Browsing by Author "Hartwig, Matthew G"

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    Donor Leukocyte Trafficking and Damage-associated Molecular Pattern Expression During Ex Vivo Lung Perfusion.
    (Transplantation Direct, 2020-03) Davis, Robert P; Yerxa, John; Gao, Qimeng; Gloria, Jared; Scheuermann, Uwe; Song, Mingqing; Zhang, Min; Parker, William; Lee, Jaewoo; Hartwig, Matthew G; Barbas, Andrew S
    Background:While ex vivo lung perfusion (EVLP) has become established in lung transplantation, the cellular processes occurring during this period are not yet fully understood. Prior studies demonstrated that donor leukocytes (DLs) migrate from the graft into the perfusate during EVLP, but the distribution of DLs in graft and perfusate compartments has not been characterized. Moreover, cell death of DLs has been implicated in mediating graft injury during EVLP, but the underlying mechanisms have not been elucidated. We hypothesized the following: (1) there is a nonspecific migration of DLs from the graft into perfusate and (2) cell death of DLs releases damage-associated molecular patterns (DAMPs) that contribute to the inflammatory milieu during EVLP. Methods:EVLP was performed on rat lungs for 3 hours (N = 6). At the end of EVLP, flow cytometry was used to quantify the distribution of different DL cell types in both the graft and perfusate compartments. During EVLP, the perfusate was also sampled hourly to measure levels of DAMPs and downstream inflammatory cytokines generated during EVLP. Results:At the conclusion of EVLP, there was a significantly higher proportion of T and B cells present in the perfusate compartment compared with the graft compartment. There was a time-dependent increase in extracellular DNA and tumor necrosis factor α in the perfusate during EVLP. Conclusions:T cells and B cells are enriched in the perfusate compartment during EVLP. Cell death of DLs contributes to an accumulation of DAMPs during EVLP.
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    Inhaled Pulmonary Vasodilator Therapy in Adult Lung Transplant: A Randomized Clinical Trial.
    (JAMA surgery, 2022-01) Ghadimi, Kamrouz; Cappiello, Jhaymie; Cooter-Wright, Mary; Haney, John C; Reynolds, John M; Bottiger, Brandi A; Klapper, Jacob A; Levy, Jerrold H; Hartwig, Matthew G; INSPIRE-FLO Investigators

    Importance

    Inhaled nitric oxide (iNO) is commonly administered for selectively inhaled pulmonary vasodilation and prevention of oxidative injury after lung transplant (LT). Inhaled epoprostenol (iEPO) has been introduced worldwide as a cost-saving alternative to iNO without high-grade evidence for this indication.

    Objective

    To investigate whether the use of iEPO will lead to similar rates of severe/grade 3 primary graft dysfunction (PGD-3) after adult LT when compared with use of iNO.

    Design, setting, and participants

    This health system-funded, randomized, blinded (to participants, clinicians, data managers, and the statistician), parallel-designed, equivalence clinical trial included 201 adult patients who underwent single or bilateral LT between May 30, 2017, and March 21, 2020. Patients were grouped into 5 strata according to key prognostic clinical features and randomized per stratum to receive either iNO or iEPO at the time of LT via 1:1 treatment allocation.

    Interventions

    Treatment with iNO or iEPO initiated in the operating room before lung allograft reperfusion and administered continously until cessation criteria met in the intensive care unit (ICU).

    Main outcomes and measures

    The primary outcome was PGD-3 development at 24, 48, or 72 hours after LT. The primary analysis was for equivalence using a two one-sided test (TOST) procedure (90% CI) with a margin of 19% for between-group PGD-3 risk difference. Secondary outcomes included duration of mechanical ventilation, hospital and ICU lengths of stay, incidence and severity of acute kidney injury, postoperative tracheostomy placement, and in-hospital, 30-day, and 90-day mortality rates. An intention-to-treat analysis was performed for the primary and secondary outcomes, supplemented by per-protocol analysis for the primary outcome.

    Results

    A total of 201 randomized patients met eligibility criteria at the time of LT (129 men [64.2%]). In the intention-to-treat population, 103 patients received iEPO and 98 received iNO. The primary outcome occurred in 46 of 103 patients (44.7%) in the iEPO group and 39 of 98 (39.8%) in the iNO group, leading to a risk difference of 4.9% (TOST 90% CI, -6.4% to 16.2%; P = .02 for equivalence). There were no significant between-group differences for secondary outcomes.

    Conclusions and relevance

    Among patients undergoing LT, use of iEPO was associated with similar risks for PGD-3 development and other postoperative outcomes compared with the use of iNO.

    Trial registration

    ClinicalTrials.gov identifier: NCT03081052.
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    Neurological Sequelae and Clinical Outcomes After Lung Transplantation.
    (Transplantation direct, 2018-04) Smith, Patrick J; Stonerock, Gregory L; Ingle, Krista K; Saulino, Caroline K; Hoffman, Benson; Wasserman, Brian; Blumenthal, James A; Palmer, Scott M; Klapper, Jacob A; Hartwig, Matthew G; Esposito, Valentine R; Snyder, Laurie D
    Neurological complications are common after lung transplantation. However, no large cohort studies have examined the incidence, predictors, and clinical significance of neurological events sustained by lung transplant recipients.We conducted a retrospective cohort analysis of a consecutive series of lung transplant recipients, transplanted at Duke University Medical Center between May 2014 and February 2017 (n = 276). Early neurological complications (ie, occurring during the first week after transplant) were documented by transplant mental health specialists and included delirium, ischemic injury, and posterior reversible encephalopathy syndrome. Analyses accounted for age, native disease, sex, type of transplant, lung allocation score, and primary graft dysfunction. The objectives of the study were to characterize the prevalence and predictors of early neurological sequelae (NSE), occurring during the first week posttransplant, and the association between NSE and subsequent clinical outcomes, including length of stay and mortality.Neurological sequelae were common, occurring in 123 (45%) patients. Fifty-seven patients died over a follow-up interval of 2.1 years. The most common NSE were postoperative delirium (n = 110 [40%]) and posterior reversible encephalopathy syndrome (n = 12 [4%]), followed by stroke/transient ischemic attack and neurotoxicity. Higher lung allocation score was the strongest predictor of delirium. The presence of a NSE was associated with longer length of hospital stay (32 days vs 17 days, P < 0.001) and greater mortality (hazard ratio, 1.90; 95% confidence interval, 1.09-3.32], P = 0.024), with the greatest mortality risk occurring approximately 2 years after transplantation.Neurological events are relatively common after lung transplantation and associated with adverse clinical outcomes.