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Despite significant advances in the diagnosis and treatment of cardiovascular diseases, recent calls have emphasized the unmet need to improve precision-based approaches in cardiovascular disease. Although some studies provide preliminary evidence of the diagnostic and prognostic potential of circulating coding and non-coding RNAs, the complex RNA biology and lack of standardization have hampered the translation of these markers into clinical practice. In this position paper of the CardioRNA COST action CA17129, we provide recommendations to standardize the RNA development process in order to catalyse efforts to investigate novel RNAs for clinical use. We list the unmet clinical needs in cardiovascular disease, such as the identification of high-risk patients with ischaemic heart disease or heart failure who require more intensive therapies. The advantages and pitfalls of the different sample types, including RNAs from plasma, extracellular vesicles, and whole blood, are discussed in the sample matrix, together with their respective analytical methods. The effect of patient demographics and highly prevalent comorbidities, such as metabolic disorders, on the expression of the candidate RNA is presented and should be reported in biomarker studies. We discuss the statistical and regulatory aspects to translate a candidate RNA from a research use only assay to an in-vitro diagnostic test for clinical use. Optimal planning of this development track is required, with input from the researcher, statistician, industry, and regulatory partners., peer-reviewed

The treatment of patients with advanced acute heart failure is still challenging. Intra-aortic balloon pump (IABP) has widely been used in the management of patients with cardiogenic shock. However, according to international guidelines, its routinary use in patients with cardiogenic shock is not recommended. This recommendation is derived from the results of the IABP-SHOCK II trial, which demonstrated that IABP does not reduce all-cause mortality in patients with acute myocardial infarction and cardiogenic shock. The present position paper, released by the Italian Association of Hospital Cardiologists, reviews the available data derived from clinical studies. It also provides practical recommendations for the optimal use of IABP in the treatment of cardiogenic shock and advanced acute heart failure.

The European Society of Cardiology guidelines on non-ST-elevation acute coronary syndromes suggest different temporal strategies for the angiographic study depending on the risk profile. The scientific evidence underlying the guideline recommendations and the critical issues currently existing in Italy, that often do not allow either an extended strategy of revascularization within 24 h or the application of the principle of the same day transfer from a spoke to a hub centre, are analysed. The position paper focuses, in particular, on the subgroup of patients with a defined diagnosis of non-ST-elevation myocardial infarction by proposing a timing of coronary angiography/revascularization that takes into account the available scientific evidence and the organizational possibilities of a considerable part of national cardiology services.

Cardiac arrhythmias are a major cause of death and disability. A large number of experimental cell and animal models have been developed to study arrhythmogenic diseases. These models have provided important insights into the underlying arrhythmia mechanisms and translational options for their therapeutic management. This position paper from the ESC Working Group on Cardiac Cellular Electrophysiology provides an overview of (i) currently available in vitro, ex vivo, and in vivo electrophysiological research methodologies, (ii) the most commonly used experimental (cellular and animal) models for cardiac arrhythmias including relevant species differences, (iii) the use of human cardiac tissue, induced pluripotent stem cell (hiPSC)-derived and in silico models to study cardiac arrhythmias, and (iv) the availability, relevance, limitations, and opportunities of these cellular and animal models to recapitulate specific acquired and inherited arrhythmogenic diseases, including atrial fibrillation, heart failure, cardiomyopathy, myocarditis, sinus node, and conduction disorders and channelopathies. By promoting a better understanding of these models and their limitations, this position paper aims to improve the quality of basic research in cardiac electrophysiology, with the ultimate goal to facilitate the clinical translation and application of basic electrophysiological research findings on arrhythmia mechanisms and therapies.

When toilet paper disappeared from store shelves across Japan in November 1973, the housewives who searched their neighborhood markets and stood in long lines for the scarce packs were described as unwitting perpetrators of a “toilet paper panic.” The word “panic” evoked well-established notions of a social frenzy, irrational and overwrought. This article overturns a conception of panic laden with condescension and adopts, instead, a more empathetic approach to examining why a run on toilet paper and other daily necessities occurred in late 1973, and why it resonated so deeply across Japan as a “panic.” In the broader context of the early 1970s, the toilet paper scare and its characterization as a “panic” can be understood as responses to sweeping and multifaceted economic challenges that destabilized daily life and threatened to upend middle-class lifestyles. After more than fifteen years of high economic growth, that sense of middle-class comfort and security was shaken by shortages and inflation as well as mounting evidence of government ineptitude and corporate profiteering. Buffeted by insecurity and uncertainty, Japanese “middle-classness” as both an experience and an ideal had never seemed as vulnerable as it did in the early 1970s.

Two novel methods of measuring the dimensions of oral lesions are described, which would be of help in deciding relative efficacies of different therapeutic agents when used in clinical trials after larger studies quantitatively assessed for inter/intraobserver variability.

Atherosclerosis often affects the coronary arterial tree. Frequently the disease does not translate in significant narrowing of the vessels, thus determining only a non-obstructive disease. This condition that is described as non-obstructive coronary artery disease (NobsCAD) should be distinguished from the absence of disease (i.e. smooth coronary arteries) as it carries a specific prognostic value. The detection and reporting of NobsCAD should prompt preventive measures that can be individualized upon the degree of the underlying burden of disease. The accompanying clinical condition, the other cardiovascular risk factors present, and the description of the severity and extent of NobsCAD should provide the framework for an individualized treatment that should also consider the best available scientific evidence and guidelines. The description of NobsCAD represents important information to be collected whenever a coronary angiogram (both invasive and non-invasive) is performed. Treating the patient according to the presence and extent of NobsCAD offers prognostic benefits well beyond those offered by considering only the traditional cardiovascular risk factors. In order to reach this goal, NobsCAD should not be confused with the absence of coronary atherosclerosis or even ignored when detected as if it was a trivial information to provide.

