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Hypertensive urgencies (HU) and hypertensive emergencies (HE) are challenges for the Emergency Department (ED). A prospective multicentre study is ongoing to characterize patients with acute hypertensive disorders, prevalence of subclinical hypertension-mediated organ damage (HMOD), short- and long-term prognosis; this is a preliminary report. Patients admitted to the ED with symptomatic blood pressure (BP) ≥180/110 mmHg were enrolled. They were managed by ED personnel according to their clinical presentations. Subsequently they underwent clinical evaluation and subclinical HMOD assessment at a Hypertension Centre within 72 h from enrolment. 122 patients were included in this report. Mean age was 60.7±13.9 years, 52.5% were females. 18 (14.8%) patients were diagnosed with HE, 108 (88.5%) with HU. There were no differences in gender, BMI, and cardiovascular comorbidities between groups. At ED discharge, 66.7% and 93.6% (p = 0.003) of HE and HU patients, respectively, had BP < 180/110 mmHg. After 72 h, 34.4% of patients resulted normotensive; 35.2%, 22.1%, and 8.2% had hypertension grade 1, 2, and 3, respectively. Patients with uncontrolled BP at office evaluation had higher vascular HMOD (49.1 vs. 25.9%, p = 0.045). Cardiac (60 vs. 34%, p = 0.049), renal (27.8 vs. 9.6%, p = 0.010) and cerebral (100 vs. 21%, p < 0.001) HMOD was more frequent in HE compared to HU group. HE showed greater cardiac, renal, and cerebral subclinical HMOD, compared to HU. 72-hours BP control is not associated with different HMOD, except for vascular HMOD; therefore, proper comprehensive examination after discharge from the ED could provide added value in cardiovascular risk stratification of such patients.

In a context of high demand for hospital services among older people, we aimed to assess the rate and determinants of inappropriate hospitalizations of older patients, and to what extent they were associated with inappropriate hospital stay. This prospective observational multicentre study evaluated a random sample of consecutive patients aged ≥ 70 years accessing the Emergency Department (ED) of two Italian tertiary hospitals. A standardized comprehensive geriatric assessment was carried out in each patient, including the Blaylock Risk Assessment Screen Scale (BRASS) for identification of patients at risk of difficult discharge. Inappropriate hospitalization was defined by the ED physician when patients did not necessitate hospital-provided procedures but was due to social reasons or lack of an alternative care-setting. Among 1877 patients (median age 80.7 years, 50.1% male), with a high prevalence of functional dependence and social isolation (around 30% and 25%, respectively), 767 (40.9%) were hospitalized. Incidence of inappropriate hospitalization was 14.6% (95% CI 12.1%-17.1%) and was associated with moderate-high risk of difficult discharge at BRASS (OR = 1.98, 95% CI 1.16-3.39, p = 0.013) and the presence of dementia with behavioural disorders (OR = 1.79, 95% CI 1.10-2.91, p = 0.020). Compared with patients appropriately admitted, inappropriate hospitalizations had shorter length of hospital stay but accounted for 1059/9154 days of stay (11.6%). Inappropriate hospitalizations occurred in less than 15% of cases, mainly accounted for by patients no longer manageable at home, but contributed to the greatest proportion of inappropriate hospital stay. These findings highlight the need of implementing appropriate home-care services and ensuring rapid access to suitable care-facilities for community-dwelling frail older patients.

The first wave (FW) of COVID-19 led to a rapid reduction in total emergency department (ED) visits and hospital admissions for other diseases. Whether this represented a transient “lockdown and fear” phenomenon, or a more persisting trend, is unknown. We divided acute from post-wave changes in ED flows, diagnoses, and hospital admissions, in an Italian city experiencing a FW peak followed by nadir. This multicenter, retrospective, cross-sectional study involved five general EDs of a large Italian city (January–August 2020). Percent changes were calculated versus 2019, using four 14-day periods (FW peak, early/mid/late post-wave). ED visits were 147,446 in 2020, versus 214,868 in 2019. During the FW peak, visits were reduced by 66.4% (P P P P = 0.001), 6.3% (P = 0.1) and 12.2% (P = 0.001), respectively. Reductions in ED flows, led by non-critical codes, persisted throughout the summer nadir of COVID-19. Hospital admissions for non-COVID-19 diseases had transient changes.

