Proarrhythmia assessment in treatment with hydroxychloroquine and azithromycin hospitalized elderly COVID-19 patients - our experience

The aim of our study was to characterize the repolarization disorders propensity induced by drug-drug interaction. In this observational retrospective study, we report our experience on all elderly patients with ascertained diagnosis of coronavirus disease 2019 through nasopharyngeal swab with real time-polymerase chain reaction at our Pugliese-Ciaccio hospital in Catanzaro, who received hydroxychloroquine (HCQ), with or without azithromycin (AZY). 33 hospitalized patients were examined. We calculated QT value, cQT, QT dispersion, and cQT dispersion and examined possible progression on the basal electrocardiogram (T0) and after the insertion of the drug (T1). The QT value is increased by T0 vs T1 (370±40.74 vs 420±36.91 ms; P=0.000), as well as the cQT value (408±25.40 vs 451.54±58.81; P=0.003), the QT dispersion (QTd: 36.36±14.53 vs 50.90±13.12 ms; P=0.000); the dispersion of cQTc (cQTd 46.27±18.72 vs 63.18±21.93 ms; P=0.001). The ΔQT was 37.44±44.09 while the ΔcQT was 32.01±56.47). The main determinant of QTc prolongation is the number of drug at risk of prolongation of the QT that could influence the ventricular repolarization phase. The use of HCQ in combination with AZY, in patients suffering from severe acute respiratory syndrome-related coronavirus-2, can favor the onset of serious side effects, even potentially fatal. Finally, the measures of QTd and cQTd confirmed additional electrocardiographic parameters useful in identifying patients being treated with drugs at risk of potential adverse arrhythmic events following drug interaction

Hydroxychloroquine and QTc: beyond COVID-19

Hydroxychloroquine is an antimalarial drug also known for its anti-inflammatory and antiviral effects, which have raised the interest of many researchers for its potential use in COVID-19 patients. It is known that this drug, being able to influence the cardiac repolarization phase with QTc interval prolongation, can be potentially harmful, chiefly in elderly subjects with frailty syndrome, several comorbidities and polypharmacotherapy. Therefore, although electrocardiogram monitoring of QTc prolongation is the focal point for reducing the arrhythmic risk of these patients, in order to identify the most exposed patients, the traditional Comprehensive Geriatric Assessment should be combined with a multiparametric risk score for QTc prolongation

Association between preoperative evaluation with lung ultrasound and outcome in frail elderly patients undergoing orthopedic surgery for hip fractures: study protocol for an Italian multicenter observational prospective study (LUSHIP)

Hip fracture is one of the most common orthopedic causes of hospital admission in frail elderly patients. Hip fracture fixation in this class of patients is considered a high-risk procedure. Preoperative physical examination, plasma natriuretic peptide levels (BNP, Pro-BNP), and cardiovascular scoring systems (ASA-PS, RCRI, NSQIP-MICA) have all been demonstrated to underestimate the risk of postoperative complications. We designed a prospective multicenter observational study to assess whether preoperative lung ultrasound examination can predict better postoperative events thanks to the additional information they provide in the form of "indirect" and "direct" cardiac and pulmonary lung ultrasound signs

Concept modelling of vehicle joints and beam-like structures through dynamic FE-based methods

This paper presents dynamic methodologies able to obtain concept models of automotive beams and joints, which compare favourably with the existing literature methods, in terms of accuracy, easiness of implementation and computational loads. For the concept beams, the proposed method is based on a dynamic Finite Element (FE) approach, which estimates the stiffness characteristics of equivalent 1D beam elements using the natural frequencies, computed by a modal analysis of the original 3D FE model of the structure. Concept beams are then connected to each other by a concept joint, which is obtained through a dynamic reduction technique that makes use of its vibration normal modes. The joint reduction is improved through the application of a new interface beam-to-joint element, able to interpolate accurately the nodal displacements of the outer contour of the section, to obtain displacements and rotations of the central connection node. The proposed approach is validated through an application case that is typical in vehicle body engineering: the analysis of a structure formed by three spot-welded thin-walled beams, connected by a joint.status: publishe

Dynamic FE-based method for concept modelling of vehicle beam-like structures

Vehicle body structures are characterized by load-carrying thin-walled beam-members, typically formed by spot-welded panels, with sections variations and discontinuities that highly influence both the static and the dynamic behaviour of the entire structure. Vehicle body concept modelling is an active field of research. Different methodologies are available, either based on the geometric analysis of the spatial mass distribution at each relevant cross-section or on static finite element (FE) based characterization of the beam properties. This paper presents a new methodology for estimating the cross-section properties of automotive structures with a beam-like behaviour. It is based on a dynamic FE approach, which allows estimating the stiffness characteristics (e.g. quadratic moments of inertia, torsional modulus, etc.) of equivalent 1D beam elements, using the natural frequencies estimated by means of a modal analysis on the original 3D FE model of the structure. The proposed method has been validated through an application case, comprising the analysis of a thin-walled beam with double-symmetric cross-section, formed by two spot-welded panels.status: publishe

Concept Modelling of Vehicle Joints and Beam-Like Structures through Dynamic FE-Based Methods

