Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course.

Infection with severe acute respiratory syndrome coronavirus 2 associates with diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse coronavirus disease 2019 (COVID-19) outcomes. Here we discovered that antibodies against specific chemokines were omnipresent post-COVID-19, were associated with favorable disease outcome and negatively correlated with the development of long COVID at 1 yr post-infection. Chemokine antibodies were also present in HIV-1 infection and autoimmune disorders, but they targeted different chemokines compared with COVID-19. Monoclonal antibodies derived from COVID-19 convalescents that bound to the chemokine N-loop impaired cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising chemokine antibodies may modulate the inflammatory response and thus bear therapeutic potential.

Use of defibrotide in COVID-19 pneumonia: comparison of a phase II study and a matched real-world cohort control.

The coronavirus disease 2019 (COVID-19) pandemic led to an unprecedented burden on healthcare systems around the world and a severe global socioeconomic crisis, with more than 750 million confirmed cases and at least 7 million deaths reported by 31st December 2023. The DEFI-VID19 study (ClinicalTrials.gov NCT04335201), a phase II, single-arm, multicenter, open-label trial was designed in mid-2020 to assess the safety and efficacy of defibrotide in treating patients with COVID-19 pneumonia. Defibrotide was administered at a dose of 25 mg/kg/d intravenously, divided into four daily doses over a planned 14-day period for patients with COVID-19 pneumonia receiving non-invasive ventilation. The primary endpoint was Respiratory Failure Free Survival (RFFS); Overall Survival (OS), the number of post-recovery days, and adverse events were the secondary endpoints. For comparison, a contemporaneous control cohort receiving standard of care only was retrospectively selected by applying the eligibility criteria of the DEFI-VID19 trial. To adjust for the imbalance between the two cohorts in terms of baseline variable distributions, an outcome regression analysis was conducted. In adjusted analysis, patients receiving defibrotide reported a trend towards higher RFFS (HR=0.71[0.95CI: 0.34 to 1.29, P= .138]) and OS (HR=0.78[0.95CI: 0.33 to 1.53, P= .248]) and showed a significantly increased number of post-recovery days (difference in means: 3.61[ 0.95CI: 0.97 to 6.26, P= .0037]). Despite concomitant thromboprophylaxis with low molecular weight heparin, the safety profile of defibrotide proved to be favorable. Taken together, our findings suggest that defibrotide may represent a valuable addition to the COVID-19 therapeutic options.

Long-Term Outcomes in Severe Community-Acquired Pneumonia.

Community-acquired pneumonia (CAP) is globally one of the major causes of hospitalization and mortality. Severe CAP (sCAP) presents great challenges and need a comprehensive understanding of its long-term outcomes. Cardiovascular events and neurological impairment, due to persistent inflammation and hypoxemia, contribute to long-term outcomes in CAP, including mortality. Very few data are available in the specific population of sCAP. Multiple studies have reported variable 1-year mortality rates for patients with CAP up to 40.7%, with a clear influence by age, comorbidities, and disease severity. In terms of treatment, the potential protective role of macrolides in reducing mortality emphasizes the importance of appropriate empiric antibiotic therapy. This narrative review explores the growing interest in the literature focusing on the long-term implications of sCAP. Improved understanding of long-term outcomes in sCAP can facilitate targeted interventions and enhance posthospitalization care protocols.

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.

Genomewide Association Study of Severe Covid-19 with Respiratory Failure.

BACKGROUND: There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19. METHODS: We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case-control panels. RESULTS: We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10-8) in the meta-analysis of the two case-control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P = 1.15×10-10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P = 4.95×10-8, respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group-specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P = 1.48×10-4) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P = 1.06×10-5). CONCLUSIONS: We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.).

Prolonged higher dose methylprednisolone versus conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS).

BACKGROUND: Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking. METHODS: We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction (P aO2 /F IO2 ) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14. RESULTS: 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in P aO2 /F IO2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points. CONCLUSION: Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia.

Current Trends for Delirium Screening within the Emergency Department.

