ANMCO/SIMEU consensus document on the use of reversal agents for antithrombotic therapies in patients with ongoing bleeding or at high risk of haemorrhagic events.

In recent decades, an incredible evolution in antithrombotic therapies used for treating patients with atherosclerosis, atrial fibrillation, and venous thromboembolism has been observed, leading to the availability of increasingly safe drugs. Nonetheless, bleeding complications remain a significant concern, with considerable health, social, and economic implications. To improve the acute management of patients experiencing or at risk for major bleeding events, specific reversal agents for antithrombotic drugs have been recently developed. While these agents demonstrate effectiveness in small-scale pharmacodynamic studies and clinical trials, it is imperative to balance the benefits of reversing antiplatelet or anticoagulant therapy against the risk of prothrombotic effects. These risks include the potential loss of antithrombotic protection and the prothrombotic tendencies associated with bleeding, major surgery, or trauma. This joint document of the Italian Association of Hospital Cardiologists (Associazione Nazionale Medici Cardiologi Ospedalieri) and the Italian Society of Emergency Medicine (Società Italiana di Medicina d'Emergenza-Urgenza) delineates the key features and efficacy of available reversal agents. It also provides practical flowcharts to guide their use in patients with active bleeding or those at elevated risk of major bleeding events.

ANMCO-SIMEU consensus document: appropriate management of atrial fibrillation in the emergency department.

Atrial fibrillation (AF) accounts for 2% of the total presentations to the emergency department (ED) and represents the most frequent arrhythmic cause for hospitalization. It steadily increases the risk of thromboembolic events and is often associated with several comorbidities that negatively affect patient's quality of life and prognosis. AF has a considerable impact on healthcare resources, making the promotion of an adequate and coordinated management of this arrhythmia necessary in order to avoid clinical complications and to implement the adoption of appropriate technological and pharmacological treatment options. AF management varies across regions and hospitals and there is also heterogeneity in the use of anticoagulation and electric cardioversion, with limited use of direct oral anticoagulants. The ED represents the first access point for early management of patients with AF. The appropriate management of this arrhythmia in the acute setting has a great impact on improving patient's quality of life and outcomes as well as on rationalization of the financial resources related to the clinical course of AF. Therefore, physicians should provide a well-structured clinical and diagnostic pathway for patients with AF who are admitted to the ED. This should be based on a tight and propositional collaboration among several specialists, i.e. the ED physician, cardiologist, internal medicine physician, anesthesiologist. The aim of this ANMCO-SIMEU consensus document is to provide shared recommendations for promoting an integrated, accurate, and up-to-date management of patients with AF admitted to the ED or Cardiology Department, in order to make it homogeneous across the national territory.

Right ventricle assessment in patients with pulmonary embolism at low risk for death based on clinical models: an individual patient data meta-analysis.

AIMS: Patients with acute pulmonary embolism (PE) at low risk for short-term death are candidates for home treatment or short-hospital stay. We aimed at determining whether the assessment of right ventricle dysfunction (RVD) or elevated troponin improves identification of low-risk patients over clinical models alone. METHODS AND RESULTS: Individual patient data meta-analysis of studies assessing the relationship between RVD or elevated troponin and short-term mortality in patients with acute PE at low risk for death based on clinical models (Pulmonary Embolism Severity Index, simplified Pulmonary Embolism Severity Index or Hestia). The primary study outcome was short-term death defined as death occurring in hospital or within 30 days. Individual data of 5010 low-risk patients from 18 studies were pooled. Short-term mortality was 0.7% [95% confidence interval (CI) 0.4-1.3]. RVD at echocardiography, computed tomography or B-type natriuretic peptide (BNP)/N-terminal pro BNP (NT-proBNP) was associated with increased risk for short-term death (1.5 vs. 0.3%; OR 4.81, 95% CI 1.98-11.68), death within 3 months (1.6 vs. 0.4%; OR 4.03, 95% CI 2.01-8.08), and PE-related death (1.1 vs. 0.04%; OR 22.9, 95% CI 2.89-181). Elevated troponin was associated with short-term death (OR 2.78, 95% CI 1.06-7.26) and death within 3 months (OR 3.68, 95% CI 1.75-7.74). CONCLUSION: RVD assessed by echocardiography, computed tomography, or elevated BNP/NT-proBNP levels and increased troponin are associated with short-term death in patients with acute PE at low risk based on clinical models. RVD assessment, mainly by BNP/NT-proBNP or echocardiography, should be considered to improve identification of low-risk patients that may be candidates for outpatient management or short hospital stay.

