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Showing papers by "University of Modena and Reggio Emilia published in 2020"



Journal ArticleDOI
01 Aug 2020
TL;DR: Assessment of the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment found it to be associated with a reduced risk.
Abstract: Summary Background No therapy is approved for COVID-19 pneumonia The aim of this study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment Methods This retrospective, observational cohort study included adults (≥18 years) with severe COVID-19 pneumonia who were admitted to tertiary care centres in Bologna and Reggio Emilia, Italy, between Feb 21 and March 24, 2020, and a tertiary care centre in Modena, Italy, between Feb 21 and April 30, 2020 All patients were treated with the standard of care (ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly selected subset of patients also received tocilizumab Tocilizumab was given either intravenously at 8 mg/kg bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (ie, 324 mg in total), when the intravenous formulation was unavailable The primary endpoint was a composite of invasive mechanical ventilation or death Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for sex, age, recruiting centre, duration of symptoms, and baseline Sequential Organ Failure Assessment (SOFA) score Findings Of 1351 patients admitted, 544 (40%) had severe COVID-19 pneumonia and were included in the study 57 (16%) of 365 patients in the standard care group needed mechanical ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab (p=0·41; 16 [18%] of 88 patients treated intravenously and 17 [19%] of 91 patients treated subcutaneously) 73 (20%) patients in the standard care group died, compared with 13 (7%; p Interpretation Treatment with tocilizumab, whether administered intravenously or subcutaneously, might reduce the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia Funding None

775 citations


Proceedings ArticleDOI
14 Jun 2020
TL;DR: The architecture improves both the image encoding and the language generation steps: it learns a multi-level representation of the relationships between image regions integrating learned a priori knowledge, and uses a mesh-like connectivity at decoding stage to exploit low- and high-level features.
Abstract: Transformer-based architectures represent the state of the art in sequence modeling tasks like machine translation and language understanding. Their applicability to multi-modal contexts like image captioning, however, is still largely under-explored. With the aim of filling this gap, we present M² - a Meshed Transformer with Memory for Image Captioning. The architecture improves both the image encoding and the language generation steps: it learns a multi-level representation of the relationships between image regions integrating learned a priori knowledge, and uses a mesh-like connectivity at decoding stage to exploit low- and high-level features. Experimentally, we investigate the performance of the M² Transformer and different fully-attentive models in comparison with recurrent ones. When tested on COCO, our proposal achieves a new state of the art in single-model and ensemble configurations on the "Karpathy" test split and on the online test server. We also assess its performances when describing objects unseen in the training set. Trained models and code for reproducing the experiments are publicly available at: https://github.com/aimagelab/meshed-memory-transformer.

660 citations


Journal ArticleDOI
TL;DR: Compared with healthy controls, COVID-19 patients’ T cell compartment displays several alterations involving naïve, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1 + CD57 + exhausted T cells, and significant alterations exist also in several lineage-specifying transcription factors and chemokine receptors.
Abstract: The immune system of patients infected by SARS-CoV-2 is severely impaired Detailed investigation of T cells and cytokine production in patients affected by COVID-19 pneumonia are urgently required Here we show that, compared with healthy controls, COVID-19 patients’ T cell compartment displays several alterations involving naive, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1+CD57+ exhausted T cells Significant alterations exist also in several lineage-specifying transcription factors and chemokine receptors Terminally differentiated T cells from patients proliferate less than those from healthy controls, whereas their mitochondria functionality is similar in CD4+ T cells from both groups Patients display significant increases of proinflammatory or anti-inflammatory cytokines, including T helper type-1 and type-2 cytokines, chemokines and galectins; their lymphocytes produce more tumor necrosis factor (TNF), interferon-γ, interleukin (IL)-2 and IL-17, with the last observation implying that blocking IL-17 could provide a novel therapeutic strategy for COVID-19 COVID-19 is a serious pandemic threat to public health, but insights on the pathophysiological and immunological conditions are only emerging Here the authors use multi-color flow cytometry to characterize CD4+ and CD8+ T cells in peripheral blood from 39 COVID-19 patients in Italy to report altered T cell activation, function and polarization

