RESUMO
OBJECTIVES: The objective was to define a safe strategy to exclude pulmonary embolism (PE) in COVID-19 outpatients, without performing CT pulmonary angiogram (CTPA). METHODS: COVID-19 outpatients from 15 university hospitals who underwent a CTPA were retrospectively evaluated. D-Dimers, variables of the revised Geneva and Wells scores, as well as laboratory findings and clinical characteristics related to COVID-19 pneumonia, were collected. CTPA reports were reviewed for the presence of PE and the extent of COVID-19 disease. PE rule-out strategies were based solely on D-Dimer tests using different thresholds, the revised Geneva and Wells scores, and a COVID-19 PE prediction model built on our dataset were compared. The area under the receiver operating characteristics curve (AUC), failure rate, and efficiency were calculated. RESULTS: In total, 1369 patients were included of whom 124 were PE positive (9.1%). Failure rate and efficiency of D-Dimer > 500 µg/l were 0.9% (95%CI, 0.2-4.8%) and 10.1% (8.5-11.9%), respectively, increasing to 1.0% (0.2-5.3%) and 16.4% (14.4-18.7%), respectively, for an age-adjusted D-Dimer level. D-dimer > 1000 µg/l led to an unacceptable failure rate to 8.1% (4.4-14.5%). The best performances of the revised Geneva and Wells scores were obtained using the age-adjusted D-Dimer level. They had the same failure rate of 1.0% (0.2-5.3%) for efficiency of 16.8% (14.7-19.1%), and 16.9% (14.8-19.2%) respectively. The developed COVID-19 PE prediction model had an AUC of 0.609 (0.594-0.623) with an efficiency of 20.5% (18.4-22.8%) when its failure was set to 0.8%. CONCLUSIONS: The strategy to safely exclude PE in COVID-19 outpatients should not differ from that used in non-COVID-19 patients. The added value of the COVID-19 PE prediction model is minor. KEY POINTS: ⢠D-dimer level remains the most important predictor of pulmonary embolism in COVID-19 patients. ⢠The AUCs of the revised Geneva and Wells scores using an age-adjusted D-dimer threshold were 0.587 (95%CI, 0.572 to 0.603) and 0.588 (95%CI, 0.572 to 0.603). ⢠The AUC of COVID-19-specific strategy to rule out pulmonary embolism ranged from 0.513 (95%CI: 0.503 to 0.522) to 0.609 (95%CI: 0.594 to 0.623).
Assuntos
COVID-19 , Embolia Pulmonar , Humanos , Estudos Retrospectivos , Pacientes Ambulatoriais , Curva ROCRESUMO
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<0.01), however, the blood volume fraction that endured significant shear stresses was always inferior to 0.03% of the volume for both ventricles in all regimens tested. An inverse association between cardiac output, beat rate, and high-molecular weight multimers ratio was found. 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.
Assuntos
Coração Artificial , Doenças de von Willebrand , Adulto , Coração Artificial/efeitos adversos , Hemoglobinas , Hemólise , Humanos , Fator de von WillebrandRESUMO
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 < 0.001), mainly Escherichia coli (6.9 cases/100 BSI in 2018); and no Klebsiella. Third-generation cephalosporins (3GC) were used most frequently (71.8%) and their use as monotherapy increased during the study period (p < 0.001). The rate of appropriate treatment decreased from 95.8 to 89.2% (p = 0.023). Appropriateness of treatment was greater using two drugs vs one (97.3% vs 89.3%, p < 0.001). Treatments with 3GC were appropriate in 92% and 98.3%, when used alone or with another antibiotic, respectively (p < 0.001). Among inappropriate treatments, 45% concerned 3GC, with 74.6% of them attributable to ESBL production. The spread of ESBL producers in the community had a direct impact on the rate of inappropriate empirical treatment. Local antimicrobial resistance monitoring is required to optimize the management of BSI in emergency departments.
Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Proteínas de Bactérias/metabolismo , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , beta-Lactamases/metabolismo , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana , Serviço Hospitalar de Emergência/estatística & dados numéricos , Enterobacteriaceae/classificação , Enterobacteriaceae/enzimologia , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prescrições , Estudos Retrospectivos , beta-Lactamases/genéticaRESUMO
OBJECTIVE: The study's aim was to analyze the capacity of human valve interstitial cells (VICs) to participate in aortic valve angiogenesis. Approach and Results: VICs were isolated from human aortic valves obtained after surgery for calcific aortic valve disease and from normal aortic valves unsuitable for grafting (control VICs). We examined VIC in vitro and in vivo potential to differentiate in endothelial and perivascular lineages. VIC paracrine effect was also examined on human endothelial colony-forming cells. A pathological VIC (VICp) mesenchymal-like phenotype was confirmed by CD90+/CD73+/CD44+ expression and multipotent-like differentiation ability. When VICp were cocultured with endothelial colony-forming cells, they formed microvessels by differentiating into perivascular cells both in vivo and in vitro. VICp and control VIC conditioned media were compared using serial ELISA regarding quantification of endothelial and angiogenic factors. Higher expression of VEGF (vascular endothelial growth factor)-A was observed at the protein level in VICp-conditioned media and confirmed at the mRNA level in VICp compared with control VIC. Conditioned media from VICp induced in vitro a significant increase in endothelial colony-forming cell proliferation, migration, and sprouting compared with conditioned media from control VIC. These effects were inhibited by blocking VEGF-A with blocking antibody or siRNA approach, confirming VICp involvement in angiogenesis by a VEGF-A dependent mechanism. CONCLUSIONS: We provide here the first proof of an angiogenic potential of human VICs isolated from patients with calcific aortic valve disease. These results point to a novel function of VICp in valve vascularization during calcific aortic valve disease, with a perivascular differentiation ability and a VEGF-A paracrine effect. Targeting perivascular differentiation and VEGF-A to slow calcific aortic valve disease progression warrants further investigation.
Assuntos
Estenose da Valva Aórtica/metabolismo , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Calcinose/metabolismo , Diferenciação Celular , Linhagem da Célula , Células Progenitoras Endoteliais/metabolismo , Neovascularização Patológica , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Estenose da Valva Aórtica/patologia , Calcinose/patologia , Estudos de Casos e Controles , Células Cultivadas , Técnicas de Cocultura , Células Progenitoras Endoteliais/patologia , Células Progenitoras Endoteliais/transplante , Feminino , Humanos , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Osteogênese , Comunicação Parácrina , Fenótipo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
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 < 0.005). VWF:CB was significantly associated (r = 0.564, p < 0.001) with HMWMs. Moreover, median ADAMTS13:Act was lower in critical (64.8 IU/dL IQR 50.0-77.7) than non-critical patients (85.0 IU/dL IQR 75.8-94.7, p < 0.001), even if no patients displayed majors deficits. VWF:Ag-to-ADAMTS13:Act ratio was highly associated with VWF:CB (r = 0.916, p < 0.001). Moreover, VWF:CB level was highly predictive of COVID-19 in-hospital mortality as shown by the ROC curve analysis (AUC = 0.92, p < 0.0001) in which we identified a VWF:CB cut-off of 446% as providing the best predictor sensitivity-specificity balance. We confirmed this cut-off thanks to a Kaplan-Meier estimator analysis (log-rank p < 0.001) and a Cox-proportional Hazard model (HR = 49.1, 95% CI 1.81-1328.2, p = 0.021) adjusted on, BMI, C-reactive protein, and D-dimer levels. CONCLUSION: VWF:CB levels could summarize both VWF increased levels and hyper-reactivity subsequent to ADAMTS13 overflow and, therefore, be a valuable and easy to perform clinical biomarker of microthrombosis and COVID-19 severity.
Assuntos
Proteína ADAMTS13/sangue , COVID-19/sangue , COVID-19/mortalidade , Pandemias , SARS-CoV-2 , Fator de von Willebrand/metabolismo , Idoso , Biomarcadores/sangue , Colágeno/metabolismo , Estudos Transversais , Feminino , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Paris/epidemiologia , Modelos de Riscos Proporcionais , Ligação Proteica , Índice de Gravidade de DoençaRESUMO
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 ß [IL-1ß] 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.
