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1.  256-Slice CT Angiographic Evaluation of Coronary Artery Bypass Grafts: Effect of Heart Rate, Heart Rate Variability and Z-Axis Location on Image Quality 
PLoS ONE  2014;9(3):e91861.
The objective of this study is to assess the effect of heart rate, heart rate variability and z-axis location on coronary artery bypass graft (CABG) image quality using a 256-slice computed tomography (CT) scanner.
A total of 78 patients with 254 CABG (762 graft segments) were recruited to undergo CABG assessment with 256-slice CT and prospective ECG-gating. Two observers rated graft segments for image quality on a 5-point scale. Quantitative measurements were also made. Logistic and cumulative link mixed models were used to assess the predictors of graft image quality.
Graft image quality was judged as diagnostic (scores 5 (excellent), 4 (good) and 3 (moderate)) in 96.6% of the 762 segments. Interobserver agreement was excellent (kappa ≥0.90). Graft image quality was not affected by heart rate level. However, high heart rate variability was associated with an important and significant image quality deterioration (odds ratio 4.31; p  =  0.036). Distal graft segments had significantly lower image quality scores than proximal segments (p ≤ 0.02). Significantly higher noise was noted at the origin of the mammary grafts (p  =  0.001), owing to streak artifacts from the shoulders.
CABG imaging with 270-msec rotation 256-slice CT and prospective ECG-gating showed an adequate image quality in 96.6% of graft segments, and an excellent interobserver agreement. Graft image quality was not influenced by heart rate level. Image quality scores were however significantly decreased in patients with high heart rate variability, as well as in distal graft segments, which are closer to the heart.
PMCID: PMC3956757  PMID: 24637891
2.  Steroids In caRdiac Surgery (SIRS) trial: acute kidney injury substudy protocol of an international randomised controlled trial 
BMJ Open  2014;4(3):e004842.
Steroids In caRdiac Surgery trial (SIRS) is a large international randomised controlled trial of methylprednisolone or placebo in patients undergoing cardiac surgery with the use of a cardiopulmonary bypass pump. At the time of surgery, compared with placebo, methylprednisolone divided into two intravenous doses of 250 mg each may reduce the risk of postoperative acute kidney injury (AKI).
Methods and analysis
With respect to the study schedule, over 7000 substudy eligible patients from 81 centres in 18 countries were randomised in December 2013. The authors will use a logistic regression to estimate the adjusted OR of methylprednisolone versus placebo on the primary outcome of AKI in the 14 days following surgery (a postoperative increase in serum creatinine of ≥50%, or ≥26.5 μmol/L, from the preoperative value). The stage of AKI will also be considered, as will the outcome of AKI in those with and without preoperative chronic kidney disease. After receipt of grant funding, the authors began to record additional perioperative serum creatinine measurements in consecutive patients enrolled at substudy participating centres, and patients were invited to enroll in a 6-month serum creatinine collection. In these trial subpopulations, the authors will consider the outcome of AKI defined in alternate ways, and the outcome of a 6-month change in kidney function from the preoperative value.
Ethics and dissemination
The authors were competitively awarded a grant from the Canadian Institutes of Health Research for this SIRS AKI substudy. Ethics approval was obtained for additional serum creatinine recordings in consecutive patients enrolled at participating centres. The additional kidney data collection first began for patients enrolled after 1 March 2012. In patients who provided consent, the last 6-month kidney outcome data will be collected in 2014. The results will be reported no later than 2015.
Clinical Trial Registration
Number NCT00427388.
PMCID: PMC3948633  PMID: 24598306
3.  Preoperative Anxiety as a Predictor of Mortality and Major Morbidity in Patients >70 Years of Age Undergoing Cardiac Surgery 
The American journal of cardiology  2013;111(1):137-142.