597 citations


Journal ArticleDOI
TL;DR: The analysis of recently published studies highlights the role of systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complications.
Abstract: The coronavirus disease 2019 (COVID-19) pandemic is a scientific, medical, and social challenge. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is centered on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment. The analysis of recently published studies highlights the role of systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complications. The following biomarkers have been identified: hematological (lymphocyte count, neutrophil count, neutrophil-lymphocyte ratio (NLR)), inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT)), immunological (interleukin (IL)-6 and biochemical (D-dimer, troponin, creatine kinase (CK), aspartate aminotransferase (AST)), especially those related to coagulation cascades in disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). New laboratory biomarkers could be identified through the accurate analysis of multicentric case series; in particular, homocysteine and angiotensin II could play a significant role.

529 citations


Journal ArticleDOI
TL;DR: The prevalence of frailty in patients with COVID-19 who were admitted to hospital is established and its association with mortality and duration of hospital stay is investigated and disease outcomes were better predicted by frailty than either age or comorbidity.
Abstract: Background The COVID-19 pandemic has placed unprecedented strain on health-care systems. Frailty is being used in clinical decision making for patients with COVID-19, yet the prevalence and effect of frailty in people with COVID-19 is not known. In the COVID-19 in Older PEople (COPE) study we aimed to establish the prevalence of frailty in patients with COVID-19 who were admitted to hospital and investigate its association with mortality and duration of hospital stay. Methods This was an observational cohort study conducted at ten hospitals in the UK and one in Italy. All adults (≥18 years) admitted to participating hospitals with COVID-19 were included. Patients with incomplete hospital records were excluded. The study analysed routinely generated hospital data for patients with COVID-19. Frailty was assessed by specialist COVID-19 teams using the clinical frailty scale (CFS) and patients were grouped according to their score (1–2=fit; 3–4=vulnerable, but not frail; 5–6=initial signs of frailty but with some degree of independence; and 7–9=severe or very severe frailty). The primary outcome was in-hospital mortality (time from hospital admission to mortality and day-7 mortality). Findings Between Feb 27, and April 28, 2020, we enrolled 1564 patients with COVID-19. The median age was 74 years (IQR 61–83); 903 (57·7%) were men and 661 (42·3%) were women; 425 (27·2%) had died at data cutoff (April 28, 2020). 772 (49·4%) were classed as frail (CFS 5–8) and 27 (1·7%) were classed as terminally ill (CFS 9). Compared with CFS 1–2, the adjusted hazard ratios for time from hospital admission to death were 1·55 (95% CI 1·00–2·41) for CFS 3–4, 1·83 (1·15–2·91) for CFS 5–6, and 2·39 (1·50–3·81) for CFS 7–9, and adjusted odds ratios for day-7 mortality were 1·22 (95% CI 0·63–2·38) for CFS 3–4, 1·62 (0·81–3·26) for CFS 5–6, and 3·12 (1·56–6·24) for CFS 7–9. Interpretation In a large population of patients admitted to hospital with COVID-19, disease outcomes were better predicted by frailty than either age or comorbidity. Our results support the use of CFS to inform decision making about medical care in adult patients admitted to hospital with COVID-19.

475 citations


Journal ArticleDOI
TL;DR: This study adds to the evidence that patients with haematological malignancies have worse outcomes and the general Italian population with COVID-19 has high mortality, by calculating standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates.

