Browsing by Author "Emtiazjoo, Amir"
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Item Open Access A Multi-Center International Analysis of Lung Transplantation Outcomes in Patients With COVID-19.(Clinical transplantation, 2024-09) Kashem, Mohammed Abul; Loor, Gabriel; Emtiazjoo, Amir; Hartwig, Matthew; Van Raemdonck, Dirk; Calvelli, Hannah; Leon Pena, Andres; Salan-Gomez, Marcelo; Zhao, Huaqing; Warnick, Michael; Villavicencio, Mauricio; Ius, Fabio; Ghadimi, Kamrouz; Salman, Jawad; Chandrashekaran, Satish; Machuca, Tiago; Sanchez, Pablo G; Subramaniam, Kathirvel; Neyrinck, Arne; Huddleston, Stephen; Ceulemans, Laurens; Osho, Asishana; D'Silva, Ethan; Ramamurthy, Uma; Shaffer, Andrew; Langer, Nathaniel; Toyoda, YoshiyaIntroduction
Lung 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.Methods
This 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.Results
Of 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).Conclusions
Patients 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.Item Open Access A novel injury site-natural antibody targeted complement inhibitor protects against lung transplant injury.(American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2021-06) Li, Changhai; Patel, Kunal; Tu, Zhenxiao; Yang, Xiaofeng; Kulik, Liudmila; Alawieh, Ali; Allen, Patterson; Cheng, Qi; Wallace, Caroline; Kilkenny, Jane; Kwon, Jennie; Gibney, Barry; Cantu, Edward; Sharma, Ashish; Pipkin, Mauricio; Machuca, Tiago; Emtiazjoo, Amir; Goddard, Martin; Holers, V Michael; Nadig, Satish; Christie, Jason; Tomlinson, Stephen; Atkinson, CarlComplement is known to play a role in ischemia and reperfusion injury (IRI). A general paradigm is that complement is activated by self-reactive natural IgM antibodies (nAbs), after they engage postischemic neoepitopes. However, a role for nAbs in lung transplantation (LTx) has not been explored. Using mouse models of LTx, we investigated the role of two postischemic neoepitopes, modified annexin IV (B4) and a subset of phospholipids (C2), in LTx. Antibody deficient Rag1-/- recipient mice were protected from LTx IRI. Reconstitution with either B4 or C2nAb restored IRI, with C2 significantly more effective than B4 nAb. Based on these information, we developed/characterized a novel complement inhibitor composed of single-chain antibody (scFv) derived from the C2 nAb linked to Crry (C2scFv-Crry), a murine inhibitor of C3 activation. Using an allogeneic LTx, in which recipients contain a full nAb repertoire, C2scFv-Crry targeted to the LTx, inhibited IRI, and delayed acute rejection. Finally, we demonstrate the expression of the C2 neoepitope in human donor lungs, highlighting the translational potential of this approach.