Biomarkers of endothelial glycocalyx damage are associated with microvascular dysfunction in resuscitated septic shock patients.

BACKGROUND: Microvascular dysfunction plays a central role in organ dysfunction during septic shock. Endothelial glycocalyx (eGC) damage could contribute to impaired microcirculation. The aim was to assess whether several eGC-damaged biomarkers are associated with microvascular dysfunction in resuscitated septic shock patients. METHODS: This cross-sectional study included resuscitated septic shock patients (N = 31), and a group of healthy individuals (N = 20). The eGC damage biomarkers measured were syndecan-1 (SDC-1), soluble CD44 (CD44s), hyaluronic acid (HYAL) in blood sample; sulfated glycosaminoglycans (GAGs) in urine sample; and thrombomodulin (TBML) in blood sample as biomarker of endothelial cell damage. Microcirculation was assessed through sublingual videocapillaroscopy using the GlycoCheck™, which estimated the perfused vascular density (PVD); the perfused boundary region (PBR), an inverse parameter of the eGC thickness; and the microvascular health score (MVHS). We defined a low MVHS (<50th percentile in septic patients) as a surrogate for more impaired microvascular function. RESULTS: The SDC-1, CD44s, TBML and GAGs levels were correlated with impaired microvascular parameters (PVD of vessels with diameter < 10 µm, MVHS and flow-adjusted PBR); p < 0.05 for all comparisons, except for GAGs and flow-adjusted PBR. The SDC-1 [78 ng/mL (interquartile range (IQR) 45-336) vs. 48 ng/mL (IQR 9-85); p = 0.052], CD44s [796ρg/mL (IQR 512-1995) vs. 526ρg/mL (IQR 287-750); p = 0.036], TBML [734ρg/mL (IQR 237-2396) vs. 95ρg/mL (IQR 63-475); p = 0.012] and GAGs levels [0.42 ρg/mg (IQR 0.04-1.40) vs. 0.07 ρg/mg (IQR 0.02-0.20); p = 0.024]; were higher in septic patients with more impaired sublingual microvascular function (low MVHS vs. high MVHS). CONCLUSION: SDC-1, CD44s, TBML and GAGs levels were associated with impaired microvascular function in resuscitated septic shock patients.

Regional myocardial sympathetic denervation precedes the development of left ventricular systolic dysfunction in chronic Chagas' cardiomyopathy.

BACKGROUND: Regional myocardial sympathetic denervation is a conspicuous and early disorder in patients with chronic Chagas' cardiomyopathy (CCC), potentially associated to the progression of myocardial dysfunction OBJECTIVE: To evaluate in a longitudinal study the association between the presence and the progression of regional myocardial sympathetic denervation with the deterioration of global and segmental left ventricular dysfunction in CCC. METHODS: 18 patients with CCC were submitted at initial evaluation and after 5.5 years to rest myocardial scintigraphy with 123Iodo-metaiodobenzylguanidine and 99mTc-sestamibi and to two-dimensional echocardiography to assess myocardial sympathetic denervation, extent of fibrosis, and the left ventricular ejection fraction (LVEF) and wall motion abnormalities. RESULTS: In the follow-up evaluation, compared to the initial one, we observed a significant decrease in LVEF (56 ± 11 to 49% ± 12; P = .01) and increased summed defects scores in the myocardial innervation scintigraphy (15 ± 10 to 20 ± 9; P < .01). The presence of regional myocardial sympathetic denervation in ventricular regions of viable non-fibrotic myocardium presented an odds ratio of 4.25 for the development of new wall motion abnormalities (P = .001). CONCLUSION: Regional and global myocardial sympathetic denervation is a progressive derangement in CCC. In addition, the regional denervation is topographically associated with areas of future development of regional systolic dysfunction in patients with CCC.

Atypical COVID-19 presentation with Budd-Chiari syndrome leading to an outbreak in the emergency department.