408 citations


Journal ArticleDOI
TL;DR: The present commentary briefly analyzes the effects of quarantine on lifestyle, including nutrition and physical activity and the impact of new technologies in dealing with this situation, and carries some long-term effects on cardiovascular disease.
Abstract: Aims CoV-19/SARS-CoV-2 is a highly pathogenic virus that is causing a global pandemic with a high number of deaths and infected people. To contain the diffusion of infection, several governments have enforced restrictions on outdoor activities or even collective quarantine on the population. The present commentary briefly analyzes the effects of quarantine on lifestyle, including nutrition and physical activity and the impact of new technologies in dealing with this situation. Data synthesis Quarantine is associated with stress and depression leading to unhealthy diet and reduced physical activity. A diet poor in fruit and vegetables is frequent during isolation, with a consequent low intake of antioxidants and vitamins. However, vitamins have recently been identified as a principal weapon in the fight against the Cov-19 virus. Some reports suggest that Vitamin D could exert a protective effect on such infection. During quarantine, strategies to further increase home-based physical activity and to encourage adherence to a healthy diet should be implemented. The WHO has just released guidance for people in self-quarantine, those without any symptoms or diagnosis of acute respiratory illness, which provides practical advice on how to stay active and reduce sedentary behavior while at home. Conclusion Quarantine carries some long-term effects on cardiovascular disease, mainly related to unhealthy lifestyle and anxiety. Following quarantine, a global action supporting healthy diet and physical activity is mandatory to encourage people to return to a good lifestyle routine.

356 citations


Journal ArticleDOI
TL;DR: Evaluating the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure found no difference in cardiovascular death between the two groups.

354 citations


Journal ArticleDOI
TL;DR: A systematic evaluation of the value of AI-based decision support in skin tumor diagnosis demonstrates the superiority of human–computer collaboration over each individual approach and supports the potential of automated approaches in diagnostic medicine.
Abstract: The rapid increase in telemedicine coupled with recent advances in diagnostic artificial intelligence (AI) create the imperative to consider the opportunities and risks of inserting AI-based support into new paradigms of care Here we build on recent achievements in the accuracy of image-based AI for skin cancer diagnosis to address the effects of varied representations of AI-based support across different levels of clinical expertise and multiple clinical workflows We find that good quality AI-based support of clinical decision-making improves diagnostic accuracy over that of either AI or physicians alone, and that the least experienced clinicians gain the most from AI-based support We further find that AI-based multiclass probabilities outperformed content-based image retrieval (CBIR) representations of AI in the mobile technology environment, and AI-based support had utility in simulations of second opinions and of telemedicine triage In addition to demonstrating the potential benefits associated with good quality AI in the hands of non-expert clinicians, we find that faulty AI can mislead the entire spectrum of clinicians, including experts Lastly, we show that insights derived from AI class-activation maps can inform improvements in human diagnosis Together, our approach and findings offer a framework for future studies across the spectrum of image-based diagnostics to improve human-computer collaboration in clinical practice

353 citations


Journal ArticleDOI
TL;DR: A suite of complementary tests will inform crucial decisions by healthcare providers and policy makers and understanding their strengths and limitations will be critical to their judicious application for the development of algorithmic approaches to treatment and public health strategies.
Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease 2019 (COVID-19) pandemic has demanded rapid upscaling of in-vitro diagnostic assays to enable mass screening and testing of high-risk groups, and simultaneous ascertainment of robust data on past SARS-CoV-2 exposure at an individual and a population level. To meet the exponential demand in testing, there has been an accelerated development of both molecular and serological assays across a plethora of platforms. The present review discusses the current literature on these modalities, including nucleic acid amplification tests, direct viral antigen tests and the rapidly expanding laboratory-based and point of care serological tests. This suite of complementary tests will inform crucial decisions by healthcare providers and policy makers, and understanding their strengths and limitations will be critical to their judicious application for the development of algorithmic approaches to treatment and public health strategies.

Proceedings Article
15 Apr 2020
TL;DR: This work works towards General Continual Learning (GCL), where task boundaries blur and the domain and class distributions shift either gradually or suddenly, through Dark Experience Replay, namely matching the network's logits sampled throughout the optimization trajectory, thus promoting consistency with its past.
Abstract: Continual Learning has inspired a plethora of approaches and evaluation settings; however, the majority of them overlooks the properties of a practical scenario, where the data stream cannot be shaped as a sequence of tasks and offline training is not viable. We work towards General Continual Learning (GCL), where task boundaries blur and the domain and class distributions shift either gradually or suddenly. We address it through mixing rehearsal with knowledge distillation and regularization; our simple baseline, Dark Experience Replay, matches the network's logits sampled throughout the optimization trajectory, thus promoting consistency with its past. By conducting an extensive analysis on both standard benchmarks and a novel GCL evaluation setting (MNIST-360), we show that such a seemingly simple baseline outperforms consolidated approaches and leverages limited resources. We further explore the generalization capabilities of our objective, showing its regularization being beneficial beyond mere performance.

