Robert C Robbins

Stanford Medicine, Stanford, California, United States

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Publications (405)1984.46 Total impact

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    ABSTRACT: Surgical myectomy and alcohol septal ablation (ASA) aim to decrease left ventricular outflow tract (LVOT) gradient in hypertrophic cardiomyopathy (HCM). Outcome of myectomy beyond 10 years has rarely been described. We describe 20 years of follow-up of surgical myectomy and 5 years of follow-up for ASA performed for obstructive HCM.
    Journal of cardiology. 09/2014;
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    ABSTRACT: Despite the introduction of antiproliferative drug-eluting stents, coronary heart disease remains the leading cause of death in the United States. In-stent restenosis and bypass graft failure are characterized by excessive smooth muscle cell (SMC) proliferation and concomitant myointima formation with luminal obliteration. Here we show that during the development of myointimal hyperplasia in human arteries, SMCs show hyperpolarization of their mitochondrial membrane potential (ΔΨm) and acquire a temporary state with a high proliferative rate and resistance to apoptosis. Pyruvate dehydrogenase kinase isoform 2 (PDK2) was identified as a key regulatory protein, and its activation proved necessary for relevant myointima formation. Pharmacologic PDK2 blockade with dichloroacetate or lentiviral PDK2 knockdown prevented ΔΨm hyperpolarization, facilitated apoptosis and reduced myointima formation in injured human mammary and coronary arteries, rat aortas, rabbit iliac arteries and swine (pig) coronary arteries. In contrast to several commonly used antiproliferative drugs, dichloroacetate did not prevent vessel re-endothelialization. Targeting myointimal ΔΨm and alleviating apoptosis resistance is a novel strategy for the prevention of proliferative vascular diseases.
    Nature 04/2014; · 38.60 Impact Factor
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    ABSTRACT: Various in vivo laboratory rodent models for the induction of artery stenosis have been established to mimic diseases that include arterial plaque formation and stenosis, as observed for example in ischemic heart disease. Two highly reproducible mouse models - both resulting in artery stenosis but each underlying a different pathway of development - are introduced here. The models represent the two most common causes of artery stenosis; namely one mouse model for each myointimal hyperplasia, and atherosclerosis are shown. To induce myointimal hyperplasia, a balloon catheter injury of the abdominal aorta is performed. For the development of atherosclerotic plaque, the ApoE -/- mouse model in combination with western fatty diet is used. Different model-adapted options for the measurement and evaluation of the results are named and described in this manuscript. The introduction and comparison of these two models provides information for scientists to choose the appropriate artery stenosis model in accordance to the scientific question asked.
    Journal of visualized experiments : JoVE. 01/2014;
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    ABSTRACT: Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design.
    Journal of Experimental Medicine 10/2013; · 13.21 Impact Factor
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    ABSTRACT: ABSTRACT Aim: In this study, we target the hypoxia inducible factor-1 alpha (HIF-1-alpha) pathway by short hairpin RNA (shRNA) interference therapy targeting prolyl hydroxylase-2 (shPHD2). We use the minicircle (MC) vector technology as an alternative for conventional nonviral plasmid (PL) vectors in order to improve neovascularization after unilateral hindlimb ischemia in a murine model. Methods and Results: Gene expression and transfection efficiency of MC and PL, both in vitro and in vivo, were assessed using bioluminescence imaging (BLI) and firefly Luciferase (Luc) reporter gene. C57Bl6 mice underwent unilateral electro-coagulation of the femoral artery and gastrocnemic muscle injection with MC-shPHD2, PL-shPHD2, or PBS as control. Blood flow recovery (BFR) was monitored using Laser Doppler Perfusion Imaging (LDPI), and collaterals were visualized by immunohistochemistry and angiography. MC-Luc showed a 4.6-fold higher in vitro BLI signal compared to PL-Luc. BLI signals in vivo were 4.3x105±3.3x105 (MC-Luc) versus 0.4x105±0.3x105 (PL-Luc) at day 28 (p=0.016). Compared to PL-shPHD2 or PBS, MC-shPHD2 significantly improved BFR, up to 50% from day 3 until day 14 after ischemia-induction. MC-shPHD2 significantly increased collateral density and capillary density, as monitored by alpha-smooth muscle actin (α-SMA) expression and CD31+ expression, respectively (CD31+: 40.3 MC-shPHD2 versus 18.1 PL-shPHD2 and 11.8 PBS). Angiography data confirmed the histological findings. Significant downregulation of PHD2 mRNA levels by MC-shPHD2 was confirmed by quantitative PCR (qPCR). Finally, Western blot analysis confirmed significant higher levels of HIF-1-alpha protein by MC-shPHD2, compared to PL-shPHD2 and PBS. Conclusions: This study provides initial evidence of a new potential therapeutic approach for peripheral artery disease (PAD). The combination of HIF-1-alpha pathway targeting by shPHD2 with the robust nonviral MC plasmid improved post-ischemic neovascularization, making this approach a promising potential treatment option for critical limb ischemia.