Assuntos
COVID-19/metabolismo , Mielopoese , Neovascularização Patológica/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , SARS-CoV-2/metabolismo , Trombose/metabolismo , COVID-19/patologia , COVID-19/terapia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Células Endoteliais/virologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Proteínas de Membrana/metabolismo , Neovascularização Patológica/patologia , Neovascularização Patológica/terapia , Neovascularização Patológica/virologia , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/virologia , Trombose/patologia , Trombose/terapia , Trombose/virologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de von Willebrand/metabolismoRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with endotheliitis and microthrombosis. OBJECTIVES: To correlate endothelial dysfunction to in-hospital mortality in a bi-centric cohort of COVID-19 adult patients. METHODS: Consecutive ambulatory and hospitalized patients with laboratory-confirmed COVID-19 were enrolled. A panel of endothelial biomarkers and von Willebrand factor (VWF) multimers were measured in each patient ≤ 48 h following admission. RESULTS: Study enrolled 208 COVID-19 patients of whom 23 were mild outpatients and 189 patients hospitalized after admission. Most of endothelial biomarkers tested were found increased in the 89 critical patients transferred to intensive care unit. However, only von Willebrand factor antigen (VWF:Ag) scaled according to clinical severity, with levels significantly higher in critical patients (median 507%, IQR 428-596) compared to non-critical patients (288%, 230-350, p < 0.0001) or COVID-19 outpatients (144%, 133-198, p = 0.007). Moreover, VWF high molecular weight multimers (HMWM) were significantly higher in critical patients (median ratio 1.18, IQR 0.86-1.09) compared to non-critical patients (0.96, 1.04-1.39, p < 0.001). Among all endothelial biomarkers measured, ROC curve analysis identified a VWF:Ag cut-off of 423% as the best predictor for in-hospital mortality. The accuracy of VWF:Ag was further confirmed in a Kaplan-Meier estimator analysis and a Cox proportional Hazard model adjusted on age, BMI, C-reactive protein and D-dimer levels. CONCLUSION: VWF:Ag is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that VWF, including excess of HMWM forms, drives microthrombosis in COVID-19.
Assuntos
COVID-19/sangue , COVID-19/mortalidade , Pandemias , SARS-CoV-2 , Fator de von Willebrand/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/química , COVID-19/fisiopatologia , Estudos Transversais , Endotélio Vascular/fisiopatologia , Feminino , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Peso Molecular , Paris/epidemiologia , Modelos de Riscos Proporcionais , Multimerização Proteica , Índice de Gravidade de Doença , Trombose/sangue , Trombose/etiologia , Fator de von Willebrand/químicaRESUMO
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.
Assuntos
COVID-19/complicações , Choque/patologia , Síndrome de Resposta Inflamatória Sistêmica/patologia , Corticosteroides/uso terapêutico , Angiopoietina-2/sangue , Biomarcadores , Proteína C-Reativa/análise , COVID-19/patologia , Cardiotônicos/uso terapêutico , Criança , Feminino , Humanos , Imunoglobulinas/uso terapêutico , Unidades de Terapia Intensiva Pediátrica , Interleucina-6/sangue , Ácido Láctico/sangue , Masculino , Respiração Artificial , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Choque Cardiogênico/patologia , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Troponina/sangue , Vasoconstritores/uso terapêutico , Função Ventricular Esquerda , Tratamento Farmacológico da COVID-19RESUMO
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<0.001). Patient and socio-demographic characteristics significantly differed between neighborhoods ( P for trend <0.001). After adjustment, a higher density of ambulances was associated with successful return of spontaneous circulation (respectively adjusted odds-ratio [aOR], 1.31 [1.14-1.51]; P<0.001 for ALS ambulances >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.
Assuntos
Suporte Vital Cardíaco Avançado , Ambulâncias/provisão & distribuição , Reanimação Cardiopulmonar , Alocação de Recursos para a Atenção à Saúde , Disparidades em Assistência à Saúde , Parada Cardíaca Extra-Hospitalar/terapia , Serviços Urbanos de Saúde/provisão & distribuição , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Desfibriladores/provisão & distribuição , Cardioversão Elétrica/instrumentação , Auxiliares de Emergência/provisão & distribuição , Feminino , Bombeiros , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/fisiopatologia , Paris , Recuperação de Função Fisiológica , Sistema de Registros , Características de Residência , Estudos Retrospectivos , Fatores de Risco , Determinantes Sociais da Saúde , Fatores Socioeconômicos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Coronavirus disease-2019 (COVID-19), a respiratory disease has been associated with ischemic complications, coagulation disorders, and an endotheliitis. OBJECTIVES: To explore endothelial damage and activation-related biomarkers in COVID-19 patients with criteria of hospitalization for referral to intensive care unit (ICU) and/or respiratory worsening. METHODS: Analysis of endothelial and angiogenic soluble markers in plasma from patients at admission. RESULTS: Study enrolled 40 consecutive COVID-19 patients admitted to emergency department that fulfilled criteria for hospitalization. Half of them were admitted in conventional wards without any ICU transfer during hospitalization; whereas the 20 others were directly transferred to ICU. Patients transferred in ICU were more likely to have lymphopenia, decreased SpO2 and increased D-dimer, CRP and creatinine levels. In those patients, soluble E-selectin and angiopoietin-2 were significantly increased (p value at 0.009 and 0.003, respectively). Increase in SELE gene expression (gene coding for E-selectin protein) was confirmed in an independent cohort of 32 patients using a whole blood gene expression profile analysis. In plasma, we found a strong association between angiopoetin-2 and CRP, creatinine and D-dimers (with p value at 0.001, 0.001 and 0.003, respectively). ROC curve analysis identified an Angiopoietin-2 cut-off of 5000 pg/mL as the best predictor for ICU outcome (Se = 80.1%, Sp = 70%, PPV = 72.7%, NPV = 77%), further confirmed in multivariate analysis after adjustment for creatinine, CRP or D-dimers. CONCLUSION: Angiopoietin-2 is a relevant predictive factor for ICU direct admission in COVID-19 patients. This result showing an endothelial activation reinforces the hypothesis of a COVID-19-associated microvascular dysfunction.