A subset of patients with coronavirus disease 2019 (COVID-19) and lung involvement pose a disposition challenge, particularly when hospital resources are constrained. Those not in respiratory failure are sent home, often with phone monitoring and/or respiratory rate and oxygen saturation monitoring. Hypoxemia may be a late presentation and is often preceded by abnormal lung findings on ultrasound. Early identification of pulmonary progression may preempt emergency hospitalization for respiratory decompensation and facilitate more timely admission. With the goal of safely isolating infected patients while providing advanced monitoring, we present a first report of patient self-performed lung ultrasound in the home with a hand-held device under the guidance of a physician using a novel teleguidance platform.

Sepsis and COVID-19 patients often manifest an imbalance in inflammation and coagulation, a complex pathological mechanism also named thromboinflammation, which strongly affects patient prognosis. Extracellular vesicles (EVs) are nanoparticles released by cells into extracellular space that have a relevant role in cell-to-cell communication. Recently, EVs have been shown to act as important players in a variety of pathologies, including cancer and cardiovascular disease. The biological properties of EVs in the mechanisms of thromboinflammation during sepsis and COVID-19 are still only partially known. Herein, we summarize the current experimental evidence on the role of EVs in thromboinflammation, both in bacterial sepsis and in COVID-19. A better understanding of EV involvement in these processes could be useful in describing novel diagnostic and therapeutic applications of EVs in these diseases.

Background: Lung Ultrasound Evaluation (LUS) is usefully applied in the Emergency Department (ED) to patients with suspected or confirmed COVID-19. Diaphragmatic Ultrasound (DUS) may provide additional insight into ventilatory function. This proof-of-concept study aimed to evaluate the feasibility of LUS and DUS in a third level ED during the COVID-19 pandemic. Methods: Adult patients presenting with COVID-19 symptoms were eligible. After the physical examination, both LUS and DUS (i.e., diaphragmatic motion and thickness) were performed. All patients were followed after 30 days to determine their need for ventilation, admission, and/or a new ED evaluation after discharge. The diagnostic accuracies of diaphragm measurements in assessing the risk of the 30-day outcome were calculated as well as the measurements’ usefulness. Bland–Altman plots were used for comparing bedside and off-line diaphragm measurements. Results: 118 patients were enrolled. Median thickness and motion were 1.7 mm (iqr 0.4) and 1.8 cm (iqr 0.7), respectively, with a mean difference of 0.009 mm (95% CI −0.037–0.056 mm) and −0.051 cm (95% CI −0.108–0.006 cm), respectively. The 30-day outcome was associated with an increase in thickness (OR 5.84, 95% CI 0.96–35.4), and a lower motion (OR 0.49, 95% CI 0.2–1.21). Conclusion: DUS seemed to be feasible and reliable in the ED in a population of patients presenting with symptoms related to COVID-19 infection.

