Predictors of bleeding and thrombotic events among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the ACTION randomized clinical trial.

Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377.

Quality improvement program in Latin America decreases mortality after cardiac surgery: a before-after intervention study.

BACKGROUND: The current challenge of cardiac surgery (CS) is to improve outcomes in adverse scenarios. The aim of this study was to assess the impact of a quality improvement program (QIP) on hospital mortality in the largest CS center in Latin America. METHODS: Patients were divided into two groups: before (Jan 2013-Dec 2015, n = 3534) and after establishment of the QIP (Jan 2017-Dec 2019, n = 3544). The QIP consisted of the implementation of 10 central initiatives during 2016. The procedures evaluated were isolated coronary artery bypass grafting surgery (CABG), mitral valve surgery, aortic valve surgery, combined mitral and aortic valve surgery, and CABG associated with heart valve surgery. Propensity Score Matching (PSM) was used to adjust for inequality in patients' preoperative characteristics before and after the implementation of QIP. A multivariate logistic regression model was built to predict hospital mortality and validated using discrimination and calibration metrics. RESULTS: The PMS paired two groups using 5 variables, obtaining 858 patients operated before (non-QIP) and 858 patients operated after the implementation of the QIP. When comparing the QIP versus Non-QIP group, there was a shorter length of stay in all phases of hospitalization. In addition, the patients evolved with less anemia (P = 0.001), use of intra-aortic balloon pump (P = 0.003), atrial fibrillation (P = 0.001), acute kidney injury (P < 0.001), cardiogenic shock (P = 0.011), sepsis (P = 0.046), and hospital mortality (P = 0.001). In the multiple model, among the predictors of hospital mortality, the lack of QIP increased the chances of mortality by 2.09 times. CONCLUSION: The implementation of a first CS QIP in Latin America was associated with a reduction in length of hospital stay, complications and mortality after the cardiac surgeries analyzed.

Tocilizumab in SARS-COVID19 following postoperative laparoscopic transhiatal esophagectomy for the adenocarcinoma of esophagogastric tumor: A case report.

INTRODUCTION AND IMPORTANCE: Esophagectomy for esophageal cancer is one of the most challenging surgical procedures, with high rates of morbidity, especially from respiratory complications. SARS-COVID19 represents a health threat nowadays. Peri-operative SARS-COVID19 infection after esophagectomy might negatively affect the postoperative outcomes. The use of tocilizumab as an alternative to reduce the inflammatory response in SARS-COVID19 is an option that has not been described in the literature after esophagectomy. CASE PRESENTATION: A SARS-COVID19-vaccinated (CORONAVAC) 73-year-old man with pulmonary emphysema, coronary artery disease, previous asymptomatic pulmonary embolism, and adenocarcinoma of the esophagogastric junction tumor was submitted to laparoscopic transhiatal esophagectomy (ypT2N0M0) after perioperative neoadjuvant chemotherapy. He was also infected with SARS-COVID19, confirmed by PCR test at the 14th postoperative day. During follow-up, mild hypoxemia persisted without evidence of infection except for SARS-COVID19, and a high-flow cannula was required to maintain oxygenation. Tocilizumab was administered following high parameters of a high-flow cannula, and invasive mechanical ventilation was avoided. DISCUSSION: Besides of the risk of secondary infection, after administration of tocilizumab, the parameters of oxygen supplementation were systematically reduced, and he stayed in the ICU for seven days. He was discharged from the ward six days later. He developed late cervical anastomotic leakage, which was treated with conservative therapy. CONCLUSION: Although the patient had high-risk comorbidities, esophagectomy, and SARS-COVID19 infection, the use of tocilizumab was safe and improved the pulmonary recovery.

Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3-0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59-1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61-8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation. FUNDING: Coalition COVID-19 Brazil, Bayer SA.

Development and Validation of a Simplified Probability Assessment Score Integrated With Age-Adjusted d-Dimer for Diagnosis of Acute Aortic Syndromes.

