SARS-CoV-2 infection in patients with multiple myeloma: survey in 23 centers across Europe and USA

Introduction: Despite several studies, the impact of coronavirus disease 2019 on patients with multiple myeloma remains uncertain. Material(s) and Method(s): We performed a survey that covered the period of the first and second waves of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 23 centers inseven countries. Out of 352 patients with myeloma and SARS-CoV-2, 23% died. Results/Conclusions: Logistic regression showed a lower risk of death among patients treated with proteasome inhibitor and a higher risk of death for those who had a severe or a very severe course of disease.Copyright © 2023 Sciendo. All rights reserved.

Development Dimensions in International Relations: reflections on industry and health in pandemic times

This article presents the results of research on the effect of the coronavirus pandemic on the medical equipment industry in Argentina, focusing on the province of Buenos Aires. It is presented as a case study that contributes to generate reflections about the complex connection between the different dimensions of the concept of development.The concept of development has been widely used in sociology and economics, but the discipline of International Relations ignored it for a long time frame. Therefore, from an international perspective, questions on development remained in the area of international economics and development studies. In Latin America, the first genuinely peripheral approach to development, structuralism, emerged also from the field of economics to discuss modernization theories. It promoted a new approach to development and industrialization to overcome the so-called underdevelopment of the region. Its central conceptual tool, dependency, was considered a fundamental pillar for Latin American International Relations and International Political Economy.The discipline of International Relations expanded its scope, while the concept of development increasingly included other dimensions that were not strictly economic, such as health. The end of the Cold War implied an important challenge for considerations about the concept and the United Nations promoted a human development approach. This had practical effects which, for example, conditioned development cooperation: the percentage of official development aid allocated to the health sector between 1995-2000 and 2007-2011 went from 7 to 13%. This gave greater visibility to health in different reports and international meetings, such as the Commission on Health Research for Development or the Project on Priority Medical Devices of the World Health Organization, which drew attention to the incompatibilities of modern and technologically complex products and the (human, technological and infrastructure) resources available in low-income countries. This was followed by a series of publications on public policies, innovation, regulations, use, priorities and even conditions for the donations of medical equipment.When the pandemic caused by the SARS-CoV-2 virus was declared, the WHO issued its list of priority medical devices for this illness, which served as a reference for the governments of the affected countries. However, the availability of these devices in regions, countries and local communities was highly uneven. At the international level, the demand for medical equipment increased notably, while different countries established export bans on those devices that were in short supply. Access to these resources became an indicator of the relative success or failure of countries in caring for the health of their citizens. The pandemic thus reinforced a certain homogenization in the priority given to medical products as indicators of development. Yet, at the same time, it generated opportunities to discuss their pertinence and relevance.In this context, the supply capacity of these products in Argentina was at the center of concerns and facilitated a multiplication of policies to support the sector, as well as public-private initiatives for the production of medical equipment, both to face the pandemic and to strengthen this industrial sector in the future. The potential capacities of this sector, which until then had not been the target of specific policies, became evident. However, at the same time, a series of limiting factors were identified, linked to the country's position in the global medical equipment industry and to the structural economic difficulties that the country has historically faced.This situation generated interest in more in-depth studies on the sector. Therefore, this article presents the characteristics of this sector in Argentina, and, in particular, the province of Buenos Aires, as well as the effects of the pandemic on it. The main part of the medical equipment industry is housed in this province. Buenos Aires represents 50% of the total manufacturing activity in the country. It is also the most populated province and this population has, at the same time, a wide margin of unsatisfied needs. In this analysis, questions about the convergence between the industrial and health dimensions, the role of public policies dedicated to one or the other, and the relevance of dedicating (material and/or human) public resources to an industrial sector, became evident. The goods produced by this sector may be a way of improving health, but they are neither the only way nor the sufficient means to do it;the social determinants of health have been widely recognized. Therefore, this case study recalls that, although the notion of development exceeds the industrial dimension, the exploration of the link between it and others, such as the health dimension, is complex and necessary.To start this exploration, the research is carried out using a qualitative methodology, through bibliographic and documentary analysis, as well as in-depth interviews and statistical data. The article starts by synthesizing the main dimensions that formed part of the concept of development since the second post-war period, concentrating on the role given to industry and health in its evolution. It identifies the structuralist approach as a tool to understand the place of the Argentine industry in the structure of the global medical equipment market, concentrated in a few companies and countries that generate a large part of the production, sales and technology of the sector. It also identifies the circular way in which human development has conceived the relationship between health and economic development, underlining the role of social debate to define the priority each society gives to one or the other. In a second section, the paper synthesizes the characteristics of the medical equipment industry at a global level to facilitate locating the Argentine industry in this global structure. Finally, it presents the characteristics of the sector in Argentina, with a particular focus on the province of Buenos Aires: a marginal sector in terms of industrial income, which registers historical trade deficit and which, at the same time, shows potential industrial capacities in terms of innovation, technology and human resources. The effects of the pandemic for this sector were limited in terms of its economic indicators and historical industrial structure, but substantial in terms of visibility of the sector on the political agenda, which generated the mentioned opportunity to discuss the relevance and pertinence of dedicating public resources to foster it. In his way, the reflections triggered by the analysis of this specific case aim to enrich the research agenda of International Relations, in particular by encouraging debate on the relationship between health, industry and development.

