Since the advent of COVID-19 as a pandemic, multiple therapeutic options have been looked into as possible options for the management of COVID-19 disease. Remdesivir, a broad-spectrum anti-viral, has since been given Emergency Use Authorization by the US Food and Drug Agency (FDA). While cohort studies have shown benefit in the use of Remdesivir, the only Randomized Controlled Trial showed no statistically significant clinical benefit, and the other results from a trial by the NIH has only shown some benefit in reducing hospital admission in early results prior to peer review. In this scenario, with data lacking, is it justified for Remdesivir to be given Emergency Use Authorization?

Diagnostic tests for identification of people infected with severe acute respiratory syndrome coronaviruses is crucial in the control and prevention of SARS-CoVs. Towards the ending of the year 2019, a novel coronavirus that resembles SARS-CoV called COVID-19 that causes respiratory disease appeared in China and later spread subsequently through more than 215 countries including Australia, Japan, Italy, Germany, South Africa, United Kingdom and the Unites States and has continue to spread worldwide. The genome of SARS-CoV is 29,727 nucleotides in length, and the genome organization is similar to that of other COVID-19. Generally, viral infection have been diagnosed in the laboratory through detection of viral antigens, nucleic acid, specific antibodies and by isolation and electron microscopy. Coronaviruses were detected usually from respiratory samples and blood by ELISA, Immunoflourescence test, Immunoblot and polymerase chain reaction. For epidemiological purposes the virus have to be cultured prior to other techniques in order to obtain good results. However, cultural technique is not recommended for COVID-19. The highest yield for the detection of SARS-CoVs results from real time polymerase chain reaction (RT-PCR). Sensitivity and specificity of IgG-IgM rapid diagnostic test (RDT) kits were acceptable as they are speedy, easy to use and cheap procedures which contribute to its application in mass testing. However, it cannot be employed instead of RT-PCR to detect COVID-19, but can be optional and complementary test. Development of rRT-PCR/IgG-IgM combined test kit could be helpful to ease diagnosis and the disease management, therefore more efforts are needed to investigate alternative diagnostics for coronaviruses.

Aim To assess clinical outcomes and adverse drug events in patients hospitalised with COVID -19 treated with off- label hydroxychloroquine and azithromycin. Methods We performed a retrospective analysis of hospitalised COVID-19+ patients who received hydroxychloroquine plus azithromycin over a 2 week period. The primary end point was clinical improvement on day 7 defined as either hospital discharge or an improvement of two points on a six-category ordinal scale. Secondary outcomes evaluated included mortality at day 28, ICU admission, requirement for mechanical ventilation and incidence of adverse drug events. Results Data from a total of 82 patients with laboratory confirmed SARS-CoV-2 infection was evaluated. Clinical improvement was seen in 26.8% of patients at Day 7. 31% of patients were admitted to ICU, 16 (19.5%) underwent mechanical ventilation and Day 28 mortality was 28%. Age over 70, history of cardiovascular disease and 3 or more comorbidities were risk factors for mortality. The incidence of adverse drug events was 42%. No patient experienced a Grade 4 or 5 toxicity. Over a fifth of patients (23) had raised LFTs (65% had raised LFTs at baseline), 11 patients experienced prolonged QT and 1 patient experienced grade 1 hypoglycaemia. Treatment was stopped early in 6(7.3%) patients due to prolonged QT interval or LFT elevations. Conclusion This descriptive study details the clinical outcomes of COVID-19 positive patients treated with these agents and highlights the importance of monitoring all repurposed agents for adverse drug events.

