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Lung Size Mismatch and Primary Graft Dysfunction after Bilateral Lung Transplantation
Abstracts Class Iia Level of Evidence B non-invasive method to rule out the presence of grade 2R rejection or greater in low risk patients between 6-months and 5-years post cardiac transplant. We present data from our single center suggesting that this strategy can be utilized to obviate endomyocardial biopsy (EMB) in all patients, regardless of race, sex, age or presence of positive panel reactive antibodies. Methods and Materials: We analyzed our experience from 2009-2012 evaluating 711 Allomap scores in 126 patients. Beginning at month 5, patients underwent alternating GEP/EMB procedures until one year post transplant. At one year, surveillance monitoring was based on GEP alone except in patients with concern for acute cellular rejection, antibody mediated rejection or history of an infiltrative/inflammatory process. Decisions regarding scores 434 (reference threshold) were made based on patient test results during the first 5 months, standard clinical assessment and echocardiographic testing. Prediction values were based on IMAGE end points (graft dysfunction, hemodynamic deterioration or death). Technical and professional charges were obtained for the EMB/pathological interpretation arm and GEP/ echocardiography for the Allomap strategy. Results: No patients with a GEP score equal to or less than 34 developed any IMAGE end points or evidence of grade 2R acute cellular rejection on subsequent EMB resulting in a negative predictive value of 100%. Our economic analysis revealed a savings of over $5,000 utilizing GEP in lieu of EMB. Conclusions: GEP is a novel, non-invasive approach that is economically attractive, positively associated with a high level of patient satisfaction and very high negative predictive values. GEP should replace EMB as the routine surveillance tool to monitor for acute cellular rejection in all clinically stable patients 6 months post cardiac transplantation.
S41 Methods and Materials: The LTx Outcomes Group is a prospective cohort study of patients undergoing first LTx at 10 centers. The pTLCratio was calculated for all adult BLTs between 3/2002-2/2010. Patients were stratified by pTLCratio41.0(oversized) and pTLCratior1.0(undersized). PGD was defined by any ISHLT grade 3 PGD within 72 hours of allograft reperfusion. Logistic regression (LR) was used to estimate odds ratios (OR) for the association of the pTLCratio and PGD. Potential confounders were selected into multivariable models based on plausible association with pTLCratio or PGD. LTx center effects were accounted for by conditional LR. Results: PGD developed in 37.6% of the 311 undersized and in 27.1% of the 501 oversized patients (p¼0.001), table. In a multivariate model accounting for diagnosis, center volume, LTx era, ischemic time, bypass, transfusions, pulmonary artery systolic pressure, BMI, age, donor smoking and tidal volume at reperfusion oversizing was associated with a decreased probability of PGD (HR0.60, 95%CI0.42-0.88, p¼0.009). This association was somewhat attenuated after additional accounting for clustering within centers (OR 0.69, 95%CI 0.46-1.01, p¼0.06). Conclusions: A pTLCratio 41.0 appears to be associated with a decreased risk of PGD after BLT. An oversized allograft may operate at relatively smaller tidal volumes and lower pulmonary vascular resistance, which could be a mechanistic link to PGD. 89 Apoptosis, Not Necrosis, during Ex-Vivo Lung Perfusion Is Correlated with Severe PGD K. Hashimoto, T. Saito, T.N. Machuca, V. Linacre, D. Nakajima, S. Azad, T.K. Waddell, M. Liu, M. Cypel, S. Keshavjee. Latner Thoracic Surgery Laboratories, University of Toronto, Toronto, ON, Canada.
