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Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic and so it is crucial the right evaluation of viral infection. According to the Centers for Disease Control and Prevention (CDC), the Real-Time Reverse Transcription PCR (RT-PCR) in respiratory samples is the gold standard for confirming the disease. However, it has practical limitations as time-consuming procedures and a high rate of false-negative results. We aim to assess the accuracy of COVID-19 classifiers based on Arificial Intelligence (AI) and statistical classification methods adapted on blood tests and other information routinely collected at the Emergency Departments (EDs)., Methods: Patients admitted to the ED of Careggi Hospital from April 7th-30th 2020 with pre-specified features of suspected COVID-19 were enrolled. Physicians prospectively dichotomized them as COVID-19 likely/unlikely case, based on clinical features and bedside imaging support. Considering the limits of each method to identify a case of COVID-19, further evaluation was performed after an independent clinical review of 30-day follow-up data. Using this as a gold standard, several classifiers were implemented: Logistic Regression (LR), Quadratic Discriminant Analysis (QDA), Random Forest (RF), Support Vector Machine (SVM), Neural Networks (NN), K-nearest neighbor (K-NN), Naive Bayes (NB)., Results: Most of the classifiers show a ROC >0.80 on both internal and external validation samples but the best results are obtained applying RF, LR and NN. The performance from the external validation sustains the proof of concept to use such mathematical models fast, robust and efficient for a first identification of COVID-19 positive patients. These tools may constitute both a bedside support while waiting for RT-PCR results, and a tool to point to a deeper investigation, by identifying which patients are more likely to develop into positive cases within 7 days., Conclusions: Considering the obtained results and with a rapidly changing virus, we believe that data processing automated procedures may provide a valid support to the physicians facing the decision to classify a patient as a COVID-19 case or not., Competing Interests: The authors declare no conflict of interest. AA is serving as one of the Editorial Board members and Guest editors of this journal. AF was the Guest Editor of this journal. We declare that AA and AF had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to RJPA., (© 2023 The Author(s). Published by IMR Press.)

Background: Lung ultrasound (LUS) has a role in the diagnosis of pulmonary embolism (PE) mainly based on the visualization of pulmonary infarctions. However, examining the whole chest to detect small peripheral infarctions by LUS may be challenging. Pleuritic pain, a frequent presenting symptom in patients with PE, is usually localized in a restricted chest area identified by the patient itself. Our hypothesis is that sensitivity of LUS for PE in patients with pleuritic chest pain may be higher due to the possibility of focusing the examination in the painful area. We combined data from three prospective studies on LUS in patients suspected of PE and extracted data regarding patients with and without pleuritic pain at presentation to compare the performances of LUS., Results: Out of 872 patients suspected of PE, 217 (24.9%) presented with pleuritic pain and 279 patients (32%) were diagnosed with PE. Pooled sensitivity of LUS for PE in patients with and without pleuritic chest pain was 81.5% (95% CI 70-90.1%) and 49.5% (95% CI 42.7-56.4%) (p < 0.001), respectively. Specificity of LUS was similar in the two groups, respectively 95.4% (95% CI 90.7-98.1%) and 94.8% (95% CI 92.3-97.7%) (p = 0.86). In patients with pleuritic pain, a diagnostic strategy combining Wells score with LUS performed better both in terms of sensitivity (93%, 95% CI 80.9-98.5% vs 90.7%, 95% CI 77.9-97.4%) and negative predictive value (96.2%, 95% CI 89.6-98.7% vs 93.3%, 95% CI 84.4-97.3%). Efficiency of Wells score + LUS outperformed the conventional strategy based on Wells score + d-dimer (56.7%, 95% CI 48.5-65% vs 42.5%, 95% CI 34.3-51.2%, p = 0.02)., Conclusions: In a population of patients suspected of PE, LUS showed better sensitivity for the diagnosis of PE when applied to the subgroup with pleuritic chest pain. In these patients, a diagnostic strategy based on Wells score and LUS performed better to exclude PE than the conventional strategy combining Wells score and d-dimer., (© 2022. The Author(s).)