We described a case report of a 50 years-old-woman admitted to the emergency department with abdominal pain associated with febrile hepatosplenomegaly with the final diagnosis of suprahepatic vein thrombosis secondary to COVID-19. Initially, this patient stayed out of a private room because of this atypical presentation and caused a COVID-19 outbreak in the emergency department.

In vivo demonstration of microvascular thrombosis in severe COVID-19.

Several autopsy studies showed microthrombi in pulmonary circulation of severe COVID-19 patients. The major limitation of these investigations is that the autopsy provided static information. Some of these alterations could be secondary to the disseminated intravascular coagulation (DIC) observed as the final standard route to the multisystem organ failure exhibited in critically ill patients. We report preliminary results of an in vivo evaluation of sublingual microcirculation in thirteen patients with severe COVID-19 requiring mechanical ventilation. We observed multiple filling defects moving within the microvessels indicative of thrombi in most of the cases 11/13 (85%). This is the first imaging documentation of microvascular thrombosis in living severe COVID-19 patients since the beginning of the hospitalization. The clinical relevance of microvascular thrombosis in this disease requires further research.

The severity of ventricular arrhythmia correlates with the extent of myocardial sympathetic denervation, but not with myocardial fibrosis extent in chronic Chagas cardiomyopathy : Chagas disease, denervation and arrhythmia.

BACKGROUND: To investigate the correlation between the extent of myocardial sympathetic denervation and fibrosis and the presence of degrees of severity of ventricular arrhythmias in chronic Chagas cardiomyopathy (CCC). METHODS: Forty-three CCC patients with left ventricular ejection fraction (LVEF) ≥ 35% were divided into three groups: SVT group-presenting Sustained Ventricular Tachycardia (SVT) (n = 15), NSVT group-exhibiting episodes of non-SVT (NSVT) on 24-h Holter monitoring (n = 11), and Control group-exhibiting neither SVT nor episodes of NSVT (n = 17). The patients underwent SPECT imaging for myocardial sympathetic innervation with 123Iodine-MIBG (MIBG) and myocardial perfusion with 99mTc-Sestamibi (MIBI) for the evaluation of regional myocardial fibrosis. RESULTS: The summed rest perfusion scores were similar in the three groups. The summed difference score between MIBG and MPI images, which evaluated the extent of denervated but viable myocardium, was significantly higher in SVT group (20.0 ± 8.0) as compared with the control group (2.0 ± 5.0, P < .0001) and with the NSVT group (11.0 ± 8.0, P < .05). CONCLUSIONS: The occurrence of ventricular arrhythmias of different degrees of severity correlates quantitatively with the extent of cardiac sympathetic denervation, but not with the extent of fibrosis, suggesting that myocardial sympathetic denervation plays a major role in triggering ventricular arrhythmia in CCC.

Prognostic evaluation of the troponin I elevation after multiple spontaneous shocks of the implantable cardioverter/defibrillator.

BACKGROUND: Multiple shocks of the implantable cardioverter/defibrillator (ICD) can cause myocardial injury, contributing to the progression of underlying heart disease. The aim was to evaluate if the elevation of troponin I after multiple ICD shocks has impact on the prognostic of these patients. METHODS: We evaluated patients with multiple ICD shocks (>3 shocks) in the last 24 hours. Troponin I was measured around 12 hours after the last shock. After this episode, these patients were followed; and events of death or heart failure hospitalization were recorded. RESULTS: Twenty-six patients were included in the study. Elevation of troponin I occurred in 16 patients (62%), who had received a higher number of shocks (14 ± 9 vs 7 ± 4, P = .03) and greater cumulative total voltage (455 ± 345 J vs 141 ± 62 J, P = .03) compared to the group without elevation of this biomarker. We observed a positive correlation between troponin I and number of shocks (r = 0.70; P = .0001). Patients with troponin I elevation after multiple ICD shocks had higher risk of death or heart failure hospitalization (hazard ratio, 7.0; 95% confidence interval, 1.2-16.0; P = .03) compared with the group without elevation of this biomarker. After adjustment for age, sex, and number of shocks, the elevation of this biomarker remained as predictor of these events (hazard ratio, 16.0; 95% confidence interval, 1.7-151.0; P = .02). CONCLUSION: A large proportion of patients with multiple ICD shocks have troponin I elevation, and these patients have a higher risk of death or hospitalization due to heart failure.