Journal ArticleDOI
TL;DR: It is hoped that the revised recommendations will assist urologist surgeons across the globe to guide the management of urological conditions during the current COVID-19 pandemic.


Journal ArticleDOI
TL;DR: During quarantine, strategies to further increase home-based physical activity and to follow a healthy diet should be implemented and following quarantine a global action supporting healthy diet and physical activity is mandatory to encourage people to return to good lifestyle.
Abstract: COVID-19 is causing a global pandemic with a high number of deaths and infected people. To contain the diffusion of COVID-19 virus, Governments have enforced restrictions on outdoor activities or even collective quarantine on the population. One important consequence of quarantine is a change in lifestyle: reduced physical activity and unhealthy diet. 2019 guidelines for primary prevention of cardiovascular disease indicate that “Adults should engage in at least 150 minute per week of accumulated moderate-intensity or 75 minute per week of vigorous-intensity aerobic physical activity (or an equivalent combination of moderate and vigorous activity) to reduce ASCVD risk.” During quarantine, strategies to further increase home-based physical activity and to follow a healthy diet should be implemented. Quarantine carries some long-term effects on cardiovascular disease, mainly related to unhealthy lifestyle and anxiety. Following quarantine a global action supporting healthy diet and physical activity is mandatory to encourage people to return to good lifestyle.

Journal ArticleDOI
TL;DR: The most difficult scientific challenge for this future vaccine obtained in the laboratory is the proof of clinical safety and efficacy of the COVID-19 vaccine.
Abstract: In the current context of the pandemic triggered by SARS-COV-2, the immunization of the population through vaccination is recognized as a public health priority. In the case of SARS‑COV‑2, the genetic sequencing was done quickly, in one month. Since then, worldwide research has focused on obtaining a vaccine. This has a major economic impact because new technological platforms and advanced genetic engineering procedures are required to obtain a COVID‑19 vaccine. The most difficult scientific challenge for this future vaccine obtained in the laboratory is the proof of clinical safety and efficacy. The biggest challenge of manufacturing is the construction and validation of production platforms capable of making the vaccine on a large scale.

Journal ArticleDOI
TL;DR: In patients with SARS-CoV-2 infection and acute respiratory failure, this study demonstrates that the utilisation of noninvasive respiratory support delivered outside the ICU was feasible and effective, but associated with a risk of staff contamination.
Abstract: INTRODUCTION: The severe acute respiratory syndrome-coronavirus 2 outbreak spread rapidly in Italy and the lack of intensive care unit (ICU) beds soon became evident, forcing the application of noninvasive respiratory support (NRS) outside the ICU, raising concerns over staff contamination. We aimed to analyse the safety of the hospital staff and the feasibility and outcomes of NRS applied to patients outside the ICU. METHODS: In this observational study, data from 670 consecutive patients with confirmed coronavirus disease 2019 referred to pulmonology units in nine hospitals between March 1 and May 10, 2020 were analysed. Data collected included medication, mode and usage of NRS (i.e. high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), noninvasive ventilation (NIV)), length of stay in hospital, endotracheal intubation (ETI) and deaths. RESULTS: 42 (11.1%) healthcare workers tested positive for infection, but only three of them required hospitalisation. Data are reported for all patients (69.3% male), whose mean±sd age was 68±13 years. The arterial oxygen tension/inspiratory oxygen fraction ratio at baseline was 152±79, and the majority (49.3%) of patients were treated with CPAP. The overall unadjusted 30-day mortality rate was 26.9%, with 16%, 30% and 30% for HFNC, CPAP and NIV, respectively, while the total ETI rate was 27%, with 29%, 25% and 28%, respectively; the relative probability of death was not related to the NRS used after adjustment for confounders. ETI and length of stay were not different among the groups. Mortality rate increased with age and comorbidity class progression. CONCLUSIONS: The application of NRS outside the ICU is feasible and associated with favourable outcomes. Nonetheless, it was associated with a risk of staff contamination.