Prognostic value of CT pulmonary angiography parameters in acute pulmonary embolism.

OBJECTIVES: Computed tomographic pulmonary angiography (CTPA) is the first-line test in acute pulmonary embolism (APE) diagnostic algorithm, but its correlation with short-term outcome remains not clear at all. The aim is to determine whether CTPA findings can predict 30-day mortality of patients with APE in Emergency Department. METHODS: This retrospective monocentric study involved 780 patients with APE diagnosed at the Emergency Department of our institution (period 2010-2019). These CTPA findings were evaluated: embolic obstruction burden score (Qanadli score), common pulmonary artery trunk diameter, right-to-left ventricular ratio, azygos vein and coronary sinus diameters. Comorbidities and fatal/nonfatal adverse outcomes within 30 days were recorded. Troponin I values were correlated with angiographic parameters with multiple logistic regression analysis. RESULTS: The all-cause and APE-related 30-day mortality rates were 5.9% and 3.6%, respectively. Patients who died within 30 days were older with higher prevalence rates of malignancy. Qanadli score and all CTPA parameters correlate with Troponin I level and the presence of RVD at echocardiography (p values < 0.0001). Instead, RV/LV ratio and coronary sinus diameter correlate with 30-day mortality (p values < 0.05). At the multivariate logistic regression analysis, only coronary sinus and RVD remained significant with an HR = 2.5 (95% CI 1.1-5.6) and HR = 1.9 (95% CI 0.95-3.7), respectively. CONCLUSION: CTPA quantification of right ventricular strain is an accurate predictor of 30-day mortality. In particular, it seems that a dilated coronary sinus (>9 mm) has an additional prognostic value in association with echocardiographic signs of right-heart disfunction and high Troponin I levels.

Integration of transthoracic focused cardiac ultrasound in the diagnostic algorithm for suspected acute aortic syndromes.

AIMS: The diagnosis of acute aortic syndromes (AASs) is challenging and requires integrated strategies. Transthoracic focused cardiac ultrasound (FoCUS) is endorsed by guidelines as a first-line/triage tool allowing rapid bedside assessment of the aorta. However, the performance of FoCUS in the European Society of Cardiology-recommended workup of AASs awaits validation. METHODS AND RESULTS: This was a prespecified subanalysis of the ADvISED multicentre prospective study. Patients with suspected AAS underwent FoCUS for detection of direct/indirect signs of AAS. Clinical probability assessment was performed with the aortic dissection detection risk score (ADD-RS). Case adjudication was based on advanced imaging, surgery, autopsy, or 14-day follow-up. An AAS was diagnosed in 146 (17.4%) of 839 patients. Presence of direct FoCUS signs had a sensitivity and specificity of 45.2% [95% confidence interval (CI) 37-53.6%] and 97.4% (95% CI 95.9-98.4%), while presence of any FoCUS sign had a sensitivity and specificity of 89% (95% CI 82.8-93.6%) and 74.5% (95% CI 71-77.7%) for AAS. The additive value of FoCUS was most evident within low clinical probability (ADD-RS ≤1). Herein, direct FoCUS signs were identified in 40 (4.8%) patients (P < 0.001), including 29 with AAS. ADD-RS ≤1 plus negative FoCUS for AAS rule-out had a sensitivity of 93.8% (95% CI 88.6-97.1%) and a failure rate of 1.9% (95% CI 0.9-3.6%). Addition of negative D-dimer led to a failure rate of 0% (95% CI 0-1.2%). CONCLUSION: FoCUS has additive value in the workup of AASs. Direct FoCUS signs can rapidly identify patients requiring advanced imaging despite low clinical probability. In integrated bundles, negative FoCUS is useful for rule-out of AASs.