The COVID-19 pandemic represents an unprecedented event that has brought deep changes in hospital facilities with reshaping of the health system organization, revealing inadequacies of current hospital and local health systems. When the COVID-19 emergency will end, further evaluation of the national health system, new organization of acute wards, and a further evolution of the entire health system will be needed to improve care during the chronic phase of disease. Therefore, new standards for healthcare personnel, more efficient organization of hospital facilities for patients with acute illnesses, improvement of technological approaches, and better integration between hospital and territorial services should be pursued. With experience derived from the COVID-19 pandemic,new models, paradigms, interventional approaches, values and priorities should be suggested and implemented.

This is a pre-copyedited, author-produced version of an article accepted for publication in European Journal of Preventive Cardiology following peer review. The version of record Kavousi, Pisinger, Barthelemy, Smedt, Koskinas, Marques-Vidal, Panagiotakos, Prescott, Tiberi, Vassiliou, Løchen. Electronic cigarettes and health with special focus on cardiovascular effects: position paper of the European Association of Preventive Cardiology (EAPC). European Journal of Preventive Cardiology (EJPC). 2020:2047487320941993, is available online at: https://doi.org/10.1177/2047487320941993. Background - Tobacco use is the single largest preventable risk factor for premature death of non-communicable diseases and the second leading cause of cardiovascular disease. In response to the harmful effects of tobacco smoking, the use of electronic cigarettes (e-cigarettes) has emerged and gained significant popularity over the past 15 years. E-cigarettes are promoted as safe alternatives for traditional tobacco smoking and are often suggested as a way to reduce or quit smoking. However, evidence suggests they are not harmless. Discussion - The rapid evolution of the e-cigarette market has outpaced the legislator’s regulatory capacity, leading to mixed regulations. The increasing use of e-cigarettes in adolescents and young individuals is of concern. While the long-term direct cardiovascular effects of e-cigarettes remain largely unknown, the existing evidence suggests that the e-cigarette should not be regarded as a cardiovascular safe product. The contribution of e-cigarette use to reducing conventional cigarette use and smoking cessation is complex, and the impact of e-cigarette use on long-term cessation lacks sufficient evidence. Conclusion - This position paper describes the evidence regarding the prevalence of e-cigarette smoking, uptake of e-cigarettes in the young, related legislations, cardiovascular effects of e-cigarettes and the impact of e-cigarettes on smoking cessation. Knowledge gaps in the field are also highlighted. The recommendations from the population science and public health section of the European Association of Preventive Cardiology are presented.

Background Cutaneous leishmaniasis (CL) is generally diagnosed by molecular methods, including PCR, using biopsy samples, skin scrapings and clinical exudates. In this study, we assessed the PCR performance for diagnosis of CL using skin of biopsy samples vs PCR of skin lesion exudate samples on filter paper and compared the diagnostic concordance of PCR using both sampling methods. Methods We assessed the PCR performance using 80 skin biopsy samples and 80 filter paper samples containing exudates from skin lesions obtained from 74 patients with clinical suspicion of CL in Cusco, Peru. Results : PCR using skin biopsy samples had superior diagnostic accuracy compared with filter paper PCR (62.5% [50/80] vs 38.7% [31/80], respectively; p˂0.005) and the diagnostic concordance between both sampling methods was ‘moderate’ (kappa coefficient=0.50, 95% CI 0.98 to 1.0). Conclusions PCR using biopsy samples remains the standard for diagnosis of CL.

In 2018, the position paper ‘Imaging the adult with congenital heart disease: a multimodality imaging approach’ was published. The paper highlights, in the first part, the different imaging modalities applied in adult congenital heart disease patients. In the second part, these modalities are discussed more detailed for moderate to complex anatomical defects. Because of the length of the paper, simple lesions were not touched on. However, imaging modalities to use for simple shunt lesions are still poorly known. One is looking for structured recommendations on which they can rely when dealing with an (undiscovered) shunt lesion. This information is lacking for the initial diagnostic process, during repair and at follow-up. Therefore, this paper will focus on atrial septal defect, ventricular septal defect, and persistent arterial duct. Pre-, intra-, and post-procedural imaging techniques will be systematically discussed. This position paper will offer algorithms that might help at a glance. The document is prepared for general cardiologists, trainees, medical students, imagers/technicians to select the most appropriate imaging modality and to detect the requested information for each specific lesion. It might serve as reference to which researchers could refer when setting up a (imaging) study.

Differences of Sex Development (DSD) comprise a variety of congenital conditions characterized by atypical chromosomal, gonadal, or anatomical sex. Diagnosis and monitoring of treatment of patients suspected of DSD conditions include clinical examination, measurement of peptide and steroid hormones, and genetic analysis. This position paper on peptide hormone analyses in the diagnosis and control of patients with DSD was jointly prepared by specialists in the field of DSD and/or peptide hormone analysis from the European Cooperation in Science and Technology (COST) Action DSDnet (BM1303) and the European Reference Network on rare Endocrine Conditions (Endo-ERN). The goal of this position paper on peptide hormone analysis was to establish laboratory guidelines that may contribute to improve optimal diagnosis and treatment control of DSD. The essential peptide hormones used in the management of patients with DSD conditions are follicle-stimulating hormone, luteinising hormone, anti-Müllerian hormone, and Inhibin B. In this context, the following position statements have been proposed: serum and plasma are the preferred matrices; the peptide hormones can all be measured by immunoassay, while use of LC-MS/MS technology has yet to be implemented in a diagnostic setting; sex- and age-related reference values are mandatory in the evaluation of these hormones; and except for Inhibin B, external quality assurance programs are widely available.