Assuntos
Angiopoietina-2/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Endotélio Vascular/metabolismo , Unidades de Terapia Intensiva , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Idoso , Betacoronavirus , Biomarcadores/sangue , COVID-19 , Cuidados Críticos/métodos , Selectina E/sangue , Feminino , Perfilação da Expressão Gênica , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Admissão do Paciente , Estudos Prospectivos , Respiração Artificial , SARS-CoV-2Assuntos
COVID-19 , Pandemias , Humanos , Mortalidade Hospitalar , Biomarcadores , Fator de von WillebrandRESUMO
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by obliteration of alveolar architecture, resulting in declining lung function and ultimately death. Pathogenic mechanisms involve a concomitant accumulation of scar tissue together with myofibroblasts activation and a strong abnormal vascular remodeling. Endothelial progenitor cells (ECFC subtype) have been investigated in several human lung diseases as a potential actor in IPF. We previously demonstrated that ECFCs are down-regulated in IPF in contrast to healthy controls. We postulated here that ECFCs might behave as a liquid biopsy in IPF patients and that they exert modified vasculogenic properties. METHODS AND RESULTS: ECFCs isolated from controls and IPF patients expressed markers of the endothelial lineage and did not differ concerning adhesion, migration, and differentiation in vitro and in vivo. However, senescent and apoptotic states were increased in ECFCs from IPF patients as shown by galactosidase staining, p16 expression, and annexin-V staining. Furthermore, conditioned medium of IPF-ECFCs had increased level of interleukin-8 that induced migration of neutrophils in vitro and in vivo. In addition, an infiltration by neutrophils was shown in IPF lung biopsies and we found in a prospective clinical study that a high level of neutrophils in peripheral blood of IPF patients was associated to a poor prognosis. CONCLUSION: To conclude, our study shows that IPF patients have a senescent ECFC phenotype associated with an increased IL-8 secretion potential that might contribute to lung neutrophils invasion during IPF.
Assuntos
Células Endoteliais/metabolismo , Células Endoteliais/patologia , Fibrose Pulmonar Idiopática/etiologia , Fibrose Pulmonar Idiopática/patologia , Interleucina-8/metabolismo , Células-Tronco/metabolismo , Células-Tronco/patologia , Adulto , Células Cultivadas , Estudos de Coortes , Células Endoteliais/fisiologia , Seguimentos , França , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Fenótipo , Cultura Primária de Células , Células-Tronco/fisiologiaRESUMO
PURPOSE: Recent doubts regarding the efficacy may have resulted in a loss of interest for targeted temperature management (TTM) in comatose cardiac arrest (CA) patients, with uncertain consequences on outcome. We aimed to identify a change in TTM use and to assess the relationship between this change and neurological outcome. METHODS: We used Utstein data prospectively collected in the Sudden Death Expertise Center (SDEC) registry (capturing CA data from all secondary and tertiary hospitals located in the Great Paris area, France) between May 2011 and December 2017. All cases of non-traumatic OHCA patients with stable return of spontaneous circulation (ROSC) were included. After adjustment for potential confounders, we assessed the relationship between changes over time in the use of TTM and neurological recovery at discharge using the Cerebral Performance Categories (CPC) scale. RESULTS: Between May 2011 and December 2017, 3925 patients were retained in the analysis, of whom 1847 (47%) received TTM. The rate of good neurological outcome at discharge (CPC 1 or 2) was higher in TTM patients as compared with no TTM (33% vs 15%, P < 0.001). Gender, age, and location of CA did not change over the years. Bystander CPR increased from 55% in 2011 to 73% in 2017 (P < 0.001) and patients with a no-flow time longer than 3 min decreased from 53 to 38% (P < 0.001). The use of TTM decreased from 55% in 2011 to 37% in 2017 (P < 0.001). Meanwhile, the rate of patients with good neurological recovery remained stable (19 to 23%, P = 0.76). After adjustment, year of CA occurrence was not associated with outcome. CONCLUSIONS: We report a progressive decrease in the use of TTM in post-cardiac arrest patients over the recent years. During this period, neurological outcome remained stable, despite an increase in bystander-initiated resuscitation and a decrease in "no flow" duration.
