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ABSTRACT: BACKGROUND: Several systems have been developed to predict mortality after intensive care unit (ICU) admission in medical and surgical patients. However, a similar tool specific to cardiac surgical patients with prolonged ICU duration does not exist. The purpose of the current study was to identify independent perioperative predictors of operative mortality among cardiac surgical patients with prolonged ICU duration. STUDY DESIGN: From 2003 to 2008, a total of 13,105 cardiac surgical patients with ICU durations >48 hours were identified within a statewide database. Perioperative factors, including Society of Thoracic Surgeons Predicted Risk of Mortality, were evaluated. Univariate and multivariate analyses identified significant correlates of operative mortality and their relative strength of association as determined by the Wald chi-square statistic. RESULTS: Mean patient age was 66.8 ± 11.2 years, median ICU duration was 76.5 hours (range 56.0 to 124.0 hours), and mean Society of Thoracic Surgeons predicted risk of mortality was 4.4% ± 6.2%. Among preoperative and operative factors, intra-aortic balloon pump use, patient age, immunosuppressive therapy, hemodialysis requirement, cardiopulmonary bypass time, and heart failure proved to be the strongest correlates of mortality (all p < 0.05) on risk-adjusted multivariate analysis. Type of cardiac procedure had no significant association with mortality after risk adjustment. Among postoperative complications, cardiac arrest, prolonged mechanical ventilation (>24 hours), and stroke were the strongest predictors of risk-adjusted mortality (all p < 0.001). CONCLUSIONS: Operative mortality can be predicted by select risk factors for cardiac surgical patients with prolonged ICU duration. Patient age, preoperative intra-aortic balloon pump, postoperative cardiac arrest, prolonged ventilation, and stroke have the strongest association with mortality. Identification of these factors in the perioperative setting can enhance resource use and improve mortality after cardiac surgery.
Journal of the American College of Surgeons 04/2013; · 4.55 Impact Factor
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ABSTRACT: BACKGROUND: Fibrocytes are integral in the development of fibroproliferative disease. The CXCL12/CXCR4 chemokine axis has been shown to play a central role in fibrocyte migration and the development of bronchiolitis obliterans (BO) after lung transplantation. Inhibition of the mammalian target of rapamycin (mTOR) pathway with rapamycin has been shown to decrease expression of both CXCR4 and its receptor agonist CXCL12. Thus, we hypothesized that rapamycin treatment would decrease fibrocyte trafficking into tracheal allografts and prevent BO. METHODS: A total alloantigenic mismatch murine heterotopic tracheal transplant (HTT) model of BO was used. Animals were either treated with rapamycin or dimethyl sulfoxide (DMSO) for 14 days after tracheal transplantation. Fibrocyte levels were assessed by flow cytometry, and allograft neutrophil, CD3(+) T-cell, macrophage, and smooth muscle actin (SMA) levels were assessed by immunohistochemistry. Tracheal luminal obliteration was assessed on hematoxylin and eosin (H&E) stains. RESULTS: Compared with DMSO-treated controls, rapamycin-treated mice showed a significant decrease in fibrocyte levels in tracheal allografts. Fibrocyte levels in recipient blood showed a similar pattern, although it was not statistically significant. Furthermore, animals treated with rapamycin showed a significant decrease in tracheal allograft luminal obliteration compared with controls. Based on immunohistochemical analyses, populations of α-SMA-positive (α-SMA(+)) cells, neutrophils, CD3(+) T cells, and macrophages were all decreased in rapamycin-treated allografts versus DMSO controls. CONCLUSIONS: Rapamycin effectively reduces recruitment of fibrocytes into tracheal allografts and mitigates development of tracheal luminal fibrosis. Further studies are needed to determine the cellular and molecular mechanisms that mediate the protective effect of rapamycin against BO.
