Joshua R Sonett

Columbia University, New York City, New York, United States

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Publications (138)612.26 Total impact

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    ABSTRACT: Since the advent of lung transplantation more than 5 decades ago, preoperative, surgical, and anesthetic management have improved. The growing experience with extracorporeal membrane oxygenation (ECMO) has enabled clinicians to expand its effective use to care for patients while bridging them to transplant (BTT). We highlight the approach in which ECMO is used to successfully bridge critically ill patients to lung transplantation when stringent daily clinical assessment is applied. In patients who continued to meet transplant criteria and were successfully transplanted, postoperative survival rates are acceptable. Larger studies are needed to inform decision algorithms for BTT patients and optimize outcomes.
    Thoracic Surgery Clinics 02/2015; 25(1):17-25. DOI:10.1016/j.thorsurg.2014.09.010 · 0.77 Impact Factor
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    ABSTRACT: This study compared differences in patient outcomes and operative parameters for extracorporeal membrane oxygenation (ECMO) versus cardiopulmonary bypass (CPB) in patients undergoing lung transplants. Between January 1, 2008, and July 13, 2013, 316 patients underwent lung transplants at our institution, 102 requiring intraoperative mechanical cardiopulmonary support (CPB, n = 55; ECMO, n = 47). We evaluated survival, blood product transfusions, bleeding complications, graft dysfunction, and rejection. Intraoperatively, the CPB group required more cell saver volume (1123 ± 701 vs 814 ± 826 mL; P = .043), fresh-frozen plasma (3.64 ± 5.0 vs 1.51 ± 3.2 units; P = .014), platelets (1.38 ± 1.6 vs 0.43 ± 1.25 units; P = .001), and cryoprecipitate (4.89 ± 6.3 vs 0.85 ± 2.8 units; P < .001) than the ECMO group. Postoperatively, the CPB group received more platelets (1.09 ± 2.6 vs 0.13 ± 0.39 units; P = .013) and was more likely to have bleeding (15 [27.3%] vs 3 [6.4%]; P = .006) and reoperation (21 [38.2%] vs 7 [14.9%]; P = .009]. The CPB group had higher rates of primary graft dysfunction at 24 and 72 hours (41 [74.5%] vs 23 [48.9%]; P = .008; and 42 [76.4%] vs 26 [56.5%]; P = .034; respectively). There were no differences in 30-day and 1-year survivals. Relative to CPB, the ECMO group required fewer transfusions and had less bleeding, fewer reoperations, and less primary graft dysfunction. There were no statistically significant survival differences at 30 days or 1 year. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
    Journal of Thoracic and Cardiovascular Surgery 11/2014; 148(5):2410-6. DOI:10.1016/j.jtcvs.2014.07.061 · 3.99 Impact Factor
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    ABSTRACT: Rationale:Obesity and underweight are contraindications to lung transplantation based on their associations with mortality in studies performed prior to implementation of the Lung Allocation Score (LAS)-based organ allocation system in the United States. Objectives:To determine the associations of the body mass index(BMI) and plasma leptin levels with survival after lung transplantation. Methods:We used multivariable-adjusted regression models to examine associations between (1) BMI and 1-year mortality in 9,073 adults who underwent lung transplantation in the United States between May 2005 and June 2011, and (2) plasma leptin and mortality in 599 Lung Transplant Outcomes Group study participants. We measured body fat and skeletal muscle mass using whole-body dual x-ray absorptiometry in 142 adult lung transplant candidates. Measurements and Main Results: Adjusted mortality rates were similar among normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9) and Class I obese (BMI 30-34.9) transplant recipients. Underweight (BMI<18.5) was associated with a 35% increased rate of death (95%CI 10-66%). Class II-III obesity (BMI≥35kg/m2) was associated with a nearly 2-fold increase in mortality (HR 1.9, 95%CI 1.3-2.8). Higher leptin levels were associated with increased mortality after transplant surgery performed without cardiopulmonary bypass (p for interaction=0.03). A BMI≥30 kg/m2 was 26% sensitive and 97% specific for total body fat-defined obesity. Conclusions: A BMI of 30.0-34.9kg/m2 is not associated with 1-year mortality after lung transplantation in the LAS era, perhaps due to its low sensitivity for obesity. The association between leptin and mortality suggests the need to validate alternative methods to measure obesity in candidates for lung transplantation. A BMI ≥30kg/m2 may no longer contraindicate lung transplantation.