Assuntos
Hipotermia Induzida/normas , Parada Cardíaca Extra-Hospitalar/terapia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Fatores de Tempo , Resultado do Tratamento , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipotermia Induzida/métodos , Hipotermia Induzida/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Parada Cardíaca Extra-Hospitalar/epidemiologia , Avaliação de Resultados em Cuidados de Saúde/normas , Paris/epidemiologia , Sistema de Registros/estatística & dados numéricosAssuntos
COVID-19 , Embolia Pulmonar , Hospitais , Humanos , Prevalência , Embolia Pulmonar/epidemiologia , Estudos Retrospectivos , SARS-CoV-2RESUMO
IMPORTANCE: Uncontrolled donation after circulatory determination of death (uDCD) has been developed and can serve as a source of kidneys for transplantation, especially when considering patients that meet extended criteria donation (ECD). OBJECTIVE: This study assessed the theorical size and characteristics of the potential pool of kidney transplants from uDCD with standard criteria donation (SCD) and ECD among patients who meet Termination of Resuscitation (TOR) criteria following Out of Hospital Cardiac Arrest (OHCA). METHODS AND PARTICIPANTS: This study focused on adult patients experiencing unexpected OHCA, who were prospectively enrolled in the Parisian registry from May 16th, 2011, to December 31st, 2020. RESULTS: During the study period, EMS attempted resuscitation for 19,976 OHCA patients, of which 64.5% (12,890) had no return of spontaneous circulation. Among them, 47.4% (9,461) had TOR criteria, representing no chance of survival, and from them, 8.8% (1,764) met SCD criteria and could be potential organ donors and 33.6% (6,720) met ECD for kidney donors. The mean potential number per year of uDCD candidates with SCD and ECD remain stable respectively around 98 (±10.8) and 672 (±103.8) cases per year. Elderly patients (≥65 y.o.) represented 61.2% (n = 5,763/9,461) of patients who met TOR and 100% (5763/5763) of patients who could have matched both ECD criteria and TOR. CONCLUSION AND RELEVANCE: Implementing uDCD program including SCD and ECD for kidney transplantation among OHCA cases quickly identified by the TOR, holds significant potential to substantially broaden the pool of organ donors. These programs could offer a viable solution to address the pressing burden of kidney shortage, particularly benefiting elderly recipients who may otherwise face prolonged waiting times and limited access to suitable organs.
Assuntos
Transplante de Rim , Parada Cardíaca Extra-Hospitalar , Sistema de Registros , Humanos , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/mortalidade , Transplante de Rim/estatística & dados numéricos , Masculino , Feminino , Pessoa de Meia-Idade , Obtenção de Tecidos e Órgãos/métodos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Idoso , Doadores de Tecidos/estatística & dados numéricos , Reanimação Cardiopulmonar/métodos , Reanimação Cardiopulmonar/estatística & dados numéricos , Estudos Prospectivos , AdultoRESUMO
To estimate the rate of inappropriate diagnosis in patients who visited the ED with thrombotic microangiopathy (TMA) and to assess the factors and outcomes associated with emergency department (ED) misdiagnosis. Retrospective multicenter study of adult patients admitted to the intensive care unit (ICU) for TMA from 2012 to 2021 who had previously attended the ED for a reason related to TMA. Patient characteristics and outcomes were compared in a univariate analysis based on whether a TMA diagnosis was mentioned in the ED or not. Forty patients were included. The diagnosis of TMA was not mentioned in the ED in 16 patients (40%). Patients for whom the diagnosis was mentioned in the ED had more frequently a request for schistocytes research, and therefore had more often objectified schistocytes. They also had more frequently a troponin dosage in the ED (even if the difference was not significant), an ECG performed or interpreted, and were admitted more quickly in the ICU (0 [0-0] vs 2 [0-2] days; P = 0.002). Hemoglobin levels decreased significantly in both groups, and creatinine levels increased significantly in the misdiagnosis group between ED arrival and ICU admission. In patients with a final diagnosis of TTP, the time to platelets durable recovery was shorter for those in whom the diagnosis was mentioned in the ED without reaching statistical significance (7 [5-11] vs 14 [5-21] days; P = 0.3).