Objectives Medication errors are among the most common medical errors. They can result in mortality, morbidity and additional healthcare costs. Surveillance of medication errors is encouraged to identify gaps in the healthcare system and work on them. This study aimed to compare medication errors in outpatient prescriptions in two hospitals in Jordan: one with a paper-based and one with an electronic prescription system. Methods This was a cross-sectional observational study in two large hospitals in Jordan over a three-month period. Prescribing and dispensing of medicines were screened for medication errors in both centres: 2500 prescriptions were screened in each hospital. Key findings In the hospital with electronic prescriptions, of the 2500 prescriptions screened, 631 medication errors were detected: 231 (36.6%) prescription errors and 400 (63.4%) dispensing errors. In the hospital with paper-based prescriptions, 3714 medication errors were found: 288 (7.8%) prescription errors and 3426 (92.2%) dispensing errors. The most common prescription and dispensing errors in electronic prescriptions were, respectively, prescription of drugs that could have a drug–drug interaction, and omitting to dispense a drug on the prescription. In the paper prescriptions, the most common prescription and dispensing errors were, respectively, inappropriate dose/quantity/frequency or route of administration, and inappropriate and/or inadequate labelling of medication when dispensed, of which there were a large number (2496 (67.2%)). Conclusion This study highlights the effect of the prescription system used by hospitals. Fewer medication errors were found in the electronic system. Healthcare policymakers, professionals and administrators are encouraged to invest in electronic systems to minimize medication errors.

Author(s): Anker, Stefan D; Butler, Javed; Khan, Muhammad Shahzeb; Abraham, William T; Bauersachs, Johann; Bocchi, Edimar; Bozkurt, Biykem; Braunwald, Eugene; Chopra, Vijay K; Cleland, John G; Ezekowitz, Justin; Filippatos, Gerasimos; Friede, Tim; Hernandez, Adrian F; Lam, Carolyn SP; Lindenfeld, JoAnn; McMurray, John JV; Mehra, Mandeep; Metra, Marco; Packer, Milton; Pieske, Burkert; Pocock, Stuart J; Ponikowski, Piotr; Rosano, Giuseppe MC; Teerlink, John R; Tsutsui, Hiroyuki; Van Veldhuisen, Dirk J; Verma, Subodh; Voors, Adriaan A; Wittes, Janet; Zannad, Faiez; Zhang, Jian; Seferovic, Petar; Coats, Andrew JS | Abstract: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has important implications for the safety of participants in clinical trials and the research staff caring for them and, consequently, for the trials themselves. Patients with heart failure may be at greater risk of infection with COVID-19 and the consequences might also be more serious, but they are also at risk of adverse outcomes if their clinical care is compromised. As physicians and clinical trialists, it is our responsibility to ensure safe and effective care is delivered to trial participants without affecting the integrity of the trial. The social contract with our patients demands no less. Many regulatory authorities from different world regions have issued guidance statements regarding the conduct of clinical trials during this COVID-19 crisis. However, international trials may benefit from expert guidance from a global panel of experts to supplement local advice and regulations, thereby enhancing the safety of participants and the integrity of the trial. Accordingly, the Heart Failure Association of the European Society of Cardiology on 21 and 22 March 2020 conducted web-based meetings with expert clinical trialists in Europe, North America, South America, Australia, and Asia. The main objectives of this Expert Position Paper are to highlight the challenges that this pandemic poses for the conduct of clinical trials in heart failure and to offer advice on how they might be overcome, with some practical examples. While this panel of experts are focused on heart failure clinical trials, these discussions and recommendations may apply to clinical trials in other therapeutic areas.

The Centers for Medicare & Medicaid Services’ Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure has appropriately established sepsis as a national priority. However, the Infectious Diseases Society of America (IDSA and five additional endorsing societies) is concerned about SEP-1’s potential to drive antibiotic overuse because it does not account for the high rate of sepsis overdiagnosis and encourages aggressive antibiotics for all patients with possible sepsis, regardless of the certainty of diagnosis or severity of illness. IDSA is also concerned that SEP-1’s complex “time zero” definition is not evidence-based and is prone to inter-observer variation. In this position paper, IDSA outlines several recommendations aimed at reducing the risk of unintended consequences of SEP-1 while maintaining focus on its evidence-based elements. IDSA’s core recommendation is to limit SEP-1 to septic shock, for which the evidence supporting the benefit of immediate antibiotics is greatest. Prompt empiric antibiotics are often appropriate for suspected sepsis without shock, but IDSA believes there is too much heterogeneity and difficulty defining this population, uncertainty about the presence of infection, and insufficient data on the necessity of immediate antibiotics to support a mandatory treatment standard for all patients in this category. IDSA believes guidance on managing possible sepsis without shock is more appropriate for guidelines that can delineate the strengths and limitations of supporting evidence and allow clinicians discretion in applying specific recommendations to individual patients. Removing sepsis without shock from SEP-1 will mitigate the risk of unnecessary antibiotic prescribing for noninfectious syndromes, simplify data abstraction, increase measure reliability, and focus attention on the population most likely to benefit from immediate empiric broad-spectrum antibiotics.

Heart failure is a complex syndrome affecting several organs including kidney, lungs, liver, brain muscles and sympathetic system. Each of these organs might contribute to its severity and prognosis. The prognosis assessment is critical for a correct heart failure management. It has already been demonstrated that a single parameter is weaker for prognosis than different parameters combined. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score has been built and validated for heart failure with reduced ejection fraction (HFrEF) patients by considering cardiopulmonary exercise test data combined with clinical, laboratory and echocardiographic measurements. The betablockers treatment is a milestone in the HFrEF management. In the MECKI score database, the association of betablockers treatment with outcome has been investigated in different settings.