    Human gene therapy 10/2013; · 4.20 Impact Factor
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    ABSTRACT: Background—Drug-induced arrhythmia is one of the most common causes of drug development failure and withdrawal from market. This study tested whether human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) combined with a low-impedance microelectrode array (MEA) system could improve on industry-standard preclinical cardiotoxicity screening methods, identify the effects of well-characterized drugs, and elucidate underlying risk factors for drug-induced arrhythmia. hiPSC-CMs may be advantageous over immortalized cell lines because they possess similar functional characteristics as primary human cardiomyocytes and can be generated in unlimited quantities. Methods and Results—Pharmacological responses of beating embryoid bodies exposed to a comprehensive panel of drugs at 65 to 95 days postinduction were determined. Responses of hiPSC-CMs to drugs were qualitatively and quantitatively consistent with the reported drug effects in literature. Torsadogenic hERG blockers, such as sotalol and quinidine, produced statistically and physiologically significant effects, consistent with patch-clamp studies, on human embryonic stem cell–derived cardiomyocytes hESC-CMs. False-negative and false-positive hERG blockers were identified accurately. Consistent with published studies using animal models, early afterdepolarizations and ectopic beats were observed in 33% and 40% of embryoid bodies treated with sotalol and quinidine, respectively, compared with negligible early afterdepolarizations and ectopic beats in untreated controls. Conclusions—We found that drug-induced arrhythmias can be recapitulated in hiPSC-CMs and documented with low impedance MEA. Our data indicate that the MEA/hiPSC-CM assay is a sensitive, robust, and efficient platform for testing drug effectiveness and for arrhythmia screening. This system may hold great potential for reducing drug development costs and may provide significant advantages over current industry standard assays that use immortalized cell lines or animal models.
    Circulation Arrhythmia Surgery. 09/2013;
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    ABSTRACT: The efficacy and safety of cardiac gene therapy depend critically on the level and the distribution of therapeutic gene expression following vector administration. We aimed to develop a titratable two-step transcriptional amplification (tTSTA) vector strategy, which allows modulation of transcriptionally targeted gene expression in the myocardium. We constructed a tTSTA plasmid vector (pcTnT-tTSTA-fluc), which uses the cardiac troponin T (cTnT) promoter to drive the expression of the recombinant transcriptional activator GAL4-mER(LBD)-VP2, whose ability to transactivate the downstream firefly luciferase reporter gene (fluc) depends on the binding of its mutant estrogen receptor (ERG521T) ligand binding domain (LBD) to an ER ligand such as raloxifene. Mice underwent either intramyocardial or hydrodynamic tail vein (HTV) injection of pcTnT-tTSTA-fluc, followed by differential modulation of fluc expression with varying doses of intraperitoneal raloxifene prior to bioluminescence imaging to assess the kinetics of myocardial or hepatic fluc expression. Intramyocardial injection of pcTnT-tTSTA-fluc followed by titration with intraperitoneal raloxifene led to up to tenfold induction of myocardial fluc expression. HTV injection of pcTnT-tTSTA-fluc led to negligible long-term hepatic fluc expression, regardless of the raloxifene dose given. The tTSTA vector strategy can effectively modulate transgene expression in a tissue-specific manner. Further refinement of this strategy should help maximize the benefit-to-risk ratio of cardiac gene therapy.
    Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 08/2013; · 2.47 Impact Factor
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    ABSTRACT: Rationale: Human embryonic stem cell (hESC) derivatives are attractive candidates for therapeutic use. The engraftment and survival of hESC derivatives as xenografts or allografts require effective immunosuppression to prevent immune cell infiltration and graft destruction. Objective: To test the hypothesis that a short-course, dual-agent regimen of two costimulation-adhesion blockade agents can induce better engraftment of hESC derivatives compared to current immunosuppressive agents. Methods and Results: We transduced hESCs with a double fusion reporter gene construct expressing firefly luciferase (Fluc) and enhanced green fluorescent protein (eGFP), and differentiated these cells to endothelial cells (hESC-ECs). Reporter gene expression enabled longitudinal assessment of cell engraftment by bioluminescence imaging (BLI). Costimulation-adhesion therapy resulted in superior hESC-EC and mouse EC engraftment compared to cyclosporine therapy in a hindlimb model. Costimulation-adhesion therapy also promoted robust hESC-EC and hESC-derived cardiomyocyte (hESC-CM) survival in an ischemic myocardial injury model. Improved hESC-EC engraftment had a cardioprotective effect after myocardial injury, as assessed by magnetic resonance imaging (MRI). Mechanistically, costimulation-adhesion therapy is associated with systemic and intra-graft upregulation of T cell immunoglobulin and mucin domain 3 (TIM3) and a reduced pro-inflammatory cytokine profile. Conclusions: Costimulation-adhesion therapy is a superior alternative to current clinical immunosuppressive strategies for preventing the post-transplant rejection of hESC derivatives. By extending the window for cellular engraftment, costimulation-adhesion therapy enhances functional preservation following ischemic injury. This regimen may function through a TIM3-dependent mechanism. Stem Cells 2013.
    Stem Cells 08/2013; · 7.70 Impact Factor
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    ABSTRACT: Hypoxia-inducible factor-1 alpha (HIF-1α) gene therapy holds great promise for the treatment of myocardial ischemia. Both pre-clinical and clinical evaluations of this therapy are underway, and can benefit from a vector strategy that allows noninvasive assessment of HIF-1α expression as an objective measure of gene delivery. We have developed a novel bi-directional plasmid vector (pcTnT-HIF-1α-VP2-TSTA-fluc), which employs the cardiac troponin T (cTnT) promoter in conjunction with a two-step transcriptional amplification (TSTA) system to drive the linked expression of a recombinant HIF-1α gene (HIF-1α-VP2) and the firefly luciferase gene (fluc). The firefly luciferase (FLuc) activity serves as a surrogate for HIF-1α-VP2 expression, and can be noninvasively assessed in mice using bioluminescence imaging following vector delivery. Transfection of cultured HL-1 cardiomyocytes with pcTnT-HIF-1α-VP2-TSTA-fluc led to a strong correlation between FLuc and HIF-1α-dependent vascular endothelial growth factor expression ( r <sup>2</sup>=0.88). Intramyocardial delivery of pcTnT-HIF-1α-VP2-TSTA-fluc into infarcted mouse myocardium led to persistent HIF-1α-VP2 expression for 4 weeks, even though it improved neither CD31+ microvessel density nor echocardiographically determined left ventricular systolic function. These results lend support to recent findings of suboptimal efficacy associated with plasmid-mediated HIF-1α therapy. The imaging techniques developed herein should be useful for further optimizing HIF-1α-VP2 therapy in pre-clinical models of myocardial ischemia.