Background Incessant pericarditis is defined as pericarditis with persistent symptoms without a symptom-free interval of 4 to 6 weeks despite therapy. On the contrary, recurrent pericarditis is characterized by recurring symptoms after a symptom-free interval of at least 4 to 6 weeks, allowing the completion of therapy. Aims The aim of this study is to assess the risk of complicated pericarditis and related hospitalizations according to the clinical pattern of incessant or recurrent pericarditis. Methods From January 2017 to December 2018, all consecutive patients admitted to AOU Città della Salute (Turin, IT) for pericarditis were included in a prospective cohort study with a clinical and echocardiographic follow-up at 1, 3, and 6 months, and then every 6 months. Results We included 147 patients (median age, 50.9 years [IQR, 28.5]; 49.7% women, 89% had idiopathic aetiology, 11% had pericarditis related to systemic inflammatory disease/postcardiac injury syndrome, 80% had pericardial effusion, and 62% had elevated C-reactive protein >5 mg/L). Patients were treated according to ESC guidelines. After a median follow-up of 14 months (IQR, 9 months), adverse events were recorded in 54/147 patients (36.7%): nonidiopathic/viral aetiology in 16 of 147 cases (10.9%), recurrent pericarditis/persistent symptoms in 53 of 147 cases (36.1%), cardiac tamponade in 4/147 cases (2.7%), persistent CP in 4/147 cases (2.7%), and hospitalization related to pericarditis in 38/147 cases (25.9%). An incessant course was reported in 18 of 147 cases (12%). The risk of complications was higher in patients with incessant pericarditis (Figure) – especially CP – compared to nonincessant course (22.2% versus 0%, respectively; P5 mg/L (hazard ratio, 5.55 [95% CI, 1.87–16.44]), and incessant course (HR, 17.10 [95% CI, 7.63–38.33]). Conclusions This study highlights that an incessant course of pericarditis is a possible new risk factor for complications and especially for developing constriction. In clinical practice, the detection of an incessant course, as well as imaging findings of constriction and pericardial thickening, should prompt more diagnostic testing, a close follow-up, and more aggressive therapy to prevent complications and persistent constriction. Funding Acknowledgement Type of funding sources: None. Figure 1

This prospective cohort enrolled all patients above 16 years of age presenting to the in the emergency department (ED) for a reported syncope was designed to test the accuracy of a point-of-care ultrasound (POCUS) integrated approach in risk stratification. The emergency physician responsible for the patient care was asked to classify the syncope risk after the initial clinical assessment and after performing POCUS evaluation. All risk group definitions were based on the 2018 European Society of Cardiology guidelines. Thirty days after the index event, all participants were followed up to assess the frequency of short-term serious outcomes as defined in the San Francisco Syncope Rule (SFSR) cohorts. We estimated the accuracy of clinical and POCUS-integrated evaluation in predicting SFSR outcomes. Between February 2016 and January 2018, 196 patients were enrolled [109 women (55.6%)]. Median age was 64 years (interquartile range 31 years). After a follow-up of 30 days, 19 patients experienced 20 SFSR outcomes. Positive and negative likelihood ratios were 1.73 (95% CI 0.87-3.44) and 0.84 (95% CI 0.62-1.12) for the clinical evaluation, and 5.93 (95% CI 2.83-12.5) and 0.63 (95% CI 0.45-0.9) for the POCUS-integrated evaluation. The POCUS-integrated approach would reduce the diagnostic error of the clinical evaluation by 4.5 cases/100 patients. This cohort study suggested that the integration of the clinical assessment with POCUS results in patients presenting to the ED for non-high-risk syncope may increase the accuracy of predicting the risk of SFSR outcomes and the usefulness of the clinical assessment alone.

Background: Antimicrobial de-escalation (ADE) is a part of antimicrobial stewardship strategies aiming to minimize unnecessary or inappropriate antibiotic exposure to decrease the rate of antimicrobial resistance. Information regarding the effectiveness and safety of ADE in the setting of emergency medicine wards (EMW) is lacking. Methods: Adult patients admitted to EMW and receiving empiric antimicrobial treatment were retrospectively studied. The primary outcome was the rate and timing of ADE. Secondary outcomes included factors associated with early ADE, length of stay, and in-hospital mortality. Results: A total of 336 patients were studied. An initial regimen combining two agents was prescribed in 54.8%. Ureidopenicillins and carbapenems were the most frequently empiric treatment prescribed (25.1% and 13.6%). The rate of the appropriateness of prescribing was 58.3%. De-escalation was performed in 111 (33%) patients. Patients received a successful de-escalation on day 2 (21%), 3 (23%), and 5 (56%). The overall in-hospital mortality was 21%, and it was significantly lower among the de-escalation group than the continuation group (16% vs 25% p = 0.003). In multivariate analysis, de-escalation strategies as well as appropriate empiric and targeted therapy were associated with reduced mortality. Conclusions: ADE appears safe and effective in the setting of EMWs despite that further research is warranted to confirm these findings.

