Case study of a critically ill person with COVID-19 on ECMO successfully treated with leronlimab

The number of confirmed cases of infection with SARS-CoV-2, the virus causing Coronavirus disease 2019 (COVID-19), continues to increase and is associated with substantial morbidity and mortality in virtually every country in the world. Although in the long-term mass vaccinations remains the most promising approach to control the pandemic, evidence suggests that new variants of the virus have emerged that may be able to evade the immune responses triggered by current vaccines. Therefore despite the recent approval of a number of SARS-CoV-2 vaccines there remains considerable urgency for effective treatments for COVID-19. Severe-to-critical COVID-19 has been shown to be associated with a dysregulated host immune response to SARS-CoV-2 with elevated levels of C–C chemokine receptor type 5 (CCR5) ligands including chemokine C–C ligands 3, 4, 5, as well as interleukins 6 and 10. Leronlimab, a CCR5-specific humanised IgG4 monoclonal antibody originally developed for the treatment of HIV has been studied for the treatment of COVID-19. In the TEMPEST trial which compared leronlimab to placebo in subjects with mild-to-moderate COVID-19, a post hoc analysis showed that leronlimab led to improvements from baseline in National Early Warning Score 2 (NEWS2) at Day 14 in the sub-set of people with more severe disease. Data has also been released on a further ongoing, randomized, placebo-controlled phase 3 registrational trial of leronlimab in 394 people with severe-to-critical COVID-19. The results show that Day 28 mortality was reduced (P ​= ​0.0319) in the subset of participants receiving leronlimab plus other pre-specified commonly used COVID-19 treatments including dexamethasone administered as part of their standard of care (SOC) compared to participants receiving placebo plus other pre-specified commonly used COVID-19 treatments including dexamethasone as part of their SOC. Several cases have recently been reported demonstrated that treatment with leronlimab restores immune function and achieves clinical improvement in people with critical COVID-19. Here we report on a further case of a critically ill person who was treated with leronlimab. This person had been on extracorporeal membrane oxygenation (ECMO) for an extended period of time before receiving 4 doses of leronlimab. The male subject received his first dose of leronlimab on Day 79 of hospitalization he was weaned off ECMO by Day 84 and discharged from the ECMO intensive care unit on Day 91

The arterial switch operation : going back to the roots

The main goal of this thesis is to investigate the possible factors playing a role in dilatation of the neo-aortic root in patients after ASO for TGA. Basic histological research as well as histological 3D reconstruction of the arterial roots has been combined with clinical investigation. The studies that resulted from this research form the basis of this thesis. We went __back to the roots__.Johnson&Johnson Medical BV, Krijnen Medical BV, Maquet Netherlands BV, Sorin Group Nederland BV, St. Jude Medical Nederland BVUBL - phd migration 201

Safety and efficacy of BAY 94–9027, an extended-half-life factor VIII, during minor surgical procedures in patients with severe haemophilia A

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Nursing and midwifery students’ mental health status and intention to leave during Covid-19 pandemic

Introduction: COVID-19 has not only affected the physical health of people but it has also had a major impact on their mental health. Objective: To investigate the nursing, midwifery, and operating room students’ mental health and intention to leave during COVID-19 pandemic. Methods: This cross-sectional study was conducted at the nursing and midwifery school of Tabriz, Iran. Over a period of three months (February–May 2021) and through random sampling, 284 students were selected. The research tool consisted of three parts including demographic information, Depression Anxiety Stress scales, and a questionnaire on intention to leave. Results: More than 20% of the students experienced some degrees of depression, anxiety, and stress. Nearly one-third of participants mentioned a high level of intention to leave. Nursing students had a higher level of a turnover tendency than other students (p =.004). Male students and who experienced moderate to high level of depression displayed greater intention to leave (p =.005). Conclusion: Students suffered from some degrees of stress, anxiety, and depression during the COVID-19, and it strengthened the participants’ intention to leave. Relevant authorities are recommended to improve mental health of the students by providing psychological counseling sessions, reducing their direct contact with patients, and providing personal protective equipment. © The Author(s) 2022

Neutrophil-Specific Antigens: Immunobiology, Genetics and Roles in Clinical Disorders