    Human Gene Therapy Methods 08/2013; · 4.02 Impact Factor
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    ABSTRACT: Mesenchymal stromal cells (MSCs) have been isolated from many tissues including gestational tissue. To date a study comparing the properties and suitability of these cells in cell-based therapies is lacking. In this study we compared the phenotype, proliferation rate, migration, immunogenicity, and immunomodulatory capabilities of human MSCs derived from umbilical cord lining (CL-MSC), umbilical cord blood (CB-MSC), placenta (P-MSC), and Wharton´s jelly (WJ-MSC). Differences were noted in differentiation, proliferation, and migration, with CL-MSCs showing the highest proliferation and migration rates resulting in prolonged survival in immunodeficient mice. Moreover, CL-MSCs showed a prolongation in survival in xenogeneic BALB/c mice which was attributed to their ability to dampen TH1 and TH2 responses. Weaker human cellular immune responses were detected against CL-MSCs and P-MSCs, which were correlated with their lower HLA I expression. Furthermore HLA II was up-regulated less substantially by CL-MSCs and CB-MSCs after IFN-γ stimulation. MSC types did not differ in indolamine 2,3-dioxygenase (IDO) expression after IFN-γ stimulation. Despite their lower IDO, HLA-G, and TGF-β1 expression, only CL-MSCs were able to reduce the release of IFN-γ by lymphocytes in a mixed lymphocyte reaction. In summary, CL-MSCs showed the best characteristics for cell-based strategies, as they are hypo-immunogenic and show high proliferation and migration rates. In addition, these studies show for the first time that although immunomodulatory molecules HLA-G, HLA-E, and TGF-β play an important role in MSC immune evasion, basal and induced HLA expression seems to be decisive in determining the immunogenicity of MSCs.
    Stem cells and development 05/2013; · 4.15 Impact Factor
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    ABSTRACT: BACKGROUND: Lung transplant (LUT) and heart-lung transplant (HLT) represent surgical options for treating medically refractory idiopathic pulmonary arterial hypertension (IPAH). The effect of the lung allocation score (LAS) on waitlist and transplant outcomes in IPAH patients is poorly described. METHODS AND RESULTS: Adults diagnosed with IPAH and listed for transplant in the 80 months before and after the LAS algorithm was implemented (N=1430) were identified in the United Network for Organ Sharing thoracic registry. Patients were stratified by organ listed and pre- and post-LAS era. The cumulative incidences of transplant and mortality for waitlisted patients in both eras were appraised with competing outcomes analysis. Post-transplant survival was assessed with the Kaplan-Meier method. These analyses were repeated in propensity-matched subgroups. Cox proportional hazards analysis evaluated the effect of pre-listing and pre-transplant characteristics on mortality. We found that post-LAS-era patients had significantly worse comorbidities; nevertheless, both LUT and HLT candidates in this era enjoyed lower waitlist mortality and a higher incidence of transplant in our unmatched and propensity-matched analyses. On multivariable analysis, HLT and double-lung transplant (DLT) were associated with improved survival from the time of waitlisting, as was being listed at a medium-to-high-volume institution. Donor/recipient gender matching predicted post-transplant survival. CONCLUSIONS: The incidence of transplant has increased while waitlist mortality has decreased in IPAH patients waitlisted for transplant in the post-LAS era. Both HLT and DLT are predictive of survival in transplant candidates with IPAH, as is being listed at a medium-to-high-volume institution. Donor/recipient gender-matching is associated with better post-transplant survival.
    Circulation 05/2013; · 15.20 Impact Factor
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    ABSTRACT: BACKGROUND: Cardiotoxicity is a leading cause for drug attrition during pharmaceutical development and has resulted in numerous preventable patient deaths. Incidents of adverse cardiac drug reactions are more common in patients with pre-existing heart disease than the general population. Here we generated a library of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from patients with various hereditary cardiac disorders to model differences in cardiac drug toxicity susceptibility for patients of different genetic backgrounds. METHODS AND RESULTS: Action potential duration (APD) and drug-induced arrhythmia were measured at the single cell level in hiPSC-CMs derived from healthy subjects and patients with hereditary long QT syndrome (LQT), familial hypertrophic cardiomyopathy (HCM), and familial dilated cardiomyopathy (DCM). Disease phenotypes were verified in LQT, HCM, and DCM iPSC-CMs by immunostaining and single cell patch clamp. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and the human ether-a-go-go-related gene (hERG) expressing human embryonic kidney (HEK293) cells were used as controls. Single cell PCR confirmed expression of all cardiac ion channels in patient-specific hiPSC-CMs as well as hESC-CMs, but not in HEK293 cells. Disease-specific hiPSC-CMs demonstrated increased susceptibility to known cardiotoxic drugs as measured by APD and quantification of drug-induced arrhythmias such as early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs). CONCLUSIONS: We have recapitulated drug-induced cardiotoxicity profiles for healthy subjects, LQT, HCM, and DCM patients at the single cell level for the first time. Our data indicate that healthy and diseased individuals exhibit different susceptibilities to cardiotoxic drugs and that use of disease-specific hiPSC-CMs may predict adverse drug responses more accurately than standard hERG test or healthy control hiPSC-CM/hESC-CM screening assays.
