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Enrico Romagnoli Enrico Romagnoli
Comparison of Coronary Artery Bypass Surgery versus Percutaneous Coronary Intervention With Drug-Eluting Stents in
Patients with Chronic Kidney Disease
Comparison of Coronary Artery Bypass Surgery versus Percutaneous Coronary Intervention With Drug-Eluting Stents in
Patients with Chronic Kidney Disease
Interventional Cardiology Unit Policlinico Casilino, Rome, Italy
Interventional Cardiology Unit Policlinico Casilino, Rome, Italy
Background IBackground I
The patient with Chronic Kidney Disease (CKD) and The patient with Chronic Kidney Disease (CKD) and Coronary Artery Disease (CAD) represents special Coronary Artery Disease (CAD) represents special challenge for interventionalists and cardiologists in challenge for interventionalists and cardiologists in general. general.
Indeed, CKD is associated to worse outcomes both with Indeed, CKD is associated to worse outcomes both with percutaneous and surgical coronary revascularization with percutaneous and surgical coronary revascularization with an increased incidence of both in-hospital and long-term an increased incidence of both in-hospital and long-term clinical events. clinical events.
Background IIBackground II
A post-hoc analysis of patients with CKD enrolled in the A post-hoc analysis of patients with CKD enrolled in the Arterial Revascularization Therapies Study (ARTS) trial Arterial Revascularization Therapies Study (ARTS) trial comparing CABG versus PCI showed equivalent mortality comparing CABG versus PCI showed equivalent mortality and morbidity at 5 year, but the requirement for repeat and morbidity at 5 year, but the requirement for repeat procedures remained significantly higher after PCI procedures remained significantly higher after PCI treatment. treatment.
More recently, the non-randomized ARTS II study More recently, the non-randomized ARTS II study demonstrated a comparable need for repeat demonstrated a comparable need for repeat revascularization both with PCI and CABG in general revascularization both with PCI and CABG in general population. population.
Rationale of the studyRationale of the study
At present, available data on DES safety and efficacy in At present, available data on DES safety and efficacy in patients with CKD are limited to small single-center patients with CKD are limited to small single-center registries, therefore it is not known whether the improved registries, therefore it is not known whether the improved outcomes in PCI with DES will be extended to patients with CKD disease.
With this study we sought to compare the impact of DES introduction on clinical outcome of patients with CKD, when compared to CABG.
Methods I: end-pointsMethods I: end-points
We retrospectively identified all patients with Chronic We retrospectively identified all patients with Chronic kidney disease who underwent coronary revascularization kidney disease who underwent coronary revascularization at San Raffaele Hospital between 2002 and 2006. at San Raffaele Hospital between 2002 and 2006.
Primary end-point of the study was freedom from Primary end-point of the study was freedom from cerebrovascular accident, non fatal MI, or death. cerebrovascular accident, non fatal MI, or death.
The Secondary end-point was the need for repeat The Secondary end-point was the need for repeat revascularization by percutaneous or surgery. revascularization by percutaneous or surgery.
Additional clinical end-points were pAdditional clinical end-points were post-operative acute ost-operative acute renal failure or contrast induced nephropathy, renal failure or contrast induced nephropathy, sepsis and sepsis and bleeding complication rates. bleeding complication rates.
MethodsMethods II: patients selection II: patients selection
For the purposes of this study, only patients who received For the purposes of this study, only patients who received DES stents were included in the percutaneous DES stents were included in the percutaneous revascularization group.revascularization group.
Patients who had a prior PCI or CABG, with valvular heart Patients who had a prior PCI or CABG, with valvular heart disease, congenital heart disease, obstructive or restrictive disease, congenital heart disease, obstructive or restrictive cardiomyopathy, and candidate for cardiac or renal cardiomyopathy, and candidate for cardiac or renal transplantation were excluded.transplantation were excluded.
In general, patients who were thought not to be equal In general, patients who were thought not to be equal candidates for either CABG or PCI with DES (e.g. limited life candidates for either CABG or PCI with DES (e.g. limited life expectancy, intolerance to aspirine or ticlopidine) were not expectancy, intolerance to aspirine or ticlopidine) were not included in the final analysis. included in the final analysis.