This study examined the association between patient-reported anxiety and post-cardiac surgery mortality and major morbidity. Frailty ABC'S was a prospective multicenter cohort study of elderly patients undergoing cardiac surgery (coronary artery bypass surgery and/or valve repair or replacement) at 4 tertiary care hospitals between 2008 and 2009. Patients were evaluated a mean of 2 days preoperatively with the Hospital Anxiety and Depression Scale (HADS), a validated questionnaire assessing depression and anxiety in hospitalized patients. The primary predictor variable was high levels of anxiety, defined by HADS score ≥11. The main outcome measure was all-cause mortality or major morbidity (stroke, renal failure, prolonged ventilation, deep sternal wound infection, or reoperation) occurring during the index hospitalization. Multivariable logistic regression examined the association between high preoperative anxiety and all-cause mortality/major morbidity, adjusting for Society of Thoracic Surgeons (STS) predicted risk, age, gender, and depression symptoms. A total of 148 patients (mean age 75.8 ± 4.4 years; 34% women) completed the HADS-A. High levels of preoperative anxiety were present in 7% of patients. There were no differences in type of surgery and STS predicted risk across preoperative levels of anxiety. After adjusting for Society of Thoracic Surgeons predicted risk, age, gender, and symptoms of depression, preoperative anxiety remained independently predictive of postoperative mortality or major morbidity (OR 5.1; 95% CI 1.3, 20.2; p=0.02). In conclusion, although high levels of anxiety were present in a minority of patients anticipating cardiac surgery, this conferred a strong and independent heightened risk of mortality or major morbidity.
PMCID: PMC3677723  PMID: 23245838
geriatric; cardiac surgery; outcomes; anxiety
4.  Predictors of Postoperative Movement and Resting Pain following Total Knee Replacement 
Pain  2012;153(11):2192-2203.
This study determined preoperative predictors of movement and resting pain following total knee replacement (TKR). We hypothesized that younger patients with higher preoperative pain intensity, pain sensitivity, trait anxiety, pain catastrophizing, and depression would be more likely to experience higher postoperative movement pain than older patients with lower scores on these variables prior to surgery and that predictors would be similar for resting pain. Demographics, analgesic intake, anxiety, depression, pain catastrophizing, resting pain, movement pain (i.e., during active knee range of motion), and quantitative sensory tests, were performed pre-operatively on 215 participants scheduled for a unilateral TKR. On postoperative day 2 (POD2), analgesic intake, resting pain, and movement pain were again assessed. Significant predictors of moderate or severe movement pain were higher preoperative movement pain, von Frey pain intensity (VFPI) and heat pain threshold (HPT). People with severe movement pain preoperatively were 20 times more likely to have severe movement pain postoperatively. When the influence of preoperative movement pain was removed, depression became a predictor. Significant predictors of moderate to severe resting pain were higher preoperative resting pain, depression, and younger age. These results suggest that patients with higher preoperative pain and depression are more likely to have higher pain following TKR and younger patients may have higher resting pain. Cutaneous pain sensitivity predicted movement pain but not resting pain, suggesting that mechanisms underlying movement pain are different from resting pain. Aggressive management of preoperative pain, pain sensitivity, and depression prior to surgery may facilitate postoperative recovery.
PMCID: PMC3472094  PMID: 22840570
Postoperative Pain; Movement Pain; Total Knee Replacement; Pain Sensitivity
5.  Composite versus conventional coronary artery bypass grafting strategy for the anterolateral territory: study protocol for a randomized controlled trial 
Trials  2013;14:270.
In severe coronary artery disease, coronary artery bypass grafting (CABG) surgery is indicated to re-establish an adequate blood supply to the ischemic myocardium. Effectiveness of CABG surgery for symptom relief and mortality decrease should therefore depend on bypass graft patency. As bypass using a left internal mammary artery (LIMA)-to-left anterior descending coronary artery (LAD) anastomosis allows the best results in terms of graft patency, we designed a new surgical technique using a saphenous vein graft as a venous bridge to distribute the LIMA flow to the cardiac anterolateral territory. This novel strategy could extend the patency benefits associated to the LIMA. Other potential benefits of this technique include easier surgical technique, possibility to use saphenous vein grafts as vein patch angioplasty, shorter saphenous vein grafts requirement and reduced or eliminated manipulations of the ascendant aorta (and associated stroke risk).