Objectives: Physicians' gestalt is central in the diagnostic pipeline of suspected COVID-19, due to the absence of a single tool allowing conclusive rule in or rule out. The aim of this study was to estimate the diagnostic test characteristics of physician's gestalt for COVID-19 in the emergency department (ED), based on clinical findings or on a combination of clinical findings and bedside imaging results., Methods: From April 1 to April 30, 2020, patients with suspected COVID-19 were prospectively enrolled in two EDs. Physicians prospectively dichotomized patients in COVID-19 likely or unlikely twice: after medical evaluation of clinical features (clinical gestalt [CG]) and after evaluation of clinical features and results of lung ultrasound or chest x-ray (clinical and bedside imaging-integrated gestalt [CBIIG]). The final diagnosis was adjudicated after independent review of 30-day follow-up data., Results: Among 838 ED enrolled patients, 193 (23%) were finally diagnosed with COVID-19. The area under the curve (AUC), sensitivity, and specificity of CG and CBIIG for COVID-19 were 80.8% and 91.6% (p < 0.01), 82.9% and 91.4% (p = 0.01), and 78.6% and 91.8% (p < 0.01), respectively. CBIIG had similar AUC and sensitivity to reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 on the first nasopharyngeal swab per se (93.5%, p = 0.24; and 87%, p = 0.17, respectively). CBIIG plus RT-PCR had a sensitivity of 98.4% for COVID-19 (p < 0.01 vs. RT-PCR alone) compared to 95.9% for CG plus RT-PCR (p = 0.05)., Conclusions: In suspected COVID-19, CG and CBIIG have fair diagnostic accuracy, in line with physicians' gestalt for other acute conditions. Negative RT-PCR plus low probability based on CBIIG can rule out COVID-19 with a relatively low number of false-negative cases., (© 2021 by the Society for Academic Emergency Medicine.)

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.

Background: Integration of transesophageal echocardiography (TEE) with Focused Cardiac Ultrasound (FoCUS) can impact decision-making, assist in the diagnosis of reversible etiologies and help guiding resuscitation of patients with cardiac arrest., Objective: To evaluate the ability of emergency physicians (EPs) to obtain and maintain skills in performing resusTEE after a course with clinical training in the cardiac surgery theatre., Methods: Ten EPs without previous TEE experience underwent a resusTEE course, based on a 2-h workshop and an 8-h hands-on training. The training was performed in a cardiac surgery theatre tutored by cardiovascular anesthesiologists. The six taught views were mid-esophageal four-chamber (ME4CH), mid-esophageal long axis (MELAX), mid-esophageal two-chamber (ME2CH), mid-esophageal bicaval view (MEbicaval), transgastric short axis (TGSAX) and aorta view (AOview). The EPs were evaluated by a cardiovascular anesthesiologist at the end of the course as well as after 12 weeks according to a standardized evaluation method. Once the course was completed, resusTEE exams, performed by EPs in Emergency Department (ED), were monitored for a 12-week period., Results: The average assessment of the ten EPs by the tutors was higher than 4 points out of 5, both at the end of the course and after 12 weeks. Probe insertion, acquisition and interpretation of the different views scored on average more than 4 points out of 5 except for TGSAX that showed worsening after 12 weeks. Trainees performed twelve resusTEE exams in ED in patients with out-of-hospital cardiac arrest (OHCA) over 12 weeks after the course. EPs used only four out of six taught views in clinical practice, in the following order of frequency: ME4CH, AOview, MEbicaval and MELAX., Conclusions: EPs, after a course with clinical training in the cardiac surgery theatre, can successfully acquire and maintain the skills needed to perform resusTEE. However, among the six views learned in the course, EPs used only four of them (ME4CH, MEbicaval, MELAX and AOview).