Journal ArticleDOI
TL;DR: The COVID-19 emergency is having a highly negative impact on the activity of dentists practicing in the area of Modena and Reggio Emilia, and the GAD-7 (General Anxiety Disorder-7) evaluation showed that 9% of respondents reported a severe anxiety.
Abstract: The outbreak and diffusion of the Severe Acute Respiratory Syndrome-Coronavirus-2 (Sars-CoV-2) and COronaVIrus Disease 19 (COVID-19) have caused an emergency status in the health system, including in the dentistry environment. Italy registered the third highest number of COVID-19 cases in the world and the second highest in Europe. An anonymous online survey composed of 40 questions has been sent to dentists practicing in the area of Modena and Reggio Emilia, one of the areas in Italy most affected by COVID-19. The survey was aimed at highlighting the practical and emotional consequences of COVID-19 emergence on daily clinical practice. Specifically, it assessed dentists’ behavioral responses, emotions and concerns following the Sars-CoV-2 pandemic restrictive measures introduced by the Italian national administrative order of 10 March 2020 (DM-10M20), as well as the dentists’ perception of infection likelihood for themselves and patients. Furthermore, the psychological impact of COVID-19 was assessed by means of the Generalized Anxiety Disorder-7 test (GAD-7), that measures the presence and severity of anxiety symptoms. Using local dental associations (ANDI-Associazione Nazionale Dentisti Italiani, CAO-Commissione Albo Odontoiatri) lists, the survey was sent by email to all dentists in the district of Modena and Reggio Emilia (874 practitioners) and was completed by 356 of them (40%). All dental practitioners closed or reduced their activity to urgent procedures, 38.2% prior to and 61.8% after the DM-10M20. All reported a routinely use of the most common protective personal equipment (PPE), but also admitted that the use of PPE had to be modified during COVID-19 pandemic. A high percentage of patients canceled their previous appointments after the DM-10M20. Almost 85% of the dentists reported being worried of contracting the infection during clinical activity. The results of the GAD-7 (General Anxiety Disorder-7) evaluation showed that 9% of respondents reported a severe anxiety. To conclude, the COVID-19 emergency is having a highly negative impact on the activity of dentists practicing in the area of Modena and Reggio Emilia. All respondents reported practice closure or strong activity reduction. The perception of this negative impact was accompanied by feelings of concern (70.2%), anxiety (46.4%) and fear (42.4%). The majority of them (89.6%) reported concerns about their professional future and the hope for economic measures to help dental practitioners.

Journal ArticleDOI
Lydia Scarfò1, Thomas Chatzikonstantinou, Gian Matteo Rigolin2, Giulia Quaresmini, Marina Motta, Candida Vitale3, José A. García-Marco, Jose Angel Hernandez-Rivas4, Fatima Miras, Mónica Baile, Juan Marquet5, Carsten Utoft Niemann6, Gianluigi Reda7, Talha Munir8, Eva Gimeno, Monia Marchetti, Francesca Maria Quaglia9, Marzia Varettoni, Julio Delgado, Sunil Iyengar10, Ann Janssens11, Roberto Marasca12, Angela Ferrari, Carolina Cuéllar-García, Gilad Itchaki13, Martin Spacek14, Lorenzo De Paoli15, Luca Laurenti, Mark-David Levin16, Enrico Lista, Francesca Romana Mauro17, Martin Simkovic, Ellen van der Spek, Elisabeth Vandenberghe18, Livio Trentin19, Ewa Wasik-Szczepanek, Rosa Ruchlemer20, Dominique Bron, Maria Rosaria De Paolis, Giovanni Del Poeta, Lucia Farina21, Myriam Foglietta, Massimo Gentile, Yair Herishanu22, Tobias Herold23, Ozren Jakšić, Arnon P. Kater24, Sabina Kersting, Lara Malerba, Lorella Orsucci, Viola Maria Popov, Paolo Sportoletti25, Mohamed A. Yassin26, Barbara Pocali, Gábor Barna27, Annalisa Chiarenza28, Gimena Dos Santos, Eugene Nikitin, Martin Andres29, Maria Dimou30, Michael Doubek, Alicia Enrico, Yervand K Hakobyan, Olga Kalashnikova, Macarena Ortiz Pareja, Maria Papaioannou, Davide Rossi, Nimish Shah31, Amit Shrestha, Oana Stanca32, Niki Stavroyianni, Vladimir Strugov, Constantine S. Tam33, Mihnea Zdrenghea34, Marta Coscia3, Kostas Stamatopoulos, Giuseppe Rossi, Alessandro Rambaldi, Emili Montserrat, Robin Foà17, Antonio Cuneo2, Paolo Ghia1 
09 Jul 2020-Leukemia
TL;DR: In CLL, COVID-19 severity increases with age; antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.
Abstract: Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79–7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.