Between July 2012 and 2016, 200 patients undergoing a primary isolated CABG surgery using cardiopulmonary bypass with a LAD bypass graft and at least another target on the anterolateral territory will be randomized (1:1) according to 1) the new composite strategy and 2) the conventional strategy with a LIMA-to-LAD anastomosis and revascularization of the other anterolateral target(s) with a separated aorto-coronary saphenous vein graft. The primary objective of the trial is to assess whether the composite strategy allows non-inferior anterolateral graft patency index (proportion of non-occluded CABGs out of the total number of CABGs) compared to the conventional technique. The primary outcome is the anterolateral graft patency index, evaluated at one year by 256-slice computed tomography angiography. Ten years of clinical follow-up is planned to assess clinical outcomes including death, myocardial infarction and need for revascularization.
This non-inferiority trial has the potential to advance the adult cardiac surgery field, given the potential benefits associated with the composite grafting strategy.
Trial registration NCT01585285.
PMCID: PMC3766263  PMID: 23971858
Cardiopulmonary bypass; Composite graft; Coronary artery bypass grafting; Doppler velocimetry; Ischemic heart disease; Left internal mammary artery; Long-term follow-up; Multislice computed tomography angiography; Randomized clinical non-inferiority trial; Saphenous vein graft
6.  A rare case of anomalous origin of the left main coronary artery in an adult patient 
Anomalous origin of left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly that causes a left-to-right shunt via the coronary system, resulting in coronary steal. We report an unusual case of a healthy 48 years-old patient presenting with dyspnea on exertion and mild chest pain who underwent surgical correction of this rare anomaly. Multiple procedures have been proposed in adults with ALCAPA. Although re-implantation of the left main coronary artery (LMCA) to the aorta remains the most physiological correction for this anomaly, the combination of LMCA ligation and coronary artery bypass grafting provides a dual coronary flow system and is preferable when re-implantation is impossible.
PMCID: PMC3554424  PMID: 23336304
Congenital heart defect; Cardiac surgery; Coronary artery bypass graft
7.  Acute renal failure following lung transplantation: risk factors, mortality, and long-term consequences 
Acute renal failure (ARF) frequently complicates lung transplantation. This study determined the prevalence, predictive factors, and consequences of ARF on long-term renal function and survival.
One hundred and seventy-four lung transplantation recipients were divided into two groups based on the presence or absence of ARF defined as a 50% decrease in creatinine clearance from baseline (group I: 67 patients with ARF; group II: 107 patients without ARF). Multivariate analysis compared pre-operative, operative, and post-operative risk factors to assess predictive factors. Renal function over time was assessed by two-way repeated measures analysis of variance (ANOVA).
ARF developed in 67 (39%) of patients. Multivariate analysis identified aprotinin (OR 2.20 (1.11; 4.36), p = 0.02) and double lung transplantation (OR 2.61 (1.32; 5.15), p = 0.006) as risk factors for post-operative renal failure. At 5 years following transplant, creatinine clearance was similar between the two groups (group I CrCl: 73 ml s−1; group II CrCl: 53 ml s−1; p = 0.54). Survival at 5 years was the same in the two groups. Multivariate analysis associated age at the time of transplantation (HR 1.030 (1.004; 1.057), p = 0.02) and intensive care unit (ICU) length of stay (HR 1.029 (1.008; 1.051), p = 0.007) with decreased survival.
The use of aprotinin and double lung transplantation are associated with ARF following lung transplantation. Age at the time of transplantation and a longer intensive care stay predict decreased survival. ARF after lung transplantation is not predictive of late renal dysfunction or decreased long-term survival.
