ECMO as a bridge to cardiac surgery: stabilizing unstable patients for a definitive procedure.

Introduction: Extracorporeal membrane oxygenation (ECMO) in adults has been used in post-cardiotomy patients who decline hemodynamically. Cardiogenic shock in patients with potential surgically correctable cardiac conditions are at significantly higher risk for post-operative morbidity and mortality. We present experience with a pre-emptive approach of ECMO institution pre-operatively to stabilize patients with cardiogenic shock. Materials and methods: This study expands on a pilot study with a group of twenty patients who were supported with ECMO pre-operatively in different institutions over a period between 2011 and 2021. The patients presented with cardiogenic shock. Peripheral veno-arterial (VA) ECMO support was used in all the patients. Cardiac surgery was performed via median sternotomy utilizing the in situ ECMO cannulae to institute cardiopulmonary bypass (CPB). Results: Seventeen patients were weaned off ECMO support following a mean duration of support of 156 h. Fifteen patients survived to discharge. The 30-day mortality and in-hospital mortality were 25% (expected 67% by European System for Cardiac Operative Risk Evaluation (EuroSCORE) II). The causes of mortality included persistent bleeding in 2 patients due to liver dysfunction, and one with low platelet counts. The other two had multi-organ failure. Conclusions: Variable period of pre-operative ECMO support provides hemodynamic stability and may prevent or reverse the multi-organ dysfunction if instituted on time in patients presenting with cardiogenic shock. This strategy allows cardiac surgery to be performed with acceptable risk.

Projecting Future Climate Impact on National Australian Respiratory-Related Intensive Care Unit Demand.

BACKGROUND AND AIMS: A robust climate-health projection model has the potential to improve health care resource allocation. We aim to explore the relationship between Australian intensive care unit (ICU) demand and various measures of the long-lived large-scale climate and to develop a future nationwide climate-health projection model. METHODS: We investigated patients admitted to ICUs in Australia between January 2003 and December 2019 who were exposed to long-lived large-scale combined climatic measures of temperature and humidity. We analysed the projected demand for respiratory-related ICU average length of stay (in days) per capita (ICUD/C) with four historical and one future projection dataset. These datasets included: i) Australian and New Zealand Intensive Care Society adult patient database, ii) Socioeconomic Data and Applications Center gridded global historical population, iii) Australian Bureau of Statistics national historical population, iv) Japanese 55-year Reanalysis historical climate (JRA55), and v) the fifth Coupled Model Inter-comparison Project future climate projections. RESULTS: 148,638 patients with respiratory issues required intensive care between 2003 and 2019. The annual growth in the population density-weighted wet-bulb-globe temperature-a combined measure of temperature and humidity-is strongly correlated with the annual per capita growth ICUD/C for respiratory-related conditions (r=0.771; p<0.001). This relationship was applied to develop a model projecting future respiratory-related ICU demand with three possible future Representative Concentration Pathways (RCP). RCP2.6 (lowest carbon emission climate scenario) showed only a 33.4% increase in Australian ICUD/C demand by 2090, while the RCP8.5 (highest carbon emission climate scenario) demonstrated almost two-fold higher demand (66.1%) than RCP2.6 by 2090. CONCLUSIONS: The annual growth in population density-weighted wet-bulb-globe temperature correlates with the annual growth in Australian ICUD/C for respiratory-related conditions. A model based on possible future climate scenarios can be developed to predict changes in ICU demand in response to CO2 changes over the coming decades.

Discovery of a Transferrin Receptor 1-Binding Aptamer and Its Application in Cancer Cell Depletion for Adoptive T-Cell Therapy Manufacturing.

The clinical manufacturing of chimeric antigen receptor (CAR) T cells includes cell selection, activation, gene transduction, and expansion. While the method of T-cell selection varies across companies, current methods do not actively eliminate the cancer cells in the patient's apheresis product from the healthy immune cells. Alarmingly, it has been found that transduction of a single leukemic B cell with the CAR gene can confer resistance to CAR T-cell therapy and lead to treatment failure. In this study, we report the identification of a novel high-affinity DNA aptamer, termed tJBA8.1, that binds transferrin receptor 1 (TfR1), a receptor broadly upregulated by cancer cells. Using competition assays, high resolution cryo-EM, and de novo model building of the aptamer into the resulting electron density, we reveal that tJBA8.1 shares a binding site on TfR1 with holo-transferrin, the natural ligand of TfR1. We use tJBA8.1 to effectively deplete B lymphoma cells spiked into peripheral blood mononuclear cells with minimal impact on the healthy immune cell composition. Lastly, we present opportunities for affinity improvement of tJBA8.1. As TfR1 expression is broadly upregulated in many cancers, including difficult-to-treat T-cell leukemias and lymphomas, our work provides a facile, universal, and inexpensive approach for comprehensively removing cancerous cells from patient apheresis products for safe manufacturing of adoptive T-cell therapies.