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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.

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.

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

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.

Severe COVID-19 is associated with a high circulating level of calprotectin, the S100A8/S100A9 alarmin heterodimer. Baseline calprotectin amount measured in peripheral blood at diagnosis correlates with disease severity. The optimal use of this biomarker along COVID-19 course remains to be delineated.We focused on patients with a WHO-defined moderate COVID-19 requiring hospitalization in a medical ward. We collected plasma and serum from three independent cohorts (N = 626 patients) and measured calprotectin amount at admission. We performed longitudinal measures of calprotectin in 457 of these patients (1461 samples) and used a joint latent class mixture model in which classes were defined by age, body mass index and comorbidities to identify calprotectin trajectories predicting the risk of transfer into an intensive care unit or death.After adjustment for age, sex, body mass index and comorbidities, the predictive value of baseline calprotectin in patients with moderate COVID19 could be refined by serial monitoring of the biomarker. We discriminated three calprotectin trajectories associated with low, moderate, and high risk of poor outcome, and we designed an algorithm available as online software (https://calpla.gustaveroussy.fr:8443/) to monitor the probability of a poor outcome in individual patients with moderate COVID-19.These results emphasize the clinical interest of serial monitoring of calprotectin amount in the peripheral blood to anticipate the risk of poor outcomes in patients with moderate COVID-19 hospitalized in a standard care unit.The study received support (research grants) from ThermoFisher immunodiagnostics (France) and Gustave Roussy Foundation.

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.

Little is known about the association between provision of post-resuscitation care and prognosis of out-of-hospital cardiac arrest (OHCA) in elderly patients. Previous studies have suggested futility after 65 years of age.We aimed to evaluate the association of early coronary angiogram (CAG) followed if necessary by percutaneous coronary intervention (PCI), with favorable outcome after OHCA among elderly patients, compared to younger patients.Using a large French registry, we included all OHCA patients with an initial shockable rhythm, transported to hospital from 2011 to 2015. Favorable outcome was defined as hospital discharge with Cerebral Performance Category (CPC) 1 or 2. and were evaluated by multivariate logistic regression. Subgroup analyses were performed according to age groups:65, 65-75 and75 years.Among 1502 included patients, 31% were older than 65 and 12% older than 75 years. An early CAG was performed in 79%, 88% and 76% of patients below 65, between 65 and 75 and above 75, respectively (P = 0.002). The rate of patients discharged with CPC1 or 2 was 42% below 65, 38% between 65 and 75 and 24% above 75 (P 0.001). Among the whole population, early CAG (OR = 6.4, 95% CI = 3.9-10.5, P 0.001) was associated with favorable outcome. In subgroups analysis, CAG was associated with favorable outcome among patients65 and 65-75. In patients75, there was a trend towards a favorable outcome (OR2.9, 95CI = 0.9-9.1).In a large registry of OHCA survivors, the early CAG use was associated with a better prognosis. This benefit was persistent up to 75 years of age, suggesting that age alone should not guide the decision for early invasive strategy.

Introduction L’arteriopathie obliterante des membres inferieurs (AOMI) est une pathologie grave, frequemment sous-evaluee. Longtemps asymptomatique, elle est pourtant facilement depistee par la mesure de l’indice de pression systolique (IPS), outil de reference et recommande par la Haute Autorite de Sante (HAS). Le but de l’etude etait d’identifier les patients de plus de 60 ans avec une AOMI ainsi qu’evaluer l’effet d’une lettre d’information sur l’AOMI sur les medecins traitants. Methode L’etude prospective et monocentrique a ete realisee au service d’accueil des urgences de l’Hopital Europeen Georges-Pompidou, Paris, entre aout et septembre 2017. Un questionnaire portant sur les signes fonctionnels d’AOMI, les antecedents, les facteurs de risque cardiovasculaires ainsi qu’une mesure des IPS etaient completes a l’inclusion. La lettre d’information etait delivree si l’IPS etait pathologique soit inferieur a 0,9 ou superieur a 1,3. Un suivi telephonique a ete realise a 6 mois portant sur les traitements, les regles hygieno-dietetiques et les examens complementaires. Resultats Cent quatre-vingt-seize patients ont ete inclus et parmi eux : 15 AOMI etaient connues (7,7 %), 82 ont ete nouvellement diagnostiquees (42 %) et enfin 46 avaient un IPS superieur 1,3 (23 %). La population avec un IPS Soixante-six patients (52 %) ont ete suivis a 6 mois et 8 sont decedes (6,2 %). Cinquante-cinq patients (94,5 %) ont adapte leur alimentation (pauvre en cholesterol et pauvre en sel), 53 (91,2 %) ont realise un echo-Doppler des membres inferieurs et 42 (72,2 %) ont realise un echo-Doppler des troncs supra-aortiques. Enfin nous avons constate via notre courrier que les patients faisaient significativement plus d’activite physique (58,2 % vs 36 % p = 0,041), prenaient plus de statines (58,6 % vs 29,3 % p = 0,003) qu’avant. Conclusion L’AOMI est une pathologie frequente dans la population a haut risque cardiovasculaire, la frequence des formes asymptomatiques justifie la necessite du depistage qui se fait par le Doppler de poche dans cette population. La sensibilisation du patient et du medecin generaliste par un courrier d’information remis au patient semble etre une bonne solution.

Introduction Le mot « malaise » est un terme utilise pour designer des situations diverses de perte de connaissance regroupant notamment les syncopes. C’est un motif frequent de consultation aux urgences (3–5 %). Alors qu’il existe des recommandations francaises et europeennes, leur prise en charge semble heterogene. Afin d’evaluer la place d’un outil informatise d’aide a la decision base sur les signes de severite, nous realisons dans un premier temps l’evaluation de la prise en charge des malaises aux urgences. Materiel et methodes Etude observationnelle retrospective de septembre a decembre 2012 dans un centre hospitalo-universitaire parisien avec analyse des dossiers medicaux informatises des patients de plus de 16 ans consultants aux urgences pour « malaise ». Les donnees sont colligees selon les dernieres recommandations, notamment les signes de severite (SS) et l’adequation a ces recommandations est analysee : Antecedents (mort subite, cardiopathie), anamnese (caractere recidivant, syncope a l’exercice ou de decubitus, histoire floue), clinique (âge > 70 ans, palpitations, signes cardiologiques ou neurologiques, anomalies electrocardiographiques). Resultats n = 329 patients (âge median 50 ans, 3 % de l’ensemble des consultations sur la periode). Parmi eux, 21,4 % ont ete hospitalises. Le taux de concordance entre le choix de l’urgentiste et les recommandations est croissant avec le nombre de signes de severite. La concordance des attitudes est de 54,2 % lorsque les patients presentent ≥ 3 SS (44,2 % ≤ 2SS). Parmi les patients presentant 2SS, un antecedent de cardiopathie et le caractere recidivant des episodes sont les signes les plus frequents ( Fig. 1 ). Discussion Devant un patient presentant un malaise, l’adequation entre l’attitude de l’urgentiste et les recommandations des societes savantes est croissante avec le nombre de signes de severite. Ainsi, plus de la moitie des patients presentant ≥ 3 SS sont hospitalises. Cependant, la gestion de ces patients reste heterogene et necessite d’etre optimisee. Dans un souci d’amelioration des pratiques, il apparait alors pertinent de mettre en place un outil informatise d’aide a la decision base sur les signes de severite.