Objectives: Guidelines recommend chest radiography (CR) in the workup of suspected acute aortic syndromes (AASs) if the pretest clinical probability is low. However, the diagnostic impact of CR integration for the rule-in and rule-out of AASs is unknown., Methods: We performed a secondary analysis of the ADvISED multicenter study. Emergency department outpatients were eligible if an AAS was clinically suspected. Clinical probability was defined with the aortic dissection detection risk score (ADD-RS). CR was evaluated blindly by a radiologist, who judged on mediastinum enlargement (ME) and other signs., Results: In 2014 through 2016, a total of 1,129 patients were enrolled and 1,030 were analyzed, including 48 (4.7%) with AASs. ADD-RS/ME and ADD-RS/any CR sign (aCRs) integration were more accurate than ADD-RS alone (area under the curve = 0.8 and 0.78 vs. 0.66, p < 0.001). The sensitivity and specificity of the integrated strategies were 66.7% (95% confidence interval [CI] = 51.5% to 79.9%) and 82.5% (95% CI = 79.9% to 84.8%) for ADD-RS/ME and 68.8% (95% CI = 53.6% to 80.9%) and 76.5% (95% CI = 73.7% to 79.1%) for ADD-RS/aCRs, respectively. The sensitivity and specificity of CR per se were 54.2% (95% CI = 39.2% to 68.6%) and 92.4% (95% CI = 90.5% to 93.9%) for ME and 60.4% (95% CI = 45.3% to 74.2%) and 85.2% (95% CI = 82.9% to 87.4%) for aCRs. The agreement (κ) between attending physicians and radiologists for ME was 0.44 (95% CI = 0.35 to 0.54). ADD-RS/ME rule-in (ADD-RS ≤ 1 and ME-present, or ADD-RS > 1) applied to 204 versus 130 patients with ADD-RS > 1, including 14 with AAS and 60 false-positives (FP). ADD-RS/aCRs rule-in (ADD-RS ≤ 1 and aCRs-present, or ADD-RS > 1) applied to 264 patients, including 15 with AAS and 119 FP. ADD-RS/ME rule-out (ADD-RS ≤ 1 and ME-absent) applied to 826 (80.2%) patients, including 16 with AAS (33.3% of cases). ADD-RS/aCRs rule-out (ADD-RS ≤ 1 and aCRs-absent) applied to 766 patients (74.4%), including 15 with AAS (31.3% of cases)., Conclusions: CR integration with clinical probability assessment showed modest rule-in efficiency and insufficient sensitivity for conclusive rule-out., (© 2019 by the Society for Academic Emergency Medicine.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: Although acute decompensated heart failure (ADHF) is a common cause of dyspnoea, its diagnosis still represents a challenge. Lung ultrasound (LUS) is an emerging point-of-care diagnostic tool, but its diagnostic performance for ADHF has not been evaluated in randomized studies. We evaluated, in patients with acute dyspnoea, accuracy and clinical usefulness of combining LUS with clinical assessment compared to the use of chest radiography (CXR) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in conjunction with clinical evaluation., Methods and Results: This was a randomized trial conducted in two emergency departments. After initial clinical evaluation, patients with acute dyspnoea were classified by the treating physician according to presumptive aetiology (ADHF or non-ADHF). Patients were subsequently randomized to continue with either LUS or CXR/NT-proBNP. A new diagnosis, integrating the results of both initial assessment and the newly obtained findings, was then recorded. Diagnostic accuracy and clinical usefulness of LUS and CXR/NT-proBNP approaches were calculated. A total of 518 patients were randomized. Addition of LUS had higher accuracy [area under the receiver operating characteristic curve (AUC) 0.95] than clinical evaluation alone (AUC 0.88) in identifying ADHF (P < 0.01). In contrast, use of CXR/NT-proBNP did not significantly increase the accuracy of clinical evaluation alone (AUC 0.87 and 0.85, respectively; P > 0.05). The diagnostic accuracy of the LUS-integrated approach was higher then that of the CXR/Nt-proBNP-integrated approach (AUC 0.95 vs. 0.87, p < 0.01). Combining LUS with the clinical evaluation reduced diagnostic errors by 7.98 cases/100 patients, as compared to 2.42 cases/100 patients in the CXR/Nt-proBNP group., Conclusion: Integration of LUS with clinical assessment for the diagnosis of ADHF in the emergency department seems to be more accurate than the current diagnostic approach based on CXR and NT-proBNP., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

Precision medicine may significantly contribute to rapid disease diagnosis and targeted therapy, but relies on the availability of detailed, subject specific, clinical information. Proton nuclear magnetic resonance (¹H⁻NMR) spectroscopy of body fluids can extract individual metabolic fingerprints. Herein, we studied 64 patients admitted to the Florence main hospital emergency room with severe abdominal pain. A blood sample was drawn from each patient at admission, and the corresponding sera underwent ¹H⁻NMR metabolomics fingerprinting. Unsupervised Principal Component Analysis (PCA) analysis showed a significant discrimination between a group of patients with symptoms of upper abdominal pain and a second group consisting of patients with diffuse abdominal/intestinal pain. Prompted by this observation, supervised statistical analysis (Orthogonal Partial Least Squares⁻Discriminant Analysis (OPLS-DA)) showed a very good discrimination (>90%) between the two groups of symptoms. This is a surprising finding, given that neither of the two symptoms points directly to a specific disease among those studied here. Actually herein, upper abdominal pain may result from either symptomatic gallstones, cholecystitis, or pancreatitis, while diffuse abdominal/intestinal pain may result from either intestinal ischemia, strangulated obstruction, or mechanical obstruction. Although limited by the small number of samples from each of these six conditions, discrimination of these diseases was attempted. In the first symptom group, >70% discrimination accuracy was obtained among symptomatic gallstones, pancreatitis, and cholecystitis, while for the second symptom group >85% classification accuracy was obtained for intestinal ischemia, strangulated obstruction, and mechanical obstruction. No single metabolite stands up as a possible biomarker for any of these diseases, while the contribution of the whole ¹H⁻NMR serum fingerprint seems to be a promising candidate, to be confirmed on larger cohorts, as a first-line discriminator for these diseases.

