Faculty Bibliography

BACKGROUND/UNASSIGNED:Evidence suggests that patients critically ill with COVID-19 have a dysregulated host immune response that contributes to end-organ damage. Extracorporeal membrane oxygenation (ECMO) has been used in this population with varying degrees of success. This study was performed to evaluate the impact of ECMO on the host immunotranscriptomic response in these patients. METHODS/UNASSIGNED:Eleven patients critically ill with COVID-19 requiring ECMO underwent an analysis of cytokines and immunotranscriptomic pathways before ECMO (T1), after ECMO for 24 hours (T2), and 2 hours after ECMO decannulation (T3). A Multiplex Human Cytokine panel was used to identify cytokine changes, and immunotranscriptomic changes in peripheral leukocytes were evaluated by PAXgene and NanoString nCounter. RESULTS/UNASSIGNED:, which code for binding ligands for the activation of toll-like receptors 2 and 4. Reactome analyses of differential gene expression demonstrated an impact on many of the body's most important immune inflammatory pathways. CONCLUSIONS/UNASSIGNED:These findings suggest a temporal impact of ECMO on the host immunotranscriptomic response in patients critically ill with COVID-19.

Lung transplantation remains the only available therapy for many patients with end-stage lung disease. The number of lung transplants performed has increased significantly, but development of the field was slow compared with other solid-organ transplants. This delayed growth was secondary to the increased complexity of transplanting lungs; the continuous needs for surgical, anesthetics, and critical care improvements; changes in immunosuppression and infection prophylaxis; and donor management and patient selection. The future of lung transplant remains promising: expansion of donor after cardiac death donors, improved outcomes, new immunosuppressants targeted to cellular and antibody-mediated rejection, and use of xenotransplantation or artificial lungs.

Xenotransplantation promises to alleviate the issue of donor organ shortages and to decrease waiting times for transplantation. Recent advances in genetic engineering have allowed for the creation of pigs with up to 16 genetic modifications. Several combinations of genetic modifications have been associated with extended graft survival and life-supporting function in experimental heart and kidney xenotransplants. Lung xenotransplantation carries specific challenges related to the large surface area of the lung vascular bed, its innate immune system's intrinsic hyperreactivity to perceived 'danger', and its anatomic vulnerability to airway flooding after even localized loss of alveolocapillary barrier function. This article discusses the current status of lung xenotransplantation, and challenges related to immunology, physiology, anatomy, and infection. Tissue engineering as a feasible alternative to develop a viable lung replacement solution is discussed.

OBJECTIVE:There is a shortage of donor lungs relative to need, but overall donor organ utilization remains low. The most common reason for refusal is organ quality, but the standards applied to selection vary. In this study we sought to characterize differences in lung utilization according to quality across several clinically distinct recipient pools. METHODS:Data on donor lungs recovered (April 2006 to September 2019) were extracted from the Scientific Registry of Transplant Recipients database. Organs were classified as ideal, standard, or extended quality according to their poorest metric among selected parameters. Subanalyses were performed on the basis of procedure type, age, lung allocation score, era, and alternative definitions of extended quality. Recipient traits and survival according to organ quality were assessed. RESULTS:Of 156,022 lungs analyzed during the study period, 25,777 (16.5%) were transplanted. There was no difference in quality distribution for single and bilateral transplants. Young candidates were more likely to receive ideal (14.7% vs 12.3%) or standard (9.5% vs 8.2%) lungs, but not extended lungs (75.9% vs 79.5%; all P < .01). Absolute differences in distribution according to lung allocation score quartile were small (<2%). Extended quality donor utilization increased over time. Survival according to donor category was similar at 1 and 3 years post transplant in unadjusted and Cox regression analyses. CONCLUSIONS:Extended quality lungs comprise an increasing share of transplants in a national sample. Organ selection varies according to recipient age and lung allocation score. However, absolute differences in quality distribution are small, and adverse effects on outcomes are limited to organs with multiple extended qualifying characteristics.

Lung transplantation is the only potentially curative treatment for end-stage lung failure and successfully improves both long-term survival and quality of life. However, lung transplantation is limited by the shortage of suitable donor lungs. This discrepancy in organ supply and demand has prompted researchers to seek alternative therapies for end-stage lung failure. Tissue engineering (bioengineering) organs has become an attractive and promising avenue of research, allowing for the customized production of organs on demand, with potentially perfect biocompatibility. While breakthroughs in tissue engineering have shown feasibility in practice, they have also uncovered challenges in solid organ applications due to the need not only for structural support, but also vascular membrane integrity and gas exchange. This requires a complex engineered interaction of multiple cell types in precise anatomical locations. In this article, we discuss the process of creating bioengineered lungs and the challenges inherent therein. We summarize the relevant literature for selecting appropriate lung scaffolds, creating decellularization protocols, and using bioreactors. The development of completely artificial lung substitutes will also be reviewed. Lastly, we describe the state of current research, as well as future studies required for bioengineered lungs to become a realistic therapeutic modality for end-stage lung disease. Applications of bioengineering may allow for earlier intervention in end-stage lung disease and have the potential to not only halt organ failure, but also significantly reverse disease progression.

Objectives/UNASSIGNED:Proning patients with acute respiratory distress syndrome (ARDS) has been associated with increased survival, though little data exists evaluating the safety and feasibility of proning ARDS patients on extracorporeal membrane oxygenation (ECMO). Methods/UNASSIGNED:, 2020 was performed. All proning events were evaluated for complications, as well as change in compliance, sweep, oxygenation and flow. The primary outcome of this study was the rate major morbidity associated with proning while on ECMO. Results/UNASSIGNED:of 86 pre to 103 post (p<0.0001). Mean ECMO flow was unchanged. Conclusions/UNASSIGNED:Proning in patients with ARDS on ECMO is safe with an associated improvement in lung mechanics. With careful planning and coordination, these data support the practice of appropriately proning patients with severe ARDS, even if they are on ECMO.

BACKGROUND:Our objective was to report the incidence, management, and outcomes of patients who developed a secondary pneumothorax while admitted for coronavirus disease 2019 (COVID-19). METHODS:A single-institution, retrospective review of patients admitted for COVID-19 with a diagnosis of pneumothorax between March 1, 2020, and April 30, 2020, was performed. The primary assessment was the incidence of pneumothorax. Secondarily, we analyzed clinical outcomes of patients requiring tube thoracostomy, including those requiring operative intervention. RESULTS:From March 1, 2020, to April 30, 2020, 118 of 1595 patients (7.4%) admitted for COVID-19 developed a pneumothorax. Of these, 92 (5.8%) required tube thoracostomy drainage for a median of 12 days (interquartile range 5-25 days). The majority of patients (95 of 118, 80.5%) were on mechanical ventilation at the time of pneumothorax, 17 (14.4%) were iatrogenic, and 25 patients (21.2%) demonstrated tension physiology. Placement of a large-bore chest tube (20 F or greater) was associated with fewer tube-related complications than a small-bore tube (14 F or less) (14 vs 26 events, P = .011). Six patients with pneumothorax (5.1%) required operative management for a persistent alveolar-pleural fistula. In patients with pneumothorax, median hospital stay was 36 days (interquartile range 20-63 days) and in-hospital mortality was significantly higher than for those without pneumothorax (58% vs 13%, P < .001). CONCLUSIONS:The incidence of secondary pneumothorax in patients admitted for COVID-19 is 7.4%, most commonly occurring in patients requiring mechanical ventilation, and is associated with an in-hospital mortality rate of 58%. Placement of large-bore chest tubes is associated with fewer complications than small-bore tubes.