774 COVID-19 patients with suspected PE. D-dimer threshold adjusted to extent of lung damage found on computed tomography (CT) was derived in a patient set (n = 337), and its safety assessed in an independent validation set (n = 337). Results According to receiver operating characteristic curves, in the derivation set, D-dimer safely excluded PE, with one false negative, when using a 900 ng/mL threshold when lung damage extent was Conclusion The Co-LEAD algorithm could safely exclude PE, and could reduce the use of CTPA in COVID-19 patients. Further prospective studies need to validate this strategy.

Rationale COVID-19 ARDS could differ from typical forms of the syndrome. Objective Pulmonary microvascular injury and thrombosis are increasingly reported as constitutive features of COVID-19 respiratory failure. Our aim was to study pulmonary mechanics and gas exchanges in COVID-2019 ARDS patients studied early after initiating protective invasive mechanical ventilation, seeking after corresponding pathophysiological and biological characteristics. Methods Between March 22 and March 30, 2020 respiratory mechanics, gas exchanges, circulating endothelial cells (CEC) as markers of endothelial damage, and D-dimers were studied in 22 moderate-to-severe COVID-19 ARDS patients, 1 [1–4] day after intubation (median [IQR]). Measurements and main results Thirteen moderate and 9 severe COVID-19 ARDS patients were studied after initiation of high PEEP protective mechanical ventilation. We observed moderately decreased respiratory system compliance: 39.5 [33.1–44.7] mL/cmH2O and end-expiratory lung volume: 2100 [1721–2434] mL. Gas exchanges were characterized by hypercapnia 55 [44–62] mmHg, high physiological dead-space (VD/VT): 75 [69–85.5] % and ventilatory ratio (VR): 2.9 [2.2–3.4]. VD/VT and VR were significantly correlated: r2 = 0.24, p = 0.014. No pulmonary embolism was suspected at the time of measurements. CECs and D-dimers were elevated as compared to normal values: 24 [12–46] cells per mL and 1483 [999–2217] ng/mL, respectively. Conclusions We observed early in the course of COVID-19 ARDS high VD/VT in association with biological markers of endothelial damage and thrombosis. High VD/VT can be explained by high PEEP settings and added instrumental dead space, with a possible associated role of COVID-19-triggered pulmonary microvascular endothelial damage and microthrombotic process.

International audience; No abstract available

Background Microvascular, arterial and venous thrombotic events have been largely described during severe coronavirus disease 19 (COVID-19). However, mechanisms underlying hemostasis dysregulation remain unclear. Methods We explored two independent cross-sectional cohorts to identify soluble markers and gene-expression signatures that discriminated COVID-19 severity and outcomes. Results We found that elevated soluble (s)P-selectin at admission was associated with disease severity. Elevated sP-selectin was predictive of intubation and death (ROC AUC = 0.67, p = 0.028 and AUC = 0.74, p = 0.0047, respectively). An optimal cutoff value was predictive of intubation with 66% negative predictive value (NPV) and 61% positive predictive value (PPV), and of death with 90% NPV and 55% PPV. An unbiased gene set enrichment analysis revealed that critically ill patients had increased expression of genes related to platelet activation. Hierarchical clustering identified ITG2AB, GP1BB, PPBP and SELPLG to be upregulated in a grade-dependent manner. ROC curve analysis for the prediction of intubation was significant for SELPLG and PPBP (AUC = 0.8, p = 0.046 for both). An optimal cutoff value for PBPP was predictive of intubation with 100% NPV and 45% PPV, and for SELPLG with 100% NPV and 50% PPV. Conclusion We provide evidence that platelets contribute to COVID-19 severity. Plasma sP-selectin level was associated with severity and in-hospital mortality. Transcriptional analysis identified PPBP/CXCL7 and SELPLG as biomarkers for intubation. These findings provide additional evidence for platelet activation in driving critical COVID-19. Specific studies evaluating the performance of these biomarkers are required.