The Annals of thoracic surgery 04/2013; · 3.74 Impact Factor
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ABSTRACT: BACKGROUND: Severe ischemia-reperfusion (IR) injury leads to primary graft dysfunction after lung transplantation. Adenosine receptors modulate inflammation after IR, and the adenosine A3 receptor (A3R) is expressed in lung tissue and inflammatory cells. This study tests the hypothesis that A3R agonism attenuates lung IR injury by a neutrophil-dependent mechanism. METHODS: Wild-type and A3R knockout (A3R-/-) mice underwent 1-hour left lung ischemia followed by 2-hours reperfusion (IR). A selective A3R agonist, Cl-IB-MECA, was administered (100 μg/kg intravenously) 5 minutes prior to ischemia. Study groups included sham, IR, and IR+Cl-IB-MECA (n = 6/group). Lung injury was assessed by measuring lung function, pulmonery edema, histopathology, and proinflammatory cytokines, and myeloperoxidase levels in bronchoalveolar lavage fluid. Parallel in vitro experiments were performed to evaluate neutrophil chemotaxis, and neutrophil activation was measured after exposure to acute hypoxia and reoxygenation. RESULTS: Treatment of wild-type mice with Cl-IB-MECA significantly improved lung function and decreased edema, cytokine expression, and neutrophil infiltration after IR. The Cl-IB-MECA had no effects in A3R-/- mice; Cl-IB-MECA significantly decreased activation of wild-type, but not A3R-/-, neutrophils after acute hypoxia and reoxygenation and inhibited chemotaxis of wild-type neutrophils. CONCLUSIONS: Exogenous activation of A3R by Cl-IB-MECA attenuates lung dysfunction, inflammation, and neutrophil infiltration after IR in wild-type but not A3R-/- mice. Results with isolated neutrophils suggest that the protective effects of Cl-IB-MECA are due, in part, to the prevention of neutrophil activation and chemotaxis. The use of A3R agonists may be a novel therapeutic strategy to prevent lung IR injury and primary graft dysfunction after transplantation.
The Annals of thoracic surgery 03/2013; · 3.74 Impact Factor
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Damien J Lapar,
Ivan K Crosby,
Gorav Ailawadi,
Niv Ad,
Elmer Choi,
Bruce D Spiess,
Jeffery B Rich,
Vigneshwar Kasirajan,
Edwin Fonner, Irving L Kron,
Alan M Speir
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ABSTRACT: Efforts to reduce blood product use have the potential to avoid transfusion-related complications and reduce health care costs. The purpose of this investigation was to determine whether a multi-institutional effort to reduce blood product use affects postoperative events after cardiac surgical operations and to determine the influence of perioperative transfusion on risk-adjusted outcomes.
A total of 14,259 patients (2006-2010) undergoing nonemergency, primary, isolated coronary artery bypass grafting operations at 17 different statewide cardiac centers were stratified according to transfusion guideline era: pre-guideline (n = 7059, age = 63.7 ± 10.6 years) versus post-guideline (n = 7200, age = 63.7 ± 10.5 years). Primary outcomes of interest were observed differences in postoperative events and mortality risk-adjusted associations as estimated by multiple regression analysis.
Overall intraoperative (24% vs 18%, P < .001) and postoperative (39% vs 33%, P < .001) blood product transfusion were significantly reduced in the post-guideline era. Patients in the post-guideline era demonstrated reduced morbidity with decreased pneumonia (P = .01), prolonged ventilation (P = .05), renal failure (P = .03), new-onset hemodialysis (P = .004), and composite incidence of major complications (P = .001). Operative mortality (1.0% vs 1.8%, P < .001) and postoperative ventilation time (22 vs 26 hours, P < .001) were similarly reduced in the post-guideline era. Of note, after mortality risk adjustment, operations performed in the post-guideline era were associated with a 47% reduction in the odds of death (adjusted odds ratio, 0.57; P < .001), whereas the risk of major complications and mortality were significantly increased after intraoperative (adjusted odds ratio, 1.86 and 1.25; both P < .001) and postoperative (adjusted odds ratio, 4.61 and 4.50, both P < .001) transfusion. Intraoperative and postoperative transfusions were associated with increased adjusted incremental total hospitalization costs ($4408 and $10,479, respectively).
Implementation of a blood use initiative significantly improves postoperative morbidity, mortality, and resource utilization. Limiting intraoperative and postoperative blood product transfusion decreases adverse postoperative events and reduces health care costs. Blood conservation efforts are bolstered by collaboration and guideline development.
