Using High-Fidelity Simulation to Introduce Communication Skills about End-of-Life to Novice Nursing Students

Background: High-fidelity simulation is being considered as a suitable environment for imparting the skills needed to deal with end-of-life (EOL) situations. The objective was to evaluate an EOL simulation project that introduced communication skills to nursing students who had not yet begun their training in real healthcare environments. Methods: A sequential approach was used. The ?questionnaire for the evaluation of the end-of-life project? was employed. Results: A total of130 students participated. Increasing the time spent in high-fidelity simulation significantly favored the exploration of feelings and fears regarding EOL (t = ?2.37, p = 0.019), encouraged dialogue (t = ?2.23, p = 0.028) and increased the acquisition of communication skills (t = ?2.32, p = 0.022).Conclusions: High-fidelity simulation promotes communication skills related to EOL in novice nursing studentsThis research was funded by the University of Cantabria (Spain). Grant number 28.0000.229

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. METHODS: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. FINDINGS: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2-11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75-1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58-1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91-1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70-1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11-0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50-0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38-0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45-0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. INTERPRETATION: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. FUNDING: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Transplantation of fetal liver cells into newborn hemophilic mice for the treatment of hemophilia A without inhibitors formation

Resumen del trabajo presentado en el 10th BIC International Conference, celebrado en Genoa (Italia), del 6 al 8 de septiembre de 2019Title Transplantation of fetal liver cells into newborn hemophilic mice for the treatment of hemophilia A without inhibitors formation Simone Merlin, Silvia Buzzi, Tamara Garcia-Leal, Maria Jose Sanchez, Antonia Follenzi Background. Hemophilia A cell therapy approaches in paediatric individuals require suitable FVIII-producing cell populations presenting stable engraftment potential. We previously showed that adult-derived FVIII-producing cells, i.e. liver sinusoidal endothelial cells (LSEC) and hematopoietic stem cells (HSC), can be used for the treatment of adult hemophilia A (HA) mice. However, after transplantation in busulfan-conditioned newborn mice, adult LSEC/HSC cannot efficiently engraft, while murine fetal liver (FL) hemato/vascular cells from day 11-13 of gestation (E11-E13) strongly reconstitute the hematopoietic compartment and showed multiorgan endothelial reconstitution potential while secreting FVIII. Aims. To investigate the engraftment of FL cells in newborn HA mice as a new strategy to develop an experimental treatment for HA in neonates. Materials and Methods. We transplanted E11-E13 GFP+ FL cells using intravenous cell transfer into myelo-ablated newborn syngeneic HA mice. The engraftment level as well as the FVIII production and activity was assessed in HA recipients starting from 4 weeks and followed-up to 1 year after transplantation. Moreover, we evaluated the presence of anti-FVIII antibodies/inhibitors in plasma of transplanted mice. Results. We transplanted FL cells from E11-E13 GFP+ mice into newborn HA mice pre-treated with busulfan (FLE11-E13+BU). Control groups received FL E11-E13 GFP+ cells without busulfan pretreatment (FLE11-E13noBU) or PBS ± busulfan. In FLE11-E13+BU group we observed >60% chimerism in peripheral blood with a concomitant FVIII activity (up to 16%) which remained stable up to 1 year after transplantation. In FLE11-E13noBU we observed low level of engraftment (¿10%) and a consequent low FVIII activity (¿3.5%). Both groups of mice, FLE11-E13+BU and E13noBU, did not develop anti-FVIII antibodies, not even after FVIII immunization. Conclusions. Transplantation of FL cells may provide a novel and highly promising neonatal preclinical models, for HA treatment, paving the way for studies aiming at deriving long-term reconstituting ¿fetal-like¿ hemato/vascular progenitors from other sources (e.g. iPS

Transplantation of fetal liver hemato/vascular cells in newborn mice for correction of hemophilia A (HA)

Trabajo presentado en el 51st Annual Scientific Meeting ISEH, celebrado en Edimburgo (Escocia) del 01 al 04 de septiembre de 2022.The development of strategies based on cell therapy approaches requires further insights into new stem/progenitor cell populations presenting stable engraftment potential and restoration capacity of the deficient factors causing the disease. We have previously shown that hemato/vascular progenitor cells from the foetal liver (FL) possess higher hematopoietic and vascular endothelial engraftment potential when transplanted to busulfan (BU) conditioned newborn mice compared to adult counterpart cells, constituting likely therapeutic targets for the treatment of congenital hemato/vascular related diseases in neonates. Hemophilia A (HA) is a coagulation disorder cause by a deficient production of factor FVIII by vascular endothelial cells and, to a lesser extent, by hematopoietic cells. Since FL cells are endowed with high hematopoietic and endothelial engraftment, we transplanted FL cells into HA new born BU conditioned mice, showing that engrafted FL-derived cells can improve FVIII production and rescued the HA bleeding phenotype. BU constitutes a mild preconditioning treatment compared to other approaches, including irradiation, still it has several side effects that can compromise the health of HA individuals. Therefore, we also explored the long-term correction of HA in unconditioned newborn mice transplanted with FL cells. Here we present the data showing that infusion of FL cells without preconditioning showed a lower hematopoietic engraftment but long term correction of HA (up to 18 months). Infusion of FL cells without preconditioning was able to move the condition of these mice from severe to moderate/mild