Aims This study aimed to develop a parent-metabolite joint population pharmacokinetic model to characterize the pharmacokinetic (PK) profile for phosphocreatine (PCr) and its metabolite creatine (Cr) in children with myocarditis, and to use this model to study the PK profile of different dosing schemes. Methods One hundred pediatric patients with myocarditis were enrolled. Blood samples were collected at baseline and, approximately 30, 40 or 50, 75 and 180 min after a single dose of phosphocreatine sodium. Plasma PCr and Cr concentrations were determined using a HPLC-MS/MS method. A nonlinear mixed-effects model approach was used to build the population pharmacokinetic model. After validation, the model was used for simulations to evaluate the PK profile of different dosing schemes. Results A total of 997 plasma concentrations (498 for PCr and 499 for Cr) were included in the analysis. A four-compartment chain model (central and peripheral compartments for both PCr and Cr) with first-order elimination adequately characterized the in vivo process of PCr and Cr. Allometric scaling based on bodyweight was applied to the PK parameters. The covariate analysis identified that the glomerular filtration rate (GFR) was strongly associated with the Cr clearance. Bootstrap and visual predictive check suggested a robust and reliable pharmacokinetic model was developed. The simulation results showed that the PCr had no accumulation in vivo. With the infusion of PCr, the concentration of Cr increased rapidly. Conclusion The joint population pharmacokinetic model for PCr and Cr in pediatric patients with myocarditis was successfully developed for the first time.

This is a response to the Letter to Editor received regarding the article “Outcomes of Non-Cardiotomy Patients Requiring Postoperative Extracorporeal Membrane Oxygenation.”

This study was attempted to review the evidence for or against the effectiveness of m-health interventions on health outcomes improvement and/or GDM management. Based on our findings, m-health interventions could enhance GDM patients’ pregnancy outcomes. M-health can be one of the most prominent technologies for the management of GDM.

The management of SARS-CoV 2 has not yet been clearly determined and is based on the potential therapeutics evaluated during the SARS-CoV and MERS-CoV epidemics. Although there is currently no antiviral treatment for the treatment of human coronavirus infections, the preclinical results with remdesivir (RDV) are promising. This antiviral is identified as a drug option to be evaluated against COVID-19, based on data on its activity in vitro and in vivo on the coronaviruses MERS-CoV and SARS-CoV. Today it is used to fight coronavirus. It acts on COVID-19 by interfering with key stages in the replication cycle of the virus.

As we deal with the COVID-19 pandemic we face a controversy concerning its pathophysiology and how to integrate available knowledge into practice while awaiting study outcomes. COVID-19’s pathophysiology remains elusive, as reflected in putative mechanisms that remain unsupported by robust evidence. Some models draw on clinical observations without reference to supporting data from genomic, proteomic, molecular, physiological, and other data pertaining to human coronaviruses. Consequently, some proposed models for COVID-19 pathophysiology and their corresponding treatment options remain highly divergent. To provide a pathophysiological model that better describes the different phenotypic presentations of the disease in concordance with existing research on the renin-angiotensin system, previously described pathophysiological processes for other human coronavirus infections and the genomic similarities between the SARS and SARS-CoV-2 viruses, we developed a conceptual model,“epithelial-endothelial crosstalk at alveolar-capillary membrane” that we believe can help explain the pathogenesis of COVID-19.

We report a case of a 34-month-old girl who has been followed up for 12 months after ingesting 105mg/kg of hydroxyurea (HU) and showed only transient mild bone marrow suppression. With anticipated increase in HU use among children with SCD in sub-Saharan Africa, the possibility of accidental ingestion should be envisaged and appropriate user-education and management guidelines established. Toxicity from accidental HU overdosage is generally mild and transient and should not constitute a barrier to its use in Nigerian children with SCD.

Background: The number of cancer survivors, including childhood cancer survivors, is increasing as a consequence of improved therapeutic options. However, the medical costs associated with therapy are high and many families are suffering from the resultant financial burden. Objective: Our study aims to determine the total medical cost for 5 years after the initial diagnosis of childhood cancers. Methods: A customized dataset from the Korean National Health Insurance Claims Database was requested for this study. A total of 7,317 patients were selected to determine the total medical cost related to their treatment. The costs are presented as the 2% trimmed mean value to exclude extreme costs. The medical costs were further classified according to cancer type, treatment phase, and socioeconomic status. Multiple linear regression analyses were performed. Results: The average total medical cost per patient is 36.8 million Korean Wons (KRW) or 30,665 United States Dollars (USD). Among childhood cancers, leukemia was associated with the highest cost at 53.5 million KRW (USD 44,556). Analysis of socioeconomic status revealed that the higher income group demonstrated higher medical expenditure when compared to other groups. Analysis of the treatment phase showed that costs associated with the early phase of treatment are the highest, especially in the first 3 months after initial diagnosis. Conclusion: Cancer treatments are expensive and are a source of significant financial stress to patients’ families. To alleviate the financial burden and reduce the socioeconomic disparities associated with medical care and costs, a better understanding of the current experience of patients and their families is required.

