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Objectives: To assess concurrent validity of the Dynamic Silver Code (DSC), a tool based on administrative data that predicts prognosis in older adults accessing the emergency department (ED), in terms of association with markers of poor functional and cognitive status., Design: Cross-sectional., Setting and Participants: Data were obtained in the AIDEA study, which enrolled a cohort of ≥75-year-old patients, accessing the ED of 2 hospitals in Florence, Italy., Methods: The DSC score and classes (I to IV, corresponding to an increasing risk of death) were obtained from administrative data. Information on health and functional status prior to ED access were collected from face-to-face, direct, or proxy interviews. The 4AT test was administered to screen for possible delirium. Bivariate comparisons of the prevalence of each functional and cognitive marker across 4 DSC classes were performed. Multinomial logistic regression was used to assess the multivariable risk of being in II, III, or IV DSC class vs I., Results: Among 3358 participants (mean age 83 years, men 44%), 32.9%, 30.3%, 19.5%, and 17.2% were in DSC class I, II, III, and IV. Preadmission abnormal functional and cognitive conditions, and delirium in the ED, were increasingly more common from DSC class I through IV (P < .001). In particular, the prevalence of total inability to walk increased from 2.9% (class I) to 23.4% (class IV). In multivariable analyses, this was the strongest predictor of being in progressively worse DSC classes, whereas feeling of exhaustion, reporting of serious falls, weight loss, and severe memory loss or diagnosis of dementia gave some contribution., Conclusions and Implications: The ability of the DSC to predict survival in older persons appears to rely on its prevailing association with markers of functional impairment. These results may support clinical use of the tool., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Leigh syndrome (LS) associated with cytochrome c oxidase (COX) deficiency is an early onset, fatal mitochondrial encephalopathy, leading to multiple neurological failure and eventually death, usually in the first decade of life. Mutations in SURF1, a nuclear gene encoding a mitochondrial protein involved in COX assembly, are among the most common causes of LS. LS SURF1 patients display severe, isolated COX deficiency in all tissues, including cultured fibroblasts and skeletal muscle. Recombinant, constitutive SURF1 -/- mice show diffuse COX deficiency, but fail to recapitulate the severity of the human clinical phenotype. Pigs are an attractive alternative model for human diseases, because of their size, as well as metabolic, physiological and genetic similarity to humans. Here, we determined the complete sequence of the swine SURF1 gene, disrupted it in pig primary fibroblast cell lines using both TALENs and CRISPR/Cas9 genome editing systems, before finally generating SURF1 -/- and SURF1 -/+ pigs by Somatic Cell Nuclear Transfer (SCNT). SURF1 -/- pigs were characterized by failure to thrive, muscle weakness and highly reduced life span with elevated perinatal mortality, compared to heterozygous SURF1 -/+ and wild type littermates. Surprisingly, no obvious COX deficiency was detected in SURF1 -/- tissues, although histochemical analysis revealed the presence of COX deficiency in jejunum villi and total mRNA sequencing (RNAseq) showed that several COX subunit-encoding genes were significantly down-regulated in SURF1 -/- skeletal muscles. In addition, neuropathological findings, indicated a delay in central nervous system development of newborn SURF1 -/- piglets. Our results suggest a broader role of sSURF1 in mitochondrial bioenergetics., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Acute dyspnea is a common symptom in the ED. The standard approach to dyspnea often relies on radiologic and laboratory results, causing excessive delay before adequate therapy is started. Use of an integrated point-of-care ultrasonography (PoCUS) approach can shorten the time needed to formulate a diagnosis, while maintaining an acceptable safety profile., Methods: Consecutive adult patients presenting with dyspnea and admitted after ED evaluation were prospectively enrolled. The gold standard was the final diagnosis assessed by two expert reviewers. Two physicians independently evaluated the patient; a sonographer performed an ultrasound evaluation of the lung, heart, and inferior vena cava, while the treating