    American Journal of Respiratory and Critical Care Medicine 09/2014; 190(9). DOI:10.1164/rccm.201405-0973OC · 11.04 Impact Factor
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    ABSTRACT: Lung cancer is a leading cause of mortality, and patients often present at a late stage. More recently, advances in screening, diagnosing, and treating lung cancer have been made. For instance, greater numbers of minimally invasive procedures are being performed, and identification of lung adenocarcinoma driver mutations has led to the implementation of targeted therapies. Advances in molecular techniques enable use of scant tissue, including cytology specimens. In addition, per recently published consensus guidelines, cytology-derived cell blocks (CBs) are preferred over direct smears. Yet, limited comparison of molecular testing of fine-needle aspiration (FNA) CBs and corresponding histology specimens has been performed. This study aimed to establish concordance of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) virus homolog testing between FNA CBs and histology samples from the same patients.
    CytoJournal 05/2014; 11(1):12. DOI:10.4103/1742-6413.132989
    This article is viewable in ResearchGate's enriched format
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    ABSTRACT: Traumatic injury to the aortic valve is an uncommon clinical entity. Rarer still is transport of such a patient using Extracorporeal Membrane Oxygenation (ECMO) to a specialized ECMO center for definitive repair. We present a case of traumatic rupture of the aortic valve complicated by severe ARDS with inter-hospital transport using ECMO and subsequent aortic valve replacement (AVR).
    ASAIO journal (American Society for Artificial Internal Organs: 1992) 03/2014; 60(3). DOI:10.1097/MAT.0000000000000068 · 1.39 Impact Factor
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    ABSTRACT: Inherent recipient factors, including pretransplant diagnosis, obesity and elevated pulmonary pressures, are established primary graft dysfunction (PGD) risks. We evaluated the relationship between preoperative lung injury biomarkers and PGD to gain further mechanistic insight in recipients. We performed a prospective cohort study of recipients in the Lung Transplant Outcomes Group enrolled between 2002 and 2010. Our primary outcome was Grade 3 PGD on Day 2 or 3. We measured preoperative plasma levels of five biomarkers (CC-16, sRAGE, ICAM-1, IL-8 and Protein C) that were previously associated with PGD when measured at the postoperative time point. We used multivariable logistic regression to adjust for potential confounders. Of 714 subjects, 130 (18%) developed PGD. Median CC-16 levels were elevated in subjects with PGD (10.1 vs. 6.0, p < 0.001). CC-16 was associated with PGD in nonidiopathic pulmonary fibrosis (non-IPF) subjects (OR for highest quartile of CC-16: 2.87, 95% CI: 1.37, 6.00, p = 0.005) but not in subjects with IPF (OR 1.38, 95% CI: 0.43, 4.45, p = 0.59). After adjustment, preoperative CC-16 levels remained associated with PGD (OR: 3.03, 95% CI: 1.26, 7.30, p = 0.013) in non-IPF subjects. Our study suggests the importance of preexisting airway epithelial injury in PGD. Markers of airway epithelial injury may be helpful in pretransplant risk stratification in specific recipients.
