ABSTRACT
Objective: To compare the outcomes of patients with refractory out-of-hospital cardiac arrest (OHCA) transported to a hospital that provides extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (ECPR) with patients transported to hospitals without ECPR capability. Design, setting: Retrospective review of patient care records in a pre-hospital and hospital setting. Participants: Adult patients with OHCA who left the scene and arrived with cardiopulmonary resuscitation in progress at 16 hospitals in Melbourne, Australia, between January 2016 and December 2019. Intervention: For selected patients transported to the ECPR centre, initiation of ECMO. Main outcome measures: Survival to hospital discharge and 12-month quality of life. Results: There were 223 eligible patients during the study period. Of 49 patients transported to the ECPR centre, 23 were commenced on ECMO. Of these, survival to hospital with good neurological recovery (Cerebral Performance Category [CPC] score 1/2) occurred in 4/23 patients. Four other patients developed return of spontaneous circulation in the ECPR centre before cannulation of whom one survived, giving overall good functional outcome at 12 months survival of 5/49 (10.2%). There were 174 patients transported to the 15 non-ECPR centres and 3/174 (2%) had good functional outcome at 12 months. After adjustment for baseline differences, the odds ratio for good neurological outcome after transport to an ECPR centre compared with a non-ECPR centre was 4.63 (95% CI, 0.97-22.11; P = 0.055). Conclusion: The survival rate of patients with refractory OHCA transported to an ECPR centre remains low. Outcomes in larger cities might be improved with shorter scene times and additional ECPR centres that would provide for earlier initiation of ECMO.
ABSTRACT
A core aspect of epithelial cell function is barrier integrity. A loss of barrier integrity is a feature of a number of respiratory diseases, including asthma, allergic rhinitis, and chronic obstructive pulmonary disease. Restoration of barrier integrity is a target for respiratory disease drug discovery. Traditional methods for assessing barrier integrity have their limitations. Transepithelial electrical resistance (TEER) and dextran permeability methods can give poor in vitro assay robustness. Traditional junctional complex imaging approaches are labor-intensive and tend to be qualitative but not quantitative. To provide a robust and quantitative assessment of barrier integrity, high-content imaging of junctional complexes was combined with TEER. A scalable immunofluorescent high-content imaging technique, with automated quantification of junctional complex proteins zonula occludens-1 and occludin, was established in 3D pseudostratified primary human bronchial epithelial cells cultured at an air-liquid interface. Ionic permeability was measured using TEER on the same culture wells.The improvements to current technologies include the design of a novel 24-well holder to enable scalable in situ confocal cell imaging without Transwell membrane excision, the development of image analysis pipelines to quantify in-focus junctional complex structures in each plane of a Z stack, and the enhancement of the TEER data analysis process to enable statistical evaluation of treatment effects on barrier integrity. This novel approach was validated by demonstrating measurable changes in barrier integrity in cells grown under conditions known to perturb epithelial cell function.