Delirium is an acute neurological disorder that involves attention and cognition. It is associated with a high risk of morbidity and mortality among older people (>65 years old). In the context of the Emergency Department (ED), it is frequently experienced by patients but often not recognized. Literature studies have identified some screening instruments for an initial evaluation of delirium. Most of these tools have not been validated yet in the context of emergencies, but, in other settings, they were very useful for assessing and maximizing the recognition of this condition among older patients. We conducted a review of the literature, including randomized control trials, clinical and observational studies, and research studies published in recent years, confirming that most of the screening tools for delirium used in the intensive care unit (ICU) or the geriatric department have not been tested in the ED, and the ideal timing and form of the delirium assessment process for older adults have not been defined yet. The aim of our review is to summarize the updated evidence about the screening tools for delirium in the context of the ED, due to the fact that overcrowding of the ED and the stressful condition of emergency situations (that contribute to the onset of delirium) could expose older patients to a high risk of complications and mortality if delirium is not promptly recognized. In conclusion, we support the evidence that delirium is a current and real condition that emergency physicians have to face daily, and we are aware that more research is needed to explore this field in order to improve the overall outcomes of older patients admitted to the ED.

Five Level Triage vs. Four Level Triage in a Quaternary Emergency Department: National Analysis on Waiting Time, Validity, and Crowding-The CREONTE (Crowding and RE-Organization National TriagE) Study Group.

Background and Objectives: Triage systems help provide the right care at the right time for patients presenting to emergency departments (EDs). Triage systems are generally used to subdivide patients into three to five categories according to the system used, and their performance must be carefully monitored to ensure the best care for patients. Materials and Methods: We examined ED accesses in the context of 4-level (4LT) and 5-level triage systems (5LT), implemented from 1 January 2014 to 31 December 2020. This study assessed the effects of a 5LT on wait times and under-triage (UT) and over-triage (OT). We also examined how 5LT and 4LT systems reflected actual patient acuity by correlating triage codes with severity codes at discharge. Other outcomes included the impact of crowding indices and 5LT system function during the COVID-19 pandemic in the study populations. Results: We evaluated 423,257 ED presentations. Visits to the ED by more fragile and seriously ill individuals increased, with a progressive increase in crowding. The length of stay (LOS), exit block, boarding, and processing times increased, reflecting a net raise in throughput and output factors, with a consequent lengthening of wait times. The decreased UT trend was observed after implementing the 5LT system. Conversely, a slight rise in OT was reported, although this did not affect the medium-high-intensity care area. Conclusions: Introducing a 5LT improved ED performance and patient care.

The effect of COVID-19 epidemic on vital signs in hospitalized patients: a pre-post heat-map study from a large teaching hospital.

The Lombardy SARS-CoV-2 outbreak in February 2020 represented the beginning of COVID-19 epidemic in Italy. Hospitals were flooded by thousands of patients with bilateral pneumonia and severe respiratory, and vital sign derangements compared to the standard hospital population. We propose a new visual analysis technique using heat maps to describe the impact of COVID-19 epidemic on vital sign anomalies in hospitalized patients. We conducted an electronic health record study, including all confirmed COVID-19 patients hospitalized from February 21st, 2020 to April 21st, 2020 as cases, and all non-COVID-19 patients hospitalized in the same wards from January 1st, 2018 to December 31st, 2018. All data on temperature, peripheral oxygen saturation, respiratory rate, arterial blood pressure, and heart rate were retrieved. Derangement of vital signs was defined according to predefined thresholds. 470 COVID-19 patients and 9241 controls were included. Cases were older than controls, with a median age of 79 vs 76 years in non survivors (p = < 0.002). Gender was not associated with mortality. Overall mortality in COVID-19 hospitalized patients was 18%, ranging from 1.4% in patients below 65 years to about 30% in patients over 65 years. Heat maps analysis demonstrated that COVID-19 patients had an increased frequency in episodes of compromised respiratory rate, acute desaturation, and fever. COVID-19 epidemic profoundly affected the incidence of severe derangements in vital signs in a large academic hospital. We validated heat maps as a method to analyze the clinical stability of hospitalized patients. This method may help to improve resource allocation according to patient characteristics.

Lung Microbiome in Idiopathic Pulmonary Fibrosis and Other Interstitial Lung Diseases.