88 Lung Size Mismatch and Primary Graft Dysfunction after Bilateral Lung Transplantation M. Eberlein,1 R.M. Reed,2 S. Bolukbas,3 J.B. Orens,4 R.G. Brower,4 C.A. Merlo,4 L.B. Ware,5 K.M. Wille,6 A. Weinacker,7 R. Shah,8 J. Diamond,8 S.M. Kawut,8 J.D. Christie.8 1University of Iowa Hospitals and Clinics, Iowa City; 2University of Maryland, Baltimore; 3 HSK, Wiesbaden, Germany; 4Johns Hopkins University, Baltimore; 5 Vanderbilt University, Nashville; 6University of Alabama, Birmingham; 7 Stanford Hospital and Clinics, Stanford; 8University of Pennsylvania, Philadelphia. Purpose: Donor to recipient lung size mismatch at lung transplantation (LTx) can be estimated by the predicted total lung capacity (pTLC) ratio (¼donor pTLC/recipient pTLC). We aimed to determine if the pTLCratio is associated with the risk of primary graft dysfunction (PGD) after bilateral LTx (BLT).
Purpose: We hypothesized that a donor lung which develops more apoptosis during ex-vivo lung perfusion (EVLP) tends to experience severer primary graft dysfunction (PGD) after transplant and that cell death markers in perfusate can be used for prediction of subsequent PGD3. Methods and Materials: This is a single-institution retrospective casecontrol study. A correlation of the outcome of recipients after EVLP and cell death markers in EVLP perfusate was investigated. From 2008 to 2012, 77 high-risk donor lungs were subjected to normothermic acellular EVLP for 4 to 6 hours. Lungs were judged for transplantation based on physiological assessment. The cases (PGD group, N¼8) were patients who developed PGD 3 within 72h after lung transplant. The matched controls (Control group, N¼8) were selected from patients who had PGD 0, 1 or 2 within 72 h after transplant. Matching factors were recipient age, gender and lung disease. A matched design was used to minimize biases of recipient factors affecting the outcome. Cell death markers including M30, M65 and HMGB-1 were measured with ELISA in perfusate at 1h and the end of EVLP. Results: M30 which indicates epithelial apoptosis didn’t show a significant difference between two groups in perfusate at 1h. However, M30 in PGD group was significantly higher compared to Control group at the end of EVLP (p¼0.015). M30 at the end of EVLP increased significantly compared to 1 h (p¼0.016). M65 which indicates epithelial apoptosis and necrosis didn’t show a significant difference between two groups in both time-points. HMGB-1, which is a mediator of inflammation / immune response and released from dead cells, was significantly higher in PGD group at the end (p¼0.035) but not at 1h of EVLP. Using ROC curve, AUC of M30 at the end of EVLP was 0.84 (95%CI: 0.62-1.06, p¼0.035) and AUC of HMGB-1 at the end of EVLP was 0.85 (95%CI: 0.64-1.06, p¼0.029). Conclusions: Epithelial cell apoptosis is related to subsequent PGD3, but necrosis didn’t correlate with PGD severity. M30 and HMGB-1 are predictive perfusate markers for PGD3. 90 Gene Set Enrichment Analysis of Bronchial Alveolar Lavage Fluid Identifies Key Innate Immune Pathways in Primary Graft Dysfunction after Lung Transplantation
S41 Methods and Materials: The LTx Outcomes Group is a prospective cohort study of patients undergoing first LTx at 10 centers. The pTLCratio was calculated for all adult BLTs between 3/2002-2/2010. Patients were stratified by pTLCratio41.0(oversized) and pTLCratior1.0(undersized). PGD was defined by any ISHLT grade 3 PGD within 72 hours of allograft reperfusion. Logistic regression (LR) was used to estimate odds ratios (OR) for the association of the pTLCratio and PGD. Potential confounders were selected into multivariable models based on plausible association with pTLCratio or PGD. LTx center effects were accounted for by conditional LR. Results: PGD developed in 37.6% of the 311 undersized and in 27.1% of the 501 oversized patients (p¼0.001), table. In a multivariate model accounting for diagnosis, center volume, LTx era, ischemic time, bypass, transfusions, pulmonary artery systolic pressure, BMI, age, donor smoking and tidal volume at reperfusion oversizing was associated with a decreased probability of PGD (HR0.60, 95%CI0.42-0.88, p¼0.009). This association was somewhat attenuated after additional accounting for clustering within centers (OR 0.69, 95%CI 0.46-1.01, p¼0.06). Conclusions: A pTLCratio 41.0 appears to be associated with a decreased risk of PGD after BLT. An oversized allograft may operate at relatively smaller tidal volumes and lower pulmonary vascular resistance, which could be a mechanistic link to PGD. 89 Apoptosis, Not Necrosis, during Ex-Vivo Lung Perfusion Is Correlated with Severe PGD K. Hashimoto, T. Saito, T.N. Machuca, V. Linacre, D. Nakajima, S. Azad, T.K. Waddell, M. Liu, M. Cypel, S. Keshavjee. Latner Thoracic Surgery Laboratories, University of Toronto, Toronto, ON, Canada.