Diagnostic Accuracy of the Aortic Dissection Detection Risk Score Plus D-Dimer for Acute Aortic Syndromes: The ADvISED Prospective Multicenter Study.

BACKGROUND: Acute aortic syndromes (AASs) are rare and severe cardiovascular emergencies with unspecific symptoms. For AASs, both misdiagnosis and overtesting are key concerns, and standardized diagnostic strategies may help physicians to balance these risks. D-dimer (DD) is highly sensitive for AAS but is inadequate as a stand-alone test. Integration of pretest probability assessment with DD testing is feasible, but the safety and efficiency of such a diagnostic strategy are currently unknown. METHODS: In a multicenter prospective observational study involving 6 hospitals in 4 countries from 2014 to 2016, consecutive outpatients were eligible if they had ≥1 of the following: chest/abdominal/back pain, syncope, perfusion deficit, and if AAS was in the differential diagnosis. The tool for pretest probability assessment was the aortic dissection detection risk score (ADD-RS, 0-3) per current guidelines. DD was considered negative (DD-) if <500 ng/mL. Final case adjudication was based on conclusive diagnostic imaging, autopsy, surgery, or 14-day follow-up. Outcomes were the failure rate and efficiency of a diagnostic strategy for ruling out AAS in patients with ADD-RS=0/DD- or ADD-RS ≤1/DD-. RESULTS: A total of 1850 patients were analyzed. Of these, 438 patients (24%) had ADD-RS=0, 1071 patients (58%) had ADD-RS=1, and 341 patients (18%) had ADD-RS >1. Two hundred forty-one patients (13%) had AAS: 125 had type A aortic dissection, 53 had type B aortic dissection, 35 had intramural aortic hematoma, 18 had aortic rupture, and 10 had penetrating aortic ulcer. A positive DD test result had an overall sensitivity of 96.7% (95% confidence interval [CI], 93.6-98.6) and a specificity of 64% (95% CI, 61.6-66.4) for the diagnosis of AAS; 8 patients with AAS had DD-. In 294 patients with ADD-RS=0/DD-, 1 case of AAS was observed. This yielded a failure rate of 0.3% (95% CI, 0.1-1.9) and an efficiency of 15.9% (95% CI, 14.3-17.6) for the ADD-RS=0/DD- strategy. In 924 patients with ADD-RS ≤1/DD-, 3 cases of AAS were observed. This yielded a failure rate of 0.3% (95% CI, 0.1-1) and an efficiency of 49.9% (95% CI, 47.7-52.2) for the ADD-RS ≤1/DD- strategy. CONCLUSIONS: Integration of ADD-RS (either ADD-RS=0 or ADD-RS ≤1) with DD may be considered to standardize diagnostic rule out of AAS. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02086136.

Acute pulmonary embolism: mortality prediction by the 2014 European Society of Cardiology risk stratification model.

The European Society of Cardiology (ESC) has proposed an updated risk stratification model for death in patients with acute pulmonary embolism based on clinical scores (Pulmonary Embolism Severity Index (PESI) or simplified PESI (sPESI)), right ventricle dysfunction (RVD) and elevated serum troponin (2014 ESC model).We assessed the ability of the 2014 ESC model to predict 30-day death after acute pulmonary embolism. Consecutive patients with symptomatic, confirmed pulmonary embolism included in prospective cohorts were merged in a collaborative database. Patients' risk was classified as high (shock or hypotension), intermediate-high (RVD and elevated troponin), intermediate-low (RVD or increased troponin or none) and low (sPESI 0). Study outcomes were death and pulmonary embolism-related death at 30 days.Among 906 patients (mean±sd age 68±16, 489 females), death and pulmonary embolism-related death occurred in 7.2% and 4.1%, respectively. Death rate was 22% in "high-risk" (95% CI 14.0-29.8), 7.7% in "intermediate-high-risk" (95% CI 4.5-10.9) and 6.0% in "intermediate-low-risk" patients (95% CI 3.4-8.6). One of the 196 "low-risk" patients died (0.5%, 95% CI 0-1.0; negative predictive value 99.5%).By using the 2014 ESC model, RVD or troponin tests would be avoided in about 20% of patients (sPESI 0), preserving a high negative predictive value. Risk stratification in patients at intermediate risk requires further improvement.