Infections by SARS CoV2 - COVID-19 became in a short time a worldwide health emergency. The present SARS-CoV-2 pandemic induced in a short time, an unprecedented impact on public health and on the pre-existing care pathways. In order to appropriately address this epidemiological emergency, urgent solutions were needed, such as remodelling or stopping hospitalization and deferrable clinical activities to avoid spreading the SARS-CoV-2 infection. After the first emergency lockdown phase, care pathways must guarantee healthcare to patients and preserve the safety of the healthcare personnel and of all the other subjects that refer to the cardiological surgeries. Rigorous prescriptive appropriateness of the requested exams with consequent reduction of unnecessary examinations is an essential requirement to preserve prioritized diagnostic and care pathways to patients in need, minimizing the risks connected to the SARS-CoV-2 contagion in hospitals. Telemedicine services represent a valid answer to cardiovascular disease patients’ need for care and assistance, including those in quarantine and voluntary isolation. These services successfully contribute to fight the spread of the virus guaranteeing at the same time therapy and support through remote services that must therefore be considered a resource to be implemented and enhanced. This document has to be used by the healthcare personnel working in hospitals and in district offices, if applicable, and aims at managing patients, in complete safety and considered not suspect/not probable (‘not at risk’) of SARS-CoV-2 infection, eligible for diagnostic activity and subsequent therapy in outpatient surgeries. In particular, this document provides indications for patient evaluation to prevent COVID-19 exposure, gives general indications on managing appointments and waiting rooms, on how to strictly adhere to environmental safety measures, on the proper use of Individual Protective Equipment (IPE). It also provides specific indications for outpatient service procedures, like electrocardiogram, cardiologic examination, cardiologic checkup, Dynamic Holter Electrocardiogram, Transthoracic Echocardiography, Echo Stress, Transoesophageal Echocardiography, Bike Ergometer stress test, Ergospirometry, Outpatient Checkup of implantable electronic cardiac devices.

The aim of this document is the management and organization of patients in need of urgent access to electrophysiology (EP) and pacing procedures during the COVID-19 emergency. Specifically, non-deferrable procedures or irreplaceable with a drug therapy prior to the resolution of the COVID-19 virus emergency [pacemaker (PM) implant/replacement/urgent defibrillator (implantable cardioverter-defibrillator, ICD) or arrhythmic storm or other indication of non-deferrable ablation]. The pacing and electrophysiological procedures urgent as they may be, less and less frequently represent situations of emergency, therefore for almost all cases, it is possible to perform a swab test to determine the positivity to COVID-19 of the patient. In cases where this is not possible, due to situations of emergency, the recommendations and procedures we have indicated are advisable, if not mandatory, in order to avoid the spreading of the virus to healthcare personnel and other patients.

Morbidity and mortality from ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and are increasing worldwide. Patients with IHD or HF might benefit from novel therapeutic strategies, such as cell-based therapies. We recently discussed the therapeutic potential of cell-based therapies and provided recommendations on how to improve the therapeutic translation of these novel strategies for effective cardiac regeneration and repair. Despite major advances in optimizing these strategies with respect to cell source and delivery method, the clinical outcome of cell-based therapy remains unsatisfactory. Major obstacles are the low engraftment and survival rate of transplanted cells in the harmful microenvironment of the host tissue, and the paucity or even lack of endogenous cells with repair capacity. Therefore, new ways of delivering cells and their derivatives are required in order to empower cell-based cardiac repair and regeneration in patients with IHD or HF. Strategies using tissue engineering (TE) combine cells with matrix materials to enhance cell retention or cell delivery in the transplanted area, and have recently received much attention for this purpose. Here, we summarize knowledge on novel approaches emerging from the TE scenario. In particular, we will discuss how combinations of cell/bio-materials (e.g. hydrogels, cell sheets, prefabricated matrices, microspheres, and injectable matrices) combinations might enhance cell retention or cell delivery in the transplantation areas, thereby increase the success rate of cell therapies for IHD and HF. We will not focus on the use of classical engineering approaches, employing fully synthetic materials, because of their unsatisfactory material properties which render them not clinically applicable. The overall aim of this Position Paper from the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to proceed in research with these novel TE strategies combined with cell-based therapies to boost cardiac repair in the clinical settings of IHD and HF. © Published on behalf of the European Society of Cardiology. All rights reserved.

Approximately 10% of patients resuscitated from out-of-hospital cardiac arrest (OHCA) survive to hospital discharge. Improved management to improve outcomes are required, and it is proposed that such patients should be preferentially treated in cardiac arrest centres (CACs). The minimum requirements of therapy modalities for the CAC are 24/7 availability of an on-site coronary angiography laboratory, an emergency department, an intensive care unit, imaging facilities, such as echocardiography, computed tomography, and magnetic resonance imaging, and a protocol outlining transfer of selected patients to CACs with additional resources (OHCA hub hospitals). These hub hospitals are regularly treating a high volume of patients and offer further treatment modalities. This consensus document describes the aims, the minimal requirements for therapeutic modalities and expertise, and the structure, of a CAC. It represents a consensus among the major European medical associations and societies involved in the treatment of OHCA patients.

At the end of 2019 a new Coronavirus appeared in China and, from there, it spread to the rest of the world On 24th May, 2020, the confirmed cases in the world were more than 5 million and the deaths almost 350 000 At the end of May, Italy reported more than 27 000 cases among healthcare professionals and 163 deaths among physicians The National Health Systems from almost all over the world, including Italy's, were unprepared for this pandemic, and this generated important consequences of organizational nature All elective and urgent specialized activities were completely reorganized, and many hospital units were partially or completely converted to the care of the COVID-19 patients A significant reduction in hospital admissions for acute heart disease were recorded during the SARS-CoV-2 pandemic and, in order to gradually resume hospital activities, the Italian National Phase 2 Plan for the partial recovery of activities, must necessarily be associated with a Phase 2 Health Plan In regards to the cardiac outpatient activities we need to identify short term goals, i e reschedule the suspended outpatient activities, revise the waiting lists, review the 'timings' of the bookings This will reduce the number of available examinations compared to the pre-Covid-19 era The GP's collaboration could represent an important resource, a structured telephone follow-up plan is advisable with the nursing staff's involvement It is equally important to set medium-long term goals, the pandemic could be an appropriate moment for making a virtue of necessity It is time to reason on prescriptive appropriateness, telemedicine implementation intended as integration to the traditional management It is time to restructure the cardiological units related to the issue of structural adjustment to the needs for functional isolation Moreover, the creation of 'grey zones' with multidisciplinary management according to the intensity of care levels seems to be necessary as well as the identification of Covid dedicated cardiologies Finally, the pandemic could represent the opportunity for a permanent renovation of the cardiological and territorial medicine activities © 2020 Oxford University Press All rights reserved