    American Journal of Transplantation 02/2014; 14(2). DOI:10.1111/ajt.12541 · 6.19 Impact Factor
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    ABSTRACT: Thoracic procurements have traditionally been performed by surgical fellows or attending cardiothoracic surgeons. Donor lung procurement protocols are well established and fairly standardized; however, specific procurement training and judgment are essential to optimizing donor utilization. Although the predicted future deficits of cardiothoracic surgeons are based on a variety of analytic models and scenarios, it appears evident that there will not be a sufficient number of trained cardiothoracic surgeons over the next 2 decades. Over the past 5 years in our institution, lung procurements have been performed by a specifically trained physician assistant; as the lead donor surgeon. This model may serve as a cost effective, reproducible, and safe alternative to using surgical fellows and attending surgeons, assuring continuity, ongoing technical expertise, and teaching while addressing future workforce issues as related to transplant. This is a single institution review of 287 consecutive lung procurements performed by either a physician assistant or fellow over 5 years. This study was approved by the Institutional Review Board of Columbia University, which waived the need for informed consent (IRB#AAAL7107). From 2008 to 2012, fellows served as senior surgeon in 90 cases (31.4%) versus 197 cases (68.6%) by the physician assistant, including 12 Donations after Cardiac Death and 6 reoperative donors. Injury rate was significantly lower for the physician assistant compared with the resident cohort (1 of 197 [0.5%] vs 22 of 90 [24%], respectively). Rates for pulmonary graft dysfunction grade 2 and 3 were found to be significantly lower in cases where the physician assistant served as senior surgeon (combined rates of 32.2% [29 of 90] vs 9.6% [19 of 197] in the physician assistant group) (p < 0.01). Use of experienced physician assistants in donor lung procurements is a safe and viable alternative offering continuity of technical expertise and evaluation of lung allografts.
    The Annals of thoracic surgery 10/2013; DOI:10.1016/j.athoracsur.2013.07.094 · 3.45 Impact Factor
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    ABSTRACT: Lungs from older adult organ donors are often unused because of concerns for increased mortality. We examined associations between donor age and transplant outcomes among 8860 adult lung transplant recipients using Organ Procurement and Transplantation Network and Lung Transplant Outcomes Group data. We used stratified Cox proportional hazard models and generalized linear mixed models to examine associations between donor age and both 1-year graft failure and primary graft dysfunction (PGD). The rate of 1-year graft failure was similar among recipients of lungs from donors age 18-64 years, but severely ill recipients (Lung Allocation Score [LAS] >47.7 or use of mechanical ventilation) of lungs from donors age 56-64 years had increased rates of 1-year graft failure (p-values for interaction = 0.04 and 0.02, respectively). Recipients of lungs from donors <18 and ≥65 years had increased rates of 1-year graft failure (adjusted hazard ratio [HR] 1.23, 95% CI 1.01-1.50 and adjusted HR 2.15, 95% CI 1.47-3.15, respectively). Donor age was not associated with the risk of PGD. In summary, the use of lungs from donors age 56 to 64 years may be safe for adult candidates without a high LAS and the use of lungs from pediatric donors is associated with a small increase in early graft failure.
    American Journal of Transplantation 08/2013; 13(10). DOI:10.1111/ajt.12428 · 6.19 Impact Factor
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    ABSTRACT: The purpose of the study was to assess the efficacy of obtaining adequate cytologic specimens by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for molecular testing of lung adenocarcinomas. This was an institutional review board-approved study of all patients who had undergone EBUS-TBNA from April 2010 through March 2012 for the diagnosis, staging, or both of lung cancer. Patients with a diagnosis of adenocarcinoma were reflexively tested for molecular markers by polymerase chain reaction, sequencing, and fluorescence in situ hybridization (FISH). All procedures were performed with patients under conscious sedation in the bronchoscopy suite. Of 205 patients who underwent EBUS-TBNA, 56 patients (24 male, 32 female) had a diagnosis of adenocarcinoma warranting molecular analysis. Molecular analysis was available for epidermal growth factor receptor (EGFR), Kirsten rat sarcoma (Kras) mutation, and anaplastic lymphoma kinase (ALK) gene rearrangement. The institution's clinical protocol involved initial testing for EGFR mutation with a reflex Kras test if the EGFR test result was negative. ALK FISH molecular testing was completed if both EGFR and Kras test results were negative. A total of 52 of 56 (93%) patients had sufficient cytologic material for complete or partial molecular testing, whereas 46 of 56 (82%) patients had sufficient material for all clinically indicated testing. EGFR, Kras, and ALK analysis yielded positive results in 5 (10%), 10 (25%), and 5 (12%) tested specimens, respectively. No complications were associated with EBUS-TBNA. EBUS-TBNA performed with the patient under moderate sedation can be expected to yield sufficient tissue for sequential molecular analysis in the majority of patients. In an era of targeted therapy for lung adenocarcinomas, EBUS-TBNA is effective in clinical practice for complete diagnosis, staging, and treatment planning in these patients.