The Journal of thoracic and cardiovascular surgery 03/2013; 145(3):796-804. · 3.41 Impact Factor
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ABSTRACT: BACKGROUND: Chronic renal failure after lung transplantation is associated with significant morbidity. However, the significance of acute kidney injury (AKI) after lung transplantation remains unclear and poorly studied. We hypothesized that hemodialysis (HD)-dependent AKI after lung transplantation is associated with significant mortality. MATERIALS AND METHODS: We performed a retrospective review of all patients undergoing lung transplantation from July 1991 to July 2009 at our institution. Recipients with AKI (creatinine > 3 mg/dL) were identified. We compared recipients without AKI versus recipients with and without HD-dependent AKI. Kaplan-Meier survival curves were compared by log rank test. RESULTS: Of 352 lung transplant recipients reviewed at our institution, 17 developed non-HD-dependent AKI (5%) and 16 developed HD-dependent AKI (4.6%). Cardiopulmonary bypass was significantly higher in patients with HD-dependent AKI. None of the recipients who required HD had recovery of renal function. The 30-day mortality was significantly greater in recipients requiring HD (63% versus 0%; P < 0.0001). One-year mortality after transplantation was significantly increased in recipients with HD-dependent AKI compared with those with non-HD-dependent AKI (87.5% versus 17.6%; P < 0.001). CONCLUSIONS: Hemodialysis is associated with mortality after lung transplantation. Fortunately, AKI that does not progress to HD commonly resolves and has a better overall survival. Avoidance, if possible, of cardiopulmonary bypass may attenuate the incidence of AKI. Aggressive measures to identify and treat early postoperative renal dysfunction and prevent progression to HD may improve outcomes after lung transplantation.
Journal of Surgical Research 02/2013; · 2.25 Impact Factor
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Castigliano M Bhamidipati,
Gaurav S Mehta,
Christopher W Moehle,
Akshaya K Meher,
Gang Su,
Navin G Vigneshwar,
Carlos Barbery,
Ashish K Sharma, Irving L Kron,
Victor E Laubach,
Gary K Owens,
Gilbert R Upchurch,
Gorav Ailawadi
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ABSTRACT: Activation of the adenosine 2A receptor (A(2A)R) reduces inflammation in models of acute injury but contribution in development of chronic abdominal aortic aneurysms (AAAs) is unknown. Elastase perfusion to induce AAA formation in A(2A)R-knockout (A(2A)RKO) and C57BL6/J wild-type (WT) mice resulted in nearly 100% larger aneurysms in A(2A)RKO compared to WT at d 14 (P<0.05), with evidence of greater elastin fragmentation, more immune cell infiltration, and increased matrix metallatoproteinase (MMP) 9 expression (P<0.05). Separately, exogenous A(2A)R antagonism in elastase-perfused WT mice also resulted in larger aneurysms (P<0.05), while A(2A)R agonism limited aortic dilatation (P<0.05). Activated Thy-1.2(+) T lymphocytes from WT mice treated in vitro with A(2A)R antagonist increased cytokine production, and treatment with A(2A)R agonist decreased cytokine production (P<0.05 for all). Primary activated CD4(+) T lymphocytes from A(2A)RKO mice exhibited greater chemotaxis (P<0.05). A(2A)R antagonist increased chemotaxis of activated CD4(+) cells from WT mice in vitro, and A(2A)R agonist reduced this effect (P<0.05). A(2A)R activation attenuates AAA formation partly by inhibiting immune cell recruitment and reducing elastin fragmentation. These findings support augmenting A(2A)R signaling as a putative target for limiting aneurysm formation.-Bhamidipati, C. M., Mehta, G. S., Moehle, C. W., Meher, A. K., Su, G., Vigneshwar, N. G., Barbery, C., Sharma, A. K., Kron, I. L., Laubach, V. E., Owens, G. K., Upchurch Jr., G. R., Ailawadi, G. Adenosine 2A receptor modulates inflammation and phenotype in experimental abdominal aortic aneurysms.
The FASEB Journal 02/2013; · 5.71 Impact Factor
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ABSTRACT: Melanoma has a high propensity for cardiac seeding, with heart involvement noted in a significant number of patients at autopsy. Therapeutic options are currently limited, and the prognosis of cardiac metastasis is poor. We report two cases of cardiac metastasis of melanoma and review the current literature. In addition, we propose an algorithm for dealing with this difficult problem.