Neuron glial antigen 2 (NG2) is a chondroitin sulphate proteoglycan 4 (CSPG4) that occurs in developing and adult central nervous systems (CNSs) as a marker of oligodendrocyte precursor cells (OPCs) together with platelet-derived growth factor receptor α (PDGFRα). It behaves variably in different pathological conditions, and is possibly involved in the origin and progression of human gliomas. In the latter, NG2/CSPG4 induces cell proliferation and migration, is highly expressed in pericytes, and plays a role in neoangiogenesis. NG2/CSPG4 expression has been demonstrated in oligodendrogliomas, astrocytomas, and glioblastomas (GB), and it correlates with malignancy. In rat tumors transplacentally induced by N -ethyl- N -nitrosourea (ENU), NG2/CSPG4 expression correlates with PDGFRα, Olig2, Sox10, and Nkx2.2, and with new vessel formation. In this review, we attempt to summarize the normal and pathogenic functions of NG2/CSPG4, as well as its potential as a therapeutic target.

Monitoring of small ruminants for transmissible spongiform encephalopathies (TSEs) has recently become more relevant after two natural scrapie suspected cases of goats were found to be positive for classical BSE (C-BSE). C-BSE probably established itself in this species unrecognized, undermining disease control measures. This opens the possibility that TSEs in goats may remain an animal source for human prion diseases. Currently, there are no data regarding the natural presence of the atypical BSE in caprines. Here we report that C-BSE and L-type atypical BSE (L-BSE) isolates from bovine species are intracerebrally transmissible to goats, with a 100% attack rate and a significantly shorter incubation period and survival time after C-BSE than after L-BSE experimental infection, suggesting a lower species barrier for classical agentin goat. All animals showed nearly the same clinical features of disease characterized by skin lesions, including broken hair and alopecia, and abnormal mental status. Histology and immunohistochemistry showed several differences between C-BSE and L-BSE infection, allowing discrimination between the two different strains. The lymphoreticular involvement we observed in the C-BSE positive goats argues in favour of a peripheral distribution of PrPSc similar to classical scrapie. Western blot and other currently approved screening tests detected both strains in the goats and were able to classify negative control animals. These data demonstrate that active surveillance of small ruminants, as applied to fallen stock and/or healthy slaughter populations in European countries, is able to correctly identify and classify classical and L-BSE and ultimately protect public health., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Treatments aiming at reperfusion of the acutely ischaemic brain tissue may result futile or even detrimental because of the so-called reperfusion injury. The processes contributing to reperfusion injury involve a number of factors, ranging from blood-brain barrier (BBB) disruption to circulating biomarkers. Our aim is to evaluate the relative effect of imaging and circulating biomarkers in relation to reperfusion injury., Methods and Analysis: Observational hospital-based study that will include 140 patients who had ischaemic stroke, treated with systemic thrombolysis, endovascular treatment or both. BBB disruption will be assessed with CT perfusion (CTP) before treatment, and levels of a large panel of biomarkers will be measured before intervention and after 24 hours. Relevant outcomes will include: (1) reperfusion injury, defined as radiologically relevant haemorrhagic transformation at 24 hours and (2) clinical status 3 months after the index stroke. We will investigate the separate and combined effect of pretreatment BBB disruption and circulating biomarkers on reperfusion injury and clinical status at 3 months. Study protocol is registered at http://www.clinicaltrials.gov (ClinicalTrials.gov ID: NCT03041753)., Ethics and Dissemination: The study protocol has been approved by ethics committee of the Azienda Ospedaliero Universitaria Careggi (Università degli Studi di Firenze). Informed consent is obtained by each patient at time of enrolment or deferred when the participant lacks the capacity to provide consent during the acute phase. Researchers interested in testing hypotheses with the data are encouraged to contact the corresponding author. Results from the study will be disseminated at national and international conferences and in medical thesis., Trial Registration Number: NCT03041753., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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., (© 2017 American Heart Association, Inc.)