Assessment of a structured management pathway for patients referred to the Emergency Department for syncope: results in a tertiary hospital.

AIMS: High hospitalization rates (39-58% in the literature) of patients admitted to Emergency Department (ED) for transient loss of consciousness (T-LOC) suspected for syncope are still an unresolved issue. The presence of an Observation Unit has reduced hospital admissions and the duration of hospitalization in controlled studies, and a Syncope Unit (SU) in the hospital may reduce hospitalization and increase the number of diagnoses in patients with T-LOC. We assessed the effect of a structured organization on hospitalization rate and outcome. METHODS AND RESULTS: Consecutive patients referred to the ED for a T-LOC of a suspected syncopal nature as the main diagnosis were included. The ED physician was trained to choose between: hospital admission (directly or after short observation); discharge after short (<48-h) observation; discharge on a fast track to the SU; and direct discharge without any further diagnostics. From January to June 2010, 362 patients were evaluated in the ED: 29% were admitted, 20% underwent short observation in the ED, 20% were referred to the SU, and 31% were directly discharged. Follow-up data were available on 295 patients who were discharged alive: of these, 1 (0.3%) previously hospitalized patient died within 30 days and 16 (5.4%) died within 1 year. Death rates were 12.9, 3.3, 0, and 2.5% among admitted, observation, SU, and ED-discharged patients, respectively. No death could be directly attributed to T-LOC. Re-admission within 1 year for any cause occurred in 72 (24%) patients; re-admission rates were 45.9, 19.3, 11.5, and 18.0% among admitted, observation, SU, and ED-discharged patients, respectively. CONCLUSIONS: The availability of short observation and a SU seems to reduce the hospitalization rate compared with previous reported historical reports from our and other centres. Most deaths during follow-up occurred in patients who had been hospitalized. High rates of re-admission to the ED within 1 year are still an issue.

Short-term clinical outcome of normotensive patients with acute PE and high plasma lactate.

BACKGROUND: Strategies for identifying normotensive patients with acute symptomatic PE at high risk of PE-related complications remain to be defined. METHODS: This prospective cohort study aimed to determine the role of plasma lactate levels in the risk assessment of normotensive patients with acute PE. Outcomes assessed over the 7 days after the diagnosis of PE included PE-related mortality and haemodynamic collapse, defined as need for cardiopulmonary resuscitation, systolic blood pressure <90 mm Hg for at least 15 min, need for catecholamine administration, or need for mechanical ventilation. RESULTS: Between December 2012 and January 2014, the study enrolled 496 normotensive outpatients with acute symptomatic PE. PE-related complications occurred in 20 (4.0%; 95% CI 2.5% to 6.2%) of the 496 patients. These patients had higher baseline lactate levels (median 2.66 mmol/L; IQR 1.56-5.96 mmol/L) than patients without complications (1.20 mmol/L; IQR 1.20-2.00 mmol/L) (p<0.001). Overall, 135 patients (27.2%) had plasma lactate ≥2 mmol/L. Fourteen (10.4%) of them had PE-related complications versus 6 of 361 patients with low lactate (negative predictive value 98.3%; p<0.001). Patients with elevated plasma lactate had an increased rate of PE-related complications (adjusted OR 5.3; 95% CI 1.9 to 14.4; p=0.001) compared with those with low lactate. The combination of elevated plasma lactate with markers of right ventricular dysfunction (by echocardiogram) and myocardial injury (by cardiac troponin) was a particularly useful prognostic indicator (positive predictive value 17.9%; 95% CI 6.1% to 36.9%). CONCLUSIONS: Plasma lactate represents a powerful predictor of short-term PE-related complications and may provide guidance for decision-making in PE care.