Journal of Cardiac Surgery 02/2013; · 0.87 Impact Factor
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ABSTRACT: OBJECTIVES: Ischemia-reperfusion injury contributes significantly to morbidity and mortality in lung transplant patients. Currently, no therapeutic agents are clinically available to prevent ischemia-reperfusion injury, and treatment strategies are limited to maintaining oxygenation and lung function. Adenosine can modulate inflammatory activity and injury by binding to various adenosine receptors; however, the role of the adenosine A(1) receptor in ischemia-reperfusion injury and inflammation is not well understood. The present study tested the hypothesis that selective, exogenous activation of the A(1) receptor would be anti-inflammatory and attenuate lung ischemia-reperfusion injury. METHODS: Wild-type and A(1) receptor knockout mice underwent 1 hour of left lung ischemia and 2 hours of reperfusion using an in vivo hilar clamp model. An A(1) receptor agonist, 2-chloro-N6-cyclopentyladenosine, was administered 5 minutes before ischemia. After reperfusion, lung function was evaluated by measuring airway resistance, pulmonary compliance, and pulmonary artery pressure. The wet/dry weight ratio was used to assess edema. The myeloperoxidase and cytokine levels in bronchoalveolar lavage fluid were measured to determine the presence of neutrophil infiltration and inflammation. RESULTS: In the wild-type mice, 2-chloro-N6-cyclopentyladenosine significantly improved lung function and attenuated edema, cytokine expression, and myeloperoxidase levels compared with the vehicle-treated mice after ischemia-reperfusion. The incidence of lung ischemia-reperfusion injury was similar in the A(1) receptor knockout and wild-type mice; and 2-chloro-N6-cyclopentyladenosine had no effects in the A(1) receptor knockout mice. In vitro treatment of neutrophils with 2-chloro-N6-cyclopentyladenosine significantly reduced chemotaxis. CONCLUSIONS: Exogenous A(1) receptor activation improves lung function and decreases inflammation, edema, and neutrophil chemotaxis after ischemia and reperfusion. These results suggest a potential therapeutic application for A(1) receptor agonists for the prevention of lung ischemia-reperfusion injury after transplantation.
The Journal of thoracic and cardiovascular surgery 02/2013; · 3.41 Impact Factor
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ABSTRACT: OBJECTIVES: Orthotopic heart transplantation is the standard of care for end-stage heart disease. Left ventricular assist device implantation offers an alternative treatment approach. Left ventricular assist device practice has changed dramatically since the 2008 Food and Drug Administration approval of the HeartMate II (Thoratec, Pleasanton, Calif), but at what societal cost? The present study examined the cost and efficacy of both treatments over time. METHODS: All patients who underwent either orthotopic heart transplantation (n = 9369) or placement of an implantable left ventricular assist device (n = 6414) from 2005 to 2009 in the Nationwide Inpatient Sample were selected. The trends in treatment use, mortality, and cost were analyzed. RESULTS: The incidence of orthotopic heart transplantation increased marginally within a 5-year period. In contrast, the annual left ventricular assist device implantation rates nearly tripled. In-hospital mortality from left ventricular assist device implantation decreased precipitously, from 42% to 17%. In-hospital mortality for orthotopic heart transplantation remained relatively stable (range, 3.8%-6.5%). The mean cost per patient increased for both orthotopic heart transplantation and left ventricular assist device placement (40% and 17%, respectively). With the observed increase in both device usage and cost per patient, the cumulative Left ventricular assist device cost increased 232% within 5 years (from $143 million to $479 million). By 2009, Medicare and Medicaid were the primary payers for nearly one half of all patients (orthotopic heart transplantation, 45%; left ventricular assist device, 51%). CONCLUSIONS: Since Food and Drug Administration approval of the HeartMate II, mortality after left ventricular assist device implantation has decreased rapidly, yet has remained greater than that after orthotopic heart transplantation. The left ventricular assist device costs have continued to increase and have been significantly greater than those for orthotopic heart transplantation. Because of the evolving healthcare economics climate, with increasing emphasis on the costs and comparative effectiveness, a concerted effort at LVAD cost containment and judicious usage is essential to preserve the viability of this invaluable treatment.
The Journal of thoracic and cardiovascular surgery 12/2012; · 3.41 Impact Factor
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ABSTRACT: OBJECTIVE: This study assessed the impact of pulmonary hypertension (PH) on morbidity and mortality after the most common cardiac operations and evaluated the accuracy of the Society of Thoracic Surgeons (STS) risk model for patients with PH. METHODS: At a single center between 1994 and 2010, all adult cardiac operations performed with recorded preoperative mean pulmonary arterial pressure (MPAP) and STS predicted mortality were reviewed. MPAP was defined as normal (<25 mm Hg) or as mild (25-34 mm Hg), moderate (35-44 mm Hg), or severe (≥45 mm Hg) PH. Multivariate analysis was performed to elucidate the contribution of PH to morbidity and mortality. RESULTS: In all, 3343 patient records were reviewed. Coronary artery bypass grafting (CABG) was the most common procedure (67.5%), followed by aortic valve replacement (24.9%) and mitral valve procedures (6.3%). Postoperative complications and mortality increased with increasing MPAP. Multivariable analysis found that both moderate (odds ratio, 7.17; P < .001) and severe (odds ratio, 13.73; P < .001) PH were significantly associated with increased mortality, even after accounting for STS risk. A subset analysis of isolated CABG cases revealed markedly increased mortality for all categories of PH (mild odds ratio, 1.99; moderate odds ratio, 11.5; severe odds ratio, 38.9; P < .001). CONCLUSIONS: Morbidity and mortality were independently associated with PH. Observed mortality was significantly higher than predicted by the STS model for patients with moderate and severe PH, particularly in isolated CABG. Addition of PH to the STS risk model should be considered, or alternative tools should be used to assess risk in these patients.