Journal ArticleDOI
TL;DR: An ETPN overview of achievements in nanomedicine serves to reinforce the drive towards further expanding and growing the maturity of nanomediine for global healthcare, accelerating the pace of transformation of its great potential into tangible medical breakthroughs.

Journal ArticleDOI
TL;DR: This guideline provides clinicians with clear advice on best practice in ovarian stimulation, based on the best evidence available, and a list of research recommendations is provided to promote further studies in ovarianstimulation.
Abstract: STUDY QUESTION What is the recommended management of ovarian stimulation, based on the best available evidence in the literature? SUMMARY ANSWER The guideline development group formulated 84 recommendations answering 18 key questions on ovarian stimulation. WHAT IS KNOWN ALREADY Ovarian stimulation for IVF/ICSI has been discussed briefly in the National Institute for Health and Care Excellence guideline on fertility problems, and the Royal Australian and New Zealand College of Obstetricians and Gynaecologist has published a statement on ovarian stimulation in assisted reproduction. There are, to our knowledge, no evidence-based guidelines dedicated to the process of ovarian stimulation. STUDY DESIGN SIZE DURATION The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 8 November 2018 and written in English were included. The critical outcomes for this guideline were efficacy in terms of cumulative live birth rate per started cycle or live birth rate per started cycle, as well as safety in terms of the rate of occurrence of moderate and/or severe ovarian hyperstimulation syndrome (OHSS). PARTICIPANTS/MATERIALS SETTING METHODS Based on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline group and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE The guideline provides 84 recommendations: 7 recommendations on pre-stimulation management, 40 recommendations on LH suppression and gonadotrophin stimulation, 11 recommendations on monitoring during ovarian stimulation, 18 recommendations on triggering of final oocyte maturation and luteal support and 8 recommendations on the prevention of OHSS. These include 61 evidence-based recommendations-of which only 21 were formulated as strong recommendations-and 19 good practice points and 4 research-only recommendations. The guideline includes a strong recommendation for the use of either antral follicle count or anti-Mullerian hormone (instead of other ovarian reserve tests) to predict high and poor response to ovarian stimulation. The guideline also includes a strong recommendation for the use of the GnRH antagonist protocol over the GnRH agonist protocols in the general IVF/ICSI population, based on the comparable efficacy and higher safety. For predicted poor responders, GnRH antagonists and GnRH agonists are equally recommended. With regards to hormone pre-treatment and other adjuvant treatments (metformin, growth hormone (GH), testosterone, dehydroepiandrosterone, aspirin and sildenafil), the guideline group concluded that none are recommended for increasing efficacy or safety. LIMITATIONS REASON FOR CAUTION Several newer interventions are not well studied yet. For most of these interventions, a recommendation against the intervention or a research-only recommendation was formulated based on insufficient evidence. Future studies may require these recommendations to be revised. WIDER IMPLICATIONS OF THE FINDINGS The guideline provides clinicians with clear advice on best practice in ovarian stimulation, based on the best evidence available. In addition, a list of research recommendations is provided to promote further studies in ovarian stimulation. STUDY FUNDING/COMPETING INTERESTS The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payment. F.B. reports research grant from Ferring and consulting fees from Merck, Ferring, Gedeon Richter and speaker's fees from Merck. N.P. reports research grants from Ferring, MSD, Roche Diagnositics, Theramex and Besins Healthcare; consulting fees from MSD, Ferring and IBSA; and speaker's fees from Ferring, MSD, Merck Serono, IBSA, Theramex, Besins Healthcare, Gedeon Richter and Roche Diagnostics. A.L.M reports research grants from Ferring, MSD, IBSA, Merck Serono, Gedeon Richter and TEVA and consulting fees from Roche, Beckman-Coulter. G.G. reports consulting fees from MSD, Ferring, Merck Serono, IBSA, Finox, Theramex, Gedeon-Richter, Glycotope, Abbott, Vitrolife, Biosilu, ReprodWissen, Obseva and PregLem and speaker's fees from MSD, Ferring, Merck Serono, IBSA, Finox, TEVA, Gedeon Richter, Glycotope, Abbott, Vitrolife and Biosilu. E.B. reports research grants from Gedeon Richter; consulting and speaker's fees from MSD, Ferring, Abbot, Gedeon Richter, Merck Serono, Roche Diagnostics and IBSA; and ownership interest from IVI-RMS Valencia. P.H. reports research grants from Gedeon Richter, Merck, IBSA and Ferring and speaker's fees from MSD, IBSA, Merck and Gedeon Richter. J.U. reports speaker's fees from IBSA and Ferring. N.M. reports research grants from MSD, Merck and IBSA; consulting fees from MSD, Merck, IBSA and Ferring and speaker's fees from MSD, Merck, IBSA, Gedeon Richter and Theramex. M.G. reports speaker's fees from Merck Serono, Ferring, Gedeon Richter and MSD. S.K.S. reports speaker's fees from Merck, MSD, Ferring and Pharmasure. E.K. reports speaker's fees from Merck Serono, Angellini Pharma and MSD. M.K. reports speaker's fees from Ferring. T.T. reports speaker's fees from Merck, MSD and MLD. The other authors report no conflicts of interest. Disclaimer This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at www.eshre.eu/guidelines.)†ESHRE Pages content is not externally peer reviewed. The manuscript has been approved by the Executive Committee of ESHRE.

