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Purpose: The aim of our study was to assess respiratory function at the time of clinical recovery and 6 weeks after discharge in patients surviving to COVID-19 pneumonia., Methods: Our case series consisted of 13 patients with COVID-19 pneumonia., Results: At the time of clinical recovery, FEV1 (2.07 ± 0.72 L) and FVC (2.25 ± 0.86 L) were lower compared to lower limit of normality (LLN) values (2.56 ± 0.53 L, p = 0.004, and 3.31 ± 0.65 L, p < 0.001, respectively), while FEV1/FVC (0.94 ± 0.07) was higher compared to upper limit of normality (ULN) values (0.89 ± 0.01, p = 0.029). After 6 weeks pulmonary function improved but FVC was still lower than ULN (2.87 ± 0.81, p = 0.014)., Conclusion: These findings suggest that COVID-19 pneumonia may result in clinically relevant alterations in pulmonary function tests, with a mainly restrictive pattern.

Abstract: COVID-19 is causing a high influx of patients suffering from serious respiratory complications leading the necessity to find effective therapies. These patients seem to present with cytokine perturbation and high levels of IL6. Tocilizumab and sarilumab could be effective in this condition.We retrospectively collected data about 112 consecutive hospitalized in a single center.Fifty (IL6 group) treated with tocilizumab (8 mg/kg intravenously [IV], 2 infusions 12 hours apart) or sarilumab 400 mg IV once and 62 treated with the standard of care but not anti-cytokine drugs (CONTROL group).To determine whether anti-IL6 drugs are effective in improving prognosis and reducing hospitalization times and mortality in COVID-19 pneumonia.To date 84% (42/50) of IL6 group patients have already been discharged and only 2/50 are still recovered and intubated in intensive care. Six/fifty patients (12%) died: 5/6 due to severe respiratory failure within a framework of severe acute respiratory distress syndrome (ARDS), 1 suffered an acute myocardial infarction, and 1 died of massive pulmonary thromboembolism. There were no adverse treatment events or infectious complications. Compared to the CONTROL group they showed a lower mortality rate (12% versus 43%), for the same number of complications and days of hospitalization.Anti-IL6 drugs seem to be effective in the treatment of medium to severe forms of COVID-19 pneumonia reducing the risk of mortality due to multi-organ failure, acting at the systemic level and reducing inflammation levels and therefore microvascular complications. However, it is essential to identify the best time for treatment, which, if delayed, is rendered useless as well as counterproductive. Further studies and ongoing clinical trials will help us to better define patients eligible as candidates for more aggressive intervention., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: A considerable number of SARS-CoV-2 infected individuals could be asymptomatic and don't need medical treatment. The clinical spectrum of SARS-CoV-2 infection ranges from asymptomatic cases, medium-intensity forms with mild to moderate symptoms, to severe ones with bilateral pneumonia and respiratory distress. In cases with severe presentation of SARS-CoV-2 infection, the induction of hypercoagulability is one of the pathophysiological mechanism that can contribute to death., Case Presentation: Here, we reported autoptic evidences of thrombotic pulmonary arterial fatal lesions in an asymptomatic COVID-19 patient, after swab negativization. Whole body complete post-mortem examination was performed, showing the presence of a large thrombus occluding the main pulmonary artery that was the cause of death. Histopathological analysis showed heterogeneous pattern of pathological changes in the lung tissue with numerous vascular thrombi, inflammatory cardiomyopathy and other histopathological modifications in kidneys, spleen and liver., Conclusions: This study provides evidences that also asymptomatic patients may be at risk to develop thrombotic complications. An appropriate diagnostic screening for thrombotic complications and the early treatment recommendations of antithrombotic drugs could represent an important topic even in asymptomatic individuals.

