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Jason D. Christie - One of the best experts on this subject based on the ideXlab platform.

  • Lung Innate Lymphoid Cell Composition Is Altered in Primary Graft Dysfunction.
    American Journal of Respiratory and Critical Care Medicine, 2020
    Co-Authors: Laurel A. Monticelli, Mary K. Porteous, Edward Cantu, Joshua M. Diamond, Steven A. Saenz, Elia D. Tait Wojno, David Artis, Jason D. Christie
    Abstract:

    Rationale: Primary Graft Dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation, but the immunologic mechanisms are poorly understood. Innate lymphoid ce...

  • diastolic Dysfunction increases the risk of Primary Graft Dysfunction after lung transplant
    American Journal of Respiratory and Critical Care Medicine, 2016
    Co-Authors: Mary K. Porteous, Jason D. Christie, Joshua M. Diamond, Rupal J. Shah, James N Kirkpatrick, Russell T Shinohara, James Lee, Steven M. Kawut
    Abstract:

    Rationale: Primary Graft Dysfunction (PGD) is a significant cause of early morbidity and mortality after lung transplant and is characterized by severe hypoxemia and infiltrates in the alloGraft. The pathogenesis of PGD involves ischemia-reperfusion injury. However, subclinical increases in pulmonary venous pressure due to left ventricular diastolic Dysfunction may contribute by exacerbating capillary leak.Objectives: To determine whether a higher ratio of early mitral inflow velocity (E) to early diastolic mitral annular velocity (e), indicative of worse left ventricular diastolic function, is associated with a higher risk of PGD.Methods: We performed a retrospective cohort study of patients in the Lung Transplant Outcomes Group who underwent bilateral lung transplant at our institution between 2004 and 2014 for interstitial lung disease, chronic obstructive pulmonary disease, or pulmonary arterial hypertension. Transthoracic echocardiograms obtained during evaluation for transplant listing were analyzed...

  • Primary Graft Dysfunction: lessons learned about the first 72 h after lung transplantation.
    Current Opinion in Organ Transplantation, 2015
    Co-Authors: Mary K. Porteous, Joshua M. Diamond, Jason D. Christie
    Abstract:

    Purpose of reviewIn 2005, the International Society for Heart and Lung Transplantation published a standardized definition of Primary Graft Dysfunction (PGD), facilitating new knowledge on this form of acute lung injury that occurs within 72 h of lung transplantation. PGD continues to be associated

  • Primary Graft Dysfunction.
    Seminars in Respiratory and Critical Care Medicine, 2013
    Co-Authors: Y. Suzuki, Edward Cantu, Jason D. Christie
    Abstract:

    Primary Graft Dysfunction (PGD) is a syndrome encompassing a spectrum of mild to severe lung injury that occurs within the first 72 hours after lung transplantation. PGD is characterized by pulmonary edema with diffuse alveolar damage that manifests clinically as progressive hypoxemia with radiographic pulmonary infiltrates. In recent years, new knowledge has been generated on risks and mechanisms of PGD. Following ischemia and reperfusion, inflammatory and immunological injury-repair responses appear to be key controlling mechanisms. In addition, PGD has a significant impact on short- and long-term outcomes; therefore, the choice of donor organ is impacted by this potential adverse consequence. Improved methods of reducing PGD risk and efforts to safely expand the pool are being developed. Ex vivo lung perfusion is a strategy that may improve risk assessment and become a promising platform to implement treatment interventions to prevent PGD. This review details recent updates in the epidemiology, pathophysiology, molecular and genetic biomarkers, and state-of-the-art technical developments affecting PGD.

  • Primary Graft Dysfunction
    Clinics in Chest Medicine, 2011
    Co-Authors: James C. Lee, Jason D. Christie
    Abstract:

    Primary Graft Dysfunction (PGD) is the most important cause of early morbidity and mortality following lung transplantation. PGD affects up to 25% of all lung transplant procedures and currently has no proven preventive therapy. Lung transplant recipients who recover from PGD may have impaired long-term function and an increased risk of bronchiolitis obliterans syndrome. This article aims to provide a state-of-the-art review of PGD epidemiology, outcomes, and risk factors, and to summarize current efforts at biomarker development and novel strategies for prevention and treatment.