A bibliometric analysis of COVID-19 publications concerning "mechanism" as a research topic in allergy journals during 2020-2021

Background: Bibliometric analysis has gained increasing interest as an efficient method to visualize COVID-19 research trends and patterns. This analysis may help to describe the profile of scientific contribution of allergy and clinical immunology specialists in the current COVID-19 pandemic. One of the arguments to support the leading role of allergists and clinical immunologists in the COVID-19 pandemic control is their expertise on disease mechanisms. We hypothesized that this role could also have an impact in the COVID-19 literature. Therefore, our objective was to compare the proportion of COVID-19 related publications dealing with the "mechanism" research topic between allergy and non-allergy journals. Method(s): This study involves a large-scale bibliometric analysis of more than 205,000 COVID-19 publications. This evaluation is embedded into the Covid Content Curation Project (0011-3638- 2020- 000001, Health Department of Navarra Government, Spain), an ongoing research to design an artificial intelligence platform for grading the relevance for decision making of COVID-19 scientific publications. We used web scraping functionalities of the Covid Content Curation platform to obtain a complete and up-to- date list of COVID-19 publications. Exclusion criteria were duplicate publications, publications from the preprint servers, publications published before March 1, 2020 or after December 31, 2021, or with any missing date data. Result(s): After exclusion criteria, 205,982 COVID-19 publications were available for analysis. The cumulative total of COVID-19 publications in allergy journals was 923 (4.48;95% CI: 4.20 to 4.78). The number of COVID-19 publications dealing with "mechanism" as a research topic was 13.22 (95% CI: 10.03 to 16.41) percentage points greater among allergy journals than non-allergy journals (p < 0.001) (Figure 1). Conclusion(s): These results show that the "mechanism" research topic is of greater prevalence in COVID-19 publications of allergy journals than non-allergy journals, and support the hypothesis that the prominent role of allergists and clinical immunologists in the COVID-19 pandemic control, based on their expertise on disease mechanisms, may also have an impact in the COVID-19 literature.

EFFECTS OF TELEWORK AND DIGITALIZATION ON SHARED READING BETWEEN PARENTS AND CHILDREN

INTRODUCTION. There are several benefits associated with shared reading. The time families invest to read with their children may be influenced by different demographic (e.g., family type and structure) and personal factors (e.g., time availability). Society experiments subsequent changes and the time dedicated to shared reading at home may be influenced by them. This study has two main objectives: first, it analyzes differences in shared reading time by considering those demographic variables that other studies have identified as relevant (e.g., parents' sex, children's age, number of children);secondly, it aims to analyze the differences in shared reading time regarding two variables strongly affected by the pandemic, that is, the employment status and reading medium (paper reading vs. digital reading). METHOD. The responses of 659 parents to a survey about reading habits before and after confinement were analysed through a descriptive-comparative analysis of demographic variables, parents' employment status and reading support. RESULTS AND DISCUSSION. The main results indicate that families spent increasing amounts of time on shared reading throughout confinement. In this sense, mothers spent more time reading with their children than fathers before and during confinement. Regarding the reading me-dium, paper continued to be used more widely for shared reading during confinement, although the time dedicated to shared reading using a digital device increased compared to its use before confinement. Finally, parents who teleworked did not invest more time on shared reading than those who worked outside the home, so that, contrary to expectations, teleworking during the pandemic did not allow for a better family-profession reconciliation or greater dedication to chil-dren's literacy. © 2023, Sociedad Espanola de Pedagogia. All rights reserved.