The pandemic of coronavirus disease (COVID)-19 is a global threat, causing high mortality, especially in the elderly. The main symptoms and the primary cause of death are related to interstitial pneumonia. Viral entry also into myocardial cells mainly via the angiotensin converting enzyme type 2 (ACE2) receptor and excessive production of pro-inflammatory cytokines, however, also make the heart susceptible to injury. In addition to the immediate damage caused by the acute inflammatory response, the heart may also suffer from long-term consequences of COVID-19, potentially causing a post-pandemic increase in cardiac complications. Although the main cause of cardiac damage in COVID-19 remains coagulopathy with micro- (and to a lesser extent macro-) vascular occlusion, open questions remain about other possible modalities of cardiac dysfunction, such as direct infection of myocardial cells, effects of cytokines storm, and mechanisms related to enhanced coagulopathy. In this opinion paper, we focus on these lesser appreciated possibilities and propose experimental approaches that could provide a more comprehensive understanding of the cellular and molecular bases of cardiac injury in COVID-19 patients. We first discuss approaches to characterize cardiac damage caused by possible direct viral infection of cardiac cells, followed by formulating hypotheses on how to reproduce and investigate the hyperinflammatory and pro-thrombotic conditions observed in the heart of COVID-19 patients using experimental in vitro systems. Finally, we elaborate on strategies to discover novel pathology biomarkers using omics platforms.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility; however, whether women with PCOS and spontaneous or drug-induced ovulatory cycles have the same reproductive potential as non-PCOS controls is a matter of debate. In the present opinion paper, the author takes the opportunity to summarize the collective evidence supporting the hypothesis of reduced fertility potential in women with PCOS, regardless of ovulatory status, and speculate that reduced reproductive potential may be caused by altered oocytes, embryo and endometrial competence, and infertility-related co-morbidities as well as an increased risk of pregnancy complications.

International audience; Advances in the diagnosis and management of congenital heart disease have led to a marked improvement in the survival of adult with congenital heart disease (ACHD) patients. However, ACHD patients are a heterogeneous population, with a large spectrum of anatomic substrates even within specific lesions. In addition, the nature of previous surgery and other intervention is highly variable rendering each patient unique and residual anatomic and haemodynamic abnormalities are very common. As the ACHD population continues to age, acquired heart disease will also require cardiac imaging assessment. It is increasingly recognized in ACHD community that the diagnostic utility of a multimodality cardiovascular approach is greater than the sum of individual tests. In ACHD patients, diagnostic information can be obtained using a variety of diagnostic tools. The aims of this document are to describe the role of each diagnostic modality in the care of ACHD patients and to provide guidelines for a multimodality approach. The goal should be to provide the most appropriate and cost-effective diagnostic pathway for each individual ACHD patient.

International audience; Acute cardiovascular care has progressed considerably since the last position paper was published 10 years ago. It is now a well-defined, complex field with demanding multidisciplinary teamworking. The Acute Cardiovascular Care Association has provided this update of the 2005 position paper on acute cardiovascular care organisation, using a multinational working group. The patient population has changed, and intensive cardiovascular care units now manage a large range of conditions from those simply requiring specialised monitoring, to critical cardiovascular diseases with associated multi-organ failure. To describe better intensive cardiovascular care units case mix, acuity of care has been divided into three levels, and then defining intensive cardiovascular care unit functional organisation. For each level of intensive cardiovascular care unit, this document presents the aims of the units, the recommended management structure, the optimal number of staff, the need for specially trained cardiologists and cardiovascular nurses, the desired equipment and architecture, and the interaction with other departments in the hospital and other intensive cardiovascular care units in the region/area. This update emphasises cardiologist training, referring to the recently updated Acute Cardiovascular Care Association core curriculum on acute cardiovascular care. The training of nurses in acute cardiovascular care is additionally addressed. Intensive cardiovascular care unit expertise is not limited to within the unit's geographical boundaries, extending to different specialties and subspecialties of cardiology and other specialties in order to optimally manage the wide scope of acute cardiovascular conditions in frequently highly complex patients. This position paper therefore addresses the need for the inclusion of acute cardiac care and intensive cardiovascular care units within a hospital network, linking university medical centres, large community hospitals, and smaller hospitals with more limited capabilities.

Background Bacterial culture is the gold standard for the diagnosis of invasive bacterial diseases (IBDs) but molecular methods are more specific and sensitive. Fresh liquid samples (FLSs) show patent limitations for shipping and storage. We aimed to evaluate the sensitivity and specificity of real-time polymerase chain reaction (PCR) performed on dried sample spots (DSSs) obtained from different biological fluids compared with real-time PCR or culture performed on FLSs. Methods FLSs positive for Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Escherichia coli, Streptococcus pyogenes, Staphylococcus aureus, Bordetella pertussis and/or Pseudomonas aeruginosa were spotted on filter paper. Real-time PCR was performed on both FLSs and DSSs and results were compared. The stability of the DSS results over time was evaluated. Results Real-time PCR performed on 114 DSSs showed a specificity of 99.1% and a sensitivity of 91.2% for IBD diagnosis. A positive correlation was found between FLS cycle threshold (Ct) and DSS Ct (r=0.84; r2=0.71) with the Pearson statistical test and Bland–Altman analysis showing that 95% of the specimens were within agreeable limits. Although we observed a trend towards signal reduction over time in the DSSs, there was no statistical evidence of an increase in Ct values. Real-time PCR on DSSs was 2.2 times more sensitive than culture. Conclusions Real-time PCR applied to DSSs may be a useful approach in different situations, such as IBD diagnosis, both for rural areas of low-income countries and family practitioners in various settings.