Michael Grimm - One of the best experts on this subject based on the ideXlab platform.

  • donor serum smarcal1 concentrations predict Primary Graft Dysfunction in cardiac transplantation
    Circulation, 2009
    Co-Authors: Seyedhossein Aharinejad, A Zuckermann, Olena Andrukhova, Matthias Gmeiner, Anita Thomas, A Z Aliabadi, Katharina Krenn, Michael Grimm
    Abstract:

    Background— Primary Graft Dysfunction (PGD) is a life-threatening complication in cardiac transplantation. A sensitive, specific, and easily measurable predictor in donors could facilitate PGD prevention. Methods and Results— SMARCAL1 is a matrix-associated regulator of chromatin with helicase and ATPase activities, and its serum concentrations were significantly increased in a targeted protein array in donors whose Grafts developed PGD. Therefore, this study analyzed SMARCAL1 serum concentrations by ELISA in 336 heart donors before and after aortic cross-clamping (ACC) and in recipients at 10, 30, and 60 minutes reperfusion. Demographic and hemodynamic parameters of donors and recipients as well as transplant procedure characteristics were documented. PGD (n=68) was defined as ventricular dilation and hypocontractility associated with systolic blood pressure 20 mm Hg, and decreased mixed venous oxygen saturation necessitating mechanical circulatory support. SMARCAL1 serum protein concentration was significantly increased only before and after ACC in donors ( P <0.0001) whose Grafts developed PGD compared to those who did not. In receiver operating characteristic curve analysis, SMARCAL1 serum concentration at a cut-off level of ≥1.25 ng/mL before ACC in donors predicted PGD ( P <0.0001, AUC=0.988, OR=17.050, 95% CI=5.200 to 55.901) with 96% sensitivity and 88% specificity. SMARCAL1 serum concentrations <1.25 ng/mL in donors before ACC resulted in 97% PGD-free outcome and SMARCAL1 concentrations ≥1.25 resulted in 83% PGD occurrence. Conclusions— Donor serum SMARCAL1 may serve as a specific, sensitive, and noninvasive predictive marker in the assessment of cardiac Graft quality.

  • Donor serum SMARCAL1 concentrations predict Primary Graft Dysfunction in cardiac transplantation.
    Circulation, 2009
    Co-Authors: Seyedhossein Aharinejad, A Zuckermann, Olena Andrukhova, Matthias Gmeiner, Anita Thomas, Katharina Krenn, Arezu Aliabadi, Michael Grimm
    Abstract:

    Background— Primary Graft Dysfunction (PGD) is a life-threatening complication in cardiac transplantation. A sensitive, specific, and easily measurable predictor in donors could facilitate PGD prevention. Methods and Results— SMARCAL1 is a matrix-associated regulator of chromatin with helicase and ATPase activities, and its serum concentrations were significantly increased in a targeted protein array in donors whose Grafts developed PGD. Therefore, this study analyzed SMARCAL1 serum concentrations by ELISA in 336 heart donors before and after aortic cross-clamping (ACC) and in recipients at 10, 30, and 60 minutes reperfusion. Demographic and hemodynamic parameters of donors and recipients as well as transplant procedure characteristics were documented. PGD (n=68) was defined as ventricular dilation and hypocontractility associated with systolic blood pressure 20 mm Hg, and decreased mixed venous oxygen saturation necessitating mechanical circulatory support. SMARCAL1 serum protein concentration was significantly increased only before and after ACC in donors ( P

  • Abstract 5848: Serum SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily a-like (SMARCAL)-1 Concentrations Predict Primary Graft Dysfunction in Cardiac Transplant Recipients
    Circulation, 2008
    Co-Authors: Seyedhossein Aharinejad, Olena Andrukhova, Katharina Krenn, Andreas Zuckermann, Daniel Zimpfer, Anita C Thomas, Michael Grimm
    Abstract:

    Primary Graft Dysfunction (PGD) is a life-threatening complication in cardiac transplantation. A sensitive, specific, easily and quickly measurable serum predictor could facilitate PGD prevention a...