Background When acute aortic syndromes (AASs) are suspected, pretest clinical probability assessment and d-dimer (DD) testing are diagnostic options allowing standardized care. Guidelines suggest use of a 12-item/3-category score (aortic dissection detection) and a DD cutoff of 500 ng/mL. However, a simplified assessment tool and a more specific DD cutoff could be advantageous. Methods and Results In a prospective derivation cohort (n=1848), 6 items identified by logistic regression (thoracic aortic aneurysm, severe pain, sudden pain, pulse deficit, neurologic deficit, hypotension), composed a simplified score (AORTAs) assigning 2 points to hypotension and 1 to the other items. AORTAs≤1 and ≥2 defined low and high clinical probability, respectively. Age-adjusted DD was calculated as years/age × 10 ng/mL (minimum 500). The AORTAs score and AORTAs≤1/age-adjusted DD rule were validated in 2 patient cohorts: a high-prevalence retrospective cohort (n=1035; 22% AASs) and a low-prevalence prospective cohort (n=447; 11% AASs) subjected to 30-day follow-up. The AUC of the AORTAs score was 0.729 versus 0.697 of the aortic dissection detection score (P=0.005). AORTAs score assessment reclassified 16.6% to 25.1% of patients, with significant net reclassification improvement of 10.3% to 32.7% for AASs and -8.6 to -17% for alternative diagnoses. In both cohorts, AORTAs≥2 had superior sensitivity and slightly lower specificity than aortic dissection detection ≥2. In the prospective validation cohort, AORTAs≤1/age-adjusted DD had a sensitivity of 100%, a specificity of 48.6%, and an efficiency of 43.3%. Conclusions AORTAs is a simplified score with increased sensitivity, improved AAS classification, and minor trade-off in specificity, amenable to integration with age-adjusted DD for diagnostic rule-out.

The Role of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Diagnosis of Left-sided Endocarditis: Native vs Prosthetic Valves Endocarditis.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) has emerged as a useful diagnostic tool for suspected infective endocarditis (IE) in patients with prosthetic valves or implantable devices. However, there is limited evidence regarding use of 18F-FDG-PET/CT for the diagnosis of native valve endocarditis (NVE). METHODS: Between 2014 and 2017, 303 episodes of left-sided suspected IE (188 prosthetic valves/ascending aortic prosthesis and 115 native valves) were studied. 18F-FDG-PET/CT accuracy was determined in the subgroups of patients with NVE and prosthetic valve endocarditis (PVE)/ascending aortic prosthesis infection (AAPI). Associations between inflammatory infiltrate patterns and 18F-FDG-PET/CT uptake were investigated in an exploratory ad hoc histological analysis. RESULTS: Among 188 patients with PVE/AAPI, the sensitivity, specificity, and positive and negative predictive values of 18F-FDG-PET/CT focal uptake were 93%, 90%, 89%, and 94%, respectively, while among 115 patients with NVE, the corresponding values were 22%, 100%, 100%, and 66%. The inclusion of abnormal 18F-FDG cardiac uptake as a major criterion at admission enabled a recategorization of 76% (47/62) of PVE/AAPI cases initially classified as "possible" to "definite" IE. In the histopathological analysis, a predominance of polymorphonuclear cell inflammatory infiltrate and a reduced extent of fibrosis were observed in the PVE group only. CONCLUSIONS: Use of 18F-FDG-PET/CT at the initial presentation of patients with suspected PVE increases the diagnostic capability of the modified Duke criteria. In patients who present with suspected NVE, the use of 18F-FDG-PET/CT is less accurate and could only be considered a complementary diagnostic tool for a specific population of patients with NVE.

Integrated Use of Conventional Chest Radiography Cannot Rule Out Acute Aortic Syndromes in Emergency Department Patients at Low Clinical Probability.