Accuracy of lung ultrasound for the diagnosis of consolidations when compared to chest computed tomography.

OBJECTIVES: Despite emerging evidences on the clinical usefulness of lung ultrasound (LUS), international guidelines still do not recommend the use of sonography for the diagnosis of pneumonia. Our study assesses the accuracy of LUS for the diagnosis of lung consolidations when compared to chest computed tomography (CT). METHODS: This was a prospective study on an emergency department population complaining of respiratory symptoms of unexplained origin. All patients who had a chest CT scan performed for clinical reasons were consecutively recruited. LUS was targeted to evaluate lung consolidations with the morphologic characteristics of pneumonia, and then compared to CT. RESULTS: We analyzed 285 patients. CT was positive for at least one consolidation in 87 patients. LUS was feasible in all patients and in 81 showed at least one consolidation, with a good inter-observer agreement (k = 0.83), sensitivity 82.8% (95% CI 73.2%-90%) and specificity 95.5% (95% CI 91.5%-97.9%). Sensitivity raised to 91.7% (95% CI 61.5%-98.6%) and specificity to 97.4% (95% CI 86.5%-99.6%) in patients complaining of pleuritic chest pain. In a subgroup of 190 patients who underwent also chest radiography (CXR), the sensitivity of LUS (81.4%, 95% CI 70.7%-89.7%) was significantly superior to CXR (64.3%, 95% CI 51.9%-75.4%) (P<.05), whereas specificity remained similar (94.2%, 95% CI 88.4%-97.6% vs. 90%, 95% CI 83.2%-94.7%). CONCLUSIONS: LUS represents a reliable diagnostic tool, alternative to CXR, for the bedside diagnosis of lung consolidations in patients with respiratory complains.

Identification of intermediate-risk patients with acute symptomatic pulmonary embolism.

The identification of normotensive patients with acute pulmonary embolism (PE) at high risk of adverse PE-related clinical events (i.e. intermediate-risk group) is a major challenge. We combined individual patient data from six studies involving 2874 normotensive patients with PE. We developed a prognostic model for intermediate-risk PE based on the clinical presentation and the assessment of right ventricular dysfunction and myocardial injury. We used a composite of PE-related death, haemodynamic collapse or recurrent PE within 30 days of follow-up as the main outcome measure. The primary outcome occurred in 198 (6.9%) patients. Predictors of complications included systolic blood pressure 90-100 mmHg (adjusted odds ratio (aOR) 2.45, 95% CI 1.50-3.99), heart rate ≥ 110 beats per min (aOR 1.87, 95% CI 1.31-2.69), elevated cardiac troponin (aOR 2.49, 95% CI 1.71-3.69) and right ventricular dysfunction (aOR 2.28, 95% CI 1.58-3.29). We used these variables to construct a multidimensional seven-point risk index; the odds ratio for complications per one-point increase in the score was 1.55 (95% CI 1.43-1.68; p<0.001). The model identified three stages (I, II and III) with 30-day PE-related complication rates of 4.2%, 10.8% and 29.2%, respectively. In conclusion, a simple grading system may assist clinicians in identifying intermediate-risk PE.

[ANMCO/SIMEU Consensus document on the use of reversal agents of antithrombotic therapies in patients with active bleeding or at high-risk of major bleeding events]. / Documento di consenso ANMCO/SIMEU sull'impiego degli agenti di reversione delle terapie antitrombotiche nei pazienti con sanguinamento in atto o ad alto rischio di eventi emorragici.