The novel corona virus, previously dubbed 2019-nCoV and now officially named SARS-CoV-2 and COVID-19 has caused major outbreaks of deadly pneumonia in the 21st century has began in Wuhan, China in late 2019 and now become a destructive to global health and therefore the utmost need of the hour is to develop therapeutic candidates or vaccines against it (Zhu et al., 2020). Numerous corona viruses, first discovered in domestic poultry in the 1930s, 2002 and 2012 cause respiratory, gastrointestinal, liver, and neurologic diseases in animals. Only 7 corona viruses are known to cause disease in humans. There is an urgent need to identify specific targets to design promising therapeutic agents against severe acute respiratory syndrome coronavirus aetiological agent of coronavirus disease 2019 (COVID-19) characterised by pulmonary infection in humans. The need exists for additional treatment options addressing antiviral replication, and against SARS-CoV-2. Virus entry and replication strategies are potential targets for antiviral drug treatments. Since NF-κB pathway is often targeted by viral pathogens to enhance viral replication, host cell survival and host immune evasion. Viruses may activate or suppress NF-kB. (Marta et al., 2014). There have many studies on SARS-COV since 2002-2003 SARS epidemics. SARS-COV2 (COVID-19) belongs to the same family of corona viruses and shares many similarities (3), including SARS-CoV-1. Here we discuss the possible mechanisms of NFκB inhibitor interference with the SARS-CoV-2 replication cycle.

Objective Affecting 1 in 500 individuals; Hypertrophic cardiomyopathy (HCM) is an autosomal dominant cardiovascular disorder which is prevalent throughout the world. Surgical myectomy and alcohol septal ablation (ASA) are two methods currently used for the management of drug refractory Hypertrophic obstructive cardiomyopathy (HOCM). ASA may prove to be a useful, less invasive tool when confronting patients with HOCM especially those who are more elderly or deemed to be a higher surgical risk. Methods Electronic literature search was conducted to identify relevant articles that discussed invasive methods to treat drug refractory HOCM. No limits were placed on timing of the publication or the type of article. Key words and MeSH terms were used to conduct the search and the results were summarized in the relevant section. Results Current evidence suggests that alcohol septal ablation is a safe and effective procedure in treating patients with HOCM with similar short- and long-term outcomes when compared with surgical myectomy. Selection of patient with appropriate assessment is the key for satisfactory outcomes. Conclusion ASA has been shown to be a safe and reliable procedure; advanced imaging techniques and dedicated multi-disciplinary teams can be used to carefully select patients with HOCM. Though surgical myectomy is recommended as gold standard treatment for drug refractory HOCM, however, ASA may play an increasing role in the near future due an ageing population; both ASA and SM can have a synergistic effect in treating those who are affected by HOCM.

Background: The COVID-19 pandemic is causing a global health emergency. Health systems are under extreme pressure because of the outbreak. Pediatric population seems to be less prone to develop a severe course of the disease. Still the information about COVID-19 infection and children affected by cancer are few. This survey aims to highlight preventive and control measures to manage COVID-19 infection in Italian Pediatric Oncology and Hematology Association (AIEOP) centers. Procedure: A multicentre, descriptive survey design was used. All the AIEOP centers were invited to complete an on-line survey. Data collection was performed between March 15, 2020 and April 15, 2020. Results: Thirty six out of 48 centers responded to the survey. All the centers implemented similar preventive measures in order to control the COVID-19 spread and 77.8% of centers have created structured pathways, specific protocols or procedures; 30% of centers reduced the number of inpatient beds and 90% outpatient activity. The prevalence data collected report 14 children positive and 35 healthcare professionals positive. Conclusion: COVID-19 is not spreading homogeneously in Italy and children are less infected. However, all the AIEOP centers showed preparedness and response actions to control the infection and to protect their own fragile patients. Patients and staff safety were maintained; services and clinical activities were sometimes adapted. It will be necessary to define new processes and new strategies to ensure safety and continuity of care to children affected by cancer, even in the future, when the lockdown will end, and new measures will be implemented.