OBJECTIVES: Guidelines recommend chest radiography (CR) in the workup of suspected acute aortic syndromes (AASs) if the pretest clinical probability is low. However, the diagnostic impact of CR integration for the rule-in and rule-out of AASs is unknown. METHODS: We performed a secondary analysis of the ADvISED multicenter study. Emergency department outpatients were eligible if an AAS was clinically suspected. Clinical probability was defined with the aortic dissection detection risk score (ADD-RS). CR was evaluated blindly by a radiologist, who judged on mediastinum enlargement (ME) and other signs. RESULTS: In 2014 through 2016, a total of 1,129 patients were enrolled and 1,030 were analyzed, including 48 (4.7%) with AASs. ADD-RS/ME and ADD-RS/any CR sign (aCRs) integration were more accurate than ADD-RS alone (area under the curve = 0.8 and 0.78 vs. 0.66, p < 0.001). The sensitivity and specificity of the integrated strategies were 66.7% (95% confidence interval [CI] = 51.5% to 79.9%) and 82.5% (95% CI = 79.9% to 84.8%) for ADD-RS/ME and 68.8% (95% CI = 53.6% to 80.9%) and 76.5% (95% CI = 73.7% to 79.1%) for ADD-RS/aCRs, respectively. The sensitivity and specificity of CR per se were 54.2% (95% CI = 39.2% to 68.6%) and 92.4% (95% CI = 90.5% to 93.9%) for ME and 60.4% (95% CI = 45.3% to 74.2%) and 85.2% (95% CI = 82.9% to 87.4%) for aCRs. The agreement (κ) between attending physicians and radiologists for ME was 0.44 (95% CI = 0.35 to 0.54). ADD-RS/ME rule-in (ADD-RS ≤ 1 and ME-present, or ADD-RS > 1) applied to 204 versus 130 patients with ADD-RS > 1, including 14 with AAS and 60 false-positives (FP). ADD-RS/aCRs rule-in (ADD-RS ≤ 1 and aCRs-present, or ADD-RS > 1) applied to 264 patients, including 15 with AAS and 119 FP. ADD-RS/ME rule-out (ADD-RS ≤ 1 and ME-absent) applied to 826 (80.2%) patients, including 16 with AAS (33.3% of cases). ADD-RS/aCRs rule-out (ADD-RS ≤ 1 and aCRs-absent) applied to 766 patients (74.4%), including 15 with AAS (31.3% of cases). CONCLUSIONS: CR integration with clinical probability assessment showed modest rule-in efficiency and insufficient sensitivity for conclusive rule-out.

Mortality reduction with use of oral beta-blockers in patients with acute coronary syndrome.

OBJECTIVES:: Recent studies have revealed a relationship between beta-blocker use and worse prognosis in acute coronary syndrome, mainly due to a higher incidence of cardiogenic shock. However, the relevance of this relationship in the reperfusion era is unknown. The aim of this study was to analyze the outcomes of patients with acute coronary syndrome that started oral beta-blockers within the first 24 hours of hospital admission (group I) compared to patients who did not use oral beta-blockers in this timeframe (group II). METHODS:: This was an observational, retrospective and multicentric study with 2,553 patients (2,212 in group I and 341 in group II). Data regarding demographic characteristics, coronary treatment and medication use in the hospital were obtained. The primary endpoint was in-hospital all-cause mortality. The groups were compared by ANOVA and the chi-square test. Multivariate analysis was conducted by logistic regression and results were considered significant when p<0.05. RESULTS:: Significant differences were observed between the groups in the use of angiotensin-converting enzyme inhibitors, enoxaparin, and statins; creatinine levels; ejection fraction; tabagism; age; and previous coronary artery bypass graft. Significant differences were also observed between the groups in mortality (2.67% vs 9.09%, OR=0.35, p=0.02) and major adverse cardiovascular events (11% vs 29.5%, OR=4.55, p=0.02). CONCLUSIONS:: Patients with acute coronary syndrome who underwent early intervention with oral beta-blockers during the first 24 hours of hospital admission had a lower in-hospital death rate and experienced fewer major adverse cardiovascular events with no increase in cardiogenic shock or sustained ventricular arrhythmias compared to patients who did not receive oral beta-blockers within this timeframe.