MethodsMethods III: CKD definition III: CKD definition
Creatinine levels were measured the day before the time of the procedure, and renal function was assessed based on the CrCl using the Cockcroft-Gault formula*:
(140-age) x weight (Kg)
CrCl (ml/min) = (x 0.85 for females)
72 x serum creatinine (mg/dl)
Renal impairment was defined as a calculated creatinine clearance <60 ml/min, the cut-off value proposed by the National Kidney Foundation’s Kidney Disease Outcome Quality Initiative Advisory Board to identify patients who have moderate renal impairment.
*Cockroft DW, Gault MH. Cockroft DW, Gault MH. NephronNephron. 1976;16:31– 41.. 1976;16:31– 41.
CABG groupCABG groupPCI groupPCI group
407407 317317
275 patients included in the final analysis
275 patients included in the final analysis
138138 137137
724 patients with CKD (<60 CrCl mil/min)
724 patients with CKD (<60 CrCl mil/min)
Study period 2002-2006Study period 2002-2006
36 patients with ESRD or dialysis
36 patients with ESRD or dialysis
26 10
149 patients with valvulopathy149 patients with valvulopathy12 137
56 patients without LAD disease56 patients without LAD disease51 5
208 patients with previous PCI or CABG
208 patients with previous PCI or CABG
180 28
OverallOverall PCI groupPCI group CABG groupCABG group ppMale gender (%)Male gender (%) 72.872.8 70.570.5 75.275.2 0.420.42
Age (year)Age (year) 75±875±8 73±873±8 77±777±7 <0.01<0.01
Creatinine (mg/dl)Creatinine (mg/dl) 1.4±0.51.4±0.5 1.5±0.51.5±0.5 1.3±0.51.3±0.5 <0.01<0.01
Creatinine Clearance (ml/min)Creatinine Clearance (ml/min) 45.3±10.445.3±10.4 44.7±10.744.7±10.7 46.0±10.046.0±10.0 0.280.28
Previous MI (%)Previous MI (%) 42.042.0 38.838.8 45.345.3 0.330.33
CAD family history (%)CAD family history (%) 29.829.8 37.037.0 22.622.6 0.010.01
Hypertension (%)Hypertension (%) 77.177.1 81.281.2 73.073.0 0.110.11
Hypercholesterolemia (%)Hypercholesterolemia (%) 53.353.3 59.059.0 47.447.4 0.070.07
Current smoker (%) Current smoker (%) 8.08.0 9.49.4 6.66.6 0.510.51
Diabetes (%)Diabetes (%) 33.033.0 33.133.1 32.832.8 1.001.00
Insulin treatment (%)Insulin treatment (%) 10.910.9 11.511.5 10.210.2 0.850.85
Left ventricle ejection fraction (%)Left ventricle ejection fraction (%) 49.2±11.749.2±11.7 48.9±11.248.9±11.2 49.4±12.149.4±12.1 0.700.70
Peripheral vascular disease (%)Peripheral vascular disease (%) 32.632.6 37.237.2 27.727.7 0.100.10
Chronic lung disease (%)Chronic lung disease (%) 15.615.6 15.815.8 15.315.3 1.001.00
Neurological dysfunction (%)Neurological dysfunction (%) 4.44.4 3.63.6 5.15.1 0.570.57
Additive EuroSCORE Additive EuroSCORE 7±37±3 7±37±3 7±37±3 0.560.56
Logistic EuroSCORELogistic EuroSCORE 12±1412±14 11±1211±12 12±1612±16 0.700.70
EuroSCORE >6EuroSCORE >6 52.552.5 53.253.2 51.851.8 0.900.90
Study population characteristicsStudy population characteristics
OverallOverall PCI groupPCI group CABG groupCABG group pp
DiagnosisDiagnosis
Acute Myocardial infarction (%)Acute Myocardial infarction (%) 1.11.1 2.22.2 0.00.0 0.250.25
Unstable angina (%)Unstable angina (%) 30.830.8 28.128.1 33.633.6 0.360.36