Background Noninvasive ventilation (NIV) is indicated to treat respiratory acidosis due to exacerbation of chronic obstructive pulmonary disease (COPD). Recent nonrandomized studies also demonstrated some physiological effects of high-flow nasal therapy (HFNT) in COPD patients. We designed a prospective, unblinded, multicenter, randomized controlled trial to assess the noninferiority of HFNT compared to NIV with respect to the reduction of arterial partial pressure of carbon dioxide (PaCO2) in patients with hypercapnic acute respiratory failure with mild-to-moderate respiratory acidosis. Methods We will enroll adult patients with acute hypercapnic respiratory failure, as defined by arterial pH between 7.25 and 7.35 and PaCO2 ≥ 55 mmHg. Patients will be randomly assigned 1:1 to receive NIV or HFNT. NIV will be applied through a mask with a dedicated ventilator in pressure support mode. Positive end-expiratory pressure will be set at 3–5 cmH2O with inspiratory support to obtain a tidal volume between 6 and 8 ml/kg of ideal body weight. HFNT will be initially set at a temperature of 37 °C and a flow of 60 L/min. At 2 and 6 h we will assess arterial blood gases, vital parameters, respiratory rate, treatment intolerance and failure, need for endotracheal intubation, time spent under mechanical ventilation (both invasive and NIV), intensive care unit and hospital length of stay, and hospital mortality. Based on an α error of 5% and a β error of 80%, with a standard deviation for PaCO2 equal to 15 mmHg and a noninferiority limit of 10 mmHg, we computed a sample size of 56 patients. Considering potential drop-outs and nonparametric analysis, the final computed sample size was 80 patients (40 per group). Discussion HFNT is more comfortable than NIV in COPD patients recovering from an episode of exacerbation. If HFNT would not be inferior to NIV, HFNT could be considered as an alternative to NIV to treat COPD patients with mild-to-moderate respiratory acidosis. Trial registration ClinicalTrials.gov, NCT03370666. Registered on December 12, 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3514-1) contains supplementary material, which is available to authorized users.

Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in patients with type 1 diabetes mellitus (T1DM). Enhanced platelet reactivity is considered a main determinant of the increased atherothrombotic risk of diabetic patients. Thrombopoietin (THPO), a humoral growth factor able to stimulate megakaryocyte proliferation and differentiation, also modulates the response of mature platelets by enhancing both activation and binding to leukocytes in response to different agonists. Increased THPO levels have been reported in different clinical conditions characterized by a generalized pro-thrombotic state, from acute coronary syndromes to sepsis/septic shock, and associated with elevated indices of platelet activation. To investigate the potential contribution of elevated THPO levels in platelet activation in T1DM patients, we studied 28 T1DM patients and 28 healthy subjects. We measured plasma levels of THPO, as well as platelet-leukocyte binding, P-selectin, and THPO receptor (THPOR) platelet expression. The priming activity of plasma from diabetic patients or healthy subjects on platelet–leukocyte binding and the role of THPO on this effect was also studied in vitro. T1DM patients had higher circulating THPO levels and increased platelet–monocyte and platelet–granulocyte binding, as well as platelet P-selectin expression, compared to healthy subjects, whereas platelet expression of THPOR did not differ between the two groups. THPO concentrations correlated with platelet–leukocyte binding, as well as with fasting glucose and Hb1Ac. In vitro, plasma from diabetic patients, but not from healthy subjects, primed platelet–leukocyte binding and platelet P-selectin expression. Blocking THPO biological activity using a specific inhibitor prevented the priming effect induced by plasma from diabetic patients. In conclusion, augmented THPO may enhance platelet activation in patients with T1DM, potentially participating in increasing atherosclerotic risk.