Disorders or differences in sex development (DSD) comprise a heterogeneous group of conditions with an atypical sex development. For optimal diagnosis, highly specialised laboratory analyses are required across European countries. Working group 3 of EU COST (European Cooperation in Science and Technology) Action BM 1303 ‘DSDnet’ ‘Harmonisation of Laboratory Assessment’ has developed recommendations on laboratory assessment for DSD regarding the use of technologies and analytes to be investigated. This position paper on steroid hormone analysis in diagnosis and treatment of DSD was compiled by a group of specialists in DSD and/or hormonal analysis, either from participating European countries or international partner countries. The topics discussed comprised analytical methods (immunoassay/mass spectrometry-based methods), matrices (urine/serum/saliva) and harmonisation of laboratory tests. The following positions were agreed upon: support of the appropriate use of immunoassay- and mass spectrometry-based methods for diagnosis and monitoring of DSD. Serum/plasma and urine are established matrices for analysis. Laboratories performing analyses for DSD need to operate within a quality framework and actively engage in harmonisation processes so that results and their interpretation are the same irrespective of the laboratory they are performed in. Participation in activities of peer comparison such as sample exchange or when available subscribing to a relevant external quality assurance program should be achieved. The ultimate aim of the guidelines is the implementation of clinical standards for diagnosis and appropriate treatment of DSD to achieve the best outcome for patients, no matter where patients are investigated or managed.

Background Statin intolerance is a clinical syndrome whereby adverse effects associated with statin therapy (most commonly muscle symptoms) result in the discontinuation of therapy. Statin discontinuation is associated with increased risk of adverse cardiac outcomes. Many patients who initially experience adverse effects are able to tolerate statin therapy to some extent. Careful stepwise diagnosis and management of individuals who experience adverse effects is essential to enable optimal reduction of cardiovascular risk. Purpose In this Position Paper of the International Lipid Expert Panel (ILEP), we present a step by step approach to the diagnosis and practical management of statin intolerance resulting from muscle symptoms, and other adverse effects with demonstrated statin causality. Methods Relevant clinical evidence and international clinical guidelines were discussed and assimilated by ILEP members. Consensus was used to formulate recommendations for the diagnosis and management of statin intolerance. Results Consensus resulted in the adoption of three parts to the recommendation. 1) diagnosis of Statin Intolerance; 2) advice for management of all patients with statin intolerance; 3) specific advice for patients who have partial (rather than complete) statin intolerance. Patients with partial statin intolerance are likely to make up the vast majority (even 95%) of statin-intolerant individuals. Each part of the recommendation consists of a four-step process and has an associated acronym to aid memory (see attached recommendations). We adopted the Banach and Mikhailidis four-step approach to diagnosis and we developed novel recommendations for management. Summary of the ILEP SI recommendations. Conclusions We present recommendations, which will enable clinicians to distinguish between rare, severe adverse effects; true statin intolerance, and symptoms incorrectly attributed to statin therapy. In each case we summarize guidelines, clinical evidence and expert opinion pertaining to the optimal management of cardiovascular disease in these patients. Acknowledgement/Funding None

Introduction MINOCA (myocardial infarction with non-obstructive coronary arteries) has been recently redefined by the last ESC guidelines. The aim of this study is to analyze clinical profile and long-term prognosis of these patients. Methods Retrospectively, between 1/2010 and 12/2016 all consecutive patients with the definitive diagnosis of MI in tertiary center were included in this observational study. Patients with unstable angina with non-obstructive coronary artery disease and those who died in-hospital were excluded. Patients were stratified according to the number of significant coronary vessel disease seen by coronary angiography into: 0 (MINOCA); 1; 2; ≥3 vessels. The definition of MINOCA was based on dedicated the 2016 ESC Working Group position paper. Patients with MINOCA were compared to their counterpounds (MIOCA; MI with obstructive CAD) regarding baseline clinical characteristics, on-admission and laboratory data and treatment at hospital discharge. The prognostic meaning of MINOCA vs MIOCA was ascertained by comparing the composite endpoint (re-ACS, stroke and death) rate among groups, using Kaplan-Meier and multivariate Cox regression analyses. Results 13.8% (n=597) pts were classified as MINOCA. They were older and more frequently women than the obstructive group. MINOCA group also had a worse cardiovascular risk profile than pts with obstructive coronary lesions. They were associated more frequently with atrial fibrillation during hospitalization (11.2% vs. 6.8%, p During 15 months (IQR: 12,3–25,5), 613 (14.2) pts had a new ACS, stroke or died (251 pts developed a new ACS, 81 had stroke, and 281 died). The incidence of the composite endpoint was 4.2% in the MINOCA pts, 4.1% in pts with 1-significant coronary vessel disease, 6.3% in the 2-significant coronary vessel disease, and 9.5% in the ≥3-significant coronary vessel disease (p Figure 1. Composite endpoint Conclusions In the present cohort MINOCA was approximately found in one of each 14 patients admitted with MI. These patients had worse CV risk profile and more history of depression. MINOCA pts have similar prognostic impact in terms of hospitalization for a new ACS, stroke and death than the obstructive group.