Stable angina (%)Stable angina (%) 73.273.2 72.772.7 73.773.7 0.890.89
Number of vessel disease (%)Number of vessel disease (%)
11 15.615.6 23.723.7 7.37.3 <0.01<0.01
22 33.033.0 39.639.6 26.326.3 0.030.03
33 51.451.4 36.736.7 66.466.4 <0.01<0.01
Left Main diseaseLeft Main disease 17.417.4 10.810.8 24.124.1 <0.01<0.01
Number of stents implanted - 3.0±1.8 - -Stented segment length (mm) - 74.0±44.6 - -Number of conduits grafted - - 2.7±1.1 -OPCAB (%) - - 59.1 -IABP use (%)
8.3 10.1 6.6 0.38
Incomplete revascularization (%) 26.1 23.7 28.5 0.41Intended (%) 17.4 18.7 16.1 0.63Unwilling (%) 8.7 5.0 12.4 0.03
Study procedural characteristicsStudy procedural characteristics
Death MI TIA/Stroke
P=0.02P=0.02P=0.02P=0.02
6.5%
16.1%
Death
1.4%3.6%
5.8%
9.5%
P=0.33P=0.33P=0.33P=0.33 P= n.s.P= n.s.P= n.s.P= n.s. P=0.44P=0.44 P=0.44P=0.44 P=0.03P=0.03P=0.03P=0.03
MI TIA/Stroke
0%
4.4%
0% 0%
TVR/TLR
Results: in-hospital outcomeResults: in-hospital outcome
primary end-pointsprimary end-points
PCIPCI CABGCABG
MAE GFR >25%
GFR>75% (dialysis)
Sepsis
PCIPCI CABGCABG
Major bleeding
Results: in-hospital outcomeResults: in-hospital outcome
P=<0.01P=<0.01P=<0.01P=<0.01 P=0.027P=0.027P=0.027P=0.027 P=0.02P=0.02P=0.02P=0.02 P=<0.01P=<0.01 P=<0.01P=<0.01 P=0.99P=0.99P=0.99P=0.99 P=0.01P=0.01P=0.01P=0.01
8.0%
47.5%
7.2%
35.7%
2.9%
10.2%
2.2% 2.9% 0.7%
9.5%
1.4%
16.0%
secondary end-pointssecondary end-points
GFR >50%
Results: 1-year follow upResults: 1-year follow up
Death MI TIA/Stroke
P=0.73P=0.73P=0.73P=0.73
17.4%19.7%
Death
8.0%7.3%
10.9%10.2%
P=0.98P=0.98P=0.98P=0.98 P=<0.01P=<0.01P=<0.01P=<0.01 P=0.99P=0.99 P=0.99P=0.99 P=0.07P=0.07P=0.07P=0.07
Cum MI TIA/Stroke
0.7%
5.1%
23.2%
2.2%
repeat revascularization
PCIPCI CABGCABG
primary end-pointsprimary end-points
Results: long term follow upResults: long term follow up
Death MI TIA/Stroke
P=0.86P=0.86P=0.86P=0.86
25.4%27.0%
Death
15.2%14.6%
11.6% 10.9%
P=0.97P=0.97P=0.97P=0.97 P=<0.01P=<0.01P=<0.01P=<0.01 P=0.98P=0.98 P=0.98P=0.98 P=0.21P=0.21P=0.21P=0.21
Cum MI TIA/Stroke
2.2%
5.8%
29.0%
4.4%
repeat revascularization
PCIPCI CABGCABG
primary end-points (median 38 months)primary end-points (median 38 months)
1-year outcome comparison1-year outcome comparison
1-year outcome comparison1-year outcome comparison
Correlation between renal failure and outcomesCorrelation between renal failure and outcomes
Correlation between renal failure and outcomesCorrelation between renal failure and outcomes
0.01 0.1 1 5 10 15
0.01 0.1 1 5 10 15
In hospital major adverse avent predictorsIn hospital major adverse avent predictors
Diabetes OR=2.4; 95%CI, 1.1-5.3, p=0.024 OR=2.4; 95%CI, 1.1-5.3, p=0.024
Unstable angina OR=1.96; 95%CI, 0.9-4.3, p=0.009
OR=5.4; 95%CI, 2.4-11.9, p=<0.01
eGFR decrease >25%
CABG OR=2.4; 95%CI, 1.1-5.6, p=0.033 OR=2.4; 95%CI, 1.1-5.6, p=0.033
Hypertension OR=2.8; 95%CI, 0.8-9.6, p=0.101 OR=2.8; 95%CI, 0.8-9.6, p=0.101
OR=2.4; 95%CI, 1.0-5.6, p=0.047 OR=2.4; 95%CI, 1.0-5.6, p=0.047 Left Main disease
Univariate Univariate analysisanalysis
0.01 0.1 1 5 10 15
0.01 0.1 1 5 10 15