The pleiotropic cytokine interleukin-6 (IL-6) has been implicated in the pathogenesis of COVID-19, but uncertainty remains about the potential benefits and harms of targeting IL-6 signalling in patients with the disease. The efficacy and safety of tocilizumab and sarilumab, which block the binding of IL-6 to its receptor, have been tested in adults with COVID-19-related acute respiratory illness in randomised trials, with important differences in trial design, characteristics of included patients, use of co-interventions, and outcome measurement scales. In this Series paper, we review the clinical and methodological heterogeneity of studies of IL-6 receptor antagonists, and consider how this heterogeneity might have influenced reported treatment effects. Timing from clinical presentation to treatment, severity of illness, and concomitant use of corticosteroids are among the factors that might have contributed to apparently inconsistent results. With an understanding of the sources of variability in these trials, available evidence could be applied to guide clinical decision making and to inform the enrichment of future studies.

Study objective Accurate diagnostic testing to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical. Although highly specific, SARS-CoV-2 reverse transcriptase–polymerase chain reaction (RT-PCR) has been shown in clinical practice to be affected by a noninsignificant proportion of false-negative results. This study seeks to explore whether the integration of lung ultrasonography with clinical evaluation is associated with increased sensitivity for the diagnosis of coronavirus disease 2019 pneumonia, and therefore may facilitate the identification of false-negative SARS-CoV-2 RT-PCR results. Methods This prospective cohort study enrolled consecutive adult patients with symptoms potentially related to SARS-CoV-2 infection who were admitted to the emergency department (ED) of an Italian academic hospital. Immediately after the initial assessment, a lung ultrasonographic evaluation was performed and the likelihood of SARS-CoV-2 infection, based on both clinical and lung ultrasonographic findings (“integrated” assessment), was recorded. RT-PCR SARS-CoV-2 detection was subsequently performed. Results We enrolled 228 patients; 107 (46.9%) had SARS-CoV-2 infection. Sensitivity and negative predictive value of the clinical–lung ultrasonographic integrated assessment were higher than first RT-PCR result (94.4% [95% confidence interval {CI} 88.2% to 97.9%] versus 80.4% [95% CI 71.6% to 87.4%] and 95% [95% CI 89.5% to 98.2%] versus 85.2% [95% CI 78.3% to 90.6%], respectively). Among the 142 patients who initially had negative RT-PCR results, 21 tested positive at a subsequent molecular test performed within 72 hours. All these false-negative cases were correctly identified by the integrated assessment. Conclusion This study suggests that, in patients presenting to the ED with symptoms commonly associated with SARS-CoV-2 infection, the integration of lung ultrasonography with clinical evaluation has high sensitivity and specificity for coronavirus disease 2019 pneumonia and it may help to identify false-negative results occurring with RT-PCR.

Primary thrombopoietic mediator thrombopoietin (THPO) is mainly produced by the liver, it may act as a growth factor for hepatic progenitors. Principal angiogenesis inducer vascular endothelial growth factor-A (VEGF-A) is critical for the complex vascular network within the liver architecture. As a cross-regulatory loop between THPO and VEGF-A has been demonstrated in the hematopoietic system, the two growth factors were hypothesized to cooperatively contribute to the progression from liver cirrhosis (LC) to hepatocellular carcinoma (HCC). The mRNA and protein expression levels of THPO, VEGF-A, and their receptors were examined, compared, and correlated in paired cancerous and LC tissues from 26 cirrhosis-related HCC patients, using qRT-PCR and immunohistochemistry. THPO and VEGF-A were alternatively silenced by small interfering RNA (siRNA) in human liver cancer cell lines Huh7 and HepG2. THPO and VEGF-A expressions significantly increased in tumor versus LC tissues. HCC and paired LC cells expressed similar levels of THPO receptor (R), whereas vascular endothelial growth factor receptor (VEGFR) -1 and VEGFR-2 levels were higher in HCC than in corresponding LC tissue samples. A significant linear correlation emerged between THPO and VEGF-A transcripts in HCC and, at the protein level, THPO and THPOR were significantly correlated with VEGF-A in tumor tissues. Both HCC and LC expressed similar levels of gene and protein hypoxia inducible factor (HIF)-1α. Positive cross-regulation occurred with the alternative administration of siRNAs targeting THPO and those targeting VEGF-A in hypoxic liver cancer cell lines. These results suggest THPO and VEGF-A might act as interdependently regulated autocrine and/or paracrine systems for cellular growth in HCC. This might be clinically interesting, since new classes of THPOR agonistic/antagonistic drugs may provide novel therapeutic options to correct the frequent hemostatic abnormality seen in HCC patients.