Objective: We investigated the reliability and accuracy of a bedside diagnostic algorithm for patients presenting with vertigo/unsteadiness to the emergency department., Methods: We enrolled consecutive adult patients presenting with vertigo/unsteadiness at a tertiary hospital. STANDING, the acronym for the four-step algorithm we have previously described, based on nystagmus observation and well-known diagnostic maneuvers includes (1) the discrimination between S pon TA neous and positional nystagmus, (2) the evaluation of the N ystagmus D irection, (3) the head I mpulse test, and (4) the evaluation of equilibrium (sta N din G ). Reliability of each step was analyzed by Fleiss' K calculation. The reference standard (central vertigo) was a composite of brain disease including stroke, demyelinating disease, neoplasm, or other brain disease diagnosed by initial imaging or during 3-month follow-up., Results: Three hundred and fifty-two patients were included. The incidence of central vertigo was 11.4% [95% confidence interval (CI) 8.2-15.2%]. The leading cause was ischemic stroke (70%). The STANDING showed a good reliability (overall Fleiss K 0.83), the second step showing the highest (0.95), and the third step the lowest (0.74) agreement. The overall accuracy of the algorithm was 88% (95% CI 85-88%), showing high sensitivity (95%, 95% CI 83-99%) and specificity (87%, 95% CI 85-87%), very high-negative predictive value (99%, 95% CI 97-100%), and a positive predictive value of 48% (95% CI 41-50%) for central vertigo., Conclusion: Using the STANDING algorithm, non-sub-specialists achieved good reliability and high accuracy in excluding stroke and other threatening causes of vertigo/unsteadiness.

Glioblastoma (GB) is a highly heterogeneous tumor. In order to identify in vivo the most malignant tumor areas, the extent of tumor infiltration and the sites giving origin to GB stem cells (GSCs), we combined positron emission tomography/computed tomography (PET/CT) and conventional and advanced magnetic resonance imaging (MRI) with histology, immunohistochemistry and molecular genetics. Prior to dura opening and tumor resection, forty-eight biopsy specimens [23 of contrast-enhancing (CE) and 25 of non-contrast enhancing (NE) regions] from 12 GB patients were obtained by a frameless image-guided stereotactic biopsy technique. The highest values of 2-[18F]-fluoro-2-deoxy-D-glucose maximum standardized uptake value ( 18 F-FDG SUV max ), relative cerebral blood volume (rCBV), Choline/Creatine (Cho/Cr), Choline/N-acetylaspartate (Cho/NAA) and Lipids/Lactate (LL) ratio have been observed in the CE region. They corresponded to the most malignant tumor phenotype, to the greatest molecular spectrum and stem cell potential. On the contrary, apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in the CE region were very variable. 18 F-FDG SUV max , Cho/Cr and Cho/NAA ratio resulted the most suitable parameters to detect tumor infiltration. In edematous areas, reactive astrocytes and microglia/macrophages were influencing variables. Combined MRI and 18 F-FDG PET/CT allowed to recognize the specific biological significance of the different identified areas of GB., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Objective: Lung and venous ultrasound are bedside diagnostic tools increasingly used in the early diagnostic approach of suspected pulmonary embolism (PE). However, the possibility of improving the conventional prediction rule for PE by integrating ultrasound has never been investigated., Methods: We performed lung and venous ultrasound in consecutive patients suspected of PE in four emergency departments. Conventional Wells score (Ws) was adjudicated by the attending physician, and ultrasound was performed by one of 20 investigators. Signs of deep venous thrombosis (DVT) at venous ultrasound and signs of pulmonary infarcts or alternative diagnoses at lung ultrasound were considered to recalculate two items of the Ws: signs and symptoms of DVT and alternative diagnosis less likely than PE. The diagnostic performances of the ultrasound-enhanced Ws (USWs) and Ws were then compared after confirmation of the final diagnosis., Results: A total of 446 patients were studied. PE was confirmed in 125 patients (28%). USWs performed significantly better than Ws, with a sensitivity of 69.6% versus 57.6% and a specificity of 88.2% versus 68.2%. In combination with D-dimer, USWs showed an optimal failure rate (0.8%) and a significantly superior efficiency than Ws (32.3% vs. 27.2%). A strategy based on lung and venous ultrasound combined with D-dimer would allow to avoid CT pulmonary angiography in 50.5% of patients with suspected PE, compared to 27.2% when the rule without ultrasound is applied., Conclusions: A pretest risk stratification enhanced by ultrasound of lung and venous performs better than Ws in the early diagnostic process of PE., (© 2016 by the Society for Academic Emergency Medicine.)