Introduction: Epinephrine (EPI) improves return of circulation after out of hospital cardiac arrest (OHCA). These beneficial cardiac effects are not accompanied by improved neurological survival possibly due to EPI induced microvascular effects and critical brain ischemia. We hypothesized that these dose-dependent adverse EPI effects may be mitigated by targeted temperature management (TTM) such that the relative benefit of TTM is greater at higher EPI doses. Methods: This was a retrospective cohort study of adult non-traumatic OHCA patients in Seattle and King County, Washington from 2008-2018, who were unconscious at hospital admission. We used logistic regression to assess the relationship among EPI dose, TTM, and survival to hospital discharge, and survival with favorable neurological status (Cerebral Performance Category (CPC) 1 or 2). The model evaluated whether TTM modified the association of increasing EPI dose using an interaction term between TTM and EPI dose. Results were stratified by initial shockable vs non-shockable rhythm. Results: Of 5254 eligible patients, the median EPI dose was 2.0 mg (IQR 1.0 - 3.0); 3052 (58%) received TTM. In all, 2177 (41%) survived to discharge, and 1889 (36%) survived with CPC 1-2. Increasing dose of EPI was associated with a decreasing likelihood of survival (OR 0.58, [95% CI 0.55-0.61] for each additional mg of EPI) and CPC 1-2 (OR 0.56, [0.53-0.59]). The dose-dependent EPI association was modified by TTM. After adjustment for Utstein covariates, for each additional mg of EPI, TTM was associated with a relative stepwise improvement in odds of survival (interaction OR 1.35, [1.23, 1.49]) and CPC 1-2 (OR 1.34, [1.21, 1.50]) (Figure). This interaction was consistent among shockable and non-shockable OHCA (Figure). Conclusions: We observed an interaction between TTM and EPI dose such that the beneficial association of TTM increased with increasing EPI dose, suggesting TTM may attenuate the adverse effects of higher dose EPI.

Background Bone marrow aspiration (BMA) is a medical procedure necessary to the diagnosis and monitoring of patients with hematological or nonhematological disorders. This procedure is considered painful, and patients are generally anxious before and during BMA. Objective This study assesses the effect of immersive virtual reality on pain during BMA. Methods This observational prospective and monocentric study enrolled 105 consecutive patients who underwent sternal BMA with lidocaine anesthesia. The study was carried on during 2 periods. First, virtual reality facemask (VRF) was proposed to all patients in the absence of exclusion criteria. During the second period, BMA was performed without the VRF. For all patients, pain intensity after the procedure was assessed using a 10-point numerical pain rating scale (NPRS). All analyses were performed on propensity score–matched cohort (with or without VRF) to evaluate efficacy on NRPS levels. Results The final matched cohort included 12 patients in the VRF group and 24 in the control group. No difference in anxiety level before BMA evaluated by the patient and by the operator was observed between groups (P=.71 and .42 respectively). No difference of NPRS was observed using VRF when compared to control group (median NPRS 3.8, IQR 2.0-6.3 vs 3.0, IQR 1.9-3.0, respectively; P=.09). Conclusions Our study did not prove the efficacy of VRF to reduce pain during BMA.

The spread of ESBL producers in the community may impact the management of patients with bloodstream infections (BSI) involving Enterobacterales in emergency departments. Thus, from 2006 to 2018, data for all BSI episodes involving Enterobacterales from the emergency department of a French teaching hospital were retrospectively included. Antimicrobial susceptibility test results and empirical antibiotic regimens were recorded. Treatment was considered as appropriate if all isolates were susceptible in vitro to at least one prescribed antibiotic. A total of 1369 BSI episodes in 1321 patients was included. Urinary tract infection was the main source of BSI (61%). The prevalence of ESBL producers increased from zero to 9.2/100 Enterobacterales BSI cases (p

Summary Background SARS-CoV-2 uses Angiotensin-Converting Enzyme 2 as a viral gateway to the cell and could interact with the renin-angiotensin-aldosterone system. Other studies have shown kalemia abnormalities in patients with severe forms of coronavirus disease 2019. Our goal was to assess the prognosis value of kalemia within ten days of symptom offset in the COVID-19 hospitalized population. Methods We analyzed data from a prospective cohort that included 65 patients with COVID-19, admitted between March 15, 2020, and March 21, 2020. The study aimed at determining the relationship between baseline kalemia and the admission to an intensive care unit (ICU) or death. Results The median age of the patients was 65 [54–79] years old, and 66.2% of the patients were men. Baseline kalemia under 3.8 mmol/l occurred in 31 patients (48%), including 11 patients (35.5%) who were admitted to an ICU and one patient (3.2%) who died before ICU admission. In the primary end-point analysis, the adjusted hazard ratios for admission to an ICU or death were 3.52 [95% confidence interval (CI), 1.12 to 11.04] among patients with low baseline kalemia. Conclusion Our study suggests that low kalemia levels within ten days of the first symptom onset might be associated with an increased risk of intensive care unit admission or death. The future perspective should be to better understand this relationship.