In recent decades, an incredible evolution in antithrombotic therapies for the treatment of patients suffering from atherosclerosis, atrial fibrillation and venous thromboembolism occurred, leading to the availability of increasingly safe drugs. However, bleeding complications associated with these drugs still have an important health, social and economic impact. Recently, with the aim of improving the acute management of patients with or at risk of major bleeding events, specific reversal agents of antithrombotic drugs have been developed. Although these agents have demonstrated their effectiveness in small pharmacodynamic studies or clinical trials, it is important to consider that the benefit of reversal of an antiplatelet or anticoagulant drug must always be counterbalanced by the possible prothrombotic effect caused by the removal of antithrombotic protection as well as by prothrombotic mechanisms related to bleeding, major surgery or trauma.In this ANMCO/SIMEU consensus document we summarize the main characteristics and efficacy studies of the currently available reversal agents and present practical flow-charts in which we suggest their possible use in patients with active bleeding or at high risk of major bleeding events.

Identification of hemodynamically stable patients with acute pulmonary embolism at high risk for death: external validation of different models.

BACKGROUND: The optimal strategy for identification of hemodynamically stable patients with acute pulmonary embolism (PE) at risk for death and clinical deterioration remains undefined. OBJECTIVES: We aimed to assess the performances of currently available models/scores for identifying hemodynamically stable patients with acute, symptomatic PE at risk of death and clinical deterioration. METHODS: This was a prospective multicenter cohort study including patients with acute PE (NCT03631810). Primary study outcome was in-hospital death within 30 days or clinical deterioration. Other outcomes were in-hospital death, death, and PE-related death, all at 30 days. We calculated positive and negative predictive values, c-statistics of European Society of Cardiology (ESC)-2014, ESC-2019, Pulmonary Embolism Thrombolysis (PEITHO), Bova, Thrombo-embolism lactate outcome study (TELOS), fatty acid binding protein, syncope and tachicardia (FAST), and National Early Warning Scale 2 (NEWS2) for the study outcomes. RESULTS: In 5036 hemodynamically stable patients with acute PE, positive predictive values for the evaluated models/scores were all below 10%, except for TELOS and NEWS2; negative predictive values were above 98% for all the models/scores, except for FAST and NEWS2. ESC-2014 and TELOS had good performances for in-hospital death or clinical deterioration (c-statistic of 0.700 and 0.722, respectively), in-hospital death (c-statistic of 0.713 and 0.723, respectively), and PE-related death (c-statistic of 0.712 and 0.777, respectively); PEITHO, Bova, and NEWS2 also had good performances for PE-related death (c-statistic of 0.738, 0.741, and 0.742, respectively). CONCLUSION: In hemodynamically stable patients with acute PE, the accuracy for identification of hemodynamically stable patients at risk for death and clinical deterioration varies across the available models/scores; TELOS seems to have the best performance. These data can inform management studies and clinical practice.

Diagnosis of acute aortic syndromes with ultrasound and d-dimer: the PROFUNDUS study.

BACKGROUND: In patients complaining common symptoms such as chest/abdominal/back pain or syncope, acute aortic syndromes (AAS) are rare underlying causes. AAS diagnosis requires urgent advanced aortic imaging (AAI), mostly computed tomography angiography. However, patient selection for AAI poses conflicting risks of misdiagnosis and overtesting. OBJECTIVES: We assessed the safety and efficiency of a diagnostic protocol integrating clinical data with point-of-care ultrasound (POCUS) and d-dimer (single/age-adjusted cutoff), to select patients for AAI. METHODS: This prospective study involved 12 Emergency Departments from 5 countries. POCUS findings were integrated with a guideline-compliant clinical score, to define the integrated pre-test probability (iPTP) of AAS. If iPTP was high, urgent AAI was requested. If iPTP was low and d-dimer was negative, AAS was ruled out. Patients were followed for 30 days, to adjudicate outcomes. RESULTS: Within 1979 enrolled patients, 176 (9 %) had an AAS. POCUS led to net reclassification improvement of 20 % (24 %/-4 % for events/non-events, P < 0.001) over clinical score alone. Median time to AAS diagnosis was 60 min if POCUS was positive vs 118 if negative (P = 0.042). Within 941 patients satisfying rule-out criteria, the 30-day incidence of AAS was 0 % (95 % CI, 0-0.41 %); without POCUS, 2 AAS were potentially missed. Protocol rule-out efficiency was 48 % (95 % CI, 46-50 %) and AAI was averted in 41 % of patients. Using age-adjusted d-dimer, rule-out efficiency was 54 % (difference 6 %, 95 % CI, 4-9 %, vs standard cutoff). CONCLUSIONS: The integrated algorithm allowed rapid triage of high-probability patients, while providing safe and efficient rule-out of AAS. Age-adjusted d-dimer maximized efficiency. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT04430400.