Background: Descriptions of the pathological features of coronavirus disease-2019 (COVID-19) caused by the novel zoonotic pathogen severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emanate from tissue biopsies, case reports, and small postmortem studies restricted to the lung and specific organs. Whole-body autopsy studies of COVID-19 patients have been sparse., Methods: To further define the pathology caused by SARS-CoV-2 across all body organs, we performed autopsies on 22 patients with COVID-19 (18 with comorbidities and 4 without comorbidities) who died at the National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS Hospital, Rome, Italy. Tissues from the lung, heart, liver, kidney, spleen, and bone marrow (but not the brain) were examined. Only lung tissues were subject to transmission electron microscopy., Results: COVID-19 caused multisystem pathology. Pulmonary and cardiovascular involvement were dominant pathological features. Extrapulmonary manifestations included hepatic, kidney, splenic, and bone marrow involvement, and microvascular injury and thrombosis were also detected. These findings were similar in patients with or without preexisting medical comorbidities., Conclusions: SARS-CoV-2 infection causes multisystem disease and significant pathology in most organs in patients with and without comorbidities., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting more than 10 million patients worldwide. Despite increasing improvements in disease management, a huge medical need still exists as its relentless progression cannot be delayed by current treatments. Therefore, scientists, clinicians, and pharmaceutical companies are hunting new drugs with 'disease-modifying' properties., Areas Covered: This review concentrates on new therapeutics - excluding cell and gene therapies - under investigation for PD with 'disease-modifying' potential. This is a global, comprehensive picture of the current innovative drug pipeline, where the main preclinical and clinical data available are provided. Drug candidates presented include α-synuclein modulating agents, neuroprotective agents and neuroinflammation modulators, kinase modulators, neurotrophic factors, and drugs acting on emerging targets., Expert Opinion: There is excitement for agents with 'disease-modifying' properties and the authors found more than 130 assets, not including cell and gene therapies under investigation - most of them still in preclinical development - meaning that the science is progressing multiple, diverse new opportunities. Many limitations hamper the successful development of these drug candidates such as the translational accuracy of preclinical models, the current clinical development paradigm as well as the lack of biomarkers to be used in diagnosis and therapy management.

The sudden worldwide outbreak of Coronavirus Disease 2019 (COVID-19) has certainly provided new challenges in the management of acute ischaemic stroke, and the risk-benefit ratio of intravenous thrombolysis in COVID-19 positive patients is not well known. We describe four COVID-19 patients treated with intravenous thrombolysis for acute ischaemic stroke. Although rt-PA administration is the main therapeutic strategy, our patients experienced unpredictable complications and showed atypical features: the overall mortality was very high. In conclusion, in this article, we provide information about these cases and discuss the possible explanation behind this trend.

Nine compounds, including two undescribed withanolides, withasomniferolides A and B (1 and 2), three known withanolides (3-5), a ferulic acid dimeric ester (6), and an inseparable mixture of three long alkyl chain ferulic acid esters (7-9), were isolated from a GABA A receptor positive activator methanol extract of the roots of Withania somnifera. The structures of the isolated compounds were elucidated based on NMR, MS, and ECD data analysis. In order to bioassay the single ferulic acid derivatives, compounds 6-9 were also synthesized. The most active compound, docosanyl ferulate (9), was able to enhance the GABA A receptor inhibitory postsynaptic currents with an IC 50 value of 7.9 μM. These results, by showing an ability to modulate the GABA A receptor function, cast fresh light on the biological activities of the secondary metabolites of W. somnifera roots.

The recent advances in the knowledge of immunological aspects of many pulmonary diseases, allowed to identify cells, biological functions, cytokines, and receptors that are preferentially involved in each disease. This is the case of asthma, where IL-13 (together with IL-4) is recognized as a central mediator. The role of IL-13 is strictly related, via complex signaling pathways, to eosinophil recruitment and activation, to mucus secretion, periostin generation and to fibrogenic processes (which are part of the remodeling process). These peculiar roles of IL-13 have suggested the hypothesis of its role in Idiopathic Pulmonary Fibrosis, and consequently of its antagonists in the treatment of such disease. We review herein the immunological roles of IL-13 in asthma and IPF, and the currently ongoing attempts to treat IPF by IL-13 antagonism strategies., (Copyright © 2017. Published by Elsevier Ltd.)