Fetal liver haemato/vascular progenitor cells as a cell based therapeutic tool for neonatal haemophilia

Resumen del trabajo presentado en el 27th ESGCT Annual Congress in collaboration with SETGyc, celebrado en Barcelona (España), del 22 al 25 de octubre de 2019The development of strategies based on cell therapy approaches requires further insights into new stem/progenitor cell populations presenting stable engraftment potential and restoration capacity of the deficient factors causing the disease. We have previously shown that hemato/vascular progenitor cells from the foetal liver (FL) possess higher hematopoietic and vascular endothelial engraftment potential when transplanted to newborn mice compared with adult-derived counterpart progenitor cells (1), constituting likely therapeutic targets for the treatment of congenital hemato/vascular related diseases in neonates. The hemophilia A (HA, a deficiency of factor FVIII) and other rare coagulation disorders, including deficiency of factor FV, are caused by mutations decreasing the production of coagulation factors by hematopoietic and/or vascular endothelial cells. We have shown that different FL-derived cell populations produce FVIII (2), suggesting its suitability as cell therapeutic targets for the treatment of hemophilia diseases. Here we will present the results on the phenotypic and functional characterization of FL progenitors, focusing in three aspects: 1) Characterization of vascular endothelial stem cells during development; 2) Determination of coagulation factor production; 3) Analysis of chimeric HA mice transplanted with wild type FLGFP-derived cells at day 1 after birth. These research should be instrumental for the establishment of a preclinical model for HA treatment in neonates. (1) Cañete el all, Stem Cells, 2017. doi.org/10.1002/stem.2494 (2) Serrano et al, Throm & Haem, 2018. doi.org/10.1055/s-0038-166135

Telephone-Cardiopulmonary Resuscitation Guided by a Telecommunicator: Design of a Guiding Algorithm for Telecommunicators

Background: Out-of-hospital cardiac arrest is considered a global problem. In the last few years, there has been a growing interest in telephone-cardiopulmonary resuscitation guided by a telecommunicator. Indeed, several studies have demonstrated that it increases the chances of survival rate. This study focuses on the key points the operator should follow when performing telephone-cardiopulmonary resuscitation. The main objective of this paper is to design an algorithm to improve the telephone-cardiopulmonary resuscitation response protocol. Methods: The available evidence and the areas of uncertainty that have not been previously mentioned in the literature are discussed. All the information has been analyzed by two discussion groups. Later, a consensus was reached among all members. Finally, a response algorithm was designed and implemented in clinical simulation. Results: All the witnesses were able to recognize the OHCA, call for emergency assistance, follow all the operator’s instructions, move the victim, and place their hands in the correct position to perform CPR. Discussion: The results of the pilot study provide us a basis for further experimental studies using randomization and experimental and control groups. Conclusions: No standardized recommendations exist for the operator to perform telephone-guided CPR. For this reason, a response algorithm was designed

Searching for a Cell-Based Therapeutic Tool for Haemophilia A within the Embryonic/Foetal Liver and the Aorta-Gonads-Mesonephros Region

The development of new strategies based on cell therapy approaches to correct haemophilia A (HA) requires further insights into new cell populations capable of producing coagulation factor VIII (FVIII) and presenting stable engraftment potential. The major producers of FVIII in the adult are liver sinusoidal endothelial cells (LSECs) and in a lesser degree bone marrow-derived cells, both of which have been shown to ameliorate the bleeding phenotype in adult HA mice after transplantation. We have previously shown that cells from the foetal liver (FL) and the aorta-gonads-mesonephros (AGM) haematopoietic locations possess higher LSEC engraftment potential in newborn mice compared with adult-derived LSECs, constituting likely therapeutic targets for the treatment of HA in neonates. However, less is known about the production of FVIII in embryonic locations. Quantitative polymerase chain reaction and Western blot analysis were performed to assess the relative level of FVIII production in different embryonic tissues and at various developmental stages, identifying the FL and AGM region from day 12 (E12) as prominent sources of FVIII. Furthermore, FL-derived VE-cad+CD45-Lyve1+/− endothelial/endothelial progenitor cells, presenting vascular engraftment potential, produced high levels of F8 ribonucleic acid compared with CD45+ blood progenitors or Dlk1+ hepatoblasts. In addition, we show that the E11 AGM explant cultures expanded cells with LSEC repopulation activity, instrumental to further understand signals for in vitro generation of LSECs. Taking into account the capacity for FVIII expression, culture expansion and newborn engraftment potential, these results support the use of cells with foetal characteristics for correction of FVIII deficiency in young individuals.This work was supported by the Spanish Ministry of Science and Technology Grant BFU2010–15801; Junta de Andalucia Research Funding Program PAI-BIO-295 and the Andalusian Association of Haemophilia ASANHEMO FV2016–20

