Comparison and combination of a hemodynamics/biomarkers-based model with simplified PESI score for prognostic stratification of acute pulmonary embolism: findings from a real world study

Background: Prognostic stratification is of utmost importance for management of acute Pulmonary Embolism (PE) in clinical practice. Many prognostic models have been proposed, but which is the best prognosticator in real life remains unclear. The aim of our study was to compare and combine the predictive values of the hemodynamics/biomarkers based prognostic model proposed by European Society of Cardiology (ESC) in 2008 and simplified PESI score (sPESI).Methods: Data records of 452 patients discharged for acute PE from Internal Medicine wards of Tuscany (Italy) were analysed. The ESC model and sPESI were retrospectively calculated and compared by using Areas under Receiver Operating Characteristics (ROC) Curves (AUCs) and finally the combination of the two models was tested in hemodinamically stable patients. All cause and PE-related in-hospital mortality and fatal or major bleedings were the analyzed endpointsResults: All cause in-hospital mortality was 25% (16.6% PE related) in high risk, 8.7% (4.7%) in intermediate risk and 3.8% (1.2%) in low risk patients according to ESC model. All cause in-hospital mortality was 10.95% (5.75% PE related) in patients with sPESI score ≥1 and 0% (0%) in sPESI score 0. Predictive performance of sPESI was not significantly different compared with 2008 ESC model both for all cause (AUC sPESI 0.711, 95% CI: 0.661-0.758 versus ESC 0.619, 95% CI: 0.567-0.670, difference between AUCs 0.0916, p=0.084) and for PE-related mortality (AUC sPESI 0.764, 95% CI: 0.717-0.808 versus ESC 0.650, 95% CI: 0.598-0.700, difference between AUCs 0.114, p=0.11). Fatal or major bleedings occurred in 4.30% of high risk, 1.60% of intermediate risk and 2.50% of low risk patients according to 2008 ESC model, whereas these occurred in 1.80% of high risk and 1.45% of low risk patients according to sPESI, respectively. Predictive performance for fatal or major bleeding between two models was not significantly different (AUC sPESI 0.658, 95% CI: 0.606-0.707 versus ESC 0.512, 95% CI: 0.459-0.565, difference between AUCs 0.145, p=0.34). In hemodynamically stable patients, the combined endpoint in-hospital PE-related mortality and/or fatal or major bleeding (adverse events) occurred in 0% of patients with low risk ESC model and sPESI score 0, whilst it occurred in 5.5% of patients with low-risk ESC model but sPESI ≥1. In intermediate risk patients according to ESC model, adverse events occurred in 3.6% of patients with sPESI score 0 and 6.65% of patients with sPESI score ≥1.Conclusions: In real world, predictive performance of sPESI and the hemodynamic/biomarkers-based ESC model as prognosticator of in-hospital mortality and bleedings is similar. Combination of sPESI 0 with low risk ESC model may identify patients with very low risk of adverse events and candidate for early hospital discharge or home treatment.

<i>Actinomyces turicensis</i>: a peculiar case of empyema after COVID-19 in a patient with ulcerative colitis

Actinomyces species are recognized as common mucosal bacteria in humans and as a newly discovered source of infection. Since its discovery in 1995, the subspecies Actinomyces turicensis has been reported as the causative pathogen of numerous infections. Only two instances of A. turicensis-related empyema, however, have been documented in the literature as of late. We report a unique case of polymicrobial empyema caused by A. turicensis shortly after a COVID-19 without any clear risk factors for anaerobic aspiration, along with a brief review of the literature. Tetracycline was successfully used for the first time to treat A. turicensis empyema, following chest drainage

Benzene exposure in childhood: Role of living environments and assessment of available tools