The Journal of thoracic and cardiovascular surgery 09/2012; · 3.41 Impact Factor
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Ashish K Sharma,
Guanyi Lu,
Andrea Jester,
William F Johnston,
Yunge Zhao,
Vanessa A Hajzus,
M Reza Saadatzadeh,
Gang Su,
Castigliano M Bhamidipati,
Gaurav S Mehta, Irving L Kron,
Victor E Laubach,
Michael P Murphy,
Gorav Ailawadi,
Gilbert R Upchurch
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ABSTRACT: Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, smooth muscle activation and matrix degradation. This study tests the hypothesis that CD4+ T-cell-produced IL-17 modulates inflammation and smooth muscle cell activation, leading to the pathogenesis of AAA and that human mesenchymal stem cell (MSC) treatment can attenuate IL-17 production and AAA formation.
Human aortic tissue demonstrated a significant increase in IL-17 and IL-23 expression in AAA patients compared with control subjects as analyzed by RT-PCR and ELISA. AAA formation was assessed in C57BL/6 (wild-type; WT), IL-23(-/-) or IL-17(-/-) mice using an elastase-perfusion model. Heat-inactivated elastase was used as control. On days 3, 7, and 14 after perfusion, abdominal aorta diameter was measured by video micrometry, and aortic tissue was analyzed for cytokines, cell counts, and IL-17-producing CD4+ T cells. Aortic diameter and cytokine production (MCP-1, RANTES, KC, TNF-α, MIP-1α, and IFN-γ) was significantly attenuated in elastase-perfused IL-17(-/-) and IL-23(-/-) mice compared with WT mice on day 14. Cellular infiltration (especially IL-17-producing CD4+ T cells) was significantly attenuated in elastase-perfused IL-17(-/-) mice compared with WT mice on day 14. Primary aortic smooth muscle cells were significantly activated by elastase or IL-17 treatment. Furthermore, MSC treatment significantly attenuated AAA formation and IL-17 production in elastase-perfused WT mice.
These results demonstrate that CD4+ T-cell-produced IL-17 plays a critical role in promoting inflammation during AAA formation and that immunomodulation of IL-17 by MSCs can offer protection against AAA formation.
Circulation 09/2012; 126(11 Suppl 1):S38-45. · 14.74 Impact Factor
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ABSTRACT: Medicaid and uninsured populations are a significant focus of current healthcare reform. We hypothesized that outcomes after coronary artery bypass grafting (CABG) in the United States is dependent on primary payer status.
From 2003 to 2007, 1 250 619 isolated CABG operations were evaluated using the Nationwide Inpatient Sample (NIS) database. Patients were stratified by primary payer status: Medicare, Medicaid, uninsured, and private insurance. Hierarchical multiple regression models were applied to assess the effect of primary payer status on postoperative outcomes. Unadjusted mortality for Medicare (3.3%), Medicaid (2.4%), and uninsured (1.9%) patients were higher compared with private insurance patients (1.1%, P<0.001). Unadjusted length of stay was longest for Medicaid patients (10.9±0.04 days) and shortest for private insurance patients (8.0±0.01 days, P<0.001). Medicaid patients accrued the highest unadjusted total costs ($113 380±386, P<0.001). Importantly, after controlling for patient risk factors, income, hospital features, and operative volume, Medicaid (odds ratio, 1.82; P<0.001) and uninsured (odds ratio, 1.62; P<0.001) payer status independently conferred the highest adjusted odds of in-hospital mortality. In addition, Medicaid payer status was associated with the longest adjusted length of stay and highest adjusted total costs (P<0.001).
Medicaid and uninsured payer status confers increased risk adjusted in-hospital mortality for patients undergoing coronary artery bypass grafting operations. Medicaid was further associated with the greatest adjusted length of stay and total costs despite risk factors. Possible explanations include delays in access to care or disparate differences in health maintenance.
Circulation 09/2012; 126(11 Suppl 1):S132-9. · 14.74 Impact Factor
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ABSTRACT: : The Agency for Healthcare Research and Quality and the Leapfrog Group use hospital procedure volume as a quality measure for pancreatic resection (PR), abdominal aortic aneurysm (AAA) repair, esophageal resection (ER), and coronary artery bypass grafting (CABG). However, controversy exists regarding the strength and validity of the evidence for the volume-outcome association. The purpose of this study was to reevaluate the volume-outcome relationship for these procedures.