Doxycycline protects against sepsis-induced endothelial glycocalyx shedding.

Endothelial glycocalyx (eGC) covers the inner surface of the vessels and plays a role in vascular homeostasis. Syndecan is considered the "backbone" of this structure. Several studies have shown eGC shedding in sepsis and its involvement in organ dysfunction. Matrix metalloproteinases (MMP) contribute to eGC shedding through their ability for syndecan-1 cleavage. This study aimed to investigate if doxycycline, a potent MMP inhibitor, could protect against eGC shedding in lipopolysaccharide (LPS)-induced sepsis and if it could interrupt the vascular hyperpermeability, neutrophil transmigration, and microvascular impairment. Rats that received pretreatment with doxycycline before LPS displayed ultrastructural preservation of the eGC observed using transmission electronic microscopy of the lung and heart. In addition, these animals exhibited lower serum syndecan-1 levels, a biomarker of eGC injury, and lower perfused boundary region (PBR) in the mesenteric video capillaroscopy, which is inversely related to the eGC thickness compared with rats that only received LPS. Furthermore, this study revealed that doxycycline decreased sepsis-related vascular hyperpermeability in the lung and heart, reduced neutrophil transmigration in the peritoneal lavage and inside the lungs, and improved some microvascular parameters. These findings suggest that doxycycline protects against LPS-induced eGC shedding, and it could reduce vascular hyperpermeability, neutrophils transmigration, and microvascular impairment.

Evaluation of cardiac involvement during dengue viral infection.

BACKGROUND: Dengue is a disease whose clinical manifestations range from asymptomatic infections to a severe disease. There have been some previous reports of myocardial involvement in dengue, but this association has not been completely established. METHODS: From January to July of 2011, patients hospitalized with dengue, confirmed through dengue nonstructural protein 1 and/or immunoglobulin M detection, were included in this study and troponin I and N terminal fragment of B-type natriuretic peptide levels were determined. Patients with abnormal biomarkers underwent echocardiography and when any abnormality was detected, they underwent cardiac magnetic resonance imaging. RESULTS: Eighty-one patients were evaluated and 12 patients (15%) presented with elevated biomarker levels. Compared to controls, they had higher leukocyte (P < .001) and platelet counts (P = .005); higher C-reactive protein (P = .02), and a lower viral load (P = .03). There was no difference according to clinical dengue classification; dengue hemorrhagic fever/dengue shock syndrome severity; duration of symptoms; or prevalence of secondary infection between the 2 groups. Two patients died secondary to cardiogenic shock before imaging studies. Necroscopic findings were compatible to myocarditis in both, and immunohistochemistry for dengue virus showed increased staining on mononuclear cells located in the myocardial tissue. Of the 10 patients who underwent echocardiography, depressed left ventricular ejection fraction (LVEF) was identified in 1, left ventricular segmental abnormalities with preserved LVEF in 2, and an important pericardial effusion with tamponade in another. Cardiac involvement was confirmed by CMR in these 4 patients. CONCLUSIONS: Dengue viruses were shown to cause cardiac disease with clinical manifestations ranging from mild elevation of biomarkers to myocarditis and/or pericarditis.

Palliative care team in a Brazilian tertiary emergency department.