Adult congenital heart disease (ACHD) patients represent a growing population with increasing use of acute emergency department (ED) care. Providing comprehensive ED care necessitates an understanding of the most common clinical scenarios to improve morbidity and mortality in this population. The aim of this position document is to provide a consensus regarding the management of the most common clinical scenarios of ACHD patients presenting to the ED.

The hospital discharge is often poorly standardized and affected by discontinuity and fragmentation of care, putting patients at high risk of both post-discharge adverse events and early readmission. The present ANMCO document reviews the modifiable components of the hospital discharge process related to adverse events or re-hospitalizations and suggests the optimal methods for redesigning the whole discharge process. The key principles for proper hospital discharge or transfer of care acknowledge that the hospital discharge: • is not an isolated event, but a process that has to be planned as soon as possible after the admission, ensuring that the patient and the caregiver understand and contribute to the planned decisions, as equal partners; • is facilitated by a comprehensive systemic approach that begins with a multidimensional evaluation process; • must be organized by an operator who is responsible for the coordination of all phases of the hospital patient journey, involving afterward the general practitioner and transferring to them the information and responsibility at discharge; • is the result of an integrated multidisciplinary team approach; • appropriately uses the transitional and intermediate care services; • is carried out in an organized system of care and continuum of services; and • programs the passage of information to after-discharge services.

α-Amylase is a starch-hydrolyzing enzyme (EC 3.2.1.1) indispensable for germination of cereal seeds, but it is also expressed during the ripening stage. Previous studies demonstrated that the enzyme is activated in developing rice seeds under extremely hot weather and triggers a loss of grain quality by hindering the accumulation of storage starch in the endosperm. Since inactive or, preferably, heat-labile α-amylases are preferable for breeding premium rice, we developed a method for rapid screening of inactive and temperature-sensitive mutants of the enzyme by combining the random mutagenesis by error-prone PCR and an on-filter activity test of the recombinant enzyme expressed by Escherichia coli. This technique was applied to a major α-amylase in the developing seed, Amy3D, and the activity of the isolated mutant enzymes was verified with both the bacteria-expressed recombinant proteins and the extract from the endosperm overexpressing each of them. Then, we identified several substitutions leading to loss of the activity of amino acid residues (Leu28, Asp112, Cys149, Trp201, Asp204, Gly295, Leu300 and Cys342), as well as a variety of heat-sensitive substitutions of Asp83, Asp187 and Glu252. Furthermore, variations of the heat-labile enzymes were created by combining these heat-sensitive mutations. The effects of the respective mutations and their relationship to the structure of the enzyme molecule are discussed.

Despite improvements in modern cardiovascular therapy, the morbidity and mortality of ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and worldwide. Patients with IHD may benefit from therapies that would accelerate natural processes of postnatal collateral vessel formation and/or muscle regeneration. Here, we discuss the use of cells in the context of heart repair, and the most relevant results and current limitations from clinical trials using cell-based therapies to treat IHD and HF. We identify and discuss promising potential new therapeutic strategies that include ex vivo cell-mediated gene therapy, the use of biomaterials and cell-free therapies aimed at increasing the success rates of therapy for IHD and HF. The overall aim of this Position Paper of the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to improve the therapeutic application of cell-based therapies for cardiac regeneration and repair.

Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults\ud has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that\ud ‘for approved indications, GH is safe’; however, the statement highlighted a number of areas for on-going surveillance of\ud long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH\ud treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard\ud to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric\ud Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of\ud rhGH. The ouput of the meeting is a concise position statement.

The COVID-19 pandemic has become a global health emergency. In Italy, the number of people infected by SARS-COVID-2 is rapidly increasing and what emerges from the current data is that the majority do not present any symptoms or only minor flu-like symptoms. In about 20% of the patients, the disease progresses towards more complex forms (interstitial pneumonia to acute respiratory distress and multiple organ failure) with the need of hospitalization in CICU and advanced ventilator assistance. The transmission of the virus occurs very easily from the symptomatic patient s droplets from coughing and sneezing and from direct contact with persons or surfaces.In a patient presenting with ST elevation (STEMI) myocardial infarction or STEMI-like, if positive to COVID-19, the reperfusion therapeutic strategy depends on the local organization and on the possibility to access without delay a PCI COVID Center, on the basis, obviously, of the risk/benefit assessment of the individual case. However, we advise to try pursuing, in the first instance, the mechanical revascularization strategy, according to the available local possibilities.

Objectives This manuscript reviews the current state of veterinary medical electronic health records and the ability to aggregate and analyze large datasets from multiple organizations and clinics. We also review analytical techniques as well as research efforts into veterinary informatics with a focus on applications relevant to human and animal medicine. Our goal is to provide references and context for these resources so that researchers can identify resources of interest and translational opportunities to advance the field. Methods and Results This review covers various methods of veterinary informatics including natural language processing and machine learning techniques in brief and various ongoing and future projects. After detailing techniques and sources of data, we describe some of the challenges and opportunities within veterinary informatics as well as providing reviews of common One Health techniques and specific applications that affect both humans and animals. Discussion Current limitations in the field of veterinary informatics include limited sources of training data for developing machine learning and artificial intelligence algorithms, siloed data between academic institutions, corporate institutions, and many small private practices, and inconsistent data formats that make many integration problems difficult. Despite those limitations, there have been significant advancements in the field in the last few years and continued development of a few, key, large data resources that are available for interested clinicians and researchers. These real-world use cases and applications show current and significant future potential as veterinary informatics grows in importance. Veterinary informatics can forge new possibilities within veterinary medicine and between veterinary medicine, human medicine, and One Health initiatives.