: Discharge data for 261,412 patients were extracted from the 2008 Nationwide Inpatient Sample. The relationship between hospital procedure volume and mortality was rigorously assessed using hierarchical general linear modeling with restricted cubic splines, adjusted for patient demographics, comorbid disease, and elective procedure status.
: Unadjusted mortality rates were PR (4.7%), AAA (12.7%), ER (5.8%), and CABG (2.2%), and the majority of operations were elective. Hospital procedure volume was not a statistically significant predictor of in-hospital mortality for any of the 4 procedures. Strong predictors of mortality included age, elective procedure status, renal failure, and malnutrition (P < 0.001). Each of the models demonstrated excellent performance in estimating the probability of death.
: Hospital procedure volume is not a significant predictor of mortality for the performance of pancreatectomy, AAA repair, esophagectomy, or CABG. Procedure volume by itself should not be used as a proxy measure for surgical quality. Patient mortality risk is primarily attributable to patient-level characteristics such as age and comorbidity.
Annals of surgery 09/2012; 256(4):606-15. · 7.90 Impact Factor
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ABSTRACT: Ex vivo lung perfusion (EVLP) is a promising modality for the evaluation and treatment of marginal donor lungs. The optimal timing of EVLP initiation and the potential for rehabilitation of donor lungs with extended warm ischemic times is unknown. The present study compared the efficacy of different treatment strategies for uncontrolled non-heart-beating donor lungs.
Mature swine underwent hypoxic arrest, followed by 60 minutes of no-touch warm ischemia. The lungs were harvested and flushed with 4°C Perfadex. Three groups (n = 5/group) were stratified according to the preservation method: cold static preservation (CSP; 4 hours of 4°C storage), immediate EVLP (I-EVLP: 4 hours EVLP at 37°C), and delayed EVLP (D-EVLP; 4 hours of CSP followed by 4 hours of EVLP). The EVLP groups were perfused with Steen solution supplemented with heparin, methylprednisolone, cefazolin, and an adenosine 2A receptor agonist. The lungs then underwent allotransplantation and 4 hours of recipient reperfusion before allograft assessment for resultant ischemia-reperfusion injury.
The donor blood oxygenation (partial pressure of oxygen/fraction of inspired oxygen ratio) before death was not different between the groups. The oxygenation after transplantation was significantly greater in the D-EVLP group than in the I-EVLP or CSP groups. The mean airway pressure, pulmonary artery pressure, and expression of interleukin-8, interleukin-1β, and tumor necrosis factor-α were all significantly reduced in the D-EVLP group. Post-transplant oxygenation exceeded the acceptable clinical levels only in the D-EVLP group.
Uncontrolled non-heart-beating donor lungs with extended warm ischemia can be reconditioned for successful transplantation. The combination of CSP and EVLP in the D-EVLP group was necessary to obtain optimal post-transplant function. This finding, if confirmed clinically, will allow expanded use of nonheart-beating donor lungs.
The Journal of thoracic and cardiovascular surgery 08/2012; 144(5):1208-16. · 3.41 Impact Factor
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ABSTRACT: OBJECTIVES: Loss of epithelial cells is one of the key factors that lead to airway fibrosis. Loss of epithelial cells may decrease the barrier to host cell infiltration into the lumen, allowing deposition of extracellular matrix, with subsequent obliteration of the airway. The objective of this study was to determine whether injection of epithelial cells/progenitor cells from the recipient into the lumen of the donor trachea could prevent bronchiolitis obliterans (BO) in a mouse heterotopic tracheal transplantation (HTT) model. METHODS: A major histocompatibility complex class I and class II mismatch of mouse HTT model of BO was used. Epithelial cells from recipient mice were isolated and reinjected into the lumen of the allografts on day 3 after transplantation. Rag-1 knock-out and isografts were also performed as controls. The grafts were analyzed by immunohistochemistry and densitometric analysis. RESULTS: The results demonstrated that tracheal epithelium was lost by day 3, regenerated between 3 to 7 days, and was lost again in all allografts, but not in the isografts or in Rag-1 knock-out groups by day 12. The reconstituted epithelium was donor originated on day 7 based on green fluorescent protein staining. Furthermore, with the injection of recipient cells into the tracheal lumen, loss of the epithelium was not observed and the luminal obliteration was significantly less in the allografts. CONCLUSIONS: Injection of recipient epithelial cells prevents the second phase of epithelial loss and significantly decreases BO development in an HTT model. Clinically, the use of injected recipient epithelial cells could be a novel treatment for BO.