Mortality reduction with use of oral beta-blockers in patients with acute coronary syndrome

OBJECTIVES: Recent studies have revealed a relationship between beta-blocker use and worse prognosis in acute coronary syndrome, mainly due to a higher incidence of cardiogenic shock. However, the relevance of this relationship in the reperfusion era is unknown. The aim of this study was to analyze the outcomes of patients with acute coronary syndrome that started oral beta-blockers within the first 24 hours of hospital admission (group I) compared to patients who did not use oral beta-blockers in this timeframe (group II). METHODS: This was an observational, retrospective and multicentric study with 2,553 patients (2,212 in group I and 341 in group II). Data regarding demographic characteristics, coronary treatment and medication use in the hospital were obtained. The primary endpoint was in-hospital all-cause mortality. The groups were compared by ANOVA and the chi-square test. Multivariate analysis was conducted by logistic regression and results were considered significant when p<0.05. RESULTS: Significant differences were observed between the groups in the use of angiotensin-converting enzyme inhibitors, enoxaparin, and statins; creatinine levels; ejection fraction; tabagism; age; and previous coronary artery bypass graft. Significant differences were also observed between the groups in mortality (2.67% vs 9.09%, OR=0.35, p=0.02) and major adverse cardiovascular events (11% vs 29.5%, OR=4.55, p=0.02). CONCLUSIONS: Patients with acute coronary syndrome who underwent early intervention with oral beta-blockers during the first 24 hours of hospital admission had a lower in-hospital death rate and experienced fewer major adverse cardiovascular events with no increase in cardiogenic shock or sustained ventricular arrhythmias compared to patients who did not receive oral beta-blockers within this timeframe.

Clinical characteristics and in-hospital outcome of patients with acute coronary syndromes and systemic lupus erythematosus.

OBJECTIVE: Due to the chronic inflammation associated with systemic lupus erythematosus (SLE), patients develop premature atherosclerosis and the disease is a risk factor for acute myocardial infarction. The best interventional treatment for acute coronary syndrome (ACS) in these patients is unclear. The objective of this study is to describe the baseline characteristics, clinical manifestations, treatment and in-hospital outcome of patients with SLE and ACS. METHODS: Eleven SLE patients with ACS were analyzed retrospectively between 2004 and 2011. The following data were obtained: age, gender, clinical and electrocardiographic characteristics, Killip class, risk factors for ACS, myocardial necrosis markers (CK-MB and troponin), creatinine clearance, left ventricular ejection fraction, inflammatory markers (C-reactive protein and erythrocyte sedimentation rate), drugs used during hospital stay, treatment (medical, percutaneous or surgical) and in-hospital outcome. The statistical analysis is presented in percentages and absolute values. RESULTS: Ten of the patients (91%) were women. The median age was 47 years. Typical precordial pain was present in 91%. Around 73% had positive erythrocyte sedimentation rate. The vessel most often affected was the anterior descending artery, in 73%. One patient underwent coronary artery bypass grafting, seven underwent percutaneous coronary intervention with bare-metal stents and three were treated medically. In-hospital mortality was 18%. CONCLUSIONS: Despite the small number of patients, our findings were similar to those in the literature, showing coronary artery disease in young people with SLE due to premature atherosclerosis and a high mortality rate.

Effect of beta-blockers on the risk of atrial fibrillation in patients with acute myocardial infarction.