Aim Unsurprisingly, much of the medical profession has focussed on treating covid-19 over the past year often to the detriment of other pathologies. Engagement with academic literature may follow a similar trend; this paper used standard social media attention and citations metrices to assess whether the pandemic has affected engagement with surgical literature. Method Twitter Mentions and Mendeley Readers Data were retrieved for all papers published in Annals of Surgery, BJS and JAMASurgery between January 2019 and October 2020. The non-parametric Mann-Whitney U test was used to compare Twitter Mentions and Mendeley Readers for COVID surgical vs non-COVID surgical publications (in 2020) and all surgical papers published before and after the advent of COVID-19. A control database of all papers published in NEJM, BMJ and Lancet over the same period of time was also created. Results There was no difference in Twitter mentions between COVID-19 and non-COVID-19 papers (p-value 0.604); however there were significantly more Mendeley readers of COVID-19 papers than non-COVID-19 papers in 2020 (55 vs 5 median readers, p Analysis of the non-surgical control dataset revealed the opposite trend; papers published in 2020 received significantly more attention than those published in 2019 (39 vs 30 median Twitter citations, p Conclusion Surgical papers published during the COVID-19 pandemic received significantly fewer social media mentions. Such reduced visibility has the potential to affect future citation metrics and dissemination of surgical knowledge

Aim Nail bed injuries are the commonest paediatric hand injuries. Optimal management is essential to restoring form and function of the nail and fingertip, however high-level evidence of nail bed injury management is lacking, leading to large discrepancies in clinical practice. This paper evaluates the 100 most cited papers in nail bed injury and analyses their study characteristics to assess current research focus and evidence levels. Method A Web of Science search was carried out using the search term “nail bed injury”. All article types were included, and no language or publication date restrictions were applied. Results were ranked by overall citation number. All abstracts were screened for study relevance and the top 100 eligible studies were analysed for study type, main study theme, journal, and year of publication. Result The three most common study types included retrospective studies (n = 33), literature reviews (n = 25), case reports/series (n = 20). The three main study themes included evaluation of repair techniques (n = 72), aetiology and epidemiology of nail bed injuries (n = 12), and anatomical assessments (n = 7). The most frequently represented journals include Journal of Hand Surgery (n = 30), Plastic and Reconstructive Surgery (n = 7) and Hand Clinics (n = 4). Conclusions The most influential papers in nail bed injury are those describing repair techniques. There remains a lack of high level evidence with most papers presenting level 3-5 evidence. This paper demonstrates a continued need for more higher level robust evidence in the field of nail bed injuries.

none 18 si The implementation of new surgical techniques offers chances but carries risks. Usually, several years pass before a critical appraisal and a balanced opinion of a new treatment method are available and rely on the evidence from the literature and expert's opinion. The frozen elephant trunk (FET) technique has been increasingly used to treat complex pathologies of the aortic arch and the descending aorta, but there still is an ongoing discussion within the surgical community about the optimal indications. This paper represents a common effort of the Vascular Domain of EACTS together with several surgeons with particular expertise in aortic surgery, and summarizes the current knowledge and the state of the art about the FET technique. The majority of the information about the FET technique has been extracted from 97 focused publications already available in the PubMed database (cohort studies, case reports, reviews, small series, meta-analyses and best evidence topics) published in English. Shrestha, M.; Bachet, J.; Bavaria, J.; Carrel, T.P.; De Paulis, R.; Di Bartolomeo, R.; Etz, C.D.; Grabenwöger, M.; Grimm, M.; Haverich, A.; Jakob, H.; Martens, A.; Mestres, C.A.; Pacini, D.; Resch, T.; Schepens, M.; Urbanski, P.P.; Czerny, M. Shrestha, M.; Bachet, J.; Bavaria, J.; Carrel, T.P.; De Paulis, R.; Di Bartolomeo, R.; Etz, C.D.; Grabenwöger, M.; Grimm, M.; Haverich, A.; Jakob, H.; Martens, A.; Mestres, C.A.; Pacini, D.; Resch, T.; Schepens, M.; Urbanski, P.P.; Czerny, M.

Heart failure is a global public health challenge frequently presenting to the emergency department. After initial stabilization and management, one of the most important decisions is to determine which patients can be safely discharged and which require hospitalization. This is a complex decision that depends on numerous subjective factors, including both the severity of the patient's underlying condition and an estimate of the acuity of the presentation. An emergency department observation period may help select the correct option. Ideally, during an observation period, risk stratification should be carried out using parameters specifically designed for use in the emergency department. Unfortunately, there is little objective literature to guide this disposition decision. An objective and reliable definition of low-risk characteristics to identify early discharge candidates is needed. Benchmarking outcomes in patients discharged from the emergency department without hospitalization could aid this process. Biomarker determinations, although undoubtedly useful in establishing diagnosis and predicting longer-term prognosis, require prospective validation for emergency department disposition guidance. The challenge of identifying emergency department acute heart failure discharge candidates will only be overcome by future multidisciplinary research defining the current knowledge gaps and identifying potential solutions.

Noroviruses are a primary cause of gastroenteritis and foodborne illness with cases that affect millions of people worldwide each year. Inexpensive tests for norovirus that do not require sophisticated laboratory equipment are important tools for ensuring that patients receive timely treatment and for containing outbreaks. Herein, we demonstrate a low-cost colorimetric assay that detects norovirus from clinical samples by combining paper-based cell-free transcription–translation systems, isothermal amplification and virus enrichment by synbodies. Using isothermal amplification and cell-free RNA sensing with toehold switches, we demonstrate that the assay enables detection of norovirus GII.4 Sydney from stool down to concentrations of 270 aM in reactions that can be directly read by eye. Furthermore, norovirus-binding synbodies and magnetic beads are used to concentrate the virus and provide a 1000-fold increase in assay sensitivity extending its detection limit to 270 zM. These results demonstrate the utility of paper-based cell-free diagnostic systems for identification of foodborne pathogens and provide a versatile diagnostic assay that can be applied to the concentration, amplification and detection of a broad range of infectious agents.