Interstitial lung diseases represent a heterogeneous and wide group of diseases in which factors leading to disease initiation and progression are not fully understood. Recent evidence suggests that the lung microbiome might influence the pathogenesis and progression of interstitial lung diseases. In recent years, the utilization of culture-independent methodologies has allowed the identification of complex and dynamic communities of microbes, in patients with interstitial lung diseases. However, the potential mechanisms by which these changes may drive disease pathogenesis and progression are largely unknown. The aim of this review is to discuss the role of the altered lung microbiome in several interstitial lung diseases. Untangling the host-microbiome interaction in the lung and airway of interstitial lung disease patients is a research priority. Thus, lung dysbiosis is a potentially treatable trait across several interstitial lung diseases, and its proper characterization and treatment might be crucial to change the natural history of these diseases and improve outcomes.

Environmental triggers for connective tissue disease: the case of COVID-19 associated with dermatomyositis-specific autoantibodies.

PURPOSE OF REVIEW: The aim of the present review is to analyze the link between autoimmune diseases and environmental factors, in particular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) as it shares numerous features with the interstitial lung disease associated with connective tissue diseases positive for rare autoantibodies directed at highly specific autoantigens (i.e., MDA5 and RIG1) among the intracellular sensors of SARS-CoV-2 in the innate response against viruses. RECENT FINDINGS: As shown in recent publications and in our original data, specific autoantibodies may be functionally relevant to COVID-19 infection. We evaluated sera from 35 hospitalized patients with COVID-19 to identify antinuclear antibodies and autoantibodies directed against specific antigenic targets, and we identified anti-nuclear antibodies (ANA) in 20/35 of patients with COVID-19 (57%), in patients with need for supplemental oxygen (90% vs. 20% in ANA-negative cases; P < 0.0001). In 7/35 COVID-19 sera, we detected anti-MJ/NXP2 (n = 3), anti-RIG1 (n = 2), anti-Scl-70/TOPO1 (n = 1), and anti-MDA5 (n = 1), overall associated with a significantly worse pulmonary involvement at lung computerized tomography scans. Eleven (31%) patients were positive for antibodies against the E2/E3 subunits of mitochondrial pyruvate dehydrogenase complex. SUMMARY: Viral infections such as COVID-19 are associated with ANA and autoantibodies directed toward antiviral signaling antigens in particular in patients with worse pulmonary involvement.

COVID-19 in Immunocompromised Patients: A Systematic Review.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was first identified as a novel coronavirus in Wuhan, Hubei province, central China, in December 2019, and is responsible for the 2019-to-present pandemic. According to the most recent data released by the World Health Organization, more than 200 million people have been infected by SARS-CoV-2 so far, and more than 4 million people died worldwide. Although our knowledge on SARS-CoV-2 and COVID-19 is constantly growing, data on COVID-19 in immunocompromised patients are still limited. The aim of the present systematic review is to describe clinical picture, disease severity, proposed treatment regimen, and response to vaccination in patients with different types and severity of immunosuppression.

Diagnosis and Initial Investigation of Bronchiectasis.

Bronchiectasis refers to both the name of a disease and a single radiological appearance that may, or may not, be associated with disease. As chronic respiratory disease, bronchiectasis is characterized by a variable range of signs and symptoms that may overlap with other chronic respiratory conditions. The proper identification of bronchiectasis as a disease in both primary and secondary care is of paramount importance. However, a standardized definition of radiologically and clinically significant bronchiectasis is still missing. Disease heterogeneity is a hallmark of bronchiectasis and applies not only to radiological features and clinical manifestations but also to other aspects of the disease, including the etiological and microbiological diagnosis as well as the evaluation of pulmonary function. Although the guidelines suggest a "minimum bundle" of tests, the diagnostic approach to bronchiectasis is challenging and may be driven by the "treatable traits" approach based on endotypes and biological characteristics. A broad spectrum of diagnostic tests could be used to investigate the etiology of bronchiectasis as well as other pulmonary, extrapulmonary, and environmental traits. Individualizing bronchiectasis workup according to the site of care (e.g., primary, secondary, and tertiary care) could help optimize patients' management and reduce healthcare costs.

Protease-Antiprotease Imbalance in Bronchiectasis.