Joshua M. Diamond - One of the best experts on this subject based on the ideXlab platform.

  • Lung Innate Lymphoid Cell Composition Is Altered in Primary Graft Dysfunction.
    American Journal of Respiratory and Critical Care Medicine, 2020
    Co-Authors: Laurel A. Monticelli, Mary K. Porteous, Edward Cantu, Joshua M. Diamond, Steven A. Saenz, Elia D. Tait Wojno, David Artis, Jason D. Christie
    Abstract:

    Rationale: Primary Graft Dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation, but the immunologic mechanisms are poorly understood. Innate lymphoid ce...

  • Primary Graft Dysfunction pgd following lung transplantation
    Seminars in Respiratory and Critical Care Medicine, 2018
    Co-Authors: Rupal J. Shah, Joshua M. Diamond
    Abstract:

    Primary Graft Dysfunction (PGD) is a form of acute lung injury that results from ischemia reperfusion injury (IRI) and is the major cause of early posttransplant morbidity and mortality. Patients who survive PGD have decreased quality of life, an increased risk of chronic lung alloGraft Dysfunction, specifically bronchiolitis obliterans syndrome, and a significantly increased risk of death. In 2017, the International Society for Heart and Lung Transplantation released updated consensus statements on the PGD definition, most up-to-date PGD risk factors, mechanisms of PGD development, and the state-of-the-art for PGD therapeutics. Risk factor identification has led to the development of PGD predictive algorithms, although their clinical utility remains limited. Ongoing areas of controversy and discussion include further refinements to the PGD grading scheme to account for technologic advances such as extracorporeal membrane oxygenation and the increased utilization of high flow nasal cannula, the use of PGD as an outcome measure in clinical trials of ex vivo lung perfusion, enhancement of predictive algorithms incorporating biochemical risk factors, and the need for development of therapies targeted at improving PGD outcomes.

  • Quantitative evidence for revising the definition of Primary Graft Dysfunction after lung transplant
    American Journal of Respiratory and Critical Care Medicine, 2018
    Co-Authors: Edward Cantu, Mary K. Porteous, Y. Suzuki, Joshua M. Diamond, David J. Lederer, Rupal J. Shah, J. Lasky, C. Schaufler, Brian Lim, Steven M. Kawut
    Abstract:

    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 ...

  • diastolic Dysfunction increases the risk of Primary Graft Dysfunction after lung transplant
    American Journal of Respiratory and Critical Care Medicine, 2016
    Co-Authors: Mary K. Porteous, Jason D. Christie, Joshua M. Diamond, Rupal J. Shah, James N Kirkpatrick, Russell T Shinohara, James Lee, Steven M. Kawut
    Abstract:

    Rationale: Primary Graft Dysfunction (PGD) is a significant cause of early morbidity and mortality after lung transplant and is characterized by severe hypoxemia and infiltrates in the alloGraft. The pathogenesis of PGD involves ischemia-reperfusion injury. However, subclinical increases in pulmonary venous pressure due to left ventricular diastolic Dysfunction may contribute by exacerbating capillary leak.Objectives: To determine whether a higher ratio of early mitral inflow velocity (E) to early diastolic mitral annular velocity (e), indicative of worse left ventricular diastolic function, is associated with a higher risk of PGD.Methods: We performed a retrospective cohort study of patients in the Lung Transplant Outcomes Group who underwent bilateral lung transplant at our institution between 2004 and 2014 for interstitial lung disease, chronic obstructive pulmonary disease, or pulmonary arterial hypertension. Transthoracic echocardiograms obtained during evaluation for transplant listing were analyzed...