PMCID: PMC3241081  PMID: 21665487
Lung transplantation; Acute renal failure; Aprotinin
8.  Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularisation Study (CORONARY): kidney substudy analytic protocol of an international randomised controlled trial 
BMJ Open  2012;2(2):e001080.
CORONARY is a large international randomised controlled trial comparing coronary artery bypass graft (CABG) surgery done with and without a bypass pump. Compared with on-pump, off-pump surgery may prevent acute kidney injury (AKI) in the short term and may better preserve kidney function 1 year following surgery. Secondary analyses may also clarify whether effects are similar in patients with and without pre-operative chronic kidney disease and whether AKI avoidance mediates preserved 1-year kidney function.
Methods and analysis
With respect to the study schedule, the last of 4752 patients from 79 sites in 19 countries were randomised in November 2011 to cardiac surgery performed with an on-pump or off-pump procedure. The authors will use regression models to compare the groups in the outcome of peri-operative AKI (per cent change in serum creatinine, ≥50% increase in serum creatinine) and 1-year kidney function (per cent change in estimated glomerular filtration rate (eGFR), ≥20% eGFR loss 1 year after surgery). The authors will use interaction terms in regression models to determine if there is a differential impact of the intervention in those with and without pre-existing chronic kidney disease. The authors will use regression-based tests to determine the proportion of the total effect of surgery type (off-pump vs on-pump CABG) on 1-year eGFR that is mediated by peri-operative AKI.
Ethics and dissemination
In the year 2009, the authors were competitively awarded a grant from the Canadian Institutes of Health Research to answer these kidney questions in CORONARY. Ethics approval was obtained for additional renal data collection in centres that agreed to study participation (>90% of participating centres). This collection began for patients enrolled after 1 January 2010. Remaining 1-year renal outcome data will be collected throughout 2012. Results will be reported in 2013.
Clinical trial registration number
NCT 00463294.
Article summary
Article focus
CORONARY is a large international randomised controlled trial comparing coronary artery bypass graft (CABG) surgery done with and without a bypass pump.
Compared with on-pump, off-pump surgery may prevent AKI in the short term and may better preserve kidney function 1 year after surgery.
Secondary analyses may also clarify whether effects are similar in patients with and without pre-operative chronic kidney disease and whether AKI avoidance mediates preserved 1-year kidney function.
Key messages
Presented is this pre-specified CORONARY kidney substudy analytic protocol.
Data collection and analysis will be completed in 2013.
Understanding the degree to which avoiding AKI preserves longer term kidney function has broader implications for the acceptability of side effects and costs of interventions which prevent AKI.
Strengths and limitations of this study
This will be largest AKI prevention trial conducted to date.
It will be one of the first trials to consider the impact of a peri-operative intervention on longer term kidney function.
International recruitment across 19 countries will provide generalisable estimates of the treatment effect.
PMCID: PMC3332245  PMID: 22514244
9.  IMPACT-CABG Trial: Implantation of CD133+ Stem Cells in Patients Undergoing Coronary Bypass Surgery—Presentation of the First Treated Patient 
The IMPACT-CABG study is the first Canadian randomized-controlled phase II clinical trial aiming to assess the effect of intramyocardial (IM) injections of CD133+-selected stem cells in patients referred for coronary artery bypass graft (CABG) with a “chronic” myocardial infarction and persistent left ventricular dysfunction. Patients are followed for 2 years with different imaging techniques including the stress magnetic resonance to evaluate the global and regional myocardial viability. Before the beginning of the randomization, the 5 first patients are treated in an open-label fashion to assess safety and feasibility of the IM CD133+ injections. Herein, we report the first Canadian patient treated with IM injection of CD133+ cells during CABG surgery as part of the IMPACT-CABG trial.