Benzene is a widespread air pollutant and a well-known human carcinogen. Evidence is needed regarding benzene intake in the pediatric age group. We investigated the use of urinary (u) trans,trans-muconic acid (t,t-MA), S-phenylmercapturic acid (SPMA), and unmodified benzene (UB) for assessing exposure to low concentrations of environmental benzene and the role of living environment on benzene exposure in childhood. u-t,t-MA, u-SPMA, u-UB and u-cotinine were measured in urine samples of 243 Italian children (5-11 years) recruited in a cross-sectional study. Analytical results were compared with data obtained from questionnaires about participants' main potential exposure factors. u-UB, u-t,t-MA and u-SPMA concentrations were about 1.5-fold higher in children living in urban areas than in those in the rural group. Univariate analyses showed that u-UB was the only biomarker able to discriminate secondhand smoke (SHS) exposure in urban and rural children (medians = 411.50 and 210.50 ng/L, respectively): these results were confirmed by the strong correlation between u-UB and u-cotinine in the SHS-exposed group and by multivariate analyses. A regression model on u-SPMA showed that the metabolite is related to residence area (p<0.001), SHS exposure (p = 0.048) and gender (p = 0.027). u-UB is the best marker of benzene exposure in children in the present study, and it can be used as a good carcinogen-derived biomarker of exposure to passive smoking, especially related to benzene, when urine sample is collected at the end of the day. In addition, it is important to highlight that SHS resulted the most important contributor to benzene exposure, underlining the need for an information campaign against passive smoking exposure. (C) 2010 Elsevier Ltd. All rights reserved

Bivalent Ligands for the Serotonin 5-HT3 Receptor

The serotonin 5-HT3 receptor is a ligand-gated ion channel, which by virtue of its pentameric architecture, can be considered to be an intriguing example of intrinsically multivalent biological receptors. This paper describes a general design approach to the study of multivalency in this multimeric ion channel. Bivalent ligands for 5-HT3 receptor have been designed by linking an arylpiperazine moiety to probes showing different functional features. Both homobivalent and heterobivalent ligands have shown 5-HT3 receptor affinity in the nanomolar range, providing evidence for the viability of our design approach. Moreover, the high affinity shown by homobivalent ligands suggests that bivalency is a promising approach in 5-HT3 receptor modulation and provides the rational basis for applying the concepts of multivalency to the study of 5-HT3 receptor function

Clinical and genetic features of a cohort of patients with MFN2-related neuropathy

Charcot\u2013Marie\u2013Tooth disease type 2A (CMT2A) is a rare inherited axonal neuropathy caused by mutations in MFN2 gene, which encodes Mitofusin 2, a transmembrane protein of the outer mitochondrial membrane. We performed a cross-sectional analysis on thirteen patients carrying mutations in MFN2, from ten families, describing their clinical and genetic characteristics. Evaluated patients presented a variable age of onset and a wide phenotypic spectrum, with most patients presenting a severe phenotype. A novel heterozygous missense variant was detected, p.K357E. It is located at a highly conserved position and predicted as pathogenic by in silico tools. At a clinical level, the p.K357E carrier shows a severe sensorimotor axonal neuropathy. In conclusion, our work expands the genetic spectrum of CMT2A, disclosing a novel mutation and its related clinical effect, and provides a detailed description of the clinical features of a cohort of patients with MFN2 mutations. Obtaining a precise genetic diagnosis in affected families is crucial both for family planning and prenatal diagnosis, and in a therapeutic perspective, as we are entering the era of personalized therapy for genetic diseases

A water-soluble eumelanin polymer with typical polyelectrolyte behaviour by triethyleneglycol N-functionalization

N-functionalization of 5,6-dihydroxyindole with a hydrophilic triethyleneglycol (TEG) chain provides access to a new class of water-soluble eumelanin-like materials with relatively high dielectric constant and polyelectrolyte behaviour, reflecting enhanced charge transport by in-depth incorporation of hydration networks

Electrical Quality Assurance for the NbTi Coils of the HL-LHC High Order Corrector Magnets

The INFN-LASA laboratory (Milano, Italy) is involved in the High-Luminosity LHC program for the design, construction, and test of 54 superconducting high-order corrector magnets. One of the challenging project stages was the transition from the construction of laboratory prototypes to the series production, awarded to industries, with the demanding requirement of maintaining high-quality production standards. Common and custom quality assurance (QA) methods were adopted for the analysis of the electrical characteristics of the coils. This paper discusses in detail the principle of the methods, their expected sensitivity, and the final observed effectiveness on the 510 produced coils. In some cases, the methods led to early defect detection thus avoiding possible severe damages during the final cold test that have already occurred for a prototype magnet not subject to the QA procedures described in this paper