Langer, Nathaniel B.

ABSTRACTIntroductionLung transplantation has become increasingly utilized in patients with COVID‐19. While several single‐center and UNOS database studies have been published on lung transplants (LTs) for end‐stage lung disease (ESLD) from Coronavirus disease 2019 (COVID‐19), there is a lack of multi‐center and international data.MethodsThis is a multicenter analysis from 11 high‐volume lung transplant centers in the United States and Europe. Data were collected through the Multi‐Institutional ECLS Registry and stratified by ESLD due to COVID‐19 versus other etiologies. Demographics and clinical variables were compared using Chi‐square test and Fisher's exact test. Survival was assessed by Kaplan‐Meier curves and compared by log‐rank test with propensity score matching.ResultsOf 1606 lung transplant recipients, 46 (2.9%) were transplanted for ESLD from COVID‐19 compared to 1560 (97.1%) without a history of COVID‐19. Among COVID‐19 patients, 30 (65.2%) had COVID‐19‐associated ARDS and 16 (34.8%) had post‐COVID‐19 fibrosis. COVID‐19 patients had higher lung allocation scores (78.0 vs. 44.4, p < 0.0001), had severely limited functional status (37.0% vs. 2.9%, p < 0.0001), had higher preoperative ECMO usage (65.2% vs. 5.4%, p < 0.0001), and spent less time on the waitlist (32 vs. 137 days, p < 0.0001). A 30‐day survival was comparable between COVID‐19 and non‐COVID‐19 patients before (100% vs. 98.7%, p = 0.39) and after propensity matching (p = 0.15).ConclusionsPatients who received LTs due to COVID‐19 had short‐term survival comparable to that of patients without COVID‐19. Our findings support the idea that lung transplantation should be considered for select patients with ESLD due to COVID‐19.

AbstractObjectivesWe provide a contemporary consideration of long‐term outcomes and trends of induction therapy use following lung transplantation in the United States. Methods: We reviewed the United Network for Organ Sharing registry from 2006 to 2018 for first‐time, adult, lung‐only transplant recipients. Long‐term survival was compared between induction classes (Interleukin‐2 inhibitors, monoclonal or polyclonal cell‐depleting agents, and no induction therapy). A 1:1 propensity score match was performed, pairing patients who received basiliximab with similar risk recipients who did not receive induction therapy. Outcomes in matched populations were compared using Cox, Kaplan‐Meier and Logistic regression modeling.Measurements and main results22 025 recipients were identified; 8003 (36.34%) were treated with no induction therapy, 11 045 (50.15%) with basiliximab, 1556 (7.06%) with alemtuzumab and 1421 (6.45%) with anti‐thymocyte globulin. Compared with those who received no induction, patients receiving basiliximab, alemtuzumab or anti‐thymocyte globulin were found on multivariable Cox‐regression analyses to have lower long‐term mortality (all p < .05). Following propensity score matching of basiliximab and no induction populations, analyses demonstrated a statistically significant association between basiliximab use and long‐ term survival (p < .001). Basiliximab was also associated with a lower risk of acute rejection (p < .001) and renal failure (p = .002).ConclusionInduction therapy for lung transplant recipients—specifically basiliximab—is associated with improved long‐term survival and a lower risk of renal failure or acute rejection.

Abstract Previously in our lab, a missense mutation in the MASTL (FLJ14813) gene on human chromosome 10 was linked to an autosomal dominantly inherited thrombocytopenia in a single pedigree. The mutation results in an amino acid change from glutamic acid at position 167 to aspartic acid and correlates with the inheritance of the disorder in all the affected individuals. The patients present with mild thrombocytopenia with an average platelet count of 60,000 platelets per microliter of blood. Northern blot analysis indicates that MASTL mRNA is restricted in its expression to hematopoietic and cancer cell lines. Functional studies presented here demonstrate a direct relationship between the transient knockdown of the Microtubule Associated Serine/Threonine Like (MASTL) kinase expression and the reduction of circulating thrombocytes in zebrafish (Danio rerio) while erythrocytes development normally. This transient knockdown of MASTL in zebrafish correlates with a decrease in the expression of the thrombopoietin receptor, c-mpl, and the CD41 platelet adhesion GpIIb protein but has no effect on essential housekeeping zebrafish gene, EF1α. The transient expression of a fluorescent protein fused to MASTL and E167D MASTL kinase demonstrates that MASTL localizes to the nucleus of cells as determined by confocal microscopy and TO-PRO-3 counterstain.