INTRODUCTION: Oral beta-blockers improve the prognosis of patients with acute myocardial infarction, while atrial fibrillation worsens the prognosis of this population. The reduction of atrial fibrillation incidence in patients treated with beta-blockers could at least in part explain the benefits of this drug. OBJECTIVE: To investigate the effect of beta-blockers on the incidence of atrial fibrillation in patients with acute myocardial infarction. METHODS: We analyzed 1401 patients with acute myocardial infarction and evaluated the occurrence or absence of atrial fibrillation, the use of oral beta-blockers and mortality during the first 24 hours. RESULTS: a) The use of beta-blockers was inversely correlated with the presence of atrial fibrillation (rho = 0.004; OR = 0.54). b) Correlations with mortality were as follows: 31.5% in patients with atrial fibrillation, 9.2% in those without atrial fibrillation (rho < 0.001; Odds Ratio = 4.52), and 17.5% in patients not treated with beta-blockers and 6.7% in those who received the drug (rho < 0.001; OR = 0.34). c) Adjusted Models: The presence of atrial fibrillation was independently correlated with mortality (OR = 2.48, rho = 0.002). The use of beta-blockers was inversely and independently correlated with mortality (OR = 0.53; rho = 0.002). The patients who used beta-blockers showed a lower risk of atrial fibrillation (OR = 0.59; rho = 0.029) in the adjusted model. CONCLUSION: The presence of atrial fibrillation and the absence of oral beta-blockers increased in-hospital mortality in patients with acute myocardial infarction. Oral beta-blockers reduced the incidence of atrial fibrillation, which might be at least partially responsible for the drug's benefit.

Semiquantitative assessment of surgical lung biopsy: predictive value and impact on survival of patients with diffuse pulmonary infiltrate.

PURPOSE: Surgical lung biopsy has been studied in distinct populations, mostly going beyond clinical issues to impinge upon routine histopathological diagnostic information in diffuse infiltrates; however, detailed tissue analyses have rarely been performed. The present study was designed to investigate the prognostic contribution provided by detailed tissue analysis in diffuse infiltrates. METHODS: Medical records and surgical lung biopsies from the period of 1982 to 2003 of 63 patients older than 18 years with diffuse infiltrates were retrospectively examined. Lung parenchyma was histologically divided into 4 anatomical compartments: interstitium, airways, vessels, and alveolar spaces. Histological changes throughout these anatomical compartments were then evaluated according to their acute or chronic evolutional character. A semiquantitative scoring system was applied to histologic findings to evaluate the intensity and extent of the pathological process. We applied logistic regression to predict the risk of death associated with acute and chronic histological changes and to estimate the odds ratios for each of the independent variables in the model. RESULTS: Impact on survival was found for male gender (P = 0.03), presence of diffuse alveolar damage (P = 0.001), and chronic histological changes (P = 0.0004) on biopsy. Thus, being male was associated with a slightly lower risk (O.R. = 0.18; P=0.03) of dying than being female. Death risk was increased 17 times in the presence of acute histological changes such as diffuse alveolar damage and 2.5 times in the presence of chronic histological changes. CONCLUSION: Detailed analysis of histological specimens can provide more than a nosological diagnosis: this approach can provide valuable information concerning prognosis.

Listeria monocytogenes peritonitis in cirrhotic patients: first description in Brazil.

Two cases of spontaneous bacterial peritonitis (SBP) caused by Listeria monocytogenes in cirrhotic patients are reported. In one of the cases, the microorganism was isolated from pleural effusion and ascites. SBP is a serious and common complication of patients with ascites caused by hepatic cirrhosis and the culture of the ascitic fluid is an important tool for the diagnosis and for the more appropriate treatment. Although a third generation cephalosporin has usually been employed for empiric treatment of SBP, it does not provide adequate coverage against Listeria spp. In such cases the use of ampicillin (with or without sulbactam) or sulfamethoxazole-trimethoprim is recommended. The last one is used for secondary prophylaxis, instead of norfloxacin. To summarize, Listeria monocytogenes infection is a rare cause of SBP, whose treatment should be specific for the bacteria.

Coronary artery disease in women: a review on prevention, pathophysiology, diagnosis, and treatment.

Despite numerous studies on women's cardiac health throughout the past decade, the number of female deaths caused by cardiovascular disease still rises and remains the leading cause of death in women in most areas of the world. Novel studies have demonstrated that cardiovascular disease, and more specifically coronary artery disease presentations in women, are different than those in men. In addition, pathology and pathophysiology of the disease present significant gender differences, which leads to difficulties concerning diagnosis, treatment and outcome of the female population. The reason for this disparity is all steps for female cardiovascular disease evaluation, treatment and prevention are not well elucidated; and an area for future research. This review brings together the most recent studies published in the field of coronary artery disease in women and points out new directions for future investigation on some of the important issues.