    The Annals of thoracic surgery 08/2013; 96(4). DOI:10.1016/j.athoracsur.2013.05.066 · 3.45 Impact Factor
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    ABSTRACT: The only definitive treatment for end-stage organ failure is orthotopic transplantation. Lung extracellular matrix (LECM) holds great potential as a scaffold for lung tissue engineering because it retains the complex architecture, biomechanics, and topologic specificity of the lung. Decellularization of human lungs rejected from transplantation could provide "ideal" biologic scaffolds for lung tissue engineering, but the availability of such lungs remains limited. The present study was designed to determine whether porcine lung could serve as a suitable substitute for human lung to study tissue engineering therapies. Human and porcine lungs were procured, sliced into sheets, and decellularized by three different methods. Compositional, ultrastructural, and biomechanical changes to the LECM were characterized. The suitability of LECM for cellular repopulation was evaluated by assessing the viability, growth, and metabolic activity of human lung fibroblasts, human small airway epithelial cells, and human adipose-derived mesenchymal stem cells over a period of 7 days. Decellularization with 3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) showed the best maintenance of both human and porcine LECM, with similar retention of LECM proteins except for elastin. Human and porcine LECM supported the cultivation of pulmonary cells in a similar way, except that the human LECM was stiffer and resulted in higher metabolic activity of the cells than porcine LECM. Porcine lungs can be decellularized with CHAPS to produce LECM scaffolds with properties resembling those of human lungs, for pulmonary tissue engineering. We propose that porcine LECM can be an excellent screening platform for the envisioned human tissue engineering applications of decellularized lungs.
    The Annals of thoracic surgery 07/2013; DOI:10.1016/j.athoracsur.2013.04.022 · 3.45 Impact Factor
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    ABSTRACT: Chronic lung allograft dysfunction (CLAD) is the major factor limiting long-term success of lung transplantation. Polymorphisms of surfactant protein D (SP-D), an important molecule within lung innate immunity, have been associated with various lung diseases. We investigated the association between donor lung SP-D polymorphisms and posttransplant CLAD and survival in 191 lung transplant recipients consecutively transplanted. Recipients were prospectively followed with routine pulmonary function tests. Donor DNA was assayed by pyrosequencing for SP-D polymorphisms of two single-nucleotide variations altering amino acids in the mature protein N-terminal domain codon 11 (Met(11) Thr), and in codon 160 (Ala(160) Thr) of the C-terminal domain. CLAD was diagnosed in 88/191 patients, and 60/191 patients have died. Recipients of allografts that expressed the homozygous Met(11) Met variant of aa11 had significantly greater freedom from CLAD development and better survival compared to those with the homozygous Thr(11) Th variant of aa11. No significant association was noted for SP-D variants of aa160. Lung allografts with the SP-D polymorphic variant Thr(11) Th of aa11 are associated with development of CLAD and reduced survival. The observed genetic differences of the donor lung, potentially with their effects on innate immunity, may influence the clinical outcomes after lung transplantation.