Langerhans Cell Histiocytosis (LCH) is a rare proliferative disease of the mononuclear phagocyte system, characterised by tissue infiltration of CD1a+ CD207+ histiocytes. The clinical presentation is variable, ranging from unifocal asymptomatic bone involvement to life-threatening multisystem disease, requiring aggressive therapeutic approaches. Intraocular involvement is uncommon and associated to poor visual and general prognosis. Herein, we report a case of LCH in a newborn with ocular and multisystem risk organ involvement, unresponsive to several lines of chemotherapy. Off-label administration of vemurafenib led to dramatic improvement at systemic level; however, chronic sequelae of ocular involvement resulted in poor visual prognosis.

The manuscript describes the features of a platform developed by the OpenChemistry consortium that bridges many prominent technologies in data sharing, analysis, and visualization. The platform unifies a web-based GUI with few computational backends  and can be used to visualize and analyze pre-existing data or newly produced computational results.The development of this platform is timely and the description in the manuscript is clear and compelling. I recommend the paper be published with minor revisions, suggested in the following.I hereby give permission to publicly associate my name to this referee report.Editor's Note: Accepted version of this manuscript https://doi.org/10.22541/au.158687268.81852407/v2

The investigation on the fatigue behaviour of the processed friction stir welded AA8011/AA6082 dissimilar joint is reported in this work. The single-pass friction stir processing technique was applied on the friction stir welded AA8011/AA6082 and AA6082/AA8011 dissimilar joints. The friction stir processing was conducted under normal conditions (room temperature). The samples were prepared for different analysis using the waterjet cutter technology. The tests conducted include tensile, microstructural analysis, microhardness, fatigue and fracture surface morphology. The microstructural analysis revealed a correlation between material positioning and grain sizes. There was a notable decrease in grain size when AA6082 was positioned on the advancing side during processing. The tensile properties of the joint processed with AA6082/AA8011 were found to be higher compared to the joint produced with AA8011/AA6082. The AA6082/AA8011 joint was found to be more ductile compared to AA8011/AA6082 joint. The stir zone microhardness for the AA8011/AA6082 and AA6082/AA8011 joints was measured to be approximately 60HV and 80HV, respectively. The fatigue strength of AA6082/AA8011 was found to be higher compared to AA8011/AA6082 fatigue strength.

An innovative computational methodology is proposed for fatigue life estimation of notched components subjected to multiaxial variable amplitude loadings. In the proposed methodology, if the calculated uniaxial fatigue damage by axial tension‐compression loading path is more than that by the pure torsional loading path, an axial strain-based multiaxial fatigue damage parameter is selected to compute multiaxial fatigue damage, or else a shear strain-based multiaxial fatigue damage parameter is selected to compute multiaxial fatigue damage. Moreover, the proposed methodology utilizes axial strain-based and shear strain-based multiaxial fatigue damage parameters in replacement of equivalent strain amplitude to take into consideration of the non-proportional additional hardening phenomenon. The fatigue data of 7050-T7451 aluminum alloy and GH4169 superalloy notched specimens are utilized to verify the proposed notch fatigue life prediction methodology, and the prediction results are satisfactory.