Despite the screening program, breast cancer is the commonest cause of cancer death in women in the industrialized world. In this study, we investigate the correlation among poorly differentiated carcinoma, epithelial to mesenchymal transition (EMT) phenomenon, and expression of NF-kB, Sonic Hedgehog (SHH), K-RAS, and PTX3 in breast cancer in 100 breast biopsies. Samples were classified as follows: 30 benign lesions (BL), 30 ductal infiltrating carcinomas low grade (MLG1), and 40 ductal infiltrating carcinomas high grade (MLG3). Expression of vimentin, CD44, β-catenin, NF-kB, SHH, K-RAS, CD44, and PTX3 was studied by immunohistochemistry. The different rate of cells with vimentin, nuclear β-catenin, and CD44 expression in MLG3 as compared with MLG1 and BL suggested that the process of de-differentiation of breast cancer cells could be related to the EMT. Our results showed a significant increase in NF-kB signal in MLG3 (2.33 ± 0.77) with respect to MLG1 (1.26 ± 0.55) and BL (0.86 ± 0.52). SHH expression appeared low in BL (1.00 ± 0.41) and homogenously widespread in MLG1 (1.23 ± 0.63) and MLG3 (1.56 ± 0.54). An important increase in K-RAS signal was observed in MLG3 compared to that in BL (2.20 ± 0.69 vs 0.82 ± 0.59). As regards PTX3, we observed a strong expression in MLG3 (2.00 ± 0.78) with respect to BL (0.58 ± 0.55) and MLG1 (1.53 ± 0.76). The recurring expression of NF-kB, SHH, K-RAS, and PTX3 in vimentin- and CD44-positive breast cancer cells allows to speculate that breast cells acquire the ability to express these molecules in concomitance to EMT phenomenon.

DNA methylation is an epigenetic modification associated with transcriptional repression of promoters and is essential for mammalian development. Establishment of DNA methylation is mediated by the de novo DNA methyltransferases DNMT3A and DNMT3B, whereas DNMT1 ensures maintenance of methylation through replication. Absence of these enzymes is lethal, and somatic mutations in these genes have been associated with several human diseases. How genomic DNA methylation patterns are regulated remains poorly understood, as the mechanisms that guide recruitment and activity of DNMTs in vivo are largely unknown. To gain insights into this matter we determined genomic binding and site-specific activity of the mammalian de novo DNA methyltransferases DNMT3A and DNMT3B. We show that both enzymes localize to methylated, CpG-dense regions in mouse stem cells, yet are excluded from active promoters and enhancers. By specifically measuring sites of de novo methylation, we observe that enzymatic activity reflects binding. De novo methylation increases with CpG density, yet is excluded from nucleosomes. Notably, we observed selective binding of DNMT3B to the bodies of transcribed genes, which leads to their preferential methylation. This targeting to transcribed sequences requires SETD2-mediated methylation of lysine 36 on histone H3 and a functional PWWP domain of DNMT3B. Together these findings reveal how sequence and chromatin cues guide de novo methyltransferase activity to ensure methylome integrity.

Clinical practice protocols for the control and prevention of respiratory infections in rehabilitation settings, especially regarding pediatric tracheostomized patients, are currently lacking. To tackle this issue, we conducted a systematization of our clinical management protocols, aiming at defining a decisional algorithm and describing its key points in more detail. We focused on infection control, improvement of respiratory functions, and weaning from tracheostomy., (Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Ventricular tachycardia or frequent premature ventricular contractions (PVCs) can occur in the absence of any detectable structural heart disease. In this clinical setting, these arrhythmias are termed idiopathic. Usually, they carry a benign prognosis and any potential ablative intervention is carried out if patients are highly symptomatic or, more importantly, if frequent ventricular arrhythmias can lead to ventricular dysfunction., Methods: In this paper, different forms of idiopathic ventricular tachycardia are reviewed. Outflow tract ventricular tachycardia from the right ventricle is the most frequent form of the so-called idiopathic ventricular tachycardia. Other forms of idiopathic ventricular arrhythmias include ventricular tachycardia/PVCs arising from tricuspid annulus, from the mitral annulus, inter-fascicular ventricular tachycardia and papillary muscle ventricular tachycardia. When interventional treatment is deemed necessary, detailed mapping ( earliest activation during VT/PVC, pace mapping ) is crucial as to identify the successful ablation site. Catheter ablation more than antiarrhythmic drug treatment is usually highly effective in eliminating idiopathic ventricular arrhythmias and providing prevention of recurrence., Conclusions: Idiopathic VTs are not considered life-threatening arrhythmias and, prevention of recurrences is often achieved by means of catheter ablation that provides an improvement of quality of life. The overall acute success rate of catheter ablation is about 85-90% with a long-term prevention of arrhythmia recurrence of about 75-80%. It is advisable that the procedure is carried out by electrophysiologists with expertise in VT catheter ablation and extensive knowledge of cardiac anatomy as to ensure a high success rate and reduce the likelihood of major complications.