The Journal of thoracic and cardiovascular surgery 08/2012; · 3.41 Impact Factor
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ABSTRACT: To develop a research productivity scoring program within an academic department of surgery that would help realign incentives to encourage and reward research. Although research is highly valued in the academic mission, financial incentives are generally aligned to reward clinical productivity.
A formula assigning points for publications and extramural grants was created and used to award a research incentive payment proportional to the research productivity score, beginning July 2007. Publication points reflect journal impact factor, author role, and manuscript type. Grant points reflect total funding and percentage of effort. Publication data were gathered from Web of Science/PubMed/Medline and grants data from the departmental grants office. An annual award is presented to the person with the greatest improvement. The research productivity score data after July 2007 were compared with control data for the 2 preceding years. A 33-question survey to 28 clinical faculty was conducted after the first year to measure satisfaction and solicit constructive feedback.
The mean annual point scores increased from the preresearch productivity score to the postresearch productivity score academic years (2180 vs 3389, respectively, P = .08), with a significant change in the grant component score (272 vs 801, P = .03). Since research productivity score implementation, the operative case volumes increased 4.3% from 2006 to 2011. With a response rate of 89%, the survey indicated that 76% of the faculty wished to devote more time to research and 52% believed 1 or more research-related behaviors would change because of the research productivity score program.
An objective, transparent research incentive program, through both monetary incentives and recognition, can stimulate productivity and was well-received by faculty.
The Journal of thoracic and cardiovascular surgery 08/2012; 144(5):1003-9. · 3.41 Impact Factor
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ABSTRACT: Our aim was to establish a novel model of abdominal aortic aneurysms (AAA) in mice using application of peri-adventitial elastase.
C57BL/6J male mice underwent infrarenal peri-adventitial application of either (1) sodium chloride (control; n = 7), (2) porcine pancreatic elastase (PPE; n = 14), or (3) PPE and doxycycline (PPE + doxycycline 200 mg/kg; n = 11) for 14 days. Aortas were analyzed by video micrometry, immunohistochemistry, qualitative polymerase chain reaction, and zymography. Groups underwent Mann-Whitney U comparisons.
At day 14 compared with baseline, control animals had minimal aortic dilation, whereas fusiform aneurysms were seen in PPE (control, 20 ± 3%; PPE, 82 ± 15%; P ≤ .003). Doxycycline abrogated aneurysm formation (PPE, 82 ± 15%; PPE + doxycycline, 37 ± 10%; P ≤ .03). Compared with control and PPE + doxycycline, immunohistochemistry demonstrated greater elastin fiber degradation, macrophage infiltration, and matrix metalloproteinase-9 expression in PPE. Ki-67 and cleaved caspase-3 were lower in control versus PPE. The loss of smooth muscle marker expression seen with PPE was preserved in PPE + doxycycline. Zymography confirmed that both MMP-2 and -9 were more active in PPE than PPE + doxycycline.
Peri-adventitial application of elastase is a simple, reproducible in vivo model of aneurysm formation leading to consistent infrarenal aortic aneurysm development by day 14, with inflammatory cell infiltration and MMP upregulation. Doxycycline inhibits AAA progression in this model via limiting matrix degradation and preserving differentiated smooth muscle cells.
Surgery 08/2012; 152(2):238-46. · 3.10 Impact Factor
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ABSTRACT: OBJECTIVES: Fibrocytes are integral in the development of fibroproliferative disease after lung transplantation. Undifferentiated fibrocytes (CD45+anti-collagen 1+CXCR4+) preferentially traffic by way of the CXCR4/CXCL12 axis and differentiate into smooth muscle actin-producing (CD45+CXCR4+α-smooth muscle actin+) cells. We postulated that an antibody directed against CXCL12 would attenuate fibrocyte migration and fibro-obliteration of heterotopic tracheal transplant allografts. METHODS: A total alloantigenic mismatch murine heterotopic tracheal transplant model of obliterative bronchiolitis was used. The mice were treated with either goat-anti-human CXCL12 F(ab')(2) or goat IgG F(ab')(2). Buffy coat, bone marrow, and trachea allografts were collected and analyzed using flow cytometry. Tracheal luminal obliteration was assessed using hematoxylin-eosin and Direct Red 80 collagen stain. RESULTS: Compared with the controls, the anti-CXCL12-treated mice showed a significant decrease in tracheal allograft fibrocyte populations at 7 and 21 days after transplantation. Bone marrow and buffy coat aspirates showed the same trend at 7 days. In the anti-CXCL12-treated mice, there was a 35% decrease in luminal obliteration at 21 days (65% vs 100% obliterated; interquartile range, 38% vs 10%; P = .010) and decreased luminal collagen deposition at 21 and 28 days after transplantation (P = .042 and P = .012, respectively). CONCLUSIONS: Understanding the role of fibrocytes in airway fibrosis after lung transplantation could lead to a paradigm shift in treatment strategy. Anti-CXCL12 antibody afforded protection against infiltrating fibrocytes and reduced the deterioration of the tracheal allografts. Thus, the CXCR4/CXCL12 axis is a novel target for the treatment of fibro-obliteration after lung transplantation, and the quantification of fibrocyte populations could provide clinicians with a biomarker of fibrosis, allowing individualized drug therapy.
