Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

The Histone Variant H3.3 Is Enriched at Drosophila Amplicon Origins but Does Not Mark Them for Activation

Eukaryotic DNA replication begins from multiple origins. The origin recognition complex (ORC) binds origin DNA and scaffolds assembly of a prereplicative complex (pre-RC), which is subsequently activated to initiate DNA replication. In multicellular eukaryotes, origins do not share a strict DNA consensus sequence, and their activity changes in concert with chromatin status during development, but mechanisms are ill-defined. Previous genome-wide analyses in Drosophila and other organisms have revealed a correlation between ORC binding sites and the histone variant H3.3. This correlation suggests that H3.3 may designate origin sites, but this idea has remained untested. To address this question, we examined the enrichment and function of H3.3 at the origins responsible for developmental gene amplification in the somatic follicle cells of the Drosophila ovary. We found that H3.3 is abundant at these amplicon origins. H3.3 levels remained high when replication initiation was blocked, indicating that H3.3 is abundant at the origins before activation of the pre-RC. H3.3 was also enriched at the origins during early oogenesis, raising the possibility that H3.3 bookmarks sites for later amplification. However, flies null mutant for both of the H3.3 genes in Drosophila did not have overt defects in developmental gene amplification or genomic replication, suggesting that H3.3 is not essential for the assembly or activation of the pre-RC at origins. Instead, our results imply that the correlation between H3.3 and ORC sites reflects other chromatin attributes that are important for origin function

Outcomes and Adverse Effects of Baricitinib Versus Tocilizumab in the Management of Severe COVID-19∗

Objectives: The National Institutes of Health and Infectious Diseases Society of America guidelines recommend tocilizumab or baricitinib in the management of severe COVID-19. Despite clinical trials on the individual agents, there are no large-scale studies comparing the two agents to guide the selection of one versus the other. The purpose of this study was to compare the outcomes and adverse effects of baricitinib versus tocilizumab in the management of severe COVID-19. Design: Retrospective, observational cohort study. Setting: Eleven acute care hospitals in a large health system in Georgia. Patients: Adult patients with severe COVID-19 who received at least one dose of either baricitinib or tocilizumab between June 2021 and October 2021. Interventions: None. Measurements and Main Results: The primary outcome was in-hospital mortality. The key secondary outcome was occurrence rate of adverse effects. A total of 956 patients were identified. The median age was 57 years, and 53% were of male sex. The median body mass index was 33.5, and more than 94% of the population was unvaccinated. Propensity score matching by baseline characteristics resulted in a total of 582 patients, 291 in each group. There was no difference in mortality between the two groups; however, the occurrence rate of adverse effects was significantly higher in the tocilizumab group compared with baricitinib: secondary infections (32% vs 22%; p \u3c 0.01); thrombotic events (24% vs 16%; p \u3c 0.01); and acute liver injury (8% vs 3%; p \u3c 0.01). Conclusions: Our propensity score-matched, retrospective, observational study in patients hospitalized with severe COVID-19 showed no difference in mortality but significantly fewer adverse effects with baricitinib compared with tocilizumab. Our data suggest that baricitinib may be a better choice when treating patients with severe COVID-19, but additional prospective, randomized trials are needed to help clinicians choose the most optimal drug

Early Use of Remdesivir in Patients Hospitalized With COVID-19 Improves Clinical Outcomes: A Retrospective Observational Study

BACKGROUND: Remdesivir treatment, like most antiviral drugs, is likely to be most effective when used early in the course of coronavirus disease 2019 (COVID-19). Optimal timing of remdesivir for the treatment of COVID-19 remains unclear. OBJECTIVES: The aim of this study was to determine whether early treatment with remdesivir improves clinical outcomes: length of stay, need for mechanical ventilation, and death. METHODS: We conducted a retrospective observational study of patients hospitalized with COVID-19 who received remdesivir therapy within 10 days of symptom onset at a large health system in Georgia, United States. RESULTS: We identified a total of 475 patients. Initiation of therapy 3 days or less from first positive SARS-CoV-2 improved length of stay (15.7 days) compared with those started on therapy more than 3 days after a positive test (19.3 days) ( = 0.03). In the ≤3 day group, further reduction in length of stay was seen in those with lower oxygen requirement at baseline ( \u3c 0.0001). Length of stay was lower in the ≤3 day group both with and without the use of corticosteroids ( = 0.0003). The odds of requiring mechanical ventilation were higher for the \u3e3 day group compared with the ≤3 day group (odds ratio, 1.5; 95% confidence interval, 0.8-2.7), and the odds of death were higher for the \u3e3 day group versus the ≤3 day group (odds ratio, 1.74; 95% confidence interval, 0.9-3.2). CONCLUSIONS: Our data show that early treatment with remdesivir in patients hospitalized with COVID-19 shortened length of stay

Early Use of Remdesivir in Patients Hospitalized With COVID-19 Improves Clinical Outcomes

