Recombinant human DNase-I improves acute respiratory distress syndrome via neutrophil extracellular trap degradation.

BACKGROUND: Respiratory failure is the primary cause of death in patients with COVID-19, whereas coagulopathy is associated with excessive inflammation and multiorgan failure. Neutrophil extracellular traps (NETs) may exacerbate inflammation and provide a scaffold for thrombus formation. OBJECTIVES: The goal of this study was to determine whether degradation of NETs by recombinant human DNase-I (rhDNase), a safe, Food and Drug Administration-approved drug, reduces excessive inflammation, reverses aberrant coagulation, and improves pulmonary perfusion after experimental acute respiratory distress syndrome (ARDS). METHODS: Intranasal poly(I:C), a synthetic double-stranded RNA, was administered to adult mice for 3 consecutive days to simulate a viral infection, and these subjects were randomized to treatment arms, which received either an intravenous placebo or rhDNase. The effects of rhDNase on immune activation, platelet aggregation, and coagulation were assessed in mice and donor human blood. RESULTS: NETs were observed in bronchoalveolar lavage fluid and within regions of hypoxic lung tissue after experimental ARDS. The administration of rhDNase mitigated peribronchiolar, perivascular, and interstitial inflammation induced by poly(I:C). In parallel, rhDNase degraded NETs, attenuated platelet-NET aggregates, reduced platelet activation, and normalized the clotting time to improve regional perfusion, as observed using gross morphology, histology, and microcomputed tomographic imaging in mice. Similarly, rhDNase reduced NETs and attenuated platelet activation in human blood. CONCLUSION: NETs exacerbate inflammation and promote aberrant coagulation by providing a scaffold for aggregated platelets after experimental ARDS. Intravenous administration of rhDNase degrades NETs and attenuates coagulopathy in ARDS, providing a promising translational approach to improve pulmonary structure and function after ARDS.

Coronavirus pandemic in the Nordic countries: Health policy and economy trade-off.

Background: Countries making up the Nordic region - Denmark, Finland, Iceland, Norway, and Sweden - have minimal socioeconomic, cultural, and geographical differences between them, allowing for a fair comparative analysis of the health policy and economy trade-off in their national approaches towards mitigating the impact of the COVID-19 pandemic. Methods: This study utilized publicly available COVID-19 data of the Nordic countries from January 2020 to January 3, 2021. COVID-19 epidemiology, public health and health policy, health system capacity, and macroeconomic data were analysed for each Nordic country. Joinpoint regression analysis was performed to identify changes in temporal trends using average monthly percent change (AMPC) and average weekly percent change (AWPC). Results: Sweden's health policy, being by far the most relaxed response to COVID-19, was found to have the largest COVID-19 incidence and mortality, and the highest AWPC increases for both indicators (13.5, 95% CI = 5.6, 22.0, P < 0.001; 6.3, 95% CI = 3.5, 9.1, P < 0.001). Denmark had the highest number of COVID-19 tests per capita, consistent with their approach of increased testing as a preventive strategy for disease transmission. Iceland had the second-highest number of tests per capita due to their mass-testing, contact tracing, quarantine and isolation response. Only Norway had a significant increase in unemployment (AMPC = 2.8%, 95% CI = 0.7-4.9, P < 0.009) while the percentage change in real Gross Domestic Product (GDP) was insignificant for all countries. Conclusions: There was no trade-off between public health policy and economy during the COVID-19 pandemic in the Nordic region. Sweden's relaxed and delayed COVID-19 health policy response did not benefit the economy in the short term, while leading to disproportionate COVID-19 hospitalizations and mortality.

Perioperative Considerations in Urgent Surgical Care of Suspected and Confirmed COVID-19 Orthopaedic Patients: Operating Room Protocols and Recommendations in the Current COVID-19 Pandemic.

By April 7, 2020, severe acute respiratory syndrome coronavirus 2 was responsible for 1,383,436 confirmed cases of Coronavirus disease 2019 (COVID-19), involving 209 countries around the world; 378,881 cases have been confirmed in the United States. During this pandemic, the urgent surgical requirements will not stop. As an example, the most recent Centers of Disease Control and Prevention reports estimate that there are 2.8 million trauma patients hospitalized in the United States. These data illustrate an increase in the likelihood of encountering urgent surgical patients with either clinically suspected or confirmed COVID-19 in the near future. Preparation for a pandemic involves considering the different levels in the hierarchy of controls and the different phases of the pandemic. Apart from the fact that this pandemic certainly involves many important health, economic, and community ramifications, it also requires several initiatives to mandate what measures are most appropriate to prepare for mitigating the occupational risks. This article provides evidence-based recommendations and measures for the appropriate personal protective equipment for different clinical and surgical activities in various settings. To reduce the occupational risk in treating suspected or confirmed COVID-19 urgent orthopaedic patients, recommended precautions and preventive actions (triage area, emergency department consultation room, induction room, operating room, and recovery room) are reviewed.