    American Journal of Transplantation 07/2013; 13(8). DOI:10.1111/ajt.12326 · 6.19 Impact Factor
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    ABSTRACT: Our group has hypothesized that the frailty phenotype might help identify those at high risk of early complications after lung transplantation. The prevalence of pre-transplant frailty among transplant recipients and the impact of frailty on outcomes after transplantation is not known.Methods and MaterialsWe performed an interim analysis of the first 46 consecutive lung transplant recipients ≥50 years old enrolled in the Lung Transplant Body Composition (LTBC) study at our center. All LTBC participants undergo a structured frailty assessment during transplant evaluation. Frailty was defined as the presence of ≥3 of the following: unintentional weight loss ≥ 4.5kg, low walking speed, self-reported exhaustion, low activity level, and low grip strength. Wilcoxon rank sum tests, Chi-square tests, Fisher’s exact tests, and log-rank tests were used to compare frail and non-frail participants.ResultsThe mean (SD) age was 62 (5) yrs, 34% were ≥ 65 yrs, 44% were female, 13% were African-American, 54% had ILD, 14% had COPD, 2% had CF, 4% were underweight, 13% were obese, the median LAS was 42 (IQR 33 to 51), 48% were bilateral, and 11 (24%) were frail. Frail recipients were more frequently African-American (37% vs. 6%, p = 0.02) but were similar with regard to age, gender, BMI, diagnosis, LAS score, PA pressure, and use of cardiopulmonary bypass. There were non-significant trends toward more intraoperative complications (28% vs 6%, p = 0.08), postoperative complications (64% vs 37%, p = 0.17), unplanned returns to the OR (18% vs 6%, p = 0.24), and deaths on the ventilator (18% vs 2%, p = 0.14) among frail vs non-frail recipients, respectively. The 30-day mortality rate was 18% among frail and 0% among non-frail (p = 0.01).Conclusions The frail phenotype is prevalent among lung transplant recipients over 50 years old at our center and is not associated with diagnosis or LAS score. Our finding of an unadjusted association of frailty with poor outcomes should be interpreted cautiously. These findings merit additional study.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S119-S120. DOI:10.1016/j.healun.2013.01.256 · 5.61 Impact Factor
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    ABSTRACT: BACKGROUND: Under the current lung allocation system, if organs are accepted for a candidate within the local donor service area (DSA), they are never offered to candidates at the broader regional level who are potentially more severely ill, even if the nonlocal candidate has a higher lung allocation score (LAS). The purpose of this study was to determine the frequency with which organs were allocated to a local lung recipient while a blood group-matched and size-matched candidate with a higher LAS existed in the same region. METHODS: United Network for Organ Sharing (UNOS) provided deidentified patient-level data. The study population included all locally allocated organs for double-lung transplants (DLTs) performed in 2009 in the United States (n = 580). All occurrences of an ABO blood group-matched, height-matched (± 10 cm), double-lung candidate in the same region, with a higher LAS than the local candidate who actually received the organs, were calculated; these occurrences were termed events. RESULTS: In 2009, 3,454 events occurred when a local DLT recipient candidate received a DLT while a DLT candidate in the same region had a higher LAS. With a mean of 5.96 events per transplant, this impacted 480 (82.8%) of the 580 DLTs. Further, 555 (16.1%) of these events involved 1 (or more) of the 185 regional candidates who ultimately did not receive transplants and died while on the waiting list. CONCLUSIONS: This analysis suggests that the locally based lung allocation system results in a high frequency of events whereby an organ is allocated to a lower-priority candidate while an appropriately matched higher priority candidate exists regionally.
    The Annals of thoracic surgery 01/2013; DOI:10.1016/j.athoracsur.2012.11.070 · 3.45 Impact Factor
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    ABSTRACT: Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K(+) channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders.
    01/2013; 49:112-24. DOI:10.1540/jsmr.49.112
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    ABSTRACT: Venovenous extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients with primary respiratory failure. Venovenous ECMO can be initiated through a single-site, dual-lumen cannula designed for insertion in the right internal jugular vein. We describe four cases of hypercapnic or hypoxemic respiratory failure, in which we performed single-site cannulation of the left internal jugular vein with 23 Fr or 27 Fr bicaval dual-lumen catheters when the right internal jugular vein was inaccessible because of either stenosis or thrombosis. The surgical approach for left-sided access is similar to the approach used for the right internal jugular vein. The left-sided approach resulted in equivalent blood flow and gas exchange compared with our previous experience with right-sided cannulation. This case series demonstrates the feasibility of placing a bicaval dual-lumen catheter in the left internal jugular vein for the initiation of venovenous ECMO when the right internal jugular vein is inaccessible.
