The cost of lung transplantation in the United States: How high is too high?

Objectives: To identify patient and process factors that contribute to the high cost of lung transplantation (LTx) in the perioperative period, which may allow transplant centers to evaluate situations in which transplantation is most cost-effective to inform judicious resource allocation, avoid futile care, and reduce costs. Methods: The MarketScan Research databases were used to identify 582 privately insured patients undergoing single or bilateral LTx between 2013 and 2019. The patients were subdivided into groups by disease etiology using the United Network of Organ Sharing classification system. Multivariable generalized linear models using a gamma distribution with a log link were fit to examine the associations between the etiology of lung disease and costs during the index admission, 3 months before admission, and 3 months after discharge. Results: Our results indicate that the index admission contributed the most to the total transplantation costs compared to the 3 months before admission and after discharge. The regression-adjusted mean index hospitalization cost was 35% higher for patients with pulmonary vascular disease compared to those with obstructive lung disease ($527,156 vs $389,055). The use of extracorporeal membrane oxygenation, mechanical ventilation, and surgical complications in the post-transplantation period were associated with higher costs during the index admission. Surprisingly, age ≥55 was associated with lower costs during the index admission. Conclusions: This analysis identifies pivotal factors influencing the high cost of LTx, emphasizing the significant impact of the index admission, particularly for patients with pulmonary vascular disease. These insights offer transplant centers an opportunity to enhance cost-effectiveness through judicious resource allocation and service bundling, ultimately reducing overall transplantation costs.

RNA Binding Proteins that Mediate LPS-induced Alternative Splicing of the MyD88 Innate Immune Regulator.

Inflammation driven by Toll-like receptor (TLR) signaling pathways is required to combat infection. However, inflammation can damage host tissues; thus it is essential that TLR signaling ultimately is terminated to prevent chronic inflammatory disorders. One mechanism that terminates persistent TLR signaling is alternative splicing of the MyD88 signaling adaptor, which functions in multiple TLR signaling pathways. While the canonical long isoform of MyD88 (MyD88-L) mediates TLR signaling and promotes inflammation, an alternatively-spliced shorter isoform of MyD88 (MyD88-S) produces a dominant negative inhibitor of TLR signaling. MyD88-S production is induced by inflammatory agonists including lipopolysaccharide (LPS), and thus MyD88-S induction is thought to act as a negative feedback loop that prevents chronic inflammation. Despite the potential role that MyD88-S production plays in inflammatory disorders, the mechanisms controlling MyD88 alternative splicing remain unclear. Here, we identify two RNA binding proteins, SRSF1 and HNRNPU, that regulate LPS-induced alternative splicing of MyD88.