    Circulation 03/2013; · 15.20 Impact Factor
  • Robert C Robbins
    The Journal of thoracic and cardiovascular surgery 02/2013; 145(2):321-5. · 3.41 Impact Factor
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    ABSTRACT: BACKGROUND: The calcium-activated potassium channel KCa3.1 is critically involved in T-cell activation as well as in the proliferation of smooth muscle cells and fibroblasts. We sought to investigate whether KCa3.1 contributes to the pathogenesis of obliterative airway disease (OAD) and whether knockout or pharmacologic blockade would prevent the development of OAD. METHODS: Tracheas from CBA donors were heterotopically transplanted into the omentum of C57Bl/6J wild-type or KCa3.1 mice. C57Bl/6J recipients were either left untreated or received the KCa3.1 blocker TRAM-34 (120 mg/kg/day). Histopathology and immunologic assays were performed on postoperative day 5 or 28. RESULTS: Subepithelial T-cell and macrophage infiltration on postoperative day 5, as seen in untreated allografts, was significantly reduced in the KCa3.1 and TRAM-34 groups. Also, systemic Th1 activation was significantly and Th2 mildly reduced by KCa3.1 knockout or blockade. After 28 days, luminal obliteration of tracheal allografts was reduced from 89%±21% in untreated recipients to 53%±26% (P=0.010) and 59%±33% (P=0.032) in KCa3.1 and TRAM-34-treated animals, respectively. The airway epithelium was mostly preserved in syngeneic grafts, mostly destroyed in the KCa3.1 and TRAM-34 groups, and absent in untreated allografts. Allografts triggered an antibody response in untreated recipients, which was significantly reduced in KCa3.1 animals. KCa3.1 was detected in T cells, airway epithelial cells, and myofibroblasts. TRAM-34 dose-dependently suppressed proliferation of wild-type C57B/6J splenocytes but did not show any effect on KCa3.1 splenocytes. CONCLUSIONS: Our findings suggest that KCa3.1 channels are involved in the pathogenesis of OAD and that KCa3.1 blockade holds promise to reduce OAD development.
    Transplantation 01/2013; 95(2):285-292. · 3.78 Impact Factor
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    ABSTRACT: Familial hypertrophic cardiomyopathy (HCM) is a prevalent hereditary cardiac disorder linked to arrhythmia and sudden cardiac death. While the causes of HCM have been identified as genetic mutations in the cardiac sarcomere, the pathways by which sarcomeric mutations engender myocyte hypertrophy and electrophysiological abnormalities are not understood. To elucidate the mechanisms underlying HCM development, we generated patient-specific induced pluripotent stem cell cardiomyocytes (iPSC-CMs) from a ten-member family cohort carrying a hereditary HCM missense mutation (Arg663His) in the MYH7 gene. Diseased iPSC-CMs recapitulated numerous aspects of the HCM phenotype including cellular enlargement and contractile arrhythmia at the single-cell level. Calcium (Ca(2+)) imaging indicated dysregulation of Ca(2+) cycling and elevation in intracellular Ca(2+) ([Ca(2+)](i)) are central mechanisms for disease pathogenesis. Pharmacological restoration of Ca(2+) homeostasis prevented development of hypertrophy and electrophysiological irregularities. We anticipate that these findings will help elucidate the mechanisms underlying HCM development and identify novel therapies for the disease.