The Journal of thoracic and cardiovascular surgery 05/2012; · 3.41 Impact Factor
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ABSTRACT: Mitral valve (MV) disease is often accompanied by concomitant tricuspid valve (TV) disease. This study determined the influence of performing TV procedures in the setting of MV operations within a multiinstitutional patient population.
From 2001 to 2008, 5,495 MV operations were performed at 17 different statewide centers. Of these, 5,062 patients (age, 63.4 ± 13.0 years) underwent an MV operation and 433 (age, 64.0 ± 14.2 years) underwent combined MV and TV (MV+TV) operations. The influence of concomitant TV procedures on operative death and the composite incidence of major complications was assessed by univariate and multivariate analyses.
Patients undergoing MV+TV were more commonly women (62.7% vs 45.5%, p < 0.001), had higher rates of heart failure (73.7% vs 50.9%, p < 0.001), and more frequently underwent reoperations (17.1% vs 7.4%, p < 0.001) compared with MV patients. Other patient characteristics, including preoperative endocarditis (8.5% vs 8.2%, p = 0.78), were similar between groups. MV replacement (63.5%) was more common than repair (36.5%, p < 0.001) in MV+TV operations, and MV+TV operations incurred longer median cardiopulmonary bypass times (181 vs 149 minutes, p < 0.001). Unadjusted operative mortality (6.0% vs 10.4%, p = 0.001) and postoperative complications were higher after MV+TV compared with MV. More important, risk adjustment showed performance of concomitant TV procedures was an independent predictor of operative death (odds ratio, 1.50; p = 0.03) and major complications (odds ratio, 1.39; p = 0.004).
A concomitant TV operation is a proxy for more advanced valve disease. Compared with MV operations alone, simultaneous MV+TV operations are associated with elevated morbidity and death, even after risk adjustment. This elevated risk should be considered during preoperative patient risk stratification.
The Annals of thoracic surgery 05/2012; 94(1):52-7; discussion 58. · 3.74 Impact Factor
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ABSTRACT: The bidirectional Glenn (BDG) procedure is most commonly used as staged palliation for complex cyanotic congenital heart defects. The benefits of a BDG procedure without the use of cardiopulmonary bypass (CPB) remain mixed within reported series. The purpose of this study was to compare short- and long-term outcomes for performance of a BDG procedure with and without the use of CPB.
From 2001 to 2010, 106 patients underwent a BDG procedure. Patients were stratified into CPB (n = 72; age = 202 days) and non-CPB (n = 34; age = 182 days) groups. Primary outcomes included operative mortality and postoperative complications as well as differences in long-term Kaplan-Meier survival.
Median follow-up was 30 months. Preoperative patient characteristics were similar among patients despite the use of CPB. The most frequent indications for a BDG procedure were hypoplastic left heart syndrome (HLHS) (35.8%) and tricuspid atresia (TA) (17.9%). Median perfusion time was 73 minutes for CPB patients. Overall mortality was 0.9% and no deaths occurred among non-CPB patients (0.0% versus 1.4%; p > 0.99). Similarly, no significant differences existed between non-CPB patients and CPB patients with respect to overall complication rates (11.8% versus 18.1%; p = 0.57) or postoperative length of stay (7.0 [5.0-12.0] versus 7.0 [5.0-11.0] days; p = 0.38). Furthermore, 1-, 3-, and 5-year survival was high and similar between groups.
The BDG procedure can be performed with no significant differences in operative mortality, morbidity, or use of resources, with or without CPB support. Long-term survival after the BDG procedure is high with both strategies. Performance of an off-pump BDG procedure should be considered a safe alternative to the conventional use of CPB for appropriately selected patients.
The Annals of thoracic surgery 05/2012; 94(1):164-70; discussion 170-1. · 3.74 Impact Factor