In hospital major adverse avent predictorsIn hospital major adverse avent predictors
Diabetes OR=2.2; 95%CI, 1.0-5.1, p=0.056 OR=2.2; 95%CI, 1.0-5.1, p=0.056
OR=4.9; 95%CI, 2.2-11.2, p=<0.01
eGFR decrease >25%
OR=2.7; 95%CI, 1.1-6.8, p=0.032 OR=2.7; 95%CI, 1.1-6.8, p=0.032 Left Main disease
Multivariate Multivariate analysisanalysis
0.01 0.1 1 5 10 15
0.01 0.1 1 5 10 15
One-year major adverse avent predictorsOne-year major adverse avent predictors
Diabetes OR=2.0; 95%CI, 1.1-3.7, p=0.035 OR=2.0; 95%CI, 1.1-3.7, p=0.035
Unstable angina OR=2.2; 95%CI, 1.2-4.2, p=0.015
Left main disease OR=1.5; 95%CI, 0.7-3.3, p=0.275 OR=1.5; 95%CI, 0.7-3.3, p=0.275
Hypertension OR=1.9; 95%CI, 0.8-4.5, p=0.136 OR=1.9; 95%CI, 0.8-4.5, p=0.136
OR=3.3; 95%CI, 0.9-12.4, p=0.070 OR=3.3; 95%CI, 0.9-12.4, p=0.070 Emergency
procedure
Univariate Univariate analysisanalysis
Male gender OR=2.1; 95%CI, 0.9-4.7, p=0.074 OR=2.1; 95%CI, 0.9-4.7, p=0.074
Smoking history OR=1.8; 95%CI, 0.9-3.4, p=0.071 OR=1.8; 95%CI, 0.9-3.4, p=0.071
OR=3.4; 95%CI, 1.7-6.6, p=<0.01
eGFR decrease >25%
0.01 0.1 1 5 10 15
0.01 0.1 1 5 10 15
One-year major adverse avent predictorsOne-year major adverse avent predictors
Unstable anginaUnstable angina OR=1.9; 95%CI, 1.0-3.8, p=0.052OR=1.9; 95%CI, 1.0-3.8, p=0.052
Multivariate Multivariate analysisanalysis
Male gender Male gender OR=2.0; 95%CI, 0.9-4.7, p=0.093 OR=2.0; 95%CI, 0.9-4.7, p=0.093
OR=2.9; 95%CI, 1.4-5.8, p=<0.01OR=2.9; 95%CI, 1.4-5.8, p=<0.01
eGFR eGFR decrease >25%decrease >25%
This study confirms patients with CKD having a worse This study confirms patients with CKD having a worse outcome with high rate of major adverse events, outcome with high rate of major adverse events, regardless of the revascularization strategy. regardless of the revascularization strategy.
At 1-year follow up, multivessel stenting with DES showed At 1-year follow up, multivessel stenting with DES showed similar outcomes of death, MI or cerebrovascular events similar outcomes of death, MI or cerebrovascular events when compared to surgical revascularization.when compared to surgical revascularization.
The higher rate of TVR at 1-year follow up in the PCI The higher rate of TVR at 1-year follow up in the PCI group suggests that use of DES does not prevent repeat group suggests that use of DES does not prevent repeat revascularization when compared to CABG.revascularization when compared to CABG.
Discussion: DES impact on CKDDiscussion: DES impact on CKD
CABG treatment is associated with an increased risk of CABG treatment is associated with an increased risk of peri-procedural major adverse events, when compared to peri-procedural major adverse events, when compared to PCI.PCI.
In particular, renal impairment and cerebrovascular event In particular, renal impairment and cerebrovascular event was 5 folds higher in the CABG group. At 1-year follow up was 5 folds higher in the CABG group. At 1-year follow up the difference is still significant for cerebrovascular events.the difference is still significant for cerebrovascular events.