Stem cells at the origin of endothelial progenitor cells and in particular endothelial colony forming cells (ECFCs) subtype have been largely supposed to be positive for the CD133 antigen, even though no clear correlation has been established between its expression and function in ECFCs. We postulated that CD133 in ECFCs might be expressed intracellularly, and could participate to vasculogenic properties. ECFCs extracted from cord blood were used either fresh (n = 4) or frozen (n = 4), at culture days30, to investigate the intracellular presence of CD133 by flow cytometry and confocal analysis. Comparison with HUVEC and HAEC mature endothelial cells was carried out. Then, CD133 was silenced in ECFCs using specific siRNA (siCD133-ECFCs) or scramble siRNA (siCtrl-ECFCs). siCD133-ECFCs (n = 12), siCtrl-ECFCs (n = 12) or PBS (n = 12) were injected in a hind-limb ischemia nude mouse model and vascularization was quantified at day 14 with HE staining and immunohistochemistry for CD31. Results of flow cytometry and confocal microscopy evidenced the positivity of CD133 in ECFCs after permeabilization compared with not permeabilized ECFCs (p 0.001) and mature endothelial cells (p 0.03). In the model of mouse hind-limb ischemia, silencing of CD133 in ECFCs significantly abolished post-ischemic revascularization induced by siCtrl-ECFCs; indeed, a significant reduction in cutaneous blood flows (p = 0.03), capillary density (CD31) (p = 0.01) and myofiber regeneration (p = 0.04) was observed. Also, a significant necrosis (p = 0.02) was observed in mice receiving siCD133-ECFCs compared to those treated with siCtrl-ECFCs. In conclusion, our work describes for the first time the intracellular expression of the stemness marker CD133 in ECFCs. This feature could resume the discrepancies found in the literature concerning CD133 positivity and ontogeny in endothelial progenitors.

Background: In out-of-hospital cardiac arrest (OHCA), geographic disparities in outcomes may reflect baseline variations in patients’ characteristics but may also result from differences in the number of ambulances providing basic life support (BLS) and advanced life support (ALS). We aimed at assessing the association between allocated ambulance resources and outcomes in OHCA patients in a large urban community. Methods: From May 2011 to January 2016, we analyzed a prospectively collected Utstein database for all OHCA adults. Cases were geocoded according to 19 neighborhoods and the number of BLS (firefighters performing cardiopulmonary resuscitation and applying automated external defibrillator) and ALS ambulances (medicalized team providing advanced care such as drugs and endotracheal intubation) was collected. We assessed the respective associations of Utstein parameters, socioeconomic characteristics, and ambulance resources of these neighborhoods using a mixed-effect model with successful return of spontaneous circulation as the primary end point and survival at hospital discharge as a secondary end point. Results: During the study period, 8754 nontraumatic OHCA occurred in the Greater Paris area. Overall return of spontaneous circulation rate was 3675 of 8754 (41.9%) and survival rate at hospital discharge was 788 of 8754 (9%), ranging from 33% to 51.1% and from 4.4% to 14.5% respectively, according to neighborhoods ( P P for trend P 1.5 per neighborhood and aOR, 1.21 [1.04–1.41]; P =0.01 for BLS ambulances >4 per neighborhood). Regarding survival at discharge, only the number of ALS ambulances >1.5 per neighborhood was significant (aOR, 1.30 [1.06–1.59] P =0.01). Conclusions: In this large urban population-based study of out-of-hospital cardiac arrests patients, we observed that allocated resources of emergency medical service are associated with outcome, suggesting that improving healthcare organization may attenuate disparities in prognosis.

Purpose To explore diagnostic pitfalls and treatment issues in out-of-hospital cardiac arrest of neurological cause (OHCA-NC). Methods Retrospective analysis of all consecutive patients from the Paris Sudden Death Expertise Centre (France) registry from May 2011 to September 2015 presenting with a sustained return of spontaneous circulation (ROSC) at hospital admission and a final diagnosis of OHCA-NC. Description of the early diagnostic check-up performed to identify the cause of cardiac arrest. Logistic multivariate regression to identify factors associated with immediate coronary angiography (iCAG) in OHCA-NC patients. Results Among 3542 patients with ROSC, a final diagnosis of OHCA-NC was established in 247 (7%). The early diagnostic check-up consisted in a total of 207 (84%) immediate cranial CT-scan, 66 (27%) iCAG and 25 (10%) chest CT-scan. The brain CT-scan allowed identifying a neurovascular cause in 116 (47%) patients. An iCAG was performed as the first line exam in 57 (23%) patients, in whom a final diagnosis of neurovascular cause for OHCA-NC was later identified in 41 patients. By multivariate analysis, decision for iCAG was independently associated with ST-segment elevation on post-ROSC electrocardiogram (OR, 5.94; 95%CI, 2.14–18.28; P = 0.0009), whereas an obvious cause of cardiac arrest on scene was negatively associated with iCAG (OR, 0.14; 95%CI, 0.02–0.51; P = 0.01). Conclusions OHCA-NC is a rare event that is mainly related to neurovascular causes. The initial ECG pattern may be a confounder regarding triage for early diagnostic check-up. Further studies are required to explore the potential harmfulness associated with decision to perform an iCAG in this population.