88 Lung Size Mismatch and Primary Graft Dysfunction after Bilateral Lung Transplantation M. Eberlein,1 R.M. Reed,2 S. Bolukbas,3 J.B. Orens,4 R.G. Brower,4 C.A. Merlo,4 L.B. Ware,5 K.M. Wille,6 A. Weinacker,7 R. Shah,8 J. Diamond,8 S.M. Kawut,8 J.D. Christie.8 1University of Iowa Hospitals and Clinics, Iowa City; 2University of Maryland, Baltimore; 3 HSK, Wiesbaden, Germany; 4Johns Hopkins University, Baltimore; 5 Vanderbilt University, Nashville; 6University of Alabama, Birmingham; 7 Stanford Hospital and Clinics, Stanford; 8University of Pennsylvania, Philadelphia. Purpose: Donor to recipient lung size mismatch at lung transplantation (LTx) can be estimated by the predicted total lung capacity (pTLC) ratio (¼donor pTLC/recipient pTLC). We aimed to determine if the pTLCratio is associated with the risk of primary graft dysfunction (PGD) after bilateral LTx (BLT).
Purpose: We hypothesized that a donor lung which develops more apoptosis during ex-vivo lung perfusion (EVLP) tends to experience severer primary graft dysfunction (PGD) after transplant and that cell death markers in perfusate can be used for prediction of subsequent PGD3. Methods and Materials: This is a single-institution retrospective casecontrol study. A correlation of the outcome of recipients after EVLP and cell death markers in EVLP perfusate was investigated. From 2008 to 2012, 77 high-risk donor lungs were subjected to normothermic acellular EVLP for 4 to 6 hours. Lungs were judged for transplantation based on physiological assessment. The cases (PGD group, N¼8) were patients who developed PGD 3 within 72h after lung transplant. The matched controls (Control group, N¼8) were selected from patients who had PGD 0, 1 or 2 within 72 h after transplant. Matching factors were recipient age, gender and lung disease. A matched design was used to minimize biases of recipient factors affecting the outcome. Cell death markers including M30, M65 and HMGB-1 were measured with ELISA in perfusate at 1h and the end of EVLP. Results: M30 which indicates epithelial apoptosis didn’t show a significant difference between two groups in perfusate at 1h. However, M30 in PGD group was significantly higher compared to Control group at the end of EVLP (p¼0.015). M30 at the end of EVLP increased significantly compared to 1 h (p¼0.016). M65 which indicates epithelial apoptosis and necrosis didn’t show a significant difference between two groups in both time-points. HMGB-1, which is a mediator of inflammation / immune response and released from dead cells, was significantly higher in PGD group at the end (p¼0.035) but not at 1h of EVLP. Using ROC curve, AUC of M30 at the end of EVLP was 0.84 (95%CI: 0.62-1.06, p¼0.035) and AUC of HMGB-1 at the end of EVLP was 0.85 (95%CI: 0.64-1.06, p¼0.029). Conclusions: Epithelial cell apoptosis is related to subsequent PGD3, but necrosis didn’t correlate with PGD severity. M30 and HMGB-1 are predictive perfusate markers for PGD3. 90 Gene Set Enrichment Analysis of Bronchial Alveolar Lavage Fluid Identifies Key Innate Immune Pathways in Primary Graft Dysfunction after Lung Transplantation