Airway inflammation plays a central role in bronchiectasis. Protease-antiprotease balance is crucial in bronchiectasis pathophysiology and increased presence of unopposed proteases activity may contribute to bronchiectasis onset and progression. Proteases' over-reactivity and antiprotease deficiency may have a role in increasing inflammation in bronchiectasis airways and may lead to extracellular matrix degradation and tissue damage. Imbalances in serine proteases and matrix-metallo proteinases (MMPs) have been associated to bronchiectasis. Active neutrophil elastase has been associated with disease severity and poor long-term outcomes in this disease. Moreover, high levels of MMPs have been associated with radiological and disease severity. Finally, severe deficiency of α1-antitrypsin (AAT), as PiSZ and PiZZ (proteinase inhibitor SZ and ZZ) phenotype, have been associated with bronchiectasis development. Several treatments are under study to reduce protease activity in lungs. Molecules to inhibit neutrophil elastase activity have been developed in both oral or inhaled form, along with compounds inhibiting dipeptydil-peptidase 1, enzyme responsible for the activation of serine proteases. Finally, supplementation with AAT is in use for patients with severe deficiency. The identification of different targets of therapy within the protease-antiprotease balance contributes to a precision medicine approach in bronchiectasis and eventually interrupts and disrupts the vicious vortex which characterizes the disease.

COVID-19 Digestive System Involvement and Clinical Outcomes in a Large Academic Hospital in Milan, Italy.

Since February 2020, the COVID-19 pandemic has spread to Italy affecting more than 100,000 people. Several studies have reported a high prevalence of gastrointestinal (GI) symptoms, and investigated their potential association with clinical outcomes.1 The timing, clinical significance, and possible impact on viral spread of GI symptoms presentation have not been fully elucidated. Elevation of liver function tests and other laboratory values has also been reported; however, their prognostic significance has not been clearly established.2.

High mortality in COVID-19 patients with mild respiratory disease.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 189 000 people in Italy, with more than 25 000 deaths. Several predictive factors of mortality have been identified; however, none has been validated in patients presenting with mild disease. METHODS: Patients with a diagnosis of interstitial pneumonia caused by SARS-CoV-2, presenting with mild symptoms, and requiring hospitalization in a non-intensive care unit with known discharge status were prospectively collected and retrospectively analysed. Demographical, clinical and biochemical parameters were recorded, as need for non-invasive mechanical ventilation and admission in intensive care unit. Univariate and multivariate logistic regression analyses were used to identify independent predictors of death. RESULTS: Between 28 February and 10 April 2020, 229 consecutive patients were included in the study cohort; the majority were males with a mean age of 60 years. 54% of patients had at least one comorbidity, with hypertension being the most commonly represented, followed by diabetes mellitus. 196 patients were discharged after a mean of 9 days, while 14.4% died during hospitalization because of respiratory failure. Age higher than 75 years, low platelet count (<150 × 103 /mm3 ) and higher ferritin levels (>750 ng/mL) were independent predictors of death. Comorbidities were not independently associated with in-hospital mortality. CONCLUSIONS: In-hospital mortality of patients with COVID-19 presenting with mild symptoms is high and is associated with older age, platelet count and ferritin levels. Identifying early predictors of outcome can be useful in the clinical practice to better stratify and manage patients with COVID-19.

Effectiveness of Streptococcus Pneumoniae Urinary Antigen Testing in Decreasing Mortality of COVID-19 Co-Infected Patients: A Clinical Investigation.