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.

Emergency department (ED) care for psychiatric patients is currently understudied despite being highly utilized. Therefore, we aimed to analyze psychiatric patients' length of stay (LOS) and LOS-related factors at the ED and to investigate and quantify the likelihood of being hospitalized after an emergency psychiatric evaluation. Charts of 408 individuals who sought help at the ED were retrospectively assessed to identify patients' sociodemographic and clinical data upon ED admission and discharge. All interventions performed at the ED (e.g., medications, hospitalization, clinical advice at discharge) were collected as well. The LOS for psychiatric patients was relatively short (6.5 h), and substance/alcohol intoxication was the main factor impacting LOS. Upon ED arrival, hospitalized patients were mostly men, most often had a yellow/severe triage code, and most often had a positive history of psychiatric illness, psychotic symptoms, euphoric mood, or suicidal ideation. Manic symptoms and suicidal ideation were the conditions most frequently leading to hospitalization. Given the paucity of real-world data on psychiatric patients’ LOS and outcomes in the ED context, our findings show that psychiatric patients are evaluated in a reasonable amount of time. Their hospitalization is mostly influenced by clinical conditions rather than predisposing (e.g., age) or system-related factors (e.g., mode of arrival).

Study objective: Early risk stratification of septic patients presenting to the emergency department (ED) is challenging. The aim of the study was to evaluate the prognostic role of plasmatic sodium level (PNa+) derangements at ED presentation in septic patients. Methods: According to PNa+ at ED presentation patients were divided in eunatremic (136–145 mEq/L), hypernatremic (>145 mEq/L) and hyponatremic (

Acute aortic syndromes (AASs) are difficult to diagnose emergencies. Plasma soluble ST2 (sST2), a prognostic biomarker for heart failure, has been proposed as a diagnostic biomarker of AASs outperforming D-dimer, the current diagnostic standard. We performed a prospective diagnostic accuracy study of sST2 for AASs in the Emergency Department (ED). In 2017–2018, patients were enrolled if they had ≥1 red-flag symptoms (chest/abdominal/back pain, syncope, perfusion deficit) and a clinical suspicion of AAS. sST2 was detected with the Presage® assay. Adjudication was based on computed tomography angiography (CTA) or on diagnostic outcome inclusive of 30-day follow-up. 297 patients were enrolled, including 88 with AASs. The median age was 67 years. In 162 patients with CTA, the median sST2 level was 41.7 ng/mL (IQR 29.4–103.2) in AASs and 34.6 ng/mL (IQR 21.4–51.5) in alternative diagnoses (P = 0.005). In ROC analysis, the AUC of sST2 was 0.63, as compared to 0.82 of D-dimer (P

Lung ultrasound (LUS) is a largely employed diagnostic tool but an operational protocol for implementation has never been proposed. The lack of standardization clearly introduces variability in LUS results. We enrolled adult patients presenting for acute dyspnea with a clinical suspect of etiology related to heart failure. We calculated agreement among four providers in assessing B-lines. We varied probes, depth, evaluation time and scanning areas and we estimated the importance of each factors on B-lines assessment. Overall agreement among raters varied from a kappa of 0.70 to 0.81. The mean number of B-lines was 5.44 (95% confidence interval, CI, 4.1–6.8). This estimate did not suffer variation by the depth used (0.03, 95% CI –0.2–0.2, more B-lines, using 19 cm versus 10 cm). The use of a convex probe and expertise in LUS reduced the number of artifacts by 1.7 (95% CI 1.5–1.9) and 1.1 in comparison with a phased array probe and naive operators. Evaluation time increased estimates by 1.2 (95% CI 1–1.5) and 2.9 (95% CI 2.7–3.9) B-lines for 4” and 7” clips (reference was 2” clips). This study suggests that the probe, the evaluation time and the level of expertise might affect the results of quantitative assessment of B-lines.