OBJECTIVES: To describe the process of implementing a palliative care team (PCT) in a Brazilian public tertiary university hospital and compare this intervention as an active in-hospital search (strategy I) with the Emergency Department (strategy II). METHODS: We described the development of a complex Palliative Care Team (PCT). We evaluated the following primary outcomes: hospital discharge, death (in-hospital and follow-up mortality) or transfer, and performance outcomes-Perception Index (difference in days between hospitalization and the evaluation by the PTC), follow-up index (difference in days between the PTC evaluation and the primary outcome), and the in-hospital stay. RESULTS: We included 1203 patients-strategy I (587; 48.8%) and strategy II (616; 51.2%). In both strategies, male and elderly patients were prevalent. Most came from internal medicine I (39.3%) and II (57.9%), p <  0.01. General clinical conditions (40%) and Oncology I (27.7%) and II (32.4%) represented the majority of the population. Over 70% of all patients had PPS 10 and ECOG 4 above 85%. There was a reduction of patients identified in ICU from I (20.9%) to II (9.2%), p <  0.01, reduction in the ward from I (60.8%) to II (42.5%), p <  0.01 and a significant increase from I (18.2%) to II (48.2%) in the emergency department, p <  0.01. Regarding in-hospital mortality, 50% of patients remained alive within 35 days of hospitalization (strategy I), while for strategy II, 50% were alive within 20 days of hospitalization (p <  0.01). As for post-discharge mortality, in strategy II, 50% of patients died 10 days after hospital discharge, while in strategy I, this number was 40 days (p <  0.01). In the Cox multivariate regression model, adjusting for possible confounding factors, strategy II increased 30% the chance of death. The perception index decreased from 10.9 days to 9.1 days, there was no change in follow-up (12 days), and the duration of in-hospital stay dropped from 24.3 to 20.7 days, p <  0.01. The primary demand was the definition of prognosis (56.7%). CONCLUSION: The present work showed that early intervention by an elaborate and complex PCT in the ED was associated with a faster perception of the need for palliative care and influenced a reduction in the length of hospital stay in a very dependent and compromised old population.

Reperfusion Therapy Optimization in Acute Myocardial Infarction with ST-Segment Elevation using WhatsApp®-Based Telemedicine. / Otimização da Terapia de Reperfusão no Infarto Agudo do Miocárdio com Supradesnível do Segmento ST por Meio de Telemedicina Baseada no WhatsApp®.

BACKGROUND: About 40% of patients with ST-segment elevation myocardial infarction (STEMI) in Brazil do not receive reperfusion therapy. OBJECTIVE: The use of a telemedicine network based on WhatsApp® could increase the percentage of patients receiving reperfusion therapy. METHODS: A cross-sectional study analyzed outcomes before and after the organization of a telemedicine network to send the electrocardiogram via WhatsApp® of patients suspected of STEMI from 25 municipalities that are members of the Regional Health Department of Ribeirão Preto (DRS-XIII) to a tertiary hospital, which could authorize immediate patient transfer using the same system. The analyzed outcomes included the percentage of patients who received reperfusion therapy and the in-hospital mortality rate. A p value < 0.05 was considered statistically significant. RESULTS: The study compared 82 patients before (February 1, 2016 to January 31, 2018) with 196 patients after this network implementation (February 1, 2018 to January 31, 2020). After implementing this network, there was a significant increase in the proportion of patients who received reperfusion therapy (60% vs. 92%), relative risk (RR): 1.594 [95% confidence interval (CI) 1.331 - 1.909], p < 0.0001 and decrease in the in-hospital mortality rate (13.4% vs. 5.6%), RR: 0.418 [95%CI 0.189 - 0.927], p = 0.028. CONCLUSION: The use of WhatsApp®-based telemedicine has led to an increase in the percentage of patients with STEMI who received reperfusion therapy and a decrease in the in-hospital mortality rate.

