The authors undertook a meta-analysis of 37 randomized trials (3369 patients) of off-pump coronary artery bypass surgery versus conventional coronary artery bypass surgery. No significant differences ...were found for 30-day mortality (odds ratio OR, 1.02; 95% confidence interval CI, 0.58-1.80), myocardial infarction (OR, 0.77; 95%CI, 0.48-1.26), stroke (OR, 0.68; 95%CI, 0.33-1.40), renal dysfunction, intraaortic balloon pump, wound infection, rethoracotomy, or reintervention. However, off-pump coronary artery bypass surgery significantly decreased atrial fibrillation (OR, 0.58; 95%CI, 0.44-0.77), transfusion (OR, 0.43; 95%CI, 0.29-0.65), inotrope requirements (OR, 0.48; 95%CI, 0.32-0.73), respiratory infections (OR, 0.41; 95%CI, 0.23-0.74), ventilation time (weighted mean difference, -3.4 h; 95%CI, -5.1 to -1.7 h), intensive care unit stay (weighted mean difference, -0.3 days; 95%CI -0.6 to -0.1 days), and hospital stay (weighted mean difference, -1.0 days; 95%CI -1.5 to -0.5 days). Patency and neurocognitive function results were inconclusive. In-hospital and 1-yr direct costs were generally higher for conventional coronary artery bypass surgery versus off-pump coronary artery bypass surgery. Therefore, this meta-analysis demonstrates that mortality, stroke, myocardial infarction, and renal failure were not reduced in off-pump coronary artery bypass surgery surgery; however, selected short-term and mid-term clinical and resource outcomes were improved compared with conventional coronary artery bypass surgery.
Acute kidney injury (AKI) after cardiac surgery is a major health issue. Lacking effective therapies, risk factor modification may offer a means of preventing this complication. The objective of the ...present study was to identify and determine the prognostic importance of such risk factors.
Data from a multicenter cohort of 3500 adult patients who underwent cardiac surgery at 7 hospitals during 2004 were analyzed (using multivariable logistic regression modeling) to determine the independent relationships between 3 thresholds of AKI (>25%, >50%, and >75% decrease in estimated glomerular filtration rate within 1 week of surgery or need for postoperative dialysis) with death rates, as well as to identify modifiable risk factors for AKI. The 3 thresholds of AKI occurred in 24% (n=829), 7% (n=228), and 3% (n=119) of the cohort, respectively. All 3 thresholds were independently associated with a >4-fold increase in the odds of death and could be predicted with several perioperative variables, including preoperative intra-aortic balloon pump use, urgent surgery, and prolonged cardiopulmonary bypass. In particular, 3 potentially modifiable variables were also independently and strongly associated with AKI. These were preoperative anemia, perioperative red blood cell transfusions, and surgical reexploration.
AKI after cardiac surgery is highly prevalent and prognostically important. Therapies aimed at mitigating preoperative anemia, perioperative red blood cell transfusions, and surgical reexploration may offer protection against this complication.
: This meta-analysis sought to determine whether minimally invasive mitral valve surgery (mini-MVS) improves clinical outcomes and resource utilization compared with conventional open mitral valve ...surgery (conv-MVS) in patients undergoing mitral valve repair or replacement.
: A comprehensive search of MEDLINE, Cochrane Library, EMBASE, CTSnet, and databases of abstracts was undertaken to identify all randomized and nonrandomized studies up to March 2010 of mini-MVS through thoracotomy versus conv-MVS through median sternotomy for mitral valve repair or replacement. Outcomes of interest included death, stroke, myocardial infarction, aortic dissection, need for reintervention, and any other reported clinically relevant outcomes or indicator of resource utilization. Relative risk and weighted mean differences and their 95% confidence intervals were analyzed as appropriate using the random effects model. Heterogeneity was measured using the I statistic.
: Thirty-five studies met the inclusion criteria (two randomized controlled trials and 33 nonrandomized studies). The mortality rate after mini-MVS versus conv-MVS was similar at 30 days (1.2% vs 1.5%), 1 year (0.9% vs 1.3%), 3 years (0.5% vs 0.5%), and 9 years (0% vs 3.7%). A number of clinical outcomes were significantly improved with mini-MVS versus conv-MVS including atrial fibrillation (18% vs 22%), chest tube drainage (578 vs 871 mL), transfusions, sternal infection (0.04% vs 0.27%), time to return to normal activity, and patient scar satisfaction. However, the 30-day risk of stroke (2.1% vs 1.2%), aortic dissection/injury (0.2% vs 0%), groin infection (2% vs 0%), and phrenic nerve palsy (3% vs 0%) were significantly increased for mini-MVS versus conv-MVS. Other clinical outcomes were similar between groups. Cross-clamp time, cardiopulmonary bypass time, and procedure time were significantly increased with mini-MVS; however, ventilation time and length of stay in intensive care unit and hospital were reduced.
: Current evidence suggests that mini-MVS maybe associated with decreased bleeding, blood product transfusion, atrial fibrillation, sternal wound infection, scar dissatisfaction, ventilation time, intensive care unit stay, hospital length of stay, and reduced time to return to normal activity, without detected adverse impact on long-term need for valvular reintervention and survival beyond 1 year. However, these potential benefits for mini-MVS may come with an increased risk of stroke, aortic dissection or aortic injury, phrenic nerve palsy, groin infections/complications, and increased cross-clamp, cardiopulmonary bypass, and procedure time. Available evidence is largely limited to retrospective comparisons of small cohorts comparing mini-MVS versus conv-MVS that provide only short-term outcomes. Given these limitations, randomized controlled trials with adequate power and duration of follow-up to measure clinically relevant outcomes are recommended to determine the balance of benefits and risks.
