Browsing by Author "Hartwig, Matthew G."

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    Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant
    (American Thoracic Society, 2018-01-15) Cantu, Edward; Diamond, Joshua M.; Suzuki, Yoshikazu; Lasky, Jared; Schaufler, Christian; Lim, Brian; Shah, Rupal; Porteous, Mary; Lederer, David J.; Kawut, Steven M.; Palmer, Scott M.; Snyder, Laurie D.; Hartwig, Matthew G.; Lama, Vibha N.; Bhorade, Sangeeta; Bermudez, Christian; Crespo, Maria; McDyer, John; Wille, Keith; Orens, Jonathan; Shah, Pali D.; Weinacker, Ann; Weill, David; Wilkes, David; Roe, David; Hage, Chadi; Ware, Lorraine B.; Bellamy, Scarlett L.; Christie, Jason D.; Medicine, School of Medicine
    RATIONALE: Primary graft dysfunction (PGD) is a form of acute lung injury that occurs after lung transplantation. The definition of PGD was standardized in 2005. Since that time, clinical practice has evolved, and this definition is increasingly used as a primary endpoint for clinical trials; therefore, validation is warranted. OBJECTIVES: We sought to determine whether refinements to the 2005 consensus definition could further improve construct validity. METHODS: Data from the Lung Transplant Outcomes Group multicenter cohort were used to compare variations on the PGD definition, including alternate oxygenation thresholds, inclusion of additional severity groups, and effects of procedure type and mechanical ventilation. Convergent and divergent validity were compared for mortality prediction and concurrent lung injury biomarker discrimination. MEASUREMENTS AND MAIN RESULTS: A total of 1,179 subjects from 10 centers were enrolled from 2007 to 2012. Median length of follow-up was 4 years (interquartile range = 2.4-5.9). No mortality differences were noted between no PGD (grade 0) and mild PGD (grade 1). Significantly better mortality discrimination was evident for all definitions using later time points (48, 72, or 48-72 hours; P < 0.001). Biomarker divergent discrimination was superior when collapsing grades 0 and 1. Additional severity grades, use of mechanical ventilation, and transplant procedure type had minimal or no effect on mortality or biomarker discrimination. CONCLUSIONS: The PGD consensus definition can be simplified by combining lower PGD grades. Construct validity of grading was present regardless of transplant procedure type or use of mechanical ventilation. Additional severity categories had minimal impact on mortality or biomarker discrimination.
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    The Impact of Donor Smoking on Primary Graft Dysfunction and Mortality after Lung Transplantation
    (American Thoracic Society, 2024) Diamond, Joshua M.; Cantu, Edward; Calfee, Carolyn S.; Anderson, Michaela R.; Clausen, Emily S.; Shashaty, Michael G. S.; Courtwright, Andrew M.; Kalman, Laurel; Oyster, Michelle; Crespo, Maria M.; Bermudez, Christian A.; Benvenuto, Luke; Palmer, Scott M.; Snyder, Laurie D.; Hartwig, Matthew G.; Todd, Jamie L.; Wille, Keith; Hage, Chadi; McDyer, John F.; Merlo, Christian A.; Shah, Pali D.; Orens, Jonathan B.; Dhillon, Gundeep S.; Weinacker, Ann B.; Lama, Vibha N.; Patel, Mrunal G.; Singer, Jonathan P.; Hsu, Jesse; Localio, A. Russell; Christie, Jason D.; Medicine, School of Medicine
    Rationale: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Prior studies implicated proxy-defined donor smoking as a risk factor for PGD and mortality. Objectives: We aimed to more accurately assess the impact of donor smoke exposure on PGD and mortality using quantitative smoke exposure biomarkers. Methods: We performed a multicenter prospective cohort study of lung transplant recipients enrolled in the Lung Transplant Outcomes Group cohort between 2012 and 2018. PGD was defined as grade 3 at 48 or 72 hours after lung reperfusion. Donor smoking was defined using accepted thresholds of urinary biomarkers of nicotine exposure (cotinine) and tobacco-specific nitrosamine (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol [NNAL]) in addition to clinical history. The donor smoking–PGD association was assessed using logistic regression, and survival analysis was performed using inverse probability of exposure weighting according to smoking category. Measurements and Main Results: Active donor smoking prevalence varied by definition, with 34–43% based on urinary cotinine, 28% by urinary NNAL, and 37% by clinical documentation. The standardized risk of PGD associated with active donor smoking was higher across all definitions, with an absolute risk increase of 11.5% (95% confidence interval [CI], 3.8% to 19.2%) by urinary cotinine, 5.7% (95% CI, −3.4% to 14.9%) by urinary NNAL, and 6.5% (95% CI, −2.8% to 15.8%) defined clinically. Donor smoking was not associated with differential post–lung transplant survival using any definition. Conclusions: Donor smoking associates with a modest increase in PGD risk but not with increased recipient mortality. Use of lungs from smokers is likely safe and may increase lung donor availability.