Double-outlet left ventricle (DOLV) is a rare congenital cardiac anomaly. The aorta and the main pulmonary arterial trunk arises predominantly from the left ventricle(LV) and is associated with a malaligned ventricular septal defect(VSD), various degrees of hypoplasia of the right ventricle, and presence or absence of pulmonary stenosis. Bi-ventricular repair is the preferred treatment option whenever possible. Various techniques for bi-ventricular repair have been described. The best option for DOLV correction is by translocating the pulmonary root to the right ventricle(RV)[1]. In this series, we report four patients who underwent biventricular repair of DOLV in our institute with excellent outcomes. All patient details were collected from the institute patient record system. Echocardiographic data were obtained from the records. Intraoperative charts were reviewed for further information on the surgical procedure and cardiopulmonary bypass. Postoperative data included survival, functional status and followup echocardiography. Of the four children, three underwent pulmonary root translocation and one child underwent Reparation al etage Ventriculaire(REV) procedure. There was no mortality and all children are in stable clinical condition in the recent follow-up and no re-operations or interventions were required following primary surgical correction. Thus DOLV is anatomically and surgically a challenging subset. Pulmonary root translocation in this anatomy is technically challenging but safe and superior option when compared to other alternative surgical procedures and it can be performed with excellent results, even in infants.

Objective: The aim of this study was to analyse the relation between adverse childhood experiences exposure and repeated induced abortion considering the potential effect of social deprivation and intimate partner violence. Design: An observational cross-sectional survey. Setting: This survey was conducted within the framework of the regional health agency of the Aquitaine area in each of the 25 induced abortion centres from June 15 to September 15, 2009, as well as to all women over 18 having an induced abortion with a liberal doctor under convention with of the centres previously referred to. Sample: 806 women asking for an induced abortion who responded to questions regarding adverse childhood experiences and previous abortion. Methods: Collecting data was achieved by a self-conducted anonymous questionnaire. Main outcome measure: The percentage of repeated induced abortion. Results: The percentage of patients with no exposure to adverse childhood experiences decreases (28%; 20%; 9%) when induced abortion are repeated according to the abortion rank (first, 2nd, 3rd or +), whereas the percentage of women with high exposure increases (17%; 27%; 32%). The adjusted odds ratio of a third request or more for abortion is 7.73 (3.56-16.77) for patients with high exposure to adverse childhood experiences when compared to women with no exposure who had a first induced abortion. Conclusion: There is a strong graded link between the magnitude of exposure to adverse childhood experiences and repeated induced abortion.

Objective: To investigate current practice patterns of tranexamic acid (TXA) use by Obstetricians and Gynecologists. Design: A cross-sectional, web based survey. Population: Members of the Central Association of Obstetricians and Gynecologists (CAOG). Methods: The anonymous survey regarding demographics, circumstances of use, and barriers of TXA use was emailed to CAOG members October 2018 – December 2018. Results: There were 81 responses with a response rate of 27%. The majority of respondents were general obstetricians and gynecologists (63%). TXA used mostly during postpartum hemorrhage (72%), followed by heavy cyclic bleeding (42%), and then benign gynecological surgeries (5%). The majority of participants had TXA as part of their hospitals hemorrhage protocol (73%) and increase use was associated with having a hospital protocol (86%). The largest concern with TXA use was thromboembolic events (48%). The majority of respondents had a favorable view of TXA being incorporated into hospital protocols (95%). Conclusion: To our knowledge this is the first survey among obstetricians and gynecologist to elicit current practice patterns with TXA. This study illustrates an association between increase use of TXA when it is incorporated into a hospital protocol for postpartum hemorrhage. This finding suggests that to an individual provider, local hospital recognition of the safety and effectiveness of TXA is more impactful and influential than the World Health Organization to an individual obstetrician in practice. The major concern with TXA use was increased risk of a thromboembolic event, an overwhelming number of respondents would support incorporating TXA into their hospital’s protocols