    ASAIO journal (American Society for Artificial Internal Organs: 1992) 10/2012; 58(6). DOI:10.1097/MAT.0b013e31826feda5 · 1.39 Impact Factor
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    ABSTRACT: SESSION TYPE: DVT/PE/Pulmonary Hypertension Posters IIPRESENTED ON: Wednesday, October 24, 2012 at 01:30 PM - 02:30 PMPURPOSE: Pulmonary arterial hypertension (PAH) is a rapidly progressive disease with significant morbidity and mortality, particularly when refractory to medical therapy or during acute decompensation; these patients may require lung transplantation but often die waiting. We describe a single center experience of 3 patients with severe group 1 PAH, refractory to targeted medical therapy, in which awake ECMO was successfully used as a bridge to recovery or lung transplantation.METHODS: Patient #1, a 22 year-old woman with severe PAH and an atrial septal defect (ASD), had progressive right heart failure and hypoxemic respiratory failure associated with hemoptysis, despite maximal PAH therapy. Venovenous ECMO was initiated with catheter-directed blood flow across the ASD via the internal jugular vein as bridge to transplantation. Patient #2, a 22 year-old woman with surgically corrected transposition of the great vessels and PAH, developed an acute respiratory infection leading to refractory hypoxemic respiratory failure. She was placed on upper-body venoarterial ECMO as bridge to recovery. Patient #3, a 34 year-old woman with PAH and decompensated right heart failure despite maximal PAH therapy, was placed on upper-body venoarterial ECMO as bridge to transplantation.RESULTS: All 3 patients were extubated within 24 hours of ECMO initiation. The upper-body ECMO configuration allowed for daily physical therapy, including ambulation of up to 2400 feet. Patient #1 underwent lung transplantation on ECMO day #7 and is now 18 months post-transplant and fully independent. Patient #2 recovered from her acute illness, was decannulated after 8 days using IV epoprostenol to bridge off ECMO, and remains only on oral therapy. Patient #3 underwent lung transplantation on ECMO day #19 and is expected to fully recover.CONCLUSIONS: We demonstrate the feasibility of awake upper-body ECMO to bridge PAH patients to recovery or lung transplantation when optimal medical therapy fails. An upper-body configuration facilitates physical therapy, preventing deconditioning and optimizing transplant candidacy.CLINICAL IMPLICATIONS: Awake ECMO should be considered in cases of refractory PAH in whom recovery or transplantation is anticipated.DISCLOSURE: Daniel Brodie: Grant monies (from industry related sources): Daniel Brodie has research support from Maquet Cardiovascular including travel awards to research meetingsMatthew Bacchetta: Grant monies (from industry related sources): Matthew Bacchetta has research support from Maquet Cardiovascular including travel awards to research meetingsThe following authors have nothing to disclose: Darryl Abrams, Erika Rosenzweig, Cara Agerstrand, Joshua SonettNo Product/Research Disclosure InformationColumbia University Medical Center, New York, NY.
    Chest 10/2012; 142(4_MeetingAbstracts):843A. DOI:10.1378/chest.1389300 · 7.13 Impact Factor
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    ABSTRACT: Monocyte chemotactic protein-1 (MCP-1), also known as "chemokine ligand 2" (CCL2), is a monocyte-attracting chemokine produced in lung epithelial cells. We previously reported an association of increased levels of plasma MCP-1 with primary graft dysfunction (PGD) after lung transplantation in a nested case-control study of extreme phenotypes using a multiplex platform. In this study, we sought to evaluate the role of plasma MCP-1 level as a biomarker across the full spectrum of PGD. We performed a prospective cohort study of 108 lung transplant recipients within the Lung Transplant Outcomes Group cohort. Plasma MCP-1 levels were measured pretransplantation and 6 and 24 hours after transplantation. The primary outcome was development of grade 3 PGD within 72 hours of transplant, with secondary analyses at the 72-hour time point. Multivariable logistic regression was used to evaluate confounding. Thirty subjects (28%) developed PGD. Median MCP-1 measured at 24 hours post-transplant was elevated in subjects with PGD (167.95 vs 103.5 pg/mL, P = .04). MCP-1 levels at 24 hours were associated with increased odds of grade 3 PGD after lung transplantation (odds ratio for each 100 pg/mL, 1.24; 95% confidence interval, 1.00-1.53) and with grade 3 PGD present at the 72-hour time point (odds ratio for each 100 pg/mL, 1.57; 95% confidence interval, 1.18-2.08), independent of confounding variables in multivariable analyses. MCP-1 levels measured preoperatively and 6 hours after transplant were not significantly associated with PGD. Persistent elevations in MCP-1 levels at 24 hours are a biomarker of grade 3 PGD post-transplantation. Monocyte chemotaxis may play a role in the pathogenesis of PGD.