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 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.

OBJECTIVES In patients at low clinical probability of acute aortic syndromes (AASs), decision on advanced aortic imaging is cumbersome. Integration of the aortic dissection detection risk score (ADD-RS) with D-dimer (DD) provides a potential pipeline for standardized diagnostic rule-out. We systematically reviewed and summarized supporting data. METHODS Cross-sectional studies assessing integration of ADD-RS with DD for diagnosis of AASs were identified on MEDLINE, EMBASE and Web Of Science databases. Two reviewers independently screened articles, assessed quality, and extracted data. The quality of design and reporting was evaluated with the QUADAS-2 and STARD tools. Individual patient data were obtained, to allow analysis of both conventional (500 ng/mL) and age-adjusted (DDage-adj ) DD cutoffs. Data were summarized for four diagnostic strategies combining ADD-RS = 0 or ≤ 1, with DD

Background/Introduction Syncope is still a challenge for risk stratification in the Emergency Department (ED), and the indication to discharge is not well established for all patients. Purpose To evaluate diagnostic accuracy and clinical utility of integration of clinical assessment and point-of-care ultrasound (POCUS) in evaluating non high-risk syncopes in the ED. Methods This observational prospective cohort study enrolled patients between February 2016 and January 2019. All adult patients presenting in the ED for a non-high risk syncope were eligible (defined according to the 2015 ESC consensus on management of syncope in the ED). Subject for whom event etiology was identified right after the clinical assessment (i.e. history, physical exam, and EKG) or showing a clinical high risk for short term serious outcomes or refuse to participate in the study were excluded. After the initial clinical assessment, the physician responsible for patient care was asked to categorize the syncope as low or neither high nor low risk. Immediately after, the same physician performed POCUS, and a new risk assessment, based on the results of both clinical and sonographic findings, was recorded. Thirty days after the ED evaluation, all participants were telephonically followed up by the investigators in order to assess the risk of short-term outcomes as defined in the San Francisco Syncope Rule cohorts. Both diagnostic accuracy, defined as sensitivity (SE) and specificity (SPE), and clinical utility, evaluated as net reclassification index (NRI) and net benefit were evaluated for clinical and POCUS-integrated assessment. Results A total of 415 patients with a syncope were eligible. Of these, 194 were enrolled (107 women - 55.2%). Median age was 63 years (interquartile range, IQR, 30 years). During the follow up, 21 patients experienced 28 events. SE and SPE of the clinical evaluation were 33.3% (95% confidence interval, CI, 14.6–57%) and 79.5% (95% CI 72.7–85.3%), and they were 42.9% (95% CI 21.8–66%), and 92.4% (95% CI 87.4–95.9) for the POCUS-integrated evaluation (p NRI for events and non-events during follow up was 9.5% and 12.7%, respectively. Using the prevalence of events in our cohort (10.8%) as the threshold probability, the use of the POCUS-integrated approach would reduce the diagnostic error of the clinical evaluation by 4.6 cases/100 patients. The median time between clinical and POCUS-integrated evaluation was 15 minutes (iqr 20 minutes). Conclusion The results of our study suggest that the integration of the clinical evaluation with POCUS for patients presenting to the ED for non high-risk syncope might be able to increase the diagnostic accuracy and the utility of the clinical assessment alone.

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.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.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).CR integration with clinical probability assessment showed modest rule-in efficiency and insufficient sensitivity for conclusive rule-out.

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 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.