  • objective estimates improve risk stratification for Primary Graft Dysfunction after lung transplantation
    American Journal of Transplantation, 2015
    Co-Authors: Rupal J. Shah, James C. Lee, Joshua M. Diamond, David J. Lederer, Ann Weinacker, Vibha N. Lama, E Cantu, Judd D Flesch, Jonathan B Orens, David S. Wilkes
    Abstract:

    Primary Graft Dysfunction (PGD) is a major cause of early mortality after lung transplant. We aimed to define objective estimates of PGD risk based on readily available clinical variables, using a prospective study of 11 centers in Lung Transplant Outcomes Group (LTOG). Derivation included 1255 subjects from 2002–2010; with separate validation in 382 subjects accrued from 2011–2012. We used logistic regression to identify predictors of grade 3 PGD at 48/72 hours, and decision curve methods to assess impact on clinical decisions. 211/1255 subjects in the derivation and 56/382 subjects in the validation developed PGD. We developed 3 prediction models, where low-risk recipients had a normal BMI (18.5–25 kg/m2), COPD/CF, and absent or mild PH (mPAP< 40mmHg). All others were considered higher-risk. Low-risk recipients had a predicted PGD risk of 4–7%, and high-risk a predicted PGD risk of 15–18%. Adding a donor-smoking lung to a higher-risk recipient significantly increased PGD risk, although risk did not change in low-risk recipients. Validation demonstrated that probability estimates were generally accurate and that models worked best at baseline PGD incidences between 5–25%. We conclude that valid estimates of PGD risk can be produced using readily-available clinical variables.

James C. Lee - One of the best experts on this subject based on the ideXlab platform.

  • Clinical Risk Factors and Prognostic Model for Primary Graft Dysfunction after Lung Transplantation in Patients with Pulmonary Hypertension.
    Annals of the American Thoracic Society, 2017
    Co-Authors: Mary K. Porteous, James C. Lee, Edward Cantu, David J. Lederer, Sangeeta Bhorade, Scott M. Palmer, Rupal J. Shah, Scarlett L. Bellamy, Vibha N. Lama, Maria Crespo
    Abstract:

    Rationale: Pulmonary hypertension from pulmonary arterial hypertension or parenchymal lung disease is associated with an increased risk for Primary Graft Dysfunction after lung transplantation.Objective: We evaluated the clinical determinants of severe Primary Graft Dysfunction in pulmonary hypertension and developed and validated a prognostic model.Methods: We conducted a retrospective cohort study of patients in the multicenter Lung Transplant Outcomes Group with pulmonary hypertension at transplant listing. Severe Primary Graft Dysfunction was defined as PaO2/FiO2 ≤200 with alloGraft infiltrates at 48 or 72 hours after transplantation. Donor, recipient, and operative characteristics were evaluated in a multivariable explanatory model. A prognostic model derived using donor and recipient characteristics was then validated in a separate cohort.Results: In the explanatory model of 826 patients with pulmonary hypertension, donor tobacco smoke exposure, higher recipient body mass index, female sex, listing ...

  • Primary Graft Dysfunction After Lung Transplantation.
    Clinics in Chest Medicine, 2017
    Co-Authors: Mary K. Porteous, James C. Lee
    Abstract:

    Primary Graft Dysfunction is a form of acute injury after lung transplantation that is associated with significant short- and long-term morbidity and mortality. Multiple mechanisms contribute to the pathogenesis of Primary Graft Dysfunction, including ischemia reperfusion injury, epithelial cell death, endothelial cell Dysfunction, innate immune activation, oxidative stress, and release of inflammatory cytokines and chemokines. This article reviews the epidemiology, pathogenesis, risk factors, prevention, and treatment of Primary Graft Dysfunction.

  • objective estimates improve risk stratification for Primary Graft Dysfunction after lung transplantation
    American Journal of Transplantation, 2015
    Co-Authors: Rupal J. Shah, James C. Lee, Joshua M. Diamond, David J. Lederer, Ann Weinacker, Vibha N. Lama, E Cantu, Judd D Flesch, Jonathan B Orens, David S. Wilkes
    Abstract:

    Primary Graft Dysfunction (PGD) is a major cause of early mortality after lung transplant. We aimed to define objective estimates of PGD risk based on readily available clinical variables, using a prospective study of 11 centers in Lung Transplant Outcomes Group (LTOG). Derivation included 1255 subjects from 2002–2010; with separate validation in 382 subjects accrued from 2011–2012. We used logistic regression to identify predictors of grade 3 PGD at 48/72 hours, and decision curve methods to assess impact on clinical decisions. 211/1255 subjects in the derivation and 56/382 subjects in the validation developed PGD. We developed 3 prediction models, where low-risk recipients had a normal BMI (18.5–25 kg/m2), COPD/CF, and absent or mild PH (mPAP< 40mmHg). All others were considered higher-risk. Low-risk recipients had a predicted PGD risk of 4–7%, and high-risk a predicted PGD risk of 15–18%. Adding a donor-smoking lung to a higher-risk recipient significantly increased PGD risk, although risk did not change in low-risk recipients. Validation demonstrated that probability estimates were generally accurate and that models worked best at baseline PGD incidences between 5–25%. We conclude that valid estimates of PGD risk can be produced using readily-available clinical variables.

  • clinical risk factors for Primary Graft Dysfunction after lung transplantation
    Journal of Heart and Lung Transplantation, 2013
    Co-Authors: Joshua M. Diamond, James C. Lee, Edward Cantu, David J. Lederer, Steven M. Kawut, Rupal J. Shah, Scarlett L. Bellamy, Benjamin A Kohl, A R Localio, Vibha N. Lama
    Abstract:

    Purpose Primary Graft Dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies of PGD risk factors have produced conflicting results due to small sample sizes, inconsistencies in PGD phenotype, inability to control for multiple confounders, and use of retrospective, single center, or administrative data. We sought to identify donor, recipient, and peri-operative risk factors for PGD. Methods and Materials We performed a 10 center prospective cohort study enrolled between March 2002 and December 2010 (the Lung Transplant Outcomes Group). The Primary outcome was grade 3 PGD at 48 or 72 hrs post transplant. The association of risk factors with PGD was analyzed using multivariable conditional logistic regression. Results 1255 patients were enrolled; 211 subjects (16.8%) developed PGD. In multivariable models, risk factors for PGD were any history of donor smoking (OR=1.8, 95%CI 1.2, 2.6, p=0.002), FiO2 at alloGraft reperfusion (OR=1.1 per 10% increase in FiO2, 95%CI 1.0, 1.2; p=0.01), single lung transplant (OR=2.0, 95%CI 1.2, 3.3; p=0.008), cardiopulmonary bypass (OR=3.4, 95%CI 2.2, 5.3; p Conclusions We identified important PGD risk factors, including donor smoking, recipient factors of pre-transplant diagnosis and BMI, and perioperative treatment variables, including use of cardiopulmonary bypass, blood transfusion volume, and FiO2 at reperfusion. Several of these risk factors are potentially modifiable, and thus may suggest preventative strategies, while other risk factors should be prioritized for future mechanistic research efforts.

  • clinical risk factors for Primary Graft Dysfunction after lung transplantation
    American Journal of Respiratory and Critical Care Medicine, 2013
    Co-Authors: Joshua M. Diamond, James C. Lee, Edward Cantu, David J. Lederer, Steven M. Kawut, Rupal J. Shah, Scarlett L. Bellamy, Russell A Localio, Benjamin A Kohl, Vibha N. Lama
    Abstract:

    Rationale: Primary Graft Dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies have yielded conflicting results for PGD risk factors.Objectives: We sought to identify donor, recipient, and perioperative risk factors for PGD.Methods: We performed a 10-center prospective cohort study enrolled between March 2002 and December 2010 (the Lung Transplant Outcomes Group). The Primary outcome was International Society for Heart and Lung Transplantation grade 3 PGD at 48 or 72 hours post-transplant. The association of potential risk factors with PGD was analyzed using multivariable conditional logistic regression.Measurements and Main Results: A total of 1,255 patients from 10 centers were enrolled; 211 subjects (16.8%) developed grade 3 PGD. In multivariable models, independent risk factors for PGD were any history of donor smoking (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2–2.6; P = 0.002); FiO2 during alloGraft reperfusion (OR, 1.1 per 10% ...