    09/2012; 160(6). DOI:10.1016/j.trsl.2012.08.003
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    ABSTRACT: Femoral artery cannulation for venoarterial extracorporeal membrane oxygenation (ECMO) can be associated with ischemic and neurologic complications. The subclavian artery offers an alternative cannulation site, which is helpful in patients with peripheral vascular disease, in those who have sustained pelvic trauma, or when ambulation is anticipated. This is a single-institution review of 20 adults who were placed on venoarterial ECMO using subclavian arterial cannulation over a 2 year period. Technical success with subclavian venoarterial ECMO was 100%. Median ECMO time was 168 hours (2.4-720 hours). Sufficient flows (median 4.24 L/min), oxygenation (median postcannulation PaO2 315 mm Hg), and ventricular unloading confirmed with intraoperative transesophageal echocardiogram were achieved in all patients. Seventy-five percent of patients were decannulated, 50% were extubated, and 45% were discharged. Seven patients (35%) had an entirely upper body ECMO configuration with the internal jugular vein serving as the venous drainage site. Complications included arterial cannula site hematoma and infection, as well as ipsilateral arm swelling. Each required conversion to femoral artery cannulation. There were no ischemic or neurologic complications. Patients with acute cardiopulmonary failure can safely be placed on subclavian venoarterial ECMO for prolonged periods with full flows, adequate oxygenation, and sufficient ventricular unloading.
    ASAIO journal (American Society for Artificial Internal Organs: 1992) 08/2012; 58(5):494-8. DOI:10.1097/MAT.0b013e318268ea15 · 1.39 Impact Factor
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    ABSTRACT: Rationale: Elevated long pentraxin-3 (PTX3) levels are associated with the development of primary graft dysfunction (PGD) after lung transplantation. Abnormalities in innate immunity, mediated by PTX3 release, may play a role in PGD pathogenesis. Objectives: Our goal was to test whether variants in the gene encoding PTX3 are risk factors for PGD. Methods: We performed a candidate gene association study in recipients from the multicenter, prospective Lung Transplant Outcomes Group cohort enrolled between July 2002 and July 2009. The primary outcome was International Society for Heart and Lung Transplantation grade 3 PGD within 72 hours of transplantation. Targeted genotyping of 10 haplotype-tagging PTX3 single-nucleotide polymorphisms (SNPs) was performed in lung transplant recipients. The association between PGD and each SNP was evaluated by logistic regression, adjusting for pretransplantation lung disease, cardiopulmonary bypass use, and population stratification. The association between SNPs and plasma PTX3 levels was tested across genotypes in a subset of recipients with idiopathic pulmonary fibrosis. Measurements and Main Results: Six hundred fifty-four lung transplant recipients were included. The incidence of PGD was 29%. Two linked 5' region variants, rs2120243 and rs2305619, were associated with PGD (odds ratio, 1.5; 95% confidence interval, 1.1 to 1.9; P = 0.006 and odds ratio, 1.4; 95% confidence interval, 1.1 to 1.9; P = 0.007, respectively). The minor allele of rs2305619 was significantly associated with higher plasma PTX3 levels measured pretransplantation (P = 0.014) and at 24 hours (P = 0.047) after transplantation in patients with idiopathic pulmonary fibrosis. Conclusions: Genetic variants of PTX3 are associated with PGD after lung transplantation, and are associated with increased PTX3 plasma levels.