Background An accurate diagnosis is essential to identify and manage SARS-CoV-2 infected patients and implement infection control measures. Although real-time reverse transcription polymerase chain reaction (RT-PCR) is the current recommended laboratory method, several rapid antigen point-of-care tests (POCTs) were developed as frontline testing for SARS-CoV-2 infection diagnosis. Objectives The aim of this study was to assess a recently CE-approved POCT, SARS-CoV-2 Ag Test on the LumiraDx™ Platform (LumiraDx GmbH, Cologne, Germany) for the identification of SARS-COV-2 infected subjects at hospital setting. Methods LumiraDx POCT was implemented in three hospital settings: adult and pediatric emergency departments and occupational medicine department along two-month period during the second peak of Italian SARS-CoV-2 pandemic. Rapid antigen testing was performed on direct nasal swabs and results were compared with those obtained by Xpert Xpress SARS-CoV-2 assay. Results Overall sensitivity, specificity, NPV and PPV were 90.3%, 92.1%, 95.1%, and 84.9%, respectively, compared to reference method. Sensitivity, specificity, PPV and NPV for symptomatic group were 89.3% [95% IC 84.2-93.3], 88.2% [95% IC 72.5-96.7], 97.8% [95% IC 94.6-99.1], and 58.8% [95% IC 48.4-68.5], respectively. Sensitivity, specificity, PPV and NPV for asymptomatic group were 92.1% [95% IC 85-96.5], 92.3% [95% IC 89.9-94.4], 67.9% [95% IC 61.3-73.8], and 98.5% [95% IC 97.1-99.2], respectively. False positive and negative antigen testing results in both symptomatic and asymptomatic group were observed. Conclusion SARS-CoV-2 Ag POCT may represent an interesting tool to rapidly identify symptomatic or asymptomatic infected subjects. However, in hospital setting in which false negative or false positive results may have relevant implications, confirmatory NAAT always remains necessary for the appropriate management of patients.

Acute aortic syndromes (AAS) are cardiovascular emergencies with unmet diagnostic needs. Copeptin is released upon stress conditions and is approved for rule-out of myocardial infarction (MI). As MI and AAS share presenting symptoms, stress mechanisms and necessity for rapid diagnosis, copeptin appears as an attractive biomarker also for AAS. We thus performed a diagnostic and observational study in Emergency Department (ED) outpatients. Inclusion criteria were chest/abdominal/back pain, syncope and/or perfusion deficit, plus AAS in differential diagnosis. Blood samples were obtained in the ED. 313 patients were analyzed and 105 (33.5%) were diagnosed with AAS. Median copeptin was 38.91 pmol/L (interquartile range, IQR, 16.33–173.4) in AAS and 7.51 pmol/L (IQR 3.58–15.08) in alternative diagnoses (P

OBJECTIVES: To derive and validate a predictive algorithm integrating a nomogram-based prediction of the pretest probability of infection with a panel of serum biomarkers, which could robustly differentiate sepsis/septic shock from noninfectious systemic inflammatory response syndrome. DESIGN:Multicenter prospective study. SETTING: At emergency department admission in five University hospitals. PATIENTS:Nine-hundred forty-seven adults in inception cohort and 185 adults in validation cohort. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A nomogram, including age, Sequential Organ Failure Assessment score, recent antimicrobial therapy, hyperthermia, leukocytosis, and high C-reactive protein values, was built in order to take data from 716 infected patients and 120 patients with noninfectious systemic inflammatory response syndrome to predict pretest probability of infection. Then, the best combination of procalcitonin, soluble phospholipase A2 group IIA, presepsin, soluble interleukin-2 receptor α, and soluble triggering receptor expressed on myeloid cell-1 was applied in order to categorize patients as "likely" or "unlikely" to be infected. The predictive algorithm required only procalcitonin backed up with soluble phospholipase A2 group IIA determined in 29% of the patients to rule out sepsis/septic shock with a negative predictive value of 93%. In a validation cohort of 158 patients, predictive algorithm reached 100% of negative predictive value requiring biomarker measurements in 18% of the population. CONCLUSIONS: We have developed and validated a high-performing, reproducible, and parsimonious algorithm to assist emergency department physicians in distinguishing sepsis/septic shock from noninfectious systemic inflammatory response syndrome