Seyedhossein Aharinejad - One of the best experts on this subject based on the ideXlab platform.

  • donor serum smarcal1 concentrations predict Primary Graft Dysfunction in cardiac transplantation
    Circulation, 2009
    Co-Authors: Seyedhossein Aharinejad, A Zuckermann, Olena Andrukhova, Matthias Gmeiner, Anita Thomas, A Z Aliabadi, Katharina Krenn, Michael Grimm
    Abstract:

    Background— Primary Graft Dysfunction (PGD) is a life-threatening complication in cardiac transplantation. A sensitive, specific, and easily measurable predictor in donors could facilitate PGD prevention. Methods and Results— SMARCAL1 is a matrix-associated regulator of chromatin with helicase and ATPase activities, and its serum concentrations were significantly increased in a targeted protein array in donors whose Grafts developed PGD. Therefore, this study analyzed SMARCAL1 serum concentrations by ELISA in 336 heart donors before and after aortic cross-clamping (ACC) and in recipients at 10, 30, and 60 minutes reperfusion. Demographic and hemodynamic parameters of donors and recipients as well as transplant procedure characteristics were documented. PGD (n=68) was defined as ventricular dilation and hypocontractility associated with systolic blood pressure 20 mm Hg, and decreased mixed venous oxygen saturation necessitating mechanical circulatory support. SMARCAL1 serum protein concentration was significantly increased only before and after ACC in donors ( P <0.0001) whose Grafts developed PGD compared to those who did not. In receiver operating characteristic curve analysis, SMARCAL1 serum concentration at a cut-off level of ≥1.25 ng/mL before ACC in donors predicted PGD ( P <0.0001, AUC=0.988, OR=17.050, 95% CI=5.200 to 55.901) with 96% sensitivity and 88% specificity. SMARCAL1 serum concentrations <1.25 ng/mL in donors before ACC resulted in 97% PGD-free outcome and SMARCAL1 concentrations ≥1.25 resulted in 83% PGD occurrence. Conclusions— Donor serum SMARCAL1 may serve as a specific, sensitive, and noninvasive predictive marker in the assessment of cardiac Graft quality.

  • Donor serum SMARCAL1 concentrations predict Primary Graft Dysfunction in cardiac transplantation.
    Circulation, 2009
    Co-Authors: Seyedhossein Aharinejad, A Zuckermann, Olena Andrukhova, Matthias Gmeiner, Anita Thomas, Katharina Krenn, Arezu Aliabadi, Michael Grimm
    Abstract:

    Background— Primary Graft Dysfunction (PGD) is a life-threatening complication in cardiac transplantation. A sensitive, specific, and easily measurable predictor in donors could facilitate PGD prevention. Methods and Results— SMARCAL1 is a matrix-associated regulator of chromatin with helicase and ATPase activities, and its serum concentrations were significantly increased in a targeted protein array in donors whose Grafts developed PGD. Therefore, this study analyzed SMARCAL1 serum concentrations by ELISA in 336 heart donors before and after aortic cross-clamping (ACC) and in recipients at 10, 30, and 60 minutes reperfusion. Demographic and hemodynamic parameters of donors and recipients as well as transplant procedure characteristics were documented. PGD (n=68) was defined as ventricular dilation and hypocontractility associated with systolic blood pressure 20 mm Hg, and decreased mixed venous oxygen saturation necessitating mechanical circulatory support. SMARCAL1 serum protein concentration was significantly increased only before and after ACC in donors ( P

  • Abstract 5848: Serum SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily a-like (SMARCAL)-1 Concentrations Predict Primary Graft Dysfunction in Cardiac Transplant Recipients
    Circulation, 2008
    Co-Authors: Seyedhossein Aharinejad, Olena Andrukhova, Katharina Krenn, Andreas Zuckermann, Daniel Zimpfer, Anita C Thomas, Michael Grimm
    Abstract:

    Primary Graft Dysfunction (PGD) is a life-threatening complication in cardiac transplantation. A sensitive, specific, easily and quickly measurable serum predictor could facilitate PGD prevention a...