Most of interventional procedures in cardiology are carried out under fluoroscopic imaging guidance. Besides other peri-interventional risks, radiation exposure should be considered for its stochastic (inducing malignancy) and deterministic effects on health (tissue reactions like erythema, hair loss and cataracts). In this article we analized the radiation risk from cardiovascular imaging to both patients and medical staff and discusses how customize the X-ray system and how to implement shielding measures in the cath lab. Finally, we reviewed the most recent developments and the latest findings in catheter navigation and 3D electronatomical mapping systems that may help to reduce patient and operator exposure.

Purpose: Contact with cardiac tissue is a determinant of lesion efficacy during atrial fibrillation (AF) ablation. The Sensei®X Robotic Catheter System (Hansen Medical, CA) has been validated for contact force sensing. The electrical coupling index (ECI) from the EnSite Contact™ system (St. Jude Medical, MN) has been validated as an indicator of tissue contact. We aimed at analyzing ECI behavior during radiofrequency (RF) pulses maintaining a stable contact through the robotic navigation contact system., Methods: In 15 patients (age, 59 ± 12) undergoing AF ablation, pulmonary vein (PV) isolation was guided by the Sensei®X System, employing the Contact™ catheter., Results: During the procedure, we assessed ECI changes associated with adequate contact based on the IntelliSense® force-sensing technology (Hansen Medical, CA. Baseline contact (27 ± 8 g/cm(2)) ECI value was 99 ± 13, whereas ECI values in a noncontact site (0 g/cm(2)) and in a light contact site (1-10 g/cm(2)) were respectively 66 ± 12 and 77 ± 10 (p < 0.0001). Baseline contact ECI values were not different depending on AF presentation (paroxysmal AF, 98 ± 9; persistent AF, 100 ± 9) or on cardiac rhythm (sinus rhythm, 97 ± 7; AF,101 ± 10). In all PVs, ECI was significantly reduced during and after ablation (ECI during RF, 56 ± 15; ECI after RF, 72 ± 16; p < 0.001). A mean reduction of 32.2% during RF delivery and 25.4% immediately after RF discontinuation compared with baseline ECI was observed., Conclusions: Successful PV isolation is associated with a significant decrease in ECI of at least 20 %. This may be used as a surrogate marker of effective lesion in AF ablation.

In the recent years, several new evidences support catheter-based ablation as a treatment modality of atrial fibrillation (AF). Based on a plenty of different applications, intracardiac echocardiography (ICE) is now a well-established technology in complex electrophysiological procedures, in particular in AF ablation. ICE contributes to improve the efficacy and safety of such procedures defining the anatomical structures involved in ablation procedures and monitoring in real time possible complications. In particular ICE allows: a correct identification of the endocardial structures; a guidance of transseptal puncture; an assessment of accurate placement of the circular mapping catheter; an indirect evaluation of evolving lesions during radiofrequency (RF) energy delivery via visualization of micro and macrobubbles tissue heating; assessment of catheter contact with cardiac tissues. Recently, also the feasibility of the integration of electroanatomical mapping (EAM) and intracardiac echocardiography has been demonstrated, combining accurate real time anatomical information with electroanatomical data. As a matter of fact, different techniques and ablation strategies have been developed throughout the years. In the setting of balloon-based ablation systems, recently adopted by an increasing number of centers, ICE might have a role in the choice of appropriate balloon size and to confirm accurate occlusion of pulmonary veins. Furthermore, in the era of minimally fluoroscopic ablation, ICE has successfully provided a contribute in reducing fluoroscopy time. The purpose of this review is to summarize the current applications of ICE in catheter based ablation strategies of atrial fibrillation, focusing-on electronically phased-array ICE.