Journal ArticleDOI
TL;DR: Current knowledge on coronaviruses from a short history to epidemiology, pathogenesis, clinical manifestation of the disease, as well as treatment and prevention strategies are addressed.
Abstract: The new outbreak of coronavirus from December 2019 has brought attention to an old viral enemy and has raised concerns as to the ability of current protection measures and the healthcare system to handle such a threat. It has been known since the 1960s that coronaviruses can cause respiratory infections in humans; however, their epidemic potential was understood only during the past two decades. In the present review, we address current knowledge on coronaviruses from a short history to epidemiology, pathogenesis, clinical manifestation of the disease, as well as treatment and prevention strategies. Although a great amount of research and efforts have been made worldwide to prevent further outbreaks of coronavirus‑associated disease, the spread and lethality of the 2019 outbreak (COVID‑19) is proving to be higher than previous epidemics on account of international travel density and immune naivety of the population. Only strong, joint and coordinated efforts of worldwide healthcare systems, researchers, and pharmaceutical companies and receptive national leaders will succeed in suppressing an outbreak of this scale.

Journal ArticleDOI
01 Jun 2020-BJUI
TL;DR: To discuss the impact of COVID‐19 on global health, particularly on urological practice and to review some of the available recommendations reported in the literature, a meta-analysis is conducted.
Abstract: OBJECTIVE: To discuss the impact of COVID-19 on global health, particularly on urological practice and to review some of the available recommendations reported in the literature. MATERIAL AND METHODS: In the current narrative review the PubMed database was searched to identify all the related reports discussing the impact of COVID-19 on the urological field. RESULTS: The COVID-19 pandemic is the latest and biggest global health threat. Medical and surgical priorities have changed dramatically to cope with the current challenge. These changes include postponements of all elective outpatient visits and surgical procedures to save facilities and resources for urgent cases and patients with COVID-19 patients. This review discuss some of the related changes in urology. CONCLUSIONS: Over the coming weeks, healthcare workers including urologists will be facing increasingly difficult challenges, and consequently, they should adopt triage strategy to avoid wasting of medical resources and they should endorse sufficient protection policies to guard against infection when dealing with COVID-19 patients.