Background Bystander cardiopulmonary resuscitation (CPR) is a critical intervention to improve survival following out‐of‐hospital cardiac arrest. We evaluated the quality of bystander CPR and whether performance varied according to the number of bystanders or provision of telecommunicator CPR (TCPR). Methods and Results We investigated non‐traumatic out‐of‐hospital cardiac arrest occurring in a large metropolitan emergency medical system during a 6‐month period. Information about bystander care was ascertained through review of the 9‐1‐1 recordings in addition to emergency medical system and hospital records to determine bystander CPR status (none versus TCPR versus unassisted), the number of bystanders on‐scene, and CPR performance metrics of compression fraction and compression rate. Of the 428 eligible out‐of‐hospital cardiac arrest, 76.4% received bystander CPR including 43.7% unassisted CPR and 56.3% TCPR; 35.2% had one bystander, 33.3% had 2 bystanders, and 31.5% had ≥3 bystanders. Overall compression fraction was 59% with a compression rate of 88 per minute. CPR differed according to TCPR status (fraction=52%, rate=87 per minute for TCPR versus fraction=69%, rate=102 for unassisted CPR, P P Conclusions Bystander CPR quality as gauged by compression fraction and rate approached guideline goals though performance depended upon the type of CPR and number of bystanders.

Background: Coronavirus disease 2019 (COVID-19) has been associated with coagulation disorders, in particular high concentrations of D-dimers, and increased frequency of venous thromboembolism. Aim: To explore the association between D-dimers at admission and in-hospital mortality in patients hospitalized for COVID-19, with or without symptomatic venous thromboembolism. Methods: From 26 February to 20 April 2020, D-dimer concentration at admission and outcomes (in-hospital mortality or venous thromboembolism) of patients hospitalized for COVID-19 in medical wards were analysed retrospectively in a multicentre study in 24 French hospitals. Results: Among 2878 patients enrolled in the study, 1154 (40.1%) patients had D-dimer measurement at admission. Receiver operating characteristic curve analysis identified a D-dimer concentration > 1128 ng/mL as the optimum cut-off value for in-hospital mortality (area under the curve 64.9%, 95% confidence interval [CI] 0.60–0.69), with a sensitivity of 71.1% (95% CI 0.62–0.78) and a specificity of 55.6% (95% CI 0.52–0.58), which did not differ in the subgroup of patients with venous thromboembolism during hospitalization. Among 545 (47.2%) patients with D-dimer concentration > 1128 ng/mL at admission, 86 (15.8%) deaths occurred during hospitalization. After adjustment, in Cox proportional hazards and logistic regression models, D-dimer concentration > 1128 ng/mL at admission was also associated with a worse prognosis, with an odds ratio of 3.07 (95% CI 2.05–4.69; P < 0.001) and an adjusted hazard ratio of 2.11 (95% CI 1.31–3.4; P < 0.01). Conclusions: D-dimer concentration > 1128 ng/mL is a relevant predictive factor for in-hospital mortality in patients hospitalized for COVID-19 in a medical ward, regardless of the occurrence of venous thromboembolism during hospitalization.

Out-of-hospital cardiac arrest (OHCA) causes brain injury. Functional status of survivors at hospital discharge is a core resuscitation measure, frequently using the Cerebral Performance Category (CPC) or modified Rankin Scale (mRS). Which scale better predicts long-term survival following OHCA is not known.We evaluated long-term survival after hospital discharge in a retrospective cohort of persons resuscitated from OHCA in King County, WA from 2007 to 2015. Patients were independently assessed at discharge using both scales, leveraging the regional quality improvement registry, which records the 5-level CPC, and concurrent research studies involving the Resuscitation Outcomes Consortium, which used the 7-level mRS, taken from information in the hospital record. The risk of mortality associated with CPC and mRS categories was estimated using Kaplan-Meier survival analysis and Cox proportional hazards regression.Among 878 eligible patients discharged alive, there were 358 deaths during 9118.5 person-years of follow-up. Overall 1, 5 and 10-year survival was 84.4%, 68.5%, and 53.7% and varied according to CPC and mRS (p0.01 per Kaplan-Meier). Compared to CPC-1, hazard ratio (HR) increased incrementally for CPC-2 = 1.33 (1.03-1.73), CPC-3 = 1.90 (1.37-2.65), and CPC-4 = 8.25 (5.63-12.10). Compared to mRS = 0, HR for mRS-1 = 1.02 (0.66-1.58), mRS-2 = 1.52 (1.00-2.32), mRS-3 = 1.41 (0.92-2.14), mRS-4 = 2.00 (1.37-2.97), and mRS-5 = 4.90 (3.23-7.44).In OHCA survivors, CPC and mRS scales both predicted long-term survival. However mRS 0-1 and 2-3 groups did not have distinct prognoses, suggesting that a consolidated mRS score may simplify capture of relevant prognostic information for survival predictions.