PMCID: PMC3505958  PMID: 23213603
10.  One-Year Safety Analysis of the COMPARE-AMI Trial: Comparison of Intracoronary Injection of CD133+ Bone Marrow Stem Cells to Placebo in Patients after Acute Myocardial Infarction and Left Ventricular Dysfunction 
Bone Marrow Research  2011;2011:385124.
Bone marrow stem cell therapy has emerged as a promising approach to improve healing of the infarcted myocardium. Despite initial excitement, recent clinical trials using non-homogenous stem cells preparations showed variable and mixed results. Selected CD133+ hematopoietic stem cells are candidate cells with high potential. Herein, we report the one-year safety analysis on the initial 20 patients enrolled in the COMPARE-AMI trial, the first double-blind randomized controlled trial comparing the safety, efficacy, and functional effect of intracoronary injection of selected CD133+ cells to placebo following acute myocardial infarction with persistent left ventricular dysfunction. At one year, there is no protocol-related complication to report such as death, myocardial infarction, stroke, or sustained ventricular arrhythmia. In addition, the left ventricular ejection fraction significantly improved at four months as compared to baseline and remained significantly higher at one year. These data indicate that in the setting of the COMPARE-AMI trial, the intracoronary injection of selected CD133+ stem cells is secure and feasible in patients with left ventricle dysfunction following acute myocardial infarction.
PMCID: PMC3200002  PMID: 22046562
Total hip arthroplasty (THA) with conventional polyethylene bearings is traditionally the standard operative treatment for endstage arthritis of the hip. This design has excellent survivorship in most populations, with a low occurrence of infection and other associated complications. Due to concern over increased wear in younger, more active populations, other bearing surfaces have been evaluated, particularly metal-on-metal with wear rates theorized to be lower than conventional THA. Unique to metal-on-metal THA, however, is the possibility of local soft tissue reactions that can mimic infection, making proper diagnosis and treatment difficult. We present a case series of nine hips in eight patients undergoing revision of metal-on-metal THA for local soft tissue reactions, three of which were also found to be concomitantly infected. The laboratory and hip aspirate data described show significant overlap between the infected and non-infected cases. Care must be taken when evaluating patients with failed metal-on-metal THA as there may be an increased incidence of co-infection in this group of patients.
PMCID: PMC3215115  PMID: 22096421
12.  Bone Marrow Stem Cell Derived Paracrine Factors for Regenerative Medicine: Current Perspectives and Therapeutic Potential 
Bone Marrow Research  2010;2011:207326.
During the past several years, there has been intense research in the field of bone marrow-derived stem cell (BMSC) therapy to facilitate its translation into clinical setting. Although a lot has been accomplished, plenty of challenges lie ahead. Furthermore, there is a growing body of evidence showing that administration of BMSC-derived conditioned media (BMSC-CM) can recapitulate the beneficial effects observed after stem cell therapy. BMSCs produce a wide range of cytokines and chemokines that have, until now, shown extensive therapeutic potential. These paracrine mechanisms could be as diverse as stimulating receptor-mediated survival pathways, inducing stem cell homing and differentiation or regulating the anti-inflammatory effects in wounded areas. The current review reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many logistical and technical issues regarding cell therapy and evaluates its future potential as an effective regenerative therapy.
PMCID: PMC3195349  PMID: 22046556
13.  High resolution optical imaging of infarction in intact organs 
BioTechniques  2005;39(3):373-376.
We describe a method to visualize green fluorescent protein (GFP)-labeled cells in intact organs through combined confocal and reflected laser light imaging. This method allows us a three-dimensional (3-D) view of specific cell types in situ. Imaging of tissues from transgenic mice in which the endothelial cells are labeled with GFP under the control of endothelial-specific tyrosine receptor kinase 2 (TIE2) shows the spatial distribution of the GFP-labeled endothelial cells in intact organs. We have used this method to examine the tissue necrosis in the intact heart and kidney resulting from myocardial and renal infarction. In myocardial infarction produced by surgically occluding the left anterior descending coronary artery, the border of the infarct was highly cellular and showed a disrupted endothelial network and scar tissue appearing as a dense layer of reflection. The induced renal infarction produced by ligating the renal artery in the pedicle showed a clear infarct border in the affected kidney. The 3-D reconstruction of specific cell types in the context of the surrounding tissues should be useful for studying the overall organization and the relationship between different structures in the intact organ in normal and disease states.