Discussion: CABG impact on CKDDiscussion: CABG impact on CKD
At multivariate analysis the occurrence of post-procedural At multivariate analysis the occurrence of post-procedural renal insufficiency is the strongest predictor of major renal insufficiency is the strongest predictor of major adverse event (death, MI, or cerebrovascular events)adverse event (death, MI, or cerebrovascular events)
There is a correlation between the grade of post-There is a correlation between the grade of post-procedural renal impairment and the rate of adverse procedural renal impairment and the rate of adverse events, with the worst outcome in patients requiring events, with the worst outcome in patients requiring dialysis treatment. dialysis treatment.
Discussion: CKD impact on CKDDiscussion: CKD impact on CKD
Study limitationsStudy limitations
Retrospective design and limited sample size constitute Retrospective design and limited sample size constitute the main limitations of this study. the main limitations of this study.
Only minority of patients were jointly evaluated by cardiac Only minority of patients were jointly evaluated by cardiac surgery and interventional cardiology consultants, then the surgery and interventional cardiology consultants, then the choice of the revascularization strategy has been left to choice of the revascularization strategy has been left to the patient-referring physician. the patient-referring physician.
ConclusionsConclusions
This is the first study to compare clinical outcomes of DES This is the first study to compare clinical outcomes of DES versus CABG in patients with CKD.versus CABG in patients with CKD.
The use of DES does not seem to confer incremental The use of DES does not seem to confer incremental benefits in death, MI or cerebrovascular events when benefits in death, MI or cerebrovascular events when compared to CABG, and does not offer comparable compared to CABG, and does not offer comparable results in term of need for repeat revascularization.results in term of need for repeat revascularization.
The lower rate of in hospital adverse events suggests that The lower rate of in hospital adverse events suggests that PCI with DES could be an acceptable and less invasive PCI with DES could be an acceptable and less invasive alternative to CABG in patients at high surgical risk. alternative to CABG in patients at high surgical risk.
Main goals during the MasterMain goals during the Master
As first author:As first author:
Romagnoli E, Sangiorgi GM, Cosgrave J, et al. Romagnoli E, Sangiorgi GM, Cosgrave J, et al. Drug eluting stenting the case for post-dilationDrug eluting stenting the case for post-dilation. . J Am Coll Cardiol IntvJ Am Coll Cardiol Intv. 2008;1:22–31.. 2008;1:22–31.
Romagnoli E, Chieffo A,Romagnoli E, Chieffo A, Ferrari A, et al. Ferrari A, et al. Randomized Comparison between Sirolimus Randomized Comparison between Sirolimus (Cypher)/Sirolimus-analogous (Xience, Promus) vs. Paclitaxel (Taxus vs. Costar) Eluting (Cypher)/Sirolimus-analogous (Xience, Promus) vs. Paclitaxel (Taxus vs. Costar) Eluting Stents in Coronary Lesions: a Single Centre Experience. The ABSOLUTE Trial Stents in Coronary Lesions: a Single Centre Experience. The ABSOLUTE Trial (submitted)(submitted)
Romagnoli E, Carminati M, Chessa M. Romagnoli E, Carminati M, Chessa M. Detachable coil use to treat residual shunt after PFO Detachable coil use to treat residual shunt after PFO percutaneous closurepercutaneous closure (submitted) (submitted)
As co-author:As co-author:
Rogacka R, Chieffo A, Michev I, et al. Rogacka R, Chieffo A, Michev I, et al. Dual antiplatelet therapy after percutaneous coronary Dual antiplatelet therapy after percutaneous coronary intervention with stent implantation in patients taking chronic oral anticoagulationintervention with stent implantation in patients taking chronic oral anticoagulation . J Am Coll . J Am Coll Cardiol Intv. Cardiol Intv. 2008;1:56–61. 2008;1:56–61.
Sangiorgi G, Romagnoli E, Biondi-Zoccai GGL, et al. Sangiorgi G, Romagnoli E, Biondi-Zoccai GGL, et al. Percutaneous coronary implantation of Percutaneous coronary implantation of sirolimus-eluting stents in unselected patients and lesions: clinical results and multiple sirolimus-eluting stents in unselected patients and lesions: clinical results and multiple outcome predictorsoutcome predictors (submitted). (submitted).