Prognostic value of plasma lactate levels among patients with acute pulmonary embolism: the thrombo-embolism lactate outcome study.

STUDY OBJECTIVE: We investigate the prognostic value of plasma lactate levels in patients with acute pulmonary embolism. METHODS: We studied adult patients with symptomatic, objectively confirmed pulmonary embolism presenting to a single emergency department. Plasma lactate and troponin I levels were tested at presentation. We considered lactate values greater than or equal to 2 mmol/L and troponin I values greater than or equal to 0.10 ng/mL to be abnormal. Right-sided ventricular dysfunction was assessed by echocardiography. Primary endpoint was all-cause death occurring on or before 30 days after presentation. Secondary endpoints were the composite of all-cause death and clinical deterioration (defined as progression to shock, mechanical ventilation, or cardiopulmonary resuscitation) and death caused by pulmonary embolism. We tested the association between lactate level greater than or equal to 2 mmol/L and the endpoints using Cox proportional hazards regression analysis. RESULTS: Of the 270 patients included in the study, the mean age was 73 years (SD 12.7 years) and 151 (55.9%) were women. Twelve patients (4.4%) showed shock or hypotension (shock or systolic arterial pressure <100 mm Hg) at presentation, 109 (40.4%) had right-sided ventricular dysfunction, 93 (34.4%) showed troponin I level greater than or equal to 0.10 ng/mL, and 81 (30%) showed lactate level greater than or equal to 2 mmol/L. Seventeen patients (6.3%) died, 12 (4.4%) because of pulmonary embolism, and 37 (13.7%) reached the composite endpoint. Patients with lactate level greater than or equal to 2 mmol/L showed higher mortality (17.3%; 95% confidence interval [CI] 11.9% to 20%) than patients with a lower level (1.6%; 95% CI 0.8% to 1.9%). Plasma lactate level was associated with all-cause death (hazard ratio 11.67; 95% CI 3.32 to 41.03) and the composite endpoint (hazard ratio 8.14; 95% CI 3.83 to 17.34) independent of shock or hypotension, right-sided ventricular dysfunction, or elevation of troponin I values. CONCLUSION: Patients with pulmonary embolism and elevated plasma lactate level are at high risk of death and adverse outcome, independent of shock or hypotension, or right-sided ventricular dysfunction or injury markers.

Unfavorable Outcome and Long-Term Sequelae in Cases with Severe COVID-19.

Emerging evidence shows that individuals with COVID-19 who survive the acute phase of illness may experience lingering symptoms in the following months. There is no clear indication as to whether these symptoms persist for a short time before resolving or if they persist for a long time. In this review, we will describe the symptoms that persist over time and possible predictors in the acute phase that indicate long-term persistence. Based on the literature available to date, fatigue/weakness, dyspnea, arthromyalgia, depression, anxiety, memory loss, slowing down, difficulty concentrating and insomnia are the most commonly reported persistent long-term symptoms. The extent and persistence of these in long-term follow-up is not clear as there are still no quality studies available. The evidence available today indicates that female subjects and those with a more severe initial disease are more likely to suffer permanent sequelae one year after the acute phase. To understand these complications, and to experiment with interventions and treatments for those at greater risk, we must first understand the physio-pathological mechanisms that sustain them.

Narrative Review: Low-Dose Ketamine for Pain Management.