    American Journal of Respiratory and Critical Care Medicine 07/2012; 186(6):546-552. DOI:10.1164/rccm.201204-0692OC · 11.04 Impact Factor
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    ABSTRACT: Respiratory failure develops in many patients on lung transplant waiting lists before a suitable donor organ becomes available. Extracorporeal membrane oxygenation may be used to bridge such patients to recovery or lung transplantation. This is a review of a single-institution's experience with placing patients on extracorporeal membrane oxygenation with the intention of bridging them to lung transplantation. End points included successful bridging, duration of extracorporeal membrane oxygenation support, extubation, weaning from extracorporeal membrane oxygenation, overall survival, and extracorporeal membrane oxygenation-related complications. During an approximate 5-year period, acute respiratory failure developed in 18 patients (median age, 34 years) on the institution's lung transplant waiting list (8 hypoxemic, 9 hypercarbic, and 1 combined) who were placed on extracorporeal membrane oxygenation (13 venovenous and 5 venoarterial). All patients achieved appropriate extracorporeal membrane oxygenation blood flow rates (median, 4.05 L/min) and good gas exchange (median, on extracorporeal membrane oxygenation partial pressure of arterial carbon dioxide 43 mm Hg and partial pressure of arterial oxygen 196 mm Hg). Thirteen patients (72%) were successfully bridged: 10 to transplant and 3 returned to baseline function. Eleven patients (61%) survived beyond 3 months, including the 10 (56%) who underwent transplantation and are still alive. The median duration of extracorporeal membrane oxygenation support for patients who underwent transplantation was 6 days (3.5-31 days) versus 13.5 days (11-19 days) for those who did not undergo transplantation (P = .45). Six patients (33%) were extubated on extracorporeal membrane oxygenation, 4 of whom underwent transplantation. Four patients (22%) who were too unstable for conventional interhospital transfer were transported on extracorporeal membrane oxygenation to Columbia University Medical Center. This subgroup had a 75% bridge to transplant or recovery rate and 100% survival in transplanted patients. Extracorporeal membrane oxygenation is a safe and effective means of bridging well-selected patients with refractory respiratory failure to lung transplantation or return to their baseline condition.
    The Journal of thoracic and cardiovascular surgery 07/2012; 144(3):716-21. DOI:10.1016/j.jtcvs.2012.05.040 · 3.41 Impact Factor

Publication Stats

2k Citations
612.26 Total Impact Points


  • 2004–2014
    • Columbia University
      • • Department of Surgery
      • • Department of Pediatrics
      • • College of Physicians and Surgeons
      • • Department of Medicine
      • • Department of Epidemiology
      New York City, New York, United States
  • 2003–2014
    • New York Presbyterian Hospital
      • • Department of Thoracic Surgery
      • • Department of Cardiothoracic Surgery
      • • Department of Pain Medicine
      New York City, New York, United States
  • 2012
    • University of Pennsylvania
      • Division of Pulmonary, Allergy and Critical Care
      Philadelphia, PA, United States
    • University of Kentucky
      • Department of Surgery
      Lexington, Kentucky, United States
  • 2003–2012
    • CUNY Graduate Center
      New York City, New York, United States
  • 2011
    • The University of Chicago Medical Center
      • Section of Thoracic Surgery
      Chicago, Illinois, United States
    • Duke University Medical Center
      • Division of Cardiovascular and Thoracic Surgery
      Durham, NC, United States
    • College of Physicians and Surgeons of British Columbia
      ノースヨーク, Ontario, Canada
  • 2006
    • Mount Sinai School of Medicine
      • Department of Medicine
      Manhattan, NY, United States
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 1998–2002
    • University of Maryland, Baltimore
      • • Department of Radiation Oncology
      • • Department of Surgery
      Baltimore, Maryland, United States
  • 1999
    • University of Maryland Medical Center
      • Greenebaum Cancer Center
      Baltimore, Maryland, United States
    • Loyola University Maryland
      Baltimore, Maryland, United States