    Cell stem cell 01/2013; 12(1):101-13. · 23.56 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 01/2013; 15(1). · 4.44 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 01/2013; 15(1). · 4.44 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 01/2013; 15(1). · 4.44 Impact Factor
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    ABSTRACT: BACKGROUND: Allosensitization in potential orthotopic heart transplant recipients is evaluated with the panel reactive antibody assay. Sensitized patients have prolonged wait times and increased waitlist and post-transplant mortality. Although low panel reactive antibody activity at the time of orthotopic heart transplantation is associated with improved outcomes, literature regarding the survival benefit of a panel reactive antibody reduction in the sensitized orthotopic heart transplant recipient remains limited. METHODS: Adult orthotopic heart transplant recipients listed in the United Network for Organ Sharing database (October 1, 1987, to June 29, 2004) were stratified by peak panel reactive antibody activity and whether a substantial decline from peak to most recent panel reactive antibody activity occurred before transplant. Propensity matching adjusted for differences in recipient and donor characteristics. Graft survival was assessed with Kaplan-Meier analysis. Cox proportional hazards regression determined predictors of graft survival. RESULTS: Pretransplant characteristics differed between sensitized patients who had a substantial decline in panel reactive antibody activity and those who did not. Propensity matching compensated for these differences. Kaplan-Meier survival analysis of matched groups showed that the median graft survival was 120 months in patients with a significant panel reactive antibody reduction and 103 months in patients with a trivial reduction (P = .007, log-rank). In Cox proportional hazards modeling, a significant reduction in panel reactive antibody activity had an independent protective effect on graft survival (hazard ratio, 0.88; confidence interval, 0.80-0.96; P = .006). CONCLUSIONS: Sensitized patients who had a substantial reduction in panel reactive antibody activity had an associated decline in the incidence of graft failure compared with those without a panel reactive antibody activity reduction. These results support efforts to reduce panel reactive antibody activity before orthotopic heart transplantation in patients with high panel reactive antibody activity.
    The Journal of thoracic and cardiovascular surgery 12/2012; · 3.41 Impact Factor

Publication Stats

9k Citations
1,984.46 Total Impact Points

Institutions

  • 1996–2014
    • Stanford Medicine
      • • Division of Cardiovascular Medicine
      • • Department of Cardiothoracic Surgery
      Stanford, California, United States
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 2007–2013
    • University of Hamburg
      • University Heart Center
      Hamburg, Hamburg, Germany
  • 1995–2012
    • Stanford University
      • • Department of Cardiothoracic Surgery
      • • Department of Medicine
      • • Department of Radiology
      • • Division of Pulmonary and Critical Care Medicine
      Stanford, CA, United States
  • 2009
    • University of Utah
      Salt Lake City, Utah, United States
    • University of Mississippi Medical Center
      Jackson, Mississippi, United States
    • Fourth Military Medical University
      Xi’an, Liaoning, China
  • 2008
    • National Academies
      Washington, Washington, D.C., United States
  • 2006
    • Johns Hopkins Medicine
      • Division of Cardiac Surgery
      Baltimore, MD, United States
  • 2005
    • National Heart, Lung, and Blood Institute
      Maryland, United States
    • Beth Israel Deaconess Medical Center
      Boston, Massachusetts, United States
  • 2000–2005
    • Leiden University Medical Centre
      • Department of Surgery
      Leiden, South Holland, Netherlands
    • The Children's Hospital of Philadelphia
      Philadelphia, Pennsylvania, United States
    • Lucile Packard Children’s Hospital at Stanford
      Palo Alto, California, United States
  • 2004
    • Massachusetts General Hospital
      • Department of Surgery
      Boston, MA, United States
  • 1998–1999
    • Nagoya University
      • Division of Thoracic Surgery
      Nagoya-shi, Aichi-ken, Japan
  • 1997
    • Columbia University
      • Department of Medicine
      New York City, NY, United States