MiniVent: A low-cost pressure-controlled ventilator system for emergency use

Objective: To address the issue of ventilator shortages due to the COVID-19 pandemic, our group developed the proof-of-concept of a low-cost and rapidly scalable open-source mechanical ventilator system for emergency use. Method(s): A simplified architecture of MiniVent was designed to meet the low-cost and easy-to-produce pre-established properties of our device. To carry out such an approach, we decided to use only components commonly available in the market or components of easy production with usual manufacturing techniques, such as 3D printing. The design of MiniVent comprises a pneumatic unit that controls the quality of the air and oxygen mixture and maintains the pressure on the patient's lungs at the desired preset value, along the respiratory cycle. The control unit was programmed on a microcontroller and is responsible for ensuring the respiratory rate and the inspiratory-expiratory ratio, selected by the user. To ensure the fulfilment of all the security and specification requirements of pandemic ventilators, we followed the mandatory specifications presented in the document - Rapidly Manufactured Ventilator System (RMVS) - published by the Medicines & Healthcare products Regulatory Agency (MHRA). A set of tests was performed using different ventilatory parameters for instrumental verification of MiniVent's physical and biological performance. A stability test was also carried out during 35 hours of uninterrupted operation to analyse whether the expected dynamics of the output pressure were maintained over this time. Result(s): The ventilator system developed allows prescribing different breathing rates, fractions inspired of oxygen (FiO2), inspiratory-expiratory ratios (I: E), positive inspiratory pressures (PIP) and positive end-expiratory pressures (PEEP), which can be easily adjustable to the patient's condition. The results of a set of tests assured the reliability of all the ventilatory parameters set by the user. Furthermore, MiniVent showed a good performance over 35 hours of uninterrupted operation, which pointed out the stability of this device. In addition, the device was tested in a porcine model showing good mechanical performance and adequate arterial blood gas throughout all test periods. When compared with commercial ventilators, MiniVent exhibited a similar performance of ventilation. Conclusion(s): MiniVent could be a reliable solution to overcome the shortage of commercial ventilators in emergencies, such as the recent COVID-19 pandemic. This device presents a production cost of under 1000 and does not need specialized technical assistance so it might be a viable solution even in lowerincome countries.

The updated SIOG COVID-19 working group recommendations on COVID-19 vaccination among older adults with cancer

Background: Older patients with cancer remain at high risk for negative outcomes from COVID-19 infection, particularly those who have multimorbidities and on immunosuppressive therapy. These patients have been excluded or underrepresented in pivotal COVID-19 vaccine clinical trials and there are ongoing concerns that they may not acquire the same level of protection from the available vaccines as the immunocompetent adults. Moreover, the level of protection wanes over time making them more susceptible to emerging COVID-19 novel variants of concern. Despite the implementation of global vaccination campaigns which have successfully reduced COVID-related hospitalisations and deaths in many parts of the world, there remains many unresolved issues and challenges to address as the pandemic ensues. With aging, concerns for age-related dysregulation and immune dysfunctions called immunosenescence may lead to potentially lower immunogenicity to vaccines. Despite receiving the primary vaccination, real-world evidence showed that both patients aged > 65 years and those with cancer have a higher risk of developing breakthrough COVID-19 infections and related complications. Subsequent booster doses are found to be effective at improving immune response, particularly against the novel variants, and the vulnerable population should be given the priority in booster campaigns. Method(s): Since the beginning of the pandemic in 2020, The International Society of Geriatric Oncology set up a COVID-19 Working Group comprised of multidisciplinary specialists by developing recommendations, advocacy, and action plans based on expert opinion and evidence related to older adults with cancer. Result(s): The table below summarises the updated recommendations from the SIOG COVID-19 Working Group. Conclusion(s): The SIOG COVID-19 Working Group supports ongoing public health interventions, continued mass immunisations, and booster campaigns targeting the most vulnerable members of the society, including older adults with cancer (Table Presented).

Bortezomib- and carfilzomib-resistant myeloma cells show increased activity of all three arms of the unfolded protein response

Proteasome inhibitors are among the most potent classes of drugs in multiple myeloma treatment. One of the main challenges in myeloma therapy is acquired resistance to drugs. Several theories have been proposed to describe the mechanisms responsible for resistance to the most commonly used proteasome inhibitors bortezomib and carfilzomib. This study aimed to describe functional differences between sensitive myeloma cells (MM1S WT) and their daughter cell lines resistant to either bortezomib (MM1S/R BTZ) or carfilzomib (MM1S/R CFZ), as well as between both resistant cell lines. Bortezomib- and carfilzomib-resistant cell lines were successfully generated by continuous exposure to the drugs. When exposed to different drugs than during the resistance generation period, MM1S/R BTZ cells showed cross-resistance to carfilzomib, whereas MM1S/R CFZ cells were similarly sensitive to bortezomib as MM1S WT cells. Following proteomic profiling, unsupervised principal component analysis revealed that the MM1S/R BTZ and MM1S/R CFZ cell lines differed significantly from the MM1S WT cell line and from each other. Canonical pathway analysis showed similar pathways enriched in both comparisons - MM1S WT vs. MM1S/R CFZ and MM1S WT vs. MM1S/R BTZ. However, important differences were present in the statistical significance of particular pathways. Key alterations included the ubiquitin-proteasome system, metabolic pathways responsible for redox homeostasis and the unfolded protein response. In functional studies, both drugs continued to reduce chymotrypsin-like proteasome activity in resistant cells. However, the baseline activity of all three catalytic domains of the proteasome was higher in the resistant cells. Differences in generation of reactive oxygen species were identified in MM1S/R BTZ (decreased) and MM1S/CFZ cells (increased) in comparison to MM1S WT cells. Both baseline and drug-induced activity of the unfolded protein response were higher in resistant cells than in MM1S WT cells and included all three arms of this pathway: IRE1α/XBP1s, ATF6 and EIF2α/ATF4 (downstream effectors of PERK). In conclusion, contrary to some previous reports, resistant MM1S cells show upregulation of unfolded protein response activity, reflecting the heterogeneity of multiple myeloma and prompting further studies on the role of this pathway in resistance to proteasome inhibitors.