Journal ArticleDOI
TL;DR: In this paper, the authors present a consensus document on risk assessment, prevention, diagnosis, and treatment of cardiac implantable electronic device (CIED) infections. But the authors do not provide guidelines on whether to use novel device alternatives expected to be less prone to infections and novel oral anticoagulants.
Abstract: Pacemakers, implantable cardiac defibrillators, and cardiac resynchronization therapy devices are potentially life-saving treatments for a number of cardiac conditions, but are not without risk. Most concerning is the risk of a cardiac implantable electronic device (CIED) infection, which is associated with significant morbidity, increased hospitalizations, reduced survival, and increased healthcare costs. Recommended preventive strategies such as administration of intravenous antibiotics before implantation are well recognized. Uncertainties have remained about the role of various preventive, diagnostic, and treatment measures such as skin antiseptics, pocket antibiotic solutions, anti-bacterial envelopes, prolonged antibiotics post-implantation, and others. Guidance on whether to use novel device alternatives expected to be less prone to infections and novel oral anticoagulants is also limited, as are definitions on minimum quality requirements for centres and operators and volumes. Moreover, an international consensus document on management of CIED infections is lacking. The recognition of these issues, the dissemination of results from important randomized trials focusing on prevention of CIED infections, and observed divergences in managing device-related infections as found in an European Heart Rhythm Association worldwide survey, provided a strong incentive for a 2019 International State-of-the-art Consensus document on risk assessment, prevention, diagnosis, and treatment of CIED infections.

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TL;DR: In this paper, the authors summarized the various strategies adopted to overcome inherent drawbacks and improve the properties of chitosan-based films, with special regards for blending with natural and synthetic biopolymers.

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TL;DR: The impact of pH and temperature on the degradation process of HDPE MPs was investigated using C,N-TiO2 and visible light, and it was found that photocatalysis at low temperature increases MPs' surface area by fragmentation, and low pH value favours hydroperoxide formation during photooxidation.

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TL;DR: The literature to date does not fully support the routine use of corticosteroids in COVID-19, but some findings suggest that methylprednisolone could lower mortality rate in more severe forms of the condition.
Abstract: The aim was to investigate the effectiveness of glucocorticoid therapy in patients with COVID-19. A systematic search of the literature across nine databases was conducted from inception until 15th March 2020, following the PRISMA guidelines. Patients with a validated diagnosis of COVID-19 and using corticosteroids were included, considering all health outcomes. Four studies with 542 Chinese participants were included. Two studies reported negative findings regarding the use of corticosteroids in patients with COVID-19, i.e., corticosteroids had a detrimental impact on clinical outcomes. One study reported no significant association between the use of corticosteroids and clinical outcomes. However, one study, on 201 participants with different stages of pneumonia due to COVID-19, found that in more severe forms, the administration of methylprednisolone significantly reduced the risk of death by 62%. The literature to date does not fully support the routine use of corticosteroids in COVID-19, but some findings suggest that methylprednisolone could lower mortality rate in more severe forms of the condition.

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TL;DR: Recommendations on cutaneous melanoma diagnosis and treatment are made based on systematic literature reviews and the experts' experience, and it is likely that these recommendations may change in the near future.

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TL;DR: It appears that the less rigid lockdown led to an insufficient decrease in mobility to reverse an outbreak such as COVID-19, and mobility decreased enough to bring down transmission promptly below the level needed to sustain the epidemic.

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TL;DR: A multidisciplinary panel of experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer was formed to update recommendations on treatment, supportive care, education and follow-up of patients with invasive cutaneous squamous cell carcinoma.