Butera G, Romagnoli E, Sangiorgi G, et al. Butera G, Romagnoli E, Sangiorgi G, et al. Patent Foramen ovale percutaneous closure: the Patent Foramen ovale percutaneous closure: the no-implannt approach. no-implannt approach. Expert Rev. Med Devices 2008;5 (in press)Expert Rev. Med Devices 2008;5 (in press)
Pz. Cause Age LVEF% Vessel disease EuroSCORE treatment
1 Pulmonary embolism 82 55 2 11 (27.5%) PCI
2 Tumore osseo 72 59 3 7 (6.7%) PCI
3 Myocardial infarction 72 45 3 12 (30.4%) PCI
4 Myocardial infarction 87 25 3 17 (71.8%) PCI
5 Infarto renale 54 46 3 7 (7.3%) PCI
6 Heart failure 73 35 2 + LM 11 (22.9%) PCI
7 Acute renal failure 65 35 3 9 (11.6%) PCI
8 Death during new PCI 79 55 3 7 (9.6%) PCI
9 Heart failure 80 37 2 + LM 12 (27.4%) PCI
10 Sudden death 75 53 3 6 (4.7%) PCI
11 Sudden death 80 55 3 8 (10.2%) PCI
12 Acute coronary syndrome 74 35 2 4 (3.5%) CABG
13 Sepsi 81 55 3 6 (5.9%) CABG
14 Acute renal failure 78 38 3 + LM 11 (23.7%) CABG
15 Heart failure 74 40 3 9 (18.6%) CABG
16 Infarto intestinale 81 50 3 + LM 8 (9.1%) CABG
17 Stroke 72 60 3 + LM 4 (2.8%) CABG
18 Sudden death 80 55 3 7 (6.0%) CABG
19 Tumore polmonare 81 60 3 + LM 10 (17.3%) CABG
• Predictor of late outcome after CABG(Toumpouls IK et al Eur J Cardiothorac Surg. 2004;Biancari F et al, Ann Thorac Surg. 2006)
• Predictor of prolonged lenght stay and specific postoperative complications such as renal failure and sepsis and/or endocarditis after CABG(Toumpoulis IK et al. Int J Cardiol 2005)
• Independent predictor of myocardial damage (Onorati F, Ann Thorac Surg. 2005)
• Predictor of late outcome after CABG(Toumpouls IK et al Eur J Cardiothorac Surg. 2004;Biancari F et al, Ann Thorac Surg. 2006)
• Predictor of prolonged lenght stay and specific postoperative complications such as renal failure and sepsis and/or endocarditis after CABG(Toumpoulis IK et al. Int J Cardiol 2005)
• Independent predictor of myocardial damage (Onorati F, Ann Thorac Surg. 2005)
Euroscore risk model evidencesEuroscore risk model evidences
• Selection criterium of off-pump CABG in high risk patients (Euroscore ≥10 and EF <30%)(Kunt AS et al, Curr Control Trials Cardiovasc Med. 2005)
• Predictor of in-hospital mortality after percutaneous Predictor of in-hospital mortality after percutaneous coronary intervention coronary intervention (Romagnoli et al, Heart 2008)(Romagnoli et al, Heart 2008)
• Selection criterium of off-pump CABG in high risk patients (Euroscore ≥10 and EF <30%)(Kunt AS et al, Curr Control Trials Cardiovasc Med. 2005)
• Predictor of in-hospital mortality after percutaneous Predictor of in-hospital mortality after percutaneous coronary intervention coronary intervention (Romagnoli et al, Heart 2008)(Romagnoli et al, Heart 2008)
Euroscore risk modelEuroscore risk model
The European System for Cardiac Operative Risk Evaluation is a method of calculating predicted operative mortality for patients undergoing cardiac surgery.
Patient-related factors
Age (score 1, per 5 years over 60 years);
Sex (score 1, per female);
Chronic pulmonary disease (score 1);
Peripheral vascular disease (score 2);
Neurological dysfunction (score 2);
Previous cardiac surgery (score 3);
Serum creatinine >200 mol/l (score 2);
Active endocarditis (score 3);
Critical pre-operative state (score 3);
Cardiac-related factors
Unstable angina (score 2);LV dysfunction
LVEF 30-50% (score 1);LVEF ≤29% (score 3);
Recent myocardial infarction (score 2);PAPS >60 mmHg (score 2);
Operation related factors
Emergency (score 2);Surgery on thoracic aorta (score 3);Post-infarct septal rupture (score 4);
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