PMCID: PMC2907652  PMID: 16206909
14.  Early Beneficial Effects of Bone Marrow Derived Mesenchymal Stem Cells Overexpressing Akt on Cardiac Metabolism after Myocardial Infarction 
Stem cells (Dayton, Ohio)  2009;27(4):971-979.
Administration of mesenchymal stem cells (MSCs) is an effective therapy to repair cardiac damage after myocardial infarction (MI) in experimental models. However, the mechanisms of action still need to be elucidated. Our group has recently suggested that MSCs mediate their therapeutic effects primarily via paracrine cytoprotective action. Furthermore, we have shown that MSCs overexpressing Akt1 (Akt-MSCs) exert even greater cytoprotection than unmodified MSCs. Thus far, little has been reported on the metabolic characteristics of infarcted hearts treated with stem cells. Here we hypothesize that Akt-MSC administration may influence the metabolic processes involved in cardiac adaptation and repair after MI.
Methods and Results
MI was performed in rats randomised in four groups: sham group and animals treated with control MSCs, Akt-MSCs or phosphate buffer solution (PBS). High energy metabolism and basal 2-deoxy-glucose (2-DG) uptake were evaluated on isolated hearts using phosphorous-31 nuclear magnetic resonance spectroscopy at 72 hours and two weeks after MI. Treatment with Akt-MSCs spared phosphocreatine stores and significantly limited the increase in 2-DG uptake in the residual intact myocardium compared to the PBS or the MSC treated animals. Furthermore, Akt-MSC treated hearts had normal pH, whereas low pH was measured in the PBS and MSC groups. Correlative analysis indicated that functional recovery after MI was inversely related to the rate of 2-DG uptake.
We conclude that administration of MSCs overexpressing Akt at the time of infarction results in preservation of normal metabolism and pH in the surviving myocardium.
PMCID: PMC2873075  PMID: 19353525
metabolism; glucose uptake; paracrine effect; mesenchymal stem cell; myocardial infarction
The Iowa Orthopaedic Journal  2010;30:109-114.
Survey studies have concluded that a lack of consensus exists between orthopaedic surgeons on indications for total hip and knee arthroplasty. Geographic variation in the rates of these operations has raised concerns that some surgeons inappropriately indicate healthier patients for surgery than others. The objective of this study was to compare primary hip and knee arthroplasty patients’pre-operative validated outcome scores between four orthopaedic surgeons operating at a single academic institution from 2003 to 2007.
A retrospective chart review was performed using CPT-4 codes to identify patients who underwent primary total hip or knee arthroplasty at our institution between June 2003 and June 2007. Pre-operative SF-36 and WOMAC scores were recorded for each patient Patient demographics including age, gender, body mass index (BMI), number of co-morbidities, life orientation score (a measure of patient optimism), smoking and alcohol use, education level, and occupation were also recorded. Statistical analysis using unbalanced analysis of variance (ANOVA) and Chi-Square test were used to compare data between the surgeons, with statistical significance set at P < 0.05.
There was no statistically significant difference in SF-36 or WOMAC stiffness and function scores between the surgeons. There was a small difference in WOMAC pain scores between the surgeons’total knee patients, but not total hip patients. The number of primary hip and total knee replacements performed by each surgeon ranged from 151 to 955, with a total of 1896 primary joint replacements by the four surgeons during the study period.
Patients undergoing primary total joint arthroplasty at our institution were equally disabled between four surgeons, despite the surgeons performing variable numbers of the procedures. Further comparative effectiveness research using validated outcome measures is warranted.
PMCID: PMC2958281  PMID: 21045982

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