Background: The diagnostic value of lung ultrasonography (LUS) and procalcitonin (PCT) in the diagnosis of lung infections is known. No studies evaluated the combination of LUS and PCT for the diagnosis of pneumonia in the emergency department (ED). We evaluated the diagnostic accuracy of the combination of LUS and PCT in the diagnosis of pneumonia., Methods: Patients with respiratory symptoms of unexplained origin who underwent a chest CT in ED were included in the study if PCT assay was available. LUS was performed before CT and was targeted to the detection of lung consolidations with the morphologic features of pneumonia. A PCT assay was performed at presentation, and cut-off of 0.25 and of 0.5 ng/ml were used to rule-out and rule-in pneumonia. The final diagnosis of pneumonia was established by independent clinicians, on the basis of clinical chart review including CT results., Results: We enrolled 128 patients and pneumonia was the final diagnosis in 61 (47.7%). In 38 patients (29.7%) LUS and PCT were negative (PCT < 0.25 ng/ml). The overall accuracy, sensitivity and negative predictive value of LUS/PCT were 88.8, 96.7 and 94.7% respectively. Sensitivity of the LUS/PCT test was significantly superior to LUS alone (85.2%) and PCT alone (73.8%) (p < 0.05 for both). Specificity and positive predictive value of the combination of positivity of LUS/PCT (PCT > 0.5 ng/ml) were 94% and 83.3% respectively. Specificity of LUS/PCT was not significantly different to LUS alone (88.1%) (p = 0.125)., Conclusions: The sensitivity of the combination of LUS with PCT for the diagnosis of pneumonia was significantly superior when compared with the sensitivity of LUS and PCT alone.

Microbiological tests on cerebrospinal fluid (CSF) utilize a common urgent-care procedure that does not take into account the chemical and cytological characteristics of the CSF, resulting sometimes in an unnecessary use of human and diagnostic resources. The aim of this study was to retrospectively validate a simple scoring system (bacterial meningitis-Careggi score [BM-CASCO]) based on blood and CSF sample chemical/cytological parameters for evaluating the probability of acute bacterial meningitis (ABM) in adults. BM-CASCO (range, 0 to 6) was defined by the following parameters: CSF cell count, CSF protein levels, CSF lactate levels, CSF glucose-to-serum glucose ratio, and peripheral neutrophil count. BM-CASCO was retrospectively calculated for 784 cases of suspected ABM in adult subjects observed during a four-and-a-half-year-period (2010 to 2014) at the emergency department (ED) of a large tertiary-care teaching hospital in Italy. Among the 28 confirmed ABM cases (3.5%), Streptococcus pneumoniae was the most frequent cause (16 cases). All ABM cases showed a BM-CASCO value of ≥3. Most negative cases (591/756) exhibited a BM-CASCO value of ≤1, which was adopted in our laboratory as a cutoff to not proceed with urgent microbiological analysis of CSF in cases of suspected ABM in adults. During a subsequent 1-year follow-up, the introduction of the BM-CASCO in the diagnostic workflow of ABM in adults resulted in a significant decrease in unnecessary microbiological analysis, with no false negatives. In conclusion, BM-CASCO appears to be an accurate and simple scoring system for optimization of the microbiological diagnostic workflow of ABM in adults., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Our aim was the assessment of the prognostic significance of right heart thrombi (RiHT) and their characteristics in pulmonary embolism in relation to established prognostic factors.138 patients (69 females) aged (mean±sd) 62±19 years with RiHT were included into a multicenter registry. A control group of 276 patients without RiHT was created by propensity scoring from a cohort of 963 contemporary patients. The primary end-point was 30-day pulmonary embolism-related mortality; the secondary end-point included 30-day all-cause mortality. In RiHT patients, pulmonary embolism mortality was higher in 31 patients with systolic blood pressure <90 mmHg than in 107 normotensives (42% versus 12%, p=0.0002) and was higher in the 83 normotensives with right ventricular dysfunction (RVD) than in the 24 normotensives without RVD (16% versus 0%, p=0.038). In multivariable analysis the simplified Pulmonary Embolism Severity Index predicted mortality (hazard ratio 2.43, 95% CI 1.58-3.73; p<0.0001), while RiHT characteristics did not. Patients with RiHT had higher pulmonary embolism mortality than controls (19% versus 8%, p=0.003), especially normotensive patients with RVD (16% versus 7%, p=0.02).30-day mortality in patients with RiHT is related to haemodynamic consequences of pulmonary embolism and not to RiHT characteristics. However, patients with RiHT and pulmonary embolism resulting in RVD seem to have worse prognosis than propensity score-matched controls., (Copyright ©ERS 2016.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Pneumoperitoneum is a rare cause of abdominal pain characterized by a high mortality. Ultrasonography (US) can detect free intraperitoneal air; however, its accuracy remains unclear. The aims of this pilot study were to define the diagnostic performance and the reliability of abdominal US for the diagnosis of pneumoperitoneum., Methods: This was a prospective observational study. Four senior and two junior physicians were shown, in an unpaired randomized order, abdominal US videos from 11 patients with and 11 patients without pneumoperitoneum. Abdominal US videos were obtained from consecutive patients presenting to ED complaining abdominal pain with the diagnosis of pneumoperitoneum established by CT. Abdominal US was performed according to a standardized protocol that included the following scans: epigastrium, right and left hypochondrium, umbilical area and right hypochondrium with the patient lying on the left flank. We evaluated accuracy, intra- and inter-observer agreement of abdominal US when reviewed by senior physicians. Furthermore, we compared the accuracy of a "2 scan-fast exam" (epigastrium and right hypochondrium) vs the full US examination and the accuracy of physicians expert in US vs nonexpert ones. Finally, accuracy of US was compared with abdominal radiography in patients with available images., Results: Considering senior revision, accuracy of abdominal US was 88.6 % (95 % CI 79.4-92.4 %) with a sensitivity of 95.5 % (95 % CI 86.3-99.2 %) and a specificity of 81.8 % (95 % CI 72.6-85.5 %). Inter- and intra-observer agreement (k) were 0.64 and 0.95, respectively. Accuracy of a "2 scan-fast exam" (87.5 %, 95 % CI 77.9-92.4 %) was similar to global exam. Sensitivity of abdominal radiography (72.2 %, 95 % CI 54.8-85.7 %) was lower than that of abdominal US, while specificity (92.5 %, 95 % CI 79.5-98.3 %) was higher. Accuracy (68.2 %, 95 % CI 51.4-80.9 %) of junior reviewers evaluating US was lower than senior reviewers., Conclusions: Senior physicians can recognize US signs of pneumoperitoneum with a good accuracy and reliability; sensitivity of US could be superior to abdominal radiography and a 2 fast-scan exam seems as accurate as full abdominal examination. US could be a useful bedside screening test for pneumoperitoneum. Trial registry ClinicalTrials.gov; No.: NCT02004925; URL: http://www.clinicaltrials.gov.