BACKGROUND: Remdesivir treatment, like most antiviral drugs, is likely to be most effective when used early in the course of coronavirus disease 2019 (COVID-19). Optimal timing of remdesivir for the treatment of COVID-19 remains unclear. OBJECTIVES: The aim of this study was to determine whether early treatment with remdesivir improves clinical outcomes: length of stay, need for mechanical ventilation, and death. METHODS: We conducted a retrospective observational study of patients hospitalized with COVID-19 who received remdesivir therapy within 10 days of symptom onset at a large health system in Georgia, United States. RESULTS: We identified a total of 475 patients. Initiation of therapy 3 days or less from first positive SARS-CoV-2 improved length of stay (15.7 days) compared with those started on therapy more than 3 days after a positive test (19.3 days) (P = 0.03). In the ≤3 day group, further reduction in length of stay was seen in those with lower oxygen requirement at baseline (P 3 day group compared with the ≤3 day group (odds ratio, 1.5; 95% confidence interval, 0.8–2.7), and the odds of death were higher for the >3 day group versus the ≤3 day group (odds ratio, 1.74; 95% confidence interval, 0.9–3.2). CONCLUSIONS: Our data show that early treatment with remdesivir in patients hospitalized with COVID-19 shortened length of stay

Development and validation of a predictive model for critical illness in adult patients requiring hospitalization for COVID-19.

BackgroundIdentifying factors that can predict severe disease in patients needing hospitalization for COVID-19 is crucial for early recognition of patients at greatest risk.Objective(1) Identify factors predicting intensive care unit (ICU) transfer and (2) develop a simple calculator for clinicians managing patients hospitalized with COVID-19.MethodsA total of 2,685 patients with laboratory-confirmed COVID-19 admitted to a large metropolitan health system in Georgia, USA between March and July 2020 were included in the study. Seventy-five percent of patients were included in the training dataset (admitted March 1 to July 10). Through multivariable logistic regression, we developed a prediction model (probability score) for ICU transfer. Then, we validated the model by estimating its performance accuracy (area under the curve [AUC]) using data from the remaining 25% of patients (admitted July 11 to July 31).ResultsWe included 2,014 and 671 patients in the training and validation datasets, respectively. Diabetes mellitus, coronary artery disease, chronic kidney disease, serum C-reactive protein, and serum lactate dehydrogenase were identified as significant risk factors for ICU transfer, and a prediction model was developed. The AUC was 0.752 for the training dataset and 0.769 for the validation dataset. We developed a free, web-based calculator to facilitate use of the prediction model (https://icucovid19.shinyapps.io/ICUCOVID19/).ConclusionOur validated, simple, and accessible prediction model and web-based calculator for ICU transfer may be useful in assisting healthcare providers in identifying hospitalized patients with COVID-19 who are at high risk for clinical deterioration. Triage of such patients for early aggressive treatment can impact clinical outcomes for this potentially deadly disease

A CRISPR-engineered isogenic model of the 22q11.2 A-B syndromic deletion

22q11.2 deletion syndrome, associated with congenital and neuropsychiatric anomalies, is the most common copy number variant (CNV)-associated syndrome. Patient-derived, induced pluripotent stem cell (iPS) models have provided insight into this condition. However, patient-derived iPS cells may harbor underlying genetic heterogeneity that can confound analysis. Furthermore, almost all available models reflect the commonly-found ~ 3 Mb "A-D" deletion at this locus. The ~ 1.5 Mb "A-B" deletion, a variant of the 22q11.2 deletion which may lead to different syndromic features, and is much more frequently inherited than the A-D deletion, remains under-studied due to lack of relevant models. Here we leveraged a CRISPR-based strategy to engineer isogenic iPS models of the 22q11.2 "A-B" deletion. Differentiation to excitatory neurons with subsequent characterization by transcriptomics and cell surface proteomics identified deletion-associated alterations in proliferation and adhesion. To illustrate in vivo applications of this model, we further implanted neuronal progenitor cells into the cortex of neonatal mice and found potential alterations in neuronal maturation. The isogenic models generated here will provide a unique resource to study this less-common variant of the 22q11.2 microdeletion syndrome

A CRISPR-engineered isogenic model of the 22q11.2 A-B syndromic deletion

Abstract 22q11.2 deletion syndrome, associated with congenital and neuropsychiatric anomalies, is the most common copy number variant (CNV)-associated syndrome. Patient-derived, induced pluripotent stem cell (iPS) models have provided insight into this condition. However, patient-derived iPS cells may harbor underlying genetic heterogeneity that can confound analysis. Furthermore, almost all available models reflect the commonly-found ~ 3 Mb “A-D” deletion at this locus. The ~ 1.5 Mb “A-B” deletion, a variant of the 22q11.2 deletion which may lead to different syndromic features, and is much more frequently inherited than the A-D deletion, remains under-studied due to lack of relevant models. Here we leveraged a CRISPR-based strategy to engineer isogenic iPS models of the 22q11.2 “A-B” deletion. Differentiation to excitatory neurons with subsequent characterization by transcriptomics and cell surface proteomics identified deletion-associated alterations in proliferation and adhesion. To illustrate in vivo applications of this model, we further implanted neuronal progenitor cells into the cortex of neonatal mice and found potential alterations in neuronal maturation. The isogenic models generated here will provide a unique resource to study this less-common variant of the 22q11.2 microdeletion syndrome