Objective: To describe the kinetic profile of arrhythmia in pregnant women with heart diseases in different cardiovascular risk according to mWHO classification. Design: Prospective observational study Setting: Cardiac and Vascular Diseases, Institute of Cardiology, CMUJ, John Paul II Hospital, Krakow, Poland Population: 103 pregnant women with organic heart disease(HD) Methods: 24-hour ECG-Holter was obtained in each trimester of pregnancy and post-partum period Main outcome measures: Supraventricular arrhythmia(SA): supraventricular tachycardia (SVT), supraventricular extrasystole (significant when SVE >30/hour), atrial tachycardia (AT), atrial fibrillation (AF);Ventricular arrhythmia(VA): ventricular premature contractions (PVCs >30/h), non-sustained, sustained tachycardia (nsVT, sVT);Conduction disturbances: low grade: AV I degree block, Mobitz I, high grade: Mobitz II,III degree blocks. Results: The prevalence of arrhythmia was 45.6 % of women, SA occured in 24.3 % and VA in 31.1%. Episodes of nsVT were more common in women with serious HD (mWHO class II-II, III, IV) than in women with milder HD (mWHO I, II) in each trimester: trimester1: 1,7% vs. 13,6%, p=0,02; trimester2: 5,1% vs. 18,2%, p=0,03; trimester3: 2,3% vs. 13,9 %, p=0,04,respectively.The kinetic profile of arrhythmia throughout pregnancy was different among groups: ventricular arrhythmia had tendency to increase in both groups, supraventricular arrhythmia declined in women with milder CHD and increased in serious CHD group. The highest rate of arrhythmia was in the 2nd trimester in both groups (29,2%). Conclusion: The kinetic profile of arrhythmia during pregnancy was different between groups with lower and higher cardiac risk, with more favorable profile in lower cardiac risk group. Keywords: Arrhythmia, Cardiovascular disease, Pregnanc

When it comes to coronavirus and biology - sex matters Scott M Nelson, MD PhD1,2Martina Capuzzo3Antonio La Marca, MD PhD31School of Medicine, University of Glasgow, UK2NIHR Bristol Biomedical Research Centre, Bristol, UK3Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, ItalyCorresponding author:Prof Scott M Nelson University of Glasgow New Lister Building Glasgow Royal Infirmary Glasgow G31 2ER, UK +44 (0)141 201 8581 Scott.Nelson@glasgow.ac.ukWord count: Text 1058The male dominance in COVID19 morbidity and mortality figures has been a consistent feature from the early reports emerging from Wuhan, to national intensive care data, through to more recent comprehensive population mortality data. Men are more than twice as likely to become severely ill and require intensive care than women and at least twice as likely to die, with further widening of the mortality discordance with increasing age. These differences do not appear to be caused by differential rates of infection, as equal numbers of men and women catch SARS-CoV-2. Nor do they appear to reflect clustering of unhealthy behaviour and comorbidities in men, as even after adjustment, male sex is associated with a hazard ratio (HR) of death from COVID19 of HR 1.99, (95%CI 1.88-2.10)1. These sex-specific differences in severity and fatality were also observed for the 2002-2003 SARS-CoV outbreak, and the Middle East respiratory syndrome (MERS)-CoV2. So, what underlies this sex-specific susceptibility difference for pathogenic coronaviruses? Several early lifestyle theories were proposed, but rather more fundamental sex-specific discordances in steroid hormones, x-linked genes and the innate immune response are likely to underlie this sexual dimorphism.

We present a patient with myocardial infarction and cardiogenic shock who underwent high-risk percutaneous coronary intervention with Impella support, and developed iliac artery thrombosis at the Impella access site. Percutaneous thrombectomy was accomplished using the FlowTriever system, highlighting this approach as a potentially safe and effective alternative to surgery.

While there is significant awareness regarding droplet and contact transmission, aerosols are generally underestimated as a potential mode of transmission of SARS-Cov-2 infection. With the gradual resumption of cardiac surgical activities, the cardiac surgical operating room will become an important potential source of infection to the cardiac surgeon and other healthcare workers participating in the operation. There is also diminished awareness about the different aerosol generating procedures (AGP) in the cardiac surgical operating room. In this mini-review we intend to highlight the various aerosol generating procedures that are common in cardiac surgery. This will help increase the awareness among surgeons to AGP. A practical approach to taking preventive measures have also been discussed.