BACKGROUND AND OBJECTIVES: Streptococcus pneumoniae urinary antigen (u-Ag) testing has recently gained attention in the early diagnosis of severe and critical acute respiratory syndrome coronavirus-2/pneumococcal co-infection. The aim of this study is to assess the effectiveness of Streptococcus pneumoniae u-Ag testing in coronavirus disease 2019 (COVID-19) patients, in order to assess whether pneumococcal co-infection is associated with different mortality rate and hospital stay in these patients. MATERIALS AND METHODS: Charts, protocols, mortality, and hospitalization data of a consecutive series of COVID-19 patients admitted to a tertiary hospital in northern Italy during COVID-19 outbreak were retrospectively reviewed. All patients underwent Streptococcus pneumoniae u-Ag testing to detect an underlying pneumococcal co-infection. Covid19+/u-Ag+ and Covid19+/u-Ag- patients were compared in terms of overall survival and length of hospital stay using chi-square test and survival analysis. RESULTS: Out of 575 patients with documented pneumonia, 13% screened positive for the u-Ag test. All u-Ag+ patients underwent treatment with Ceftriaxone and Azithromycin or Levofloxacin. Lopinavir/Ritonavir or Darunavir/Cobicistat were added in 44 patients, and hydroxychloroquine and low-molecular-weight heparin (LMWH) in 47 and 33 patients, respectively. All u-Ag+ patients were hospitalized. Mortality was 15.4% and 25.9% in u-Ag+ and u-Ag- patients, respectively (p = 0.09). Survival analysis showed a better prognosis, albeit not significant, in u-Ag+ patients. Median hospital stay did not differ among groups (10 vs. 9 days, p = 0.71). CONCLUSIONS: The routine use of Streptococcus pneumoniae u-Ag testing helped to better target antibiotic therapy with a final trend of reduction in mortality of u-Ag+ COVID-19 patients having a concomitant pneumococcal infection. Randomized trials on larger cohorts are necessary in order to draw definitive conclusion.

Transitory effusive-constrictive pericarditis.

Pericardial effusion of various sizes is a quite common clinical finding, while its progression to effusive-constrictive pericarditis occurs in about 1.4-14% of cases. Although available evidence on prevalence and prognosis of this rare pericardial syndrome is poor, apparently a considerable proportion of patients conservatively managed has a spontaneous resolution after several weeks. A 61-year-old female presented to our emergency department reporting fatigue, effort dyspnea and abdominal swelling. The echocardiography showed large pericardial effusion with initial hemodynamic impact, so she underwent a pericardiocentesis with drainage of 800-850cm3 of exudative fluid, on which diagnostic investigations were undertaken: possible viral and bacterial infections, medical conditions, iatrogenic causes, neoplastic and connective tissue diseases were all excluded. Despite empirical therapy with NSAIDs and colchicine, after about one week she had a recurrence of pericardial effusion and progressive development of constriction. Echocardiography performed after a few weeks of anti-inflammatory therapy showed resolution of constriction and PE, with clinical improvement. If progression of pericardial syndromes to a constrictive form is rarely described in literature, cases of transitory effusive-constrictive phase are even more uncommon, mainly reported during the evolution of pericardial effusion. According to the available data, risk of progression to a constrictive form is very low in case of idiopathic pericardial effusion. We report a case of large idiopathic subacute pericardial effusion, treated with pericardiocentesis and then evolved into an effusive-constrictive pericarditis. A prolonged anti-inflammatory treatment leads to complete resolution of pericardial syndrome without necessity of pericardiectomy.

A real life evaluation of non invasive ventilation in acute cardiogenic pulmonary edema: a multicenter, perspective, observational study for the ACPE SIMEU study group.

BACKGROUND: During the past three decades conflicting evidences have been published on the use of non-invasive ventilation (NIV) in patients with acute cardiogenic pulmonary edema (ACPE). The aim of this study is to describe the management of acute respiratory failure (ARF) due to ACPE in twelve Italian emergency departments (EDs). We evaluated prevalence, characteristics and outcomes of ACPE patients treated with oxygen therapy, continuous positive airway pressure (CPAP) or Bi-level positive airway pressure (BiPAP) on admission to the EDs. METHODS: In this multicenter, prospective, observational study, consecutive adult patients with ACPE were enrolled in 12 EDs in Italy from May 2009 to December 2013. Three study groups were identified according to the initial respiratory treatment: patients receiving oxygen therapy, those treated with CPAP and those treated with BiPAP. Treatment failure was evaluated as study outcome. RESULTS: We enrolled 1293 patients with acute cardiogenic pulmonary edema. 273 (21%) began with oxygen, 788 (61%) with CPAP and 232 (18%) with BiPAP. One out of four patient who began with oxygen was subsequently switched to NIV and initial treatment with oxygen therapy had an odds ratio for treatment failure of 3.65 (95% CI: 2.55-5.23, p < 0.001). CONCLUSIONS: NIV seems to be the first choice for treatment of ARF due to ACPE, showing high clinical effectiveness and representing a rescue option for patients not improving with conventional oxygen therapy.