FUNDAMENTO: Cerca de 40% dos pacientes com infarto agudo do miocárdio com supradesnível do segmento ST (IAMCSST) no Brasil não recebem terapia de reperfusão. OBJETIVO: A utilização de uma rede de telemedicina baseada no WhatsApp® poderia aumentar a porcentagem de pacientes que recebem terapia de reperfusão. MÉTODOS: Estudo transversal do tipo antes e depois da organização de uma rede de telemedicina para envio e análise do eletrocardiograma através do WhatsApp® dos pacientes suspeitos de IAMCSST oriundos dos 25 municípios integrantes do Departamento Regional de Saúde de Ribeirão Preto (DRS−XIII), para hospital terciário que poderia autorizar a transferência imediata do paciente utilizando o mesmo sistema. O desfechos analisados foram a porcentagem de pacientes que receberam terapia de reperfusão e a taxa de mortalidade intra-hospitalar. Considerou-se valor de p <0,05 como estatisticamente significativo. RESULTADOS: Foram comparados 82 pacientes antes desta rede (1º de fevereiro de 2016 a 31 de janeiro de 2018) com 196 pacientes depois da implantação da mesma (1º de fevereiro de 2018 a 31 de janeiro de 2020). Após a implantação da rede, houve aumento significativo da proporção de pacientes que receberam terapia de reperfusão (60% vs. 92%), risco relativo (RR): 1,594 [intervalo de confiança (IC) 95% 1,331 ­ 1,909], p <0,0001 e redução da mortalidade intra-hospitalar (13,4% vs. 5,6%), RR: 0,418 [IC 95% 0,189 ­ 0,927], p = 0,028. CONCLUSÃO: Rede de telemedicina baseada no WhatsApp® associou-se a aumento da porcentagem de pacientes com IAMCSST que receberam terapia de reperfusão e a redução na mortalidade intra-hospitalar.

Impact of a dental care intervention on the hospital mortality of critically ill patients admitted to intensive care units: A quasi-experimental study.

BACKGROUND: We aimed to evaluate the impact of providing dental care to critically ill patients on their risk of death and ventilator-associated pneumonia (VAP). METHODS: A quasi-experimental study was conducted in 2 intensive care units (ICU) from 2016 to 2019. The intervention consisted of implementing routine dental care, focusing on oral hygiene and periodontal treatment, at least 3 times a week, for patients admitted to the study units. In the pre-intervention period, routine oral hygiene was provided by the ICU nursing staff. The primary and secondary study outcomes were mortality, evaluated at the end of the ICU stay, and VAP incidence density, respectively. Data were analyzed using the ARIMA (autoregressive integrated moving average) time series model in R software. RESULTS: During the intervention period, 5,147 dental procedures were performed among 355 patients. The time series showed that ICU mortality was 36.11%, 32.71%, and 32.30% within the 3 years before the intervention, and 28.71% during the intervention period (P = .015). VAP incidence density did not significantly change during the study period (P = .716). CONCLUSION: A dental care intervention focused on oral hygiene and periodontal treatment regularly provided by dentists to critically ill patients may decrease their risk of dying in the ICU. Randomized clinical trials should be performed to confirm these findings. TRIAL REGISTRATION: WHO-affiliated Brazilian Clinical Trials Registry. RBR-4jmz36. Registered 7 October 2018, before first patient enrollment.

Clinical impact of implementing a rapid-response team based on the Modified Early Warning Score in wards that offer emergency department support.

BACKGROUND: Emergency department (ED) crowding is a frequent situation. To decrease this overload, patients without a life-threating condition are transferred to wards that offer ED support. This study aimed to evaluate if implementing a rapid response team (RRT) triggered by the modified early warning score (MEWS) in high-risk wards offering ED support is associated with decreased in-hospital mortality rate. METHODS: A before-and-after cross-sectional study compared in-hospital mortality rates before and after implementation of an RRT triggered by the MEWS ≥4 in two wards of a tertiary hospital that offer ED support. RESULTS: We included 6863 patients hospitalized in these wards before RRT implementation from July 2015 through June 2017 and 6944 patients hospitalized in these same wards after RRT implementation from July 2018 through June 2020. We observed a statistically significant decrease in the in-hospital mortality rate after intervention, 449 deaths/6944 hospitalizations [6.47% (95% confidence interval (CI) 5.91%- 7.07%)] compared to 534 deaths/6863 hospitalizations [7.78% (95% CI 7.17-8.44)] before intervention; with an absolute risk reduction of -1.31% (95% CI -2.20 --0.50). CONCLUSION: RRT trigged by the MEWS≥4 in high-risk wards that offer ED support was found to be associated with a decreased in-hospital mortality rate. A further cluster-randomized trial should evaluate the impact of this intervention in this setting.