physician requested traditional tests as needed. Time needed to formulate the ultrasound and the ED diagnoses was recorded and compared. Accuracy and concordance of the ultrasound and the ED diagnoses were calculated., Results: A total of 2,683 patients were enrolled. The average time needed to formulate the ultrasound diagnosis was significantly lower than that required for ED diagnosis (24 ± 10 min vs 186 ± 72 min; P = .025). The ultrasound and the ED diagnoses showed good overall concordance (κ = 0.71). There were no statistically significant differences in the accuracy of PoCUS and the standard ED evaluation for the diagnosis of acute coronary syndrome, pneumonia, pleural effusion, pericardial effusion, pneumothorax, and dyspnea from other causes. PoCUS was significantly more sensitive for the diagnosis of heart failure, whereas a standard ED evaluation performed better in the diagnosis of COPD/asthma and pulmonary embolism., Conclusions: PoCUS represents a feasible and reliable diagnostic approach to the patient with dyspnea, allowing a reduction in time to diagnosis. This protocol could help to stratify patients who should undergo a more detailed evaluation., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Acute aortic dissection (AD) represents a diagnostic conundrum. Validated algorithms are particularly needed to identify patients where AD could be ruled out without aortic imaging. We evaluated the diagnostic accuracy of a strategy combining the aortic dissection detection (ADD) risk score with D-dimer, a sensitive biomarker of AD., Methods: Patients from two clinical centers with suspected AD were prospectively enrolled in a registry, from January 2008 to March 2013. The ADD risk score was calculated by retrospective blinded chart review. For D-dimer, a cutoff of 500 ng/ml was applied., Results: AD was diagnosed in 233 of 1035 (22.5%) patients. The ADD risk score was 0 in 322 (31.1%), 1 in 508 (49.1%) and >1 in 205 (19.8%) patients. The sensitivity and the failure rate of D-dimer were 100% and 0% in patients with ADD score 0, versus 97.5% (95% CI 91.4-99.6%) and 4.2% (95% CI 0.7-12.5%) in patients with ADD risk score >1. In patients with ADD risk score ≤ 1, the sensitivity and the failure rate of D-dimer were 98.7% (95% CI 95.3-99.8%) and 0.8% (95% CI 0.1-2.6%). The diagnostic efficiency of D-dimer in patients with ADD risk score 0 and ≤ 1 was 8.9% (95% CI 7.2-10.7%) and 23.6% (95% CI 21.1-26.2%) respectively., Conclusions: In a large cohort of patients with suspected AD, the presence of ADD risk score 0 or ≤ 1 combined with a negative D-dimer accurately and efficiently ruled out AD., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Presenting signs and symptoms of pulmonary embolism (PE) are nonspecific, favoring a large use of second-line diagnostic tests such as multidetector CT pulmonary angiography (MCTPA), thus exposing patients to high-dose radiation and to potential serious complications. We investigated the diagnostic performance of multiorgan ultrasonography (lung, heart, and leg vein ultrasonography) and whether multiorgan ultrasonography combined to Wells score and D-dimer could safely reduce MCTPA tests., Methods: Consecutive adult patients suspected of PE and with a Wells score &gt; 4 or a positive D-dimer result were prospectively enrolled in three EDs. Final diagnosis was obtained with MCTPA. Multiorgan ultrasonography was performed before MCTPA and considered diagnostic for PE if one or more subpleural infarcts, right ventricular dilatation, or DVT was detected. If multiorgan ultrasonography was negative for PE, an alternative ultrasonography diagnosis was sought. Accuracies of each single-organ and multiorgan ultrasonography were calculated., Results: PE was diagnosed in 110 of 357 enrolled patients (30.8%). Multiorgan ultrasonography yielded a sensitivity of 90% and a specificity of 86.2%, lung ultrasonography 60.9% and 95.9%, heart ultrasonography 32.7% and 90.9%, and vein ultrasonography 52.7% and 97.6%, respectively. Among the 132 patients (37%) with multiorgan ultrasonography negative for PE plus an alternative ultrasonographic diagnosis or plus a negative D-dimer result, no patients received PE as a final diagnosis., Conclusions: Multiorgan ultrasonography is more sensitive than single-organ ultrasonography, increases the accuracy of clinical pretest probability estimation in patients with suspected PE, and may safely reduce the MCTPA burden., Trial Registry: ClinicalTrials.gov; No.: NCT01635257; URL: www.clinicaltrials.gov.