Objectives: The diagnostic performance of transthoracic focused cardiac ultrasound (FoCUS) performed by emergency physicians (EP) to estimate ascending aorta dimensions in the acute setting has not been prospectively studied. The diagnostic accuracy and the interobserver variability of EP-performed FoCUS were investigated to estimate thoracic aortic dilation and aneurysm compared with the results of computed tomography angiography (CTA)., Methods: This was a prospective single-center cohort study of a convenience sample of patients who underwent CTA in the emergency department for suspected aortic pathology. FoCUS was performed before CTA, and the maximum ascending aorta diameter evaluated in parasternal long-axis view. Aorta diameter < 40 mm by visual estimation or by diameter measurement was considered normal. Measurements were recorded in all patients with aorta diameter ≥ 40 mm. Diagnostic accuracy of FoCUS for detection of aortic dilation (diameter ≥ 40 mm) and aneurysm (diameter ≥ 45 mm) were calculated considering the CTA result as reference standard. In a subgroup of patients, a second EP-sonographer performed FoCUS to evaluate interobserver agreement for the diagnosis of ascending aorta dilation., Results: A total of 140 patients were enrolled in the study. Ascending aorta dilation and aneurysm were detected with FoCUS in 50 (35.7%) and in 27 (17.8%) patients, respectively. Sensitivity and specificity of FoCUS were 78.6% (95% confidence interval [CI] = 65.6% to 88.4%) and 92.9% (95% CI = 85.1% to 97.3%), respectively, for ascending aorta dilation and 64.7% (95% CI = 46.5% to 80.2%) and 95.3% (95% CI = 89.3% to 98.4%), respectively, for ascending aorta aneurysm. Interobserver agreement of FoCUS was k = 0.82., Conclusions: FoCUS performed by EP is specific for ascending aorta dilation and aneurysm when compared to CTA and appears a reproducible technique., (© 2015 by the Society for Academic Emergency Medicine.)