Clinical Competence in ST-segment Elevation Myocardial Infarction Management by Recently Graduated Physicians Applying for a Medical Residency Program.

BACKGROUND: A significant reduction in the morbidity and mortality related to ST-segment elevation myocardial infarction (STEMI) has been achieved with the development of reperfusion therapies. Early diagnosis and correct initial management are important to ensure this benefit. In Brazil, recent graduates in medicine are responsible for a large part of the initial care provided for these patients. OBJECTIVE: To assess the clinical competence in the diagnosis and initial treatment of STEMI by newly graduated physicians applying for a medical residency program. METHODS: We assessed the performance of 771 applicants for the direct entry selection process of the FMRP-USP Clinical Hospital Medicine Residency Program, performed in a simulated setting of STEMI, with professional actors and medical evaluators, using a standardized checklist following the recommendations of the Brazilian Guidelines for the management of this disease. RESULTS: The general performance score presented a median of 7 and an interquartile range of 5.5-8.0. In relation to the items assessed: 83% required ECG monitoring, 57% requested the insertion of a peripheral venous access catheter, 95% administered acetylsalicylic acid, 80% administered a second antiplatelet agent (p2y12 inhibitor), 66% administered nitrate, 71% administered morphine, 69% recognized the diagnosis of STEMI, 71% assessed the pain duration, 63% recognized the need for immediate transfer, 34% showed adequate communication skills and only 25% insisted on the transfer even in case of non-availability of beds. CONCLUSIONS: The initial diagnosis and management of STEMI need to be improved in medical undergraduate courses and inserted into the reality of the hierarchical network structure of the Brazilian Unified Health System (SUS).

Endothelial glycocalyx shedding in the acute respiratory distress syndrome after flu syndrome.

BACKGROUND: Scientific evidence indicates that endothelial glycocalyx (EG) shedding contributes to the pathophysiological installation of acute respiratory distress syndrome (ARDS) after bacterial sepsis. The aim was to evaluate the EG shedding in ARDS installation after flu syndrome. METHODS: This cross-sectional study included patients with flu syndrome during the influenza outbreak divided into two groups: patients with and without ARDS. Healthy subjects without flu syndrome were included in a control group. We measured EG damage biomarkers (hyaluronan, syndecan-1) and endothelial cell injury biomarker (soluble thrombomodulin) during the first medical evaluation. Histological assessment of the perimeter of the hyaline membrane and the number of neutrophils infiltrated in the alveolar septum was performed in patients who died. RESULTS: ARDS group had 30 patients (44 ± 16 years old, 57% men), the non-ARDS group had 36 patients (39 ± 17 years old, 42% men), and the control group had 35 individuals (44 ± 9 years old, 51% men). Hyaluronan levels were significantly higher in the ARDS group than the two groups [31 ng/ml (interquartile range-IQR 12-56) vs. 5 ng/ml (IQR 3-10) vs. 5 ng/ml (IQR 2-8); p < 0.0001]. Hyaluronan levels above 19 ng/ml in patients with flu syndrome were associated with a significant increase in 28-day mortality rate: relative risk (RR): 6.95; (95% confidence interval 1.88-25.67); p = 0.0017. A positive correlation was observed between hyaline membrane perimeter and soluble thrombomodulin levels (r = 0.89; p = 0.05) as well as between the number of neutrophils in the alveolar septum and hyaluronan levels (r = 0.89; p = 0.05). CONCLUSIONS: Evidence of EG shedding was found in ARDS established after flu syndrome.

Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID).