Neutrophils are the most abundant nucleated cells in blood circulation and play important roles in the innate and adaptive immune responses. Neutrophil-specific antigens, only expressed on neutrophils, are glycoproteins originally identified in studies on neonatal neutropenia due to fetal-maternal incompatibility and autoimmune neutropenia of infancy. The most investigated neutrophil–specific antigens are the NA and NB antigens that their incompatibilities also cause transfusion-induced febrile reactions and acute lung injury, a potentially fatal reaction, and in bone marrow transplantation, causing graft rejection. NA antigens are members of the immunoglobulin superfamily and are low-affinity Fc-receptors FcγRIIIb (CD16b). Fc receptors connect the F(ab), the antigen-binding fragment of the antibody molecules, to neutrophils and lead them to recognize and phagocytize the targeted antigens. The NB (CD177) antigen belongs to the urokinase-type Plasminogen Activator Receptor Superfamily (uPAR, CD59, Ly6), but its specific functions have not been fully determined. It is known, however, that NB antigen binds proteinase-3 (PR3 to the neutrophil membrane), a serine protease. In clinical studies, it was also demonstrated that NB expression is highly elevated in Polycythemia Vera and is unexpectedly expressed in some cancer tissues. Neutrophil-specific antigens are examples of antigens that have important biological and clinical activities beyond antigenicity

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe

To access publisher's full text version of this article click on the hyperlink belowAll-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.UNSW (Sydney, Australia) CanHepC Trainee Program (Canada) National Health and Medical Research Council Australian Government Department of Healt

In vivo and in vitro Activation of T-Antigen Receptors on Leukocytes and Platelets 1

Serological studies on a patient whose red cells are polyagglutinable due to T activation have demonstrated concomitant T activity of the separated leukocytes and platelets. Normal leukocytes and platelets are not T active, but activation can be induced in vitro by treatment with neuraminidase or with Pneumo-coccus type III filtrate. Such T-active cells absorb anti-T from Arachis hypogea lectin. Tests on different types of separated leukocytes show that both neutrophils and lymphocytes have latent T antigen receptors. Neuraminidase treatment of platelets does not change their ability to promote clot retraction, to aggregate with ADP, or to take up serotonin.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73987/1/j.1423-0410.1976.tb02217.x.pd

The Therapeutic Approaches for Hepatitis C Virus: Protease Inhibitors and Polymerase Inhibitors

The current standard of care for hepatitis C infection is peginterferon/ribavirin (PegIFN/RBV). We are entering the era where direct-acting antiviral agents (DAAs) will be added to PegIFN/RBV, leading to higher sustained response rates in genotype 1 infected individuals. Currently DAAs are directed toward specific proteins involved in hepatitis C replication with NS3/NS4A protease inhibitors furthest in development. Telaprevir and boceprevir are both NS3/NS4a inhibitors that significantly improve sustained response when added to PegIFN and RBV. The hepatitis C virus (HCV) polymerase inhibitors are another promising DAA class. These molecules are divided into nucleoside/nucleotide polymerase inhibitors and nonnucleotide/nucleoside polymerase inhibitors. Nucleoside/nucleotide polymerase inhibitors have a high barrier to resistance and appear to be effective across a broad range of genotypes. Nonnucleoside polymerase inhibitors have a lower barrier of resistance and appear to be genotype specific. Preliminary data with these compounds are also promising. A third class, NS5A inhibitors, has also shown potent HCV RNA suppression in preliminary studies as monotherapy and with PegIFN and RBV. Combinations of these agents are also entering clinical trials and indeed a preliminary report has demonstrated that the combination of an NS3/4A protease inhibitor and NS5B polymerase inhibitor can effectively suppress virus in genotype 1 individuals. Future studies will concentrate on combinations of direct-acting antiviral agents without and with PegIFN and RBV. Clinicians will need to be familiar with managing side effects as well as resistance as we enter this new era

Non-Thermal Radio Frequency and Static Magnetic Fields Increase Rate of Hemoglobin Deoxygenation in a Cell-Free Preparation

The growing body of clinical and experimental data regarding electromagnetic field (EMF) bioeffects and their therapeutic applications has contributed to a better understanding of the underlying mechanisms of action. This study reports that two EMF modalities currently in clinical use, a pulse-modulated radiofrequency (PRF) signal, and a static magnetic field (SMF), applied independently, increased the rate of deoxygenation of human hemoglobin (Hb) in a cell-free assay. Deoxygenation of Hb was initiated using the reducing agent dithiothreitol (DTT) in an assay that allowed the time for deoxygenation to be controlled (from several min to several hours) by adjusting the relative concentrations of DTT and Hb. The time course of Hb deoxygenation was observed using visible light spectroscopy. Exposure for 10–30 min to either PRF or SMF increased the rate of deoxygenation occurring several min to several hours after the end of EMF exposure. The sensitivity and biochemical simplicity of the assay developed here suggest a new research tool that may help to further the understanding of basic biophysical EMF transduction mechanisms. If the results of this study were to be shown to occur at the cellular and tissue level, EMF-enhanced oxygen availability would be one of the mechanisms by which clinically relevant EMF-mediated enhancement of growth and repair processes could occur