Pain is the leading cause of medical consultations and occurs in 50-70% of emergency department visits. To date, several drugs have been used to manage pain. The clinical use of ketamine began in the 1960s and it immediately emerged as a manageable and safe drug for sedation and anesthesia. The analgesic properties of this drug were first reported shortly after its use; however, its psychomimetic effects have limited its use in emergency departments. Owing to the misuse and abuse of opioids in some countries worldwide, ketamine has become a versatile tool for sedation and analgesia. In this narrative review, ketamine's role as an analgesic is discussed, with both known and new applications in various contexts (acute, chronic, and neuropathic pain), along with its strengths and weaknesses, especially in terms of psychomimetic, cardiovascular, and hepatic effects. Moreover, new scientific evidence has been reviewed on the use of additional drugs with ketamine, such as magnesium infusion for improving analgesia and clonidine for treating psychomimetic symptoms. Finally, this narrative review was refined by the experience of the Pain Group of the Italian Society of Emergency Medicine (SIMEU) in treating acute and chronic pain with acute manifestations in Italian Emergency Departments.

[ANMCO-SIMEU Consensus document: Appropriate management of atrial fibrillation in the emergency department]. / Documento di consenso ANMCO-SIMEU: Gestione appropriata della fibrillazione atriale in Pronto Soccorso.

Atrial fibrillation (AF) accounts for 2% of the total presentations to the emergency department (ED) and represents the most frequent arrhythmic cause for hospitalization. It steadily increases the risk of thromboembolic events and is often associated with several comorbidities that negatively affect patient's quality of life and prognosis. AF has a considerable on healthcare resources, making the promotion of an adequate and coordinated management of this arrhythmia necessary in order to avoid clinical complications and to implement the adoption of appropriate technological and pharmacological treatment options. AF management varies across regions and hospitals and there is also heterogeneity in the use of anticoagulation and electric cardioversion, with limited use of direct oral anticoagulants. The ED represents the first access point for early management of patients with AF. The appropriate management of this arrhythmia in the acute setting has a great impact on improving patient's quality of life and outcomes as well as on rationalization of the financial resources related to the clinical course of AF. Therefore, physicians should provide a well-structured clinical and diagnostic pathway for patients with AF who are admitted to the ED. This should be based on a tight and propositional collaboration among several specialists, i.e. the ED physician, cardiologist, internal medicine physician, anesthesiologist. The aim of this ANMCO-SIMEU consensus document is to provide shared recommendations for promoting an integrated, accurate, and up-to-date management of patients with AF admitted to the ED or Cardiology Department, so as to make it homogeneous across the national territory.

Contemporary anticoagulant treatment strategies in patients with acute pulmonary embolism at different risk for death.

INTRODUCTION: Availability of new treatment strategies for patients with acute pulmonary embolism (PE) have changed clinical practice with potential influence in short-term patients' outcomes. We aimed at assessing contemporary anticoagulation strategies and mortality in patients with acute PE included in the prospective, non-interventional, multicentre, COntemporary management of PE study. MATERIALS AND METHODS: Anticoagulant treatment at admission, during hospital-stay, at discharge and at 30-day are described in the overall population and by clinical severity. RESULTS: Overall, 5158 patients received anticoagulant treatment (99%); during the hospital-stay, 2298 received completely parenteral, 926 completely oral and 1934 parenteral followed by oral anticoagulation (1670 DOACs, 264 VKAs). Comorbidities and PE severity influenced the choice of in-hospital anticoagulation. The use of completely parenteral and completely oral anticoagulation varied based on PE severity. In patients treated with thrombolysis, DOACs were used in 46.4% and 80.1% during the hospital stay and at discharge, respectively. Death at 30 days occurred in 34.6% of patients not receiving anticoagulant treatment and in 1.5, 1.3, 3.4 and 8.1% of patients receiving completely oral, sequential with DOACs, sequential with VKAs and completely parenteral regimens, respectively. Increased mortality in patients receiving completely parenteral anticoagulation persisted after adjustment for PE severity. Completely oral anticoagulation was effective and safe also in patients at intermediate-high risk of death. CONCLUSIONS: Contemporary anticoagulation for acute PE includes parenteral agents in over 90% of patients; DOACs are used in the large majority of PE patients at discharge and their early use seems effective and safe also in selected intermediate-risk patients. TRIAL REGISTRATION NUMBER: NCT03631810.