INTRODUCTION: Coronavirus disease 2019 (COVID-19) causes a hypercoagulable state. Several autopsy studies have found microthrombi in pulmonary circulation. METHODS: In this randomized, open-label, phase II study, we randomized COVID-19 patients requiring mechanical ventilation to receive either therapeutic enoxaparin or the standard anticoagulant thromboprophylaxis. We evaluated the gas exchange over time through the ratio of partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) at baseline, 7, and 14 days after randomization, the time until successful liberation from mechanical ventilation, and the ventilator-free days. RESULTS: Ten patients were assigned to the therapeutic enoxaparin and ten patients to prophylactic anticoagulation. There was a statistically significant increase in the PaO2/FiO2 ratio over time in the therapeutic group (163 [95% confidence interval - CI 133-193] at baseline, 209 [95% CI 171-247] after 7 days, and 261 [95% CI 230-293] after 14 days), p = 0.0004. In contrast, we did not observe this improvement over time in the prophylactic group (184 [95% CI 146-222] at baseline, 168 [95% CI 142-195] after 7 days, and 195 [95% CI 128-262] after 14 days), p = 0.487. Patients of the therapeutic group had a higher ratio of successful liberation from mechanical ventilation (hazard ratio: 4.0 [95% CI 1.035-15.053]), p = 0.031 and more ventilator-free days (15 days [interquartile range IQR 6-16] versus 0 days [IQR 0-11]), p = 0.028 when compared to the prophylactic group. CONCLUSION: Therapeutic enoxaparin improves gas exchange and decreases the need for mechanical ventilation in severe COVID-19. TRIAL REGISTRATION: REBEC RBR-949z6v.

Pulmonary Vascular Volume Estimated by Automated Software is a Mortality Predictor after Acute Pulmonary Embolism. / Volume Vascular Pulmonar Estimado por Software Automatizado é um Preditor de Mortalidade após Embolia Pulmonar Aguda.

BACKGROUND: Acute pulmonary embolism (APE) has a variable clinical outcome. Computed tomography pulmonary angiography (CTPA) is the gold standard for this diagnosis. OBJECTIVE: To evaluate if the pulmonary vascular volume (PVV) quantified by automated software is a mortality predictor after APE. METHODS: Retrospective cohort study where the CTPA imaging of 61 patients with APE was reanalyzed. Pulmonary vascular volume (PVV) and pulmonary volume (PV) were automatically estimated using the Yacta software. We calculated the adjusted PVV by the ratio: PVV(cm3)/PV(liters). Classical prognostic CTPA parameters (clot load index, right ventricle/left ventricle diameter ratio, pulmonary artery/aorta diameter ratio, ventricular septal bowing, pulmonary infarction and reflux of contrast into the hepatic vein) were assessed. The outcome assessed was one-month mortality. We considered a p-value <0.05 as statistically significant. RESULTS: Seven deaths (11%) occurred at one month among these 61 patients. PVV<23cm3/L was an independent predictor of one-month mortality in the univariate [odds ratio (OR): 26; 95% confidence interval (CI): 3-244; p=0.004] and multivariate analyses [adjusted OR: 19; 95%CI: 1.3-270; p=0.03]. The classical CTPA parameters were not associated with one-month mortality in this sample. The PVV<23cm3/L showed a sensitivity of 86%, a specificity of 82%, a negative predictive value of 94% and a positive predictive value of 64% to identify the patients who died. CONCLUSION: PVV<23cm3/L was an independent predictor of one-month mortality after APE. This parameter showed better prognostic performance than other classical CTPA findings. (Arq Bras Cardiol. 2020; 115(5):809-818).