Antimicrobial prophylaxis in adults and children undergoing hematopoietic cell transplantation: 2021 Polish recommendations

Infections are still one of the most common causes of death after hematopoietic cell transplantation (HCT). Antimicrobial prophylaxis plays a crucial role in decreasing non-relapse mortality after HCT. The objective of this guideline paper was the presentation of current recommendations of antimicrobial prophylaxis for children and adults after hematopoietic cell transplantation, prepared in cooperation with Polish scientific hematological societies. Recommendations were prepared by the working group and finally approved by all 23 Polish transplant centers for children and adults. Existing (European Conference on Infections in Leukemia (ECIL) and European Society of Blood and Marrow Transplantation (EBMT) guidelines, as well as the results of a survey performed among all Polish transplant centers, were the background material for the working group. Recommendations are presented in sections dedicated to antibacterial prophylaxis, antifungal prophylaxis, antiviral prophylaxis, as well as prophylaxis of toxoplasmosis and infections with Pneumocystis jiroveci. Recommendations on the principles of vaccination against COVID-19 are provided based on the state of knowledge in September 2021. A section on guidelines of environmental prophylaxis is also presented.

Safety and cost effectiveness of outpatient autologous hematopoietic stem cell transplantation for multiple myeloma - Single-center experience of a pilot Early Discharge Program

Introduction: Multiple myeloma (MM) is the leading indication for autologous stem cell transplantation (ASCT), with over 12,000 transplants per year in Europe. Due to low toxicity, an entirely outpatient procedure or an early discharge after ASCT can be considered as alternatives to inpatient transplantation. Thus, we launched an Early Discharge Program (EDP) for patients qualified for ASCT due to MM who were under 60 years of age, without significant comorbidities, who had a caregiver available 24/7, and who lived within a 60-minute drive of our hospital. Material and methods: Patients spent 72 hours in the hospital being administered melphalan 200 mg/m2 intravenous followed by an infusion of hematopoietic stem cells. They were eventually discharged and remained under outpatient care. The program was launched in September 2019 and was temporarily halted due to the coronavirus disease 19 (COVID-19) pandemic in early 2020. Five patients were enrolled to the EDP. Results: Non-hematological toxicity was mild and manageable in an outpatient setting. Only one patient was readmitted due to exacerbation of ulcerative colitis that was probably not related to ASCT. We observed neither infections nor bleeding. Due to hematological toxicity, three of the five patients received platelet transfusion on the 6th day after ASCT as outpatients. No packed erythrocytes were transfused. The EDP demonstrated lower costs compared to an inpatient approach. Conclusions: We believe that early discharge, which is an intermediate step to full at-home transplantation due to patients' wellbeing, reduction of infections caused by resistant microorganisms, and costs, will eventually replace a full inpatient procedure for a significant population of patients suffering from multiple myeloma and indeed other diseases.

Security, Autonomy and Industry: Medical Equipment in MERCOSUR

This article aims to analyze the main characteristics of the medical equipment industry in MERCOSUR, as well as decisions on this industry adopted since the COVID-19 pandemic. It starts by referring to the main theoretical discussions on health security and autonomy, identifying the role of medical equipment in both concepts. Afterward, the main characteristics of the medical equipment industry in Brazil and Argentina are analyzed, as well as the decisions adopted on a national and regional level. With a qualitative methodology, this research is based on a review of primary and secondary sources, as well as in-depth interviews. It is concluded that, even if Brazil and Argentina did recognize a renewed value of this industry, the lack of a regional perspective limits its capability of becoming a relevant sector for health security and autonomy in Latin America.

Pediatric anesthesia techniques during the COVID-19 pandemic

The pediatric population is a contagion fuel for SARS CoV-2, putting health care workers at risk. Exposure to respiratory droplets and aerosols are a major cause of disease transmission during airway procedures. Crying, coughing, laryngospasm, airway obstruction and hypoxia, which are more frequent in children than adults, directly or indirectly increase aerosol production and hence the risk of transmission to health workers. We present recommendations for the perioperative management of children suspected or confirmed positive for COVID-19, with the aim of reducing the risk of infection in these patients and in the healthcare team.