Vertigo is generally due to a benign disorder, but it is the most common symptom associated with misdiagnosis of stroke. In this pilot study, we preliminarily assessed the diagnostic performance of a structured bedside algorithm to differentiate central from non-central acute vertigo (AV). Adult patients presenting to a single Emergency Department with vertigo were evaluated with STANDING (SponTAneous Nystagmus, Direction, head Impulse test, standiNG) by one of five trained emergency physicians or evaluated ordinarily by the rest of the medical staff (control group). The gold standard was a complete audiologic evaluation by a clinicians who are experts in assessing dizzy patients and neuroimaging. Reliability, sensibility and specificity of STANDING were calculated. Moreover, to evaluate the potential clinical impact of STANDING, neuroimaging and hospitalisation rates were compared with control group. A total of 292 patients were included, and 48 (16.4%) had a diagnosis of central AV. Ninety-eight (33.4%) patients were evaluated with STANDING. The test had good interobserver agreement (k = 0.76), with very high sensitivity (100%, 95%CI 72.3-100%) and specificity (94.3%, 95%CI 90.7-94.3%). Furthermore, hospitalisation and neuroimaging test rates were lower in the STANDING than in the control group (27.6% vs. 50.5% and 31.6% vs. 71.1%, respectively). In conclusion, STANDING seems to be a promising simple structured bedside algorithm that in this preliminary study identified central AV with a very high sensitivity, and was associated with significant reduction of neuroimaging and hospitalisation rates.

Objectives: The objective was to investigate the prognostic value of plasma lactate in patients with acute pulmonary embolism (PE)., Methods: This was a retrospective study at the emergency department (ED) of a third-level teaching hospital. The authors considered consecutive patients with a diagnosis of PE established by lung scan or spiral computed tomography (CT) and confirmed by pulmonary angiography if necessary. Only patients for whom plasma lactate levels had been tested within 6 hours from presentation to the ED were included. Primary outcome was in-hospital death due to any cause; secondary outcome was mortality related to PE., Results: From September 1997 to June 2006, a total of 384 patients were diagnosed with PE in the ED. Of these patients, 287 had registered plasma lactate levels and were included in this analysis. Included patients had a mean age of 70 (SD ± 15 years, range = 18 to 100 years), 163 (57%) were female, 26 (9%) showed systolic blood pressure lower than 100 mm Hg at presentation, and 160 (56%) had echocardiographic evidence of right ventricular dysfunction (RVD). Twenty patients died during their hospital stay (7%). Plasma lactate levels ≥ 2 mmol/L were associated with in-hospital mortality from all causes (odds ratio [OR] = 4.60, 95% confidence interval [CI] = 1.57 to 13.53) and with PE-related mortality (OR = 4.94, 95% CI = 1.38 to 17.63), independent of hypotension or RVD at presentation., Conclusions: High plasma lactate was associated with increased in-hospital mortality in this sample of patients with acute PE., (© 2011 by the Society for Academic Emergency Medicine.)

Recent epidemiological reports showed that smoking has a negative impact on renal function and elevates the renal risk not only in the renal patient but perhaps also in the healthy population. Studies suggested that nicotine, a major tobacco alkaloid, links smoking to renal dysfunction. While several studies showed that smoking/chronic nicotine exposure exacerbates the progression of chronic renal diseases, its impact on acute kidney injury is virtually unknown. Here, we studied the effects of chronic nicotine exposure on acute renal ischemic injury. We found that chronic nicotine exposure increased the extent of renal injury induced by warm ischemia-reperfusion as evidenced by morphological changes, increase in plasma creatinine level, and kidney injury molecule-1 expression. We also found that chronic nicotine exposure elevated markers of oxidative stress such as nitrotyrosine as well as malondialdehyde. Interestingly, chronic nicotine exposure alone increased oxidative stress and injury in the kidney without morphological alterations. Chronic nicotine treatment not only increased reactive oxygen species (ROS) production and injury but also exacerbated oxidative stress-induced ROS generation through NADPH oxidase and mitochondria in cultured renal proximal tubule cells. The resultant oxidative stress provoked injury through JNK-mediated activation of the activator protein (AP)-1 transcription factor in vitro. This mechanism might exist in vivo as phosphorylation of JNK and its downstream target c-jun, a component of the AP-1 transcription factor, is elevated in the ischemic kidneys exposed to chronic nicotine. Our results imply that smoking may sensitize the kidney to ischemic insults and perhaps facilitates progression of acute kidney injury to chronic kidney injury.