FUNDAMENTO: A embolia pulmonar aguda (EPA) tem desfecho clínico variável. A angiotomografia computadorizada (angio-CT) é considerada o padrão-ouro para o diagnóstico. OBJETIVO: Avaliar se o volume vascular pulmonar (VVP) quantificado por software automatizado é um preditor de mortalidade após EPA. MÉTODOS: Estudo de coorte retrospectivo no qual a imagem da angio-CT de 61 pacientes com EPA foi reanalisada. O VVP e o volume pulmonar (VP) foram estimados automaticamente pelo software Yacta. Calculamos o VVP ajustado pela razão: VVP(cm3)/VP(litros). Parâmetros prognósticos clássicos da angio-CT (carga embólica; razão do diâmetro do ventrículo direito/ventrículo esquerdo; razão do diâmetro da artéria pulmonar/aorta; desvio do septo interventricular; infarto pulmonar e refluxo de contraste na veia hepática) foram avaliados. A mortalidade em 1 mês foi o desfecho analisado. Consideramos um valor de p <0,05 como estatisticamente significativo. RESULTADOS: Sete mortes (11%) ocorreram entre os 61 pacientes durante 1 mês de seguimento. O VVP ajustado <23cm3/L foi um preditor independente de mortalidade na análise univariada (odds ratio [OR]: 26; intervalo de confiança de 95% [IC95%]: 3-244; p=0,004) e na análise multivariada (OR ajustado: 19 [IC95%: 1,3-270]; p=0,03). Os parâmetros clássicos da angio-CT não foram associados à mortalidade em 1 mês nesta amostra. O VVP ajustado <23cm3/L apresentou sensibilidade de 86%, especificidade de 82%, valor preditivo negativo de 94% e valor preditivo positivo de 64% para identificação dos pacientes que morreram. CONCLUSÃO: VVP ajustado <23cm3/L foi um preditor independente de mortalidade após EPA. Esse parâmetro mostrou melhor desempenho prognóstico do que os outros achados clássicos da angio-CT. (Arq Bras Cardiol. 2020; 115(5):809-818).

Anticoagulant interventions in hospitalized patients with COVID-19: A scoping review of randomized controlled trials and call for international collaboration.

INTRODUCTION: Coronavirus disease (COVID-19) is associated with a high incidence of thrombosis and mortality despite standard anticoagulant thromboprophylaxis. There is equipoise regarding the optimal dose of anticoagulant intervention in hospitalized patients with COVID-19 and consequently, immediate answers from high-quality randomized trials are needed. METHODS: The World Health Organization's International Clinical Trials Registry Platform was searched on June 17, 2020 for randomized controlled trials comparing increased dose to standard dose anticoagulant interventions in hospitalized COVID-19 patients. Two authors independently screened the full records for eligibility and extracted data in duplicate. RESULTS: A total of 20 trials were included in the review. All trials are open label, 5 trials use an adaptive design, 1 trial uses a factorial design, 2 trials combine multi-arm parallel group and factorial designs in flexible platform trials, and at least 15 trials have multiple study sites. With individual target sample sizes ranging from 30 to 3000 participants, the pooled sample size of all included trials is 12 568 participants. Two trials include only intensive care unit patients, and 10 trials base patient eligibility on elevated D-dimer levels. Therapeutic intensity anticoagulation is evaluated in 14 trials. All-cause mortality is part of the primary outcome in 14 trials. DISCUSSION: Several trials evaluate different dose regimens of anticoagulant interventions in hospitalized patients with COVID-19. Because these trials compete for sites and study participants, a collaborative effort is needed to complete trials faster, conduct pooled analyses and bring effective interventions to patients more quickly.

SARS-CoV-2-triggered neutrophil extracellular traps mediate COVID-19 pathology.

Severe COVID-19 patients develop acute respiratory distress syndrome that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that neutrophil extracellular traps (NETs) have been described as important mediators of tissue damage in inflammatory diseases, we investigated whether NETs would be involved in COVID-19 pathophysiology. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and healthy controls were enrolled. The concentration of NETs was augmented in plasma, tracheal aspirate, and lung autopsies tissues from COVID-19 patients, and their neutrophils released higher levels of NETs. Notably, we found that viable SARS-CoV-2 can directly induce the release of NETs by healthy neutrophils. Mechanistically, NETs triggered by SARS-CoV-2 depend on angiotensin-converting enzyme 2, serine protease, virus replication, and PAD-4. Finally, NETs released by SARS-CoV-2-activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represents a potential therapeutic target for COVID-19.