This paper presents dynamic methodologies able to obtain concept models of automotive beams and joints, which compare favourably with the existing literature methods, in terms of accuracy, easiness of implementation, and computational loads. For the concept beams, the proposed method is based on a dynamic finite element (FE) approach, which estimates the stiffness characteristics of equivalent 1D beam elements using the natural frequencies, computed by a modal analysis of the detailed 3D FE model of the structure. Concept beams are then connected to each other by a concept joint, which is obtained through a dynamic reduction technique that makes use of its vibration normal modes. The joint reduction is improved through the application of a new interface beam-to-joint element, able to interpolate accurately the nodal displacements of the outer contour of the section, to obtain displacements and rotations of the central connection node. The proposed approach is validated through an application case that is typical in vehicle body engineering: the analysis of a structure formed by three spot-welded thin-walled beams, connected by a joint.status: publishe

Innovative Concept Modelling of sandwich beam-like structures

Sandwich structures are widely used in many technical applications, because their composition combines high rigidity and strength with a good energy absorption, keeping low weights. Their static and dynamic behaviour can be studied by performing series of experi-mental tests, which, however, are expensive and require much setting and execution times. For this reason, it is common to use Finite Element (FE) simulation models, achieving good static and dynamic accuracy. However, difficulties in defining and modifying a complex mod-el led to the development of simplified models, such as 3D equivalent models. These homoge-neous models are based on specific laws and have geometric and stiffness characteristics equivalent to those of complex models. Many efforts have been spent to obtain models resem-bling the characteristics of honeycomb structures. These models have reached accurate static prediction performance, but obtaining a good accuracy for dynamic loads is still a challenge. Concept modelling approaches proved very useful for defining equivalent reduced models, able to reduce computational resources as well as the time needed for model modifications. In this paper, a dynamic FE-based method is used to obtain a concept model of honeycomb sandwich beams, that can reproduce accurately their static and dynamic behaviours. The method consists of two steps. First, a detailed FE model of one honeycomb beam-structure is developed and validated against experimental data obtained from literature. Its natural fre-quencies are estimated by means of a modal analysis in free-free conditions. Then, the analyt-ical modal model of the beam is used to derive cross-sectional stiffness properties of the equivalent 1D concept beam from the frequencies estimated by analysing the original 3D model. The analysis of a sandwich beam with a honeycomb aluminium core is presented as an application case to assess the accuracy of the proposed method.status: publishe

An examination of the anxiolytic effects of exercise for people with anxiety and stress-related disorders:A meta-analysis

The literature regarding exercise for people with established anxiety disorders is equivocal. To address this issue, we conducted a systematic review and meta-analysis investigating the benefits of exercise compared to usual treatment or control conditions in people with an anxiety and/or stress-related disorders. Major electronic databases were searched from inception until December/2015 and a random effect meta-analysis conducted. Altogether, six randomized control trials (RCTs) including 262 adults (exercise n=132, 34.74 [9.6] years; control n=130, 37.34 [10.0] years) were included. Exercise significantly decreased anxiety symptoms more than control conditions, with a moderate effect size (Standardized Mean Difference= 120.582, 95%CI 121.0 to 120.76, p=0.02). Our data suggest that exercise is effective in improving anxiety symptoms in people with a current diagnosis of anxiety and/ or stress-related disorders. Taken together with the wider benefits of exercise on wellbeing and cardiovascular health, these findings reinforce exercise as an important treatment option in people with anxiety/stress disorders. \ua9 2017 Elsevier Ireland Lt

Anti-htert sirna-loaded nanoparticles block the growth of anaplastic thyroid cancer xenograft

The high frequency of hTERT-promoting mutations and the increased expression of hTERT mRNA in anaplastic thyroid cancer (ATC) make TERT a suitable molecular target for the treatment of this lethal neoplasm. In this study, we encapsulated an anti-hTERT oligonucleotide in biocompatible nanoparticles and analyzed the effects of this novel pharmaceutical preparation in preclinical models of ATC. Biocompatible nanoparticles were obtained in an acidified aqueous solution containing chitosan, anti-hTERT oligoRNAs and poloxamer 188 as a stabilizer. The effects of these anti-hTERT -nanoparticles (Na-siTERT) were tested in vitro on ATC cell lines (CAL-62 and 8505C) and in vivo on xenograft tumors obtained by flank injection of CAL-62 cells into SCID-mice. The Na-siTERT reduced the viability and migration of CAL-62 and 8505C cells after 48 h incubation. Intra-venous administration (every 48 h for 13 days) of this encapsulated drug in mice hosting a xenograft thyroid cancer determined a great reduction in the growth of the neoplasm (about 50% vs untreated animals or mice receiving empty nanoparticles), and decreased levels of Ki67 associated with lower hTERT expression. Moreover, the treatment resulted in minimal invasion of near-by tissues and reduced the vascularity of the xenograft tumor. No signs of toxicity appeared following this treatment. Telomere length was not modified by the Na-siTERT, indicating that the inhibitory effects of neoplasm growth was independent from the enzymatic telomerase function. These findings demonstrate the potential suitability of this anti-TERT nanoparticle formulation as a novel tool for ATC treatment