Background: In patients with acute pulmonary embolism (PE), the correlation between the embolic burden assessed by multidetector CT (MDCT) scan and clinical outcomes remains unclear. Patients with symptomatic acute PE diagnosed based on MDCT angiography were included in a multicenter study aimed at assessing the prognostic role of the embolic burden evaluated with MDCT scan., Methods: Embolic burden was assessed as (1) localization of the emboli as central (saddle or at least one main pulmonary artery), lobar, or distal (segmental or subsegmental arteries) and (2) the obstruction index by the scoring system of Qanadli. The primary outcome was 30-day all-cause death or clinical deterioration. Predictors of all-cause death or clinical deterioration were identified by Cox regression statistics., Results: Overall, 579 patients were included in the study; 60 (10.4%) died or had clinical deterioration at 30 days. Central localization of emboli was not associated with all-cause death or clinical deterioration (hazard ratio [HR], 2.42; 95% CI, 0.77-7.59; P 5 .13). However, in 516 hemodynamically stable patients, central localization of emboli (HR, 8.3; 95% CI, 1.0-67; P 5 .047) was an independent predictor of all-cause death or clinical deterioration, whereas distal emboli were inversely associated with these outcome events (HR, 0.12; 95% CI, 0.015-0.97; P 5 .047). No correlation was found between obstruction index (evaluated in 448 patients) and all-cause death or clinical deterioration in the overall study population and in the hemodynamically stable patients., Conclusions: In hemodynamically stable patients with acute PE, central emboli are associated with an increased risk for all-cause death or clinical deterioration. This risk is low in patients with segmental or subsegmental PE.

Background: Recently, some prognostic models for acute pulmonary embolism (PE) have been proposed. We investigated whether the Pulmonary Embolism Severity Index (PESI) and the European Society of Cardiology (ESC) prognostic approaches result in different prognoses., Methods: Consecutive adult patients with acute PE were included. According to the ESC guidelines, high-risk patients were identified by the presence of shock/hypotension, intermediate-risk patients by elevated troponin I or right ventricular dysfunction as assessed by echocardiography, and low-risk patients by the absence of any of the above. In the PESI model, 11 clinical variables, easily accessible at the bedside, were used to generate three risk classes. The main outcomes were all-cause and PE-related in-hospital mortality., Results: Forty-one patients (8%, 95% confidence interval [CI] 5.8-10.8) of 510 died. According to the ESC model, 40% were at low risk of short-term mortality, 54% at intermediate risk, and 6% at high risk. The distribution according to the PESI model was 31% (P < 0.05 vs. ESC), 49% and 20% (P < 0.05 vs. ESC), respectively. Mortality increased through the risk classes (P < 0.01), without significant differences between the models. The ESC model identified with higher accuracy than the PESI model both high-risk and low-risk patients (P < 0.05 for both). When patients with shock/hypotension were excluded, the PESI model stratified patients into classes with increasing PE-related mortality (0.7%, 4.3%, and 11.6%, P < 0.05). Troponin I and right ventricular dysfunction added incremental prognostic value to the PESI model, particularly in normotensive patients at intermediate risk., Conclusions: The ESC model showed higher accuracy than the PESI model in identifying high-risk and low-risk patients. In normotensive patients, the PESI model could guide clinical management as well as troponin I and echocardiography testing., (© 2011 International Society on Thrombosis and Haemostasis.)

Background: The absence of a rapidly available and sensitive diagnostic test represents an important limitation in the triage of patients with suspected stroke., Objectives: The aim of the present study was to investigate the triage accuracy of a novel test that measures blood-borne biomarkers (triage stroke panel, TSP) and to compare its accuracy with that of the Cincinnati Prehospital Stroke Scale (CPSS)., Methods: Consecutive patients with suspected stroke presenting to the Emergency Departments of three Italian hospitals underwent triage by a trained nurse according to the CPSS and had blood drawn for TSP testing. The TSP simultaneously measures four markers (B-type natriuretic peptide, D-dimer, matrix metalloproteinase-9, and S100β) presenting a single composite result, the Multimarker Index (MMX). Stroke diagnosis was established by an expert committee blinded to MMX and CPSS results., Results: There were 155 patients enrolled, 87 (56%) of whom had a final diagnosis of stroke. The area under the receiver operating characteristic (ROC) curve for CPSS was 0.77 (95% confidence interval [CI] 0.70-0.84) and that of MMX was 0.74 (95% CI 0.66-0.82) (p = 0.285). Thus, both tests, when used alone, failed to recognize approximately 25% of strokes. The area under the ROC curve of the combination of the two tests (0.86, 95% CI 0.79-0.91) was significantly greater than that of either single test (p = 0.01 vs. CPSS and p < 0.001 vs. TSP)., Conclusions: In an emergency care setting, a panel test using multiple biochemical markers showed triage accuracy similar to that of CPSS. Further studies are needed before biomarkers can be introduced in the clinical work-up of patients with suspected stroke., (Copyright © 2011 Elsevier Inc. All rights reserved.)