Transplantation of Fetal Liver Cells into Newborn Hemophilic Mice for Hemophilia A Cell Therapy

Trabajo presentado en ISTH 2020 Virtual Congress, celebrado en modalidad virtual del 12 al 14 de julio de 2020.[Background]: Hemophilia A cell therapy approaches in pediatric individuals require suitable FVIII-producing cell populations presenting stable engraftment potential. We previously showed that adult-derived FVIIIproducing cells, i.e. liver sinusoidal endothelial cells (LSEC) and hematopoietic stem cells (HSC), can be used for the treatment of adult hemophilia A (HA) mice. However, after transplantation in busulfan-conditioned newborn mice, adult LSEC/HSC cannot ef¿ciently engraft, while murine fetal liver (FL) hemato/vascular cells from day 11-13 of gestation (E11-E13) strongly reconstitute the hematopoietic compartment and showed multiorgan endothelial reconstitution potential while secreting FVIII. [Aims]: To investigate the engraftment of FL cells in newborn HA mice as a new strategy for the treatment of paediatric HA patients. [Methods]: We transplanted FL cells from E11-E13 GFP+ mice into newborn HA mice pre-treated with busulfan (FLE11-E13+BU). Control groups received FLE11-E13 GFP+ cells without busulfan pretreatment (FLE11-E13noBU) or PBS±BU. The engraftment level as well as the FVIII production and activity was assessed in recipients starting from 4 weeks and followed-up for 18 months after transplantation. Moreover, we evaluated the presence of anti-FVIII antibodies/inhibitors in plasma of transplanted mice. [Results]: In FLE11-E13+BU group we observed >60% engraftment in peripheral blood with concomitant FVIII activity (up to 16%) which remained stable up to 18 months after transplantation, while engraftment and FVIII activity were lower in absence of preconditioning. Additionally, FLE11-E13+BU group showed the presence of up to 4% of GFP+ LSEC 18 months after transplantation, demonstrating that transplanted FL cells in BU-conditioned newborn mice contributed in reconstituting the hemato/vascular compartment. Mice of FLE11-E13+BU and E13noBU groups did not develop anti-FVIII antibodies, not even after FVIII immunization. [Conclusions]: FL cells transplantation may provide a novel and highly promising preclinical model for HA treatment, paving the way for studies aiming at deriving long-term reconstituting ¿fetal-like¿ hemato/vascular progenitors from other sources (e.g. iPSC)

Image1_Inherited bone marrow failure syndromes: phenotype as a tool for early diagnostic suspicion at a major reference center in Mexico.jpeg

Introduction: The inherited bone marrow failure syndromes (IBMFSs) are a group of rare disorders characterized by bone marrow failure (BMF), physical abnormalities, and an increased risk of neoplasia. The National Institute of Pediatrics (INP) is a major medical institution in Mexico, where patients with BMF receive a complete approach that includes paraclinical tests. Readily recognizable features, such as the hematological and distinctive physical phenotypes, identified by clinical dysmorphologists, remain crucial for the diagnosis and management of these patients, particularly in circumstances where next-generation sequencing (NGS) is not easily available. Here, we describe a group of Mexican patients with a high clinical suspicion of an IBMFS.Methods: We performed a systematic retrospective analysis of the medical records of patients who had a high IBMFS suspicion at our institution from January 2018 to July 2021. An initial assessment included first ruling out acquired causes of BMF by the Hematology Department and referral of the patient to the Department of Human Genetics for physical examination to search for specific phenotypes suggesting an IBMFS. Patients with high suspicion of having an IBMFS were classified into two main groups: 1) specific IBMFS, including dyskeratosis congenita (DC), Diamond–Blackfan anemia (DBA), Shwachman–Diamond syndrome (SDS), thrombocytopenia with absent radii (TAR), and severe congenital neutropenia (SCN); 2) undefined IBMFS (UI).Results: We established a high suspicion of having an IBMFS in 48 patients. At initial evaluation, the most common hematologic features were bicytopenia (20%) and aplastic anemia (16%); three patients received hematopoietic stem cell transplantation. Among patients with a suspicion of an IBMFS, the most common physical abnormality was minor craniofacial features in 83% of patients and neurodevelopmental disorders in 52%. The specific suspicions that we built were DBA (31%), SDS (18%), DC (14%), TAR (4%), and SCN (4%), whereas 27% of cases remained as undefined IBMFS. SDS, TAR, and SCN were more commonly suspected at an earlier age (Conclusions: Thorough examination of reported clinical data allowed us to highly suspect a specific IBMFS in approximately 70% of patients; however, an important number of patients remained with suspicion of an undefined IBMFS. Implementation of NGS and telomere length measurement are forthcoming measures to improve IBMFS diagnosis in Mexico.</p