: The purpose of this consensus conference was to deliberate the evidence regarding whether minimally invasive mitral valve surgery via thoracotomy improves clinical and resource outcomes compared ...with conventional open mitral valve surgery via median sternotomy in adults who require surgical intervention for mitral valve disease.
: Before the consensus conference, the consensus panel reviewed the best available evidence up to March 2010, whereby systematic reviews, randomized trials, and nonrandomized trials were considered in descending order of validity and importance. The accompanying meta-analysis article in this issue of the Journal provides the systematic review of the evidence. Based on this systematic review, evidence-based statements were created for prespecified clinical questions, and consensus processes were used to derive recommendations. The American Heart Association/American College of Cardiology system was used to label the level of evidence and class of each recommendation.
: Considering the underlying level of evidence, and notwithstanding the limitations of the evidence base (retrospective studies with important differences in baseline patient characteristics, which may produce bias in results of the evidence syntheses), the consensus panel provided the following evidence-based statements and overall recommendation:In patients with mitral valve disease, minimally invasive surgery may be an alternative to conventional mitral valve surgery (Class IIb), given that there was comparable short-term and long-term mortality (level B), comparable in-hospital morbidity (renal, pulmonary, cardiac complications, pain perception, and readmissions) (level B), reduced sternal complications, transfusions, postoperative atrial fibrillation, duration of ventilation, and intensive care unit and hospital length of stay (level B). However, this should be considered against the increased risk of stroke (2.1% vs 1.2%) (level B), aortic dissection (0.2% vs 0%) (level B), phrenic nerve palsy (3% vs 0%) (level B), groin infections/complications (2% vs 0%) (level B), and, prolonged cross-clamp time, cardiopulmonary bypass time, and procedure time (level B). The available evidence consists almost entirely of observational studies and must not be considered definitive until future adequately controlled randomized trials further address the risk of stroke, aortic complications, phrenic nerve complications, pain, long-term survival, need for reintervention, quality of life, and cost-effectiveness.
Head and neck squamous cell carcinomas (HNSCC) are treated with surgery, radiotherapy and cisplatin-based chemotherapy, but survival from locally-advanced disease remains poor, particularly in ...patients whose tumors are negative for Human papillomavirus (HPV). Type 1 IGF receptor (IGF-1R) is known to promote tumorigenesis and resistance to cancer therapeutics. Here, we assessed IGF-1R immunohistochemistry on tissue microarrays containing 852 cores from 346 HNSCC patients with primary tumors in the oropharynx (n = 231), larynx (85), hypopharynx (28), oral cavity (2). Of these, 236 (68%) were HPV-negative, 110 (32%) positive. IGF-1R was detected in the cell membrane of 36% and cytoplasm of 92% of HNSCCs; in 64 cases with matched normal tonsillar epithelium, IGF-1R was overexpressed in the HNSCCs (P < 0.001). Overall survival (OS) and disease-specific survival (DSS) were reduced in patients whose tumors contained high membrane IGF-1R OS: hazard ratio (HR) = 1.63, P = 0.006; DSS: HR = 1.63, P = 0.016, cytoplasmic IGF-1R (OS: HR = 1.58, P = 0.009; DSS: HR = 1.58, P = 0.024) and total IGF-1R (OS: HR = 2.02, P < 0.001; DSS: HR = 2.2, P < 0.001). High tumor IGF-1R showed significant association with high-tumor T-stage (P < 0.001) and HPV-negativity (P < 0.001), and was associated with shorter OS when considering patients with HPV-positive (P = 0.01) and negative (P = 0.006) tumors separately. IGF-1R was independently associated with survival in multivariate analysis including HPV, but not when lymphovascular invasion, perineural spread and T-stage were included. Of these factors, only IGF-1R can be manipulated; the association of IGF-1R with aggressive disease supports experimental incorporation of anti-IGF-1R agents into multimodality treatment programs for HPV-negative and high IGF-1R HPV-positive HNSCC.
At this consensus conference, we developed evidence-informed consensus statements and recommendations on the practice of off-pump coronary artery bypass graft (OPCAB) by systematically reviewing and ...performing meta-analysis of the randomized controlled trials (RCTs) comparing OPCAB and conventional coronary artery bypass (CCAB).
All RCTs of OPCAB versus CCAB through April 2013 were screened, and 102 relevant RCTs (19,101 patients) were included in a systematic review and meta-analysis (15 RCTs of 9551 high-risk patients; and 87 RCTs of 9550 low-risk patients) in accordance with the Cochrane Collaboration and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology. Consensus statements for the risks and benefits of OPCAB surgery in mortality, morbidity, and resource use were developed based on best available evidence.
Compared to CCAB, it is reasonable to perform OPCAB to reduce risks of stroke class IIa, level of evidence (LOE) A, renal dysfunction/failure (class IIa, LOE A), blood transfusion (class I, LOE A), respiratory failure (class I, LOE A), atrial fibrillation (class I, LOE A), wound infection (class I, LOE A), ventilation time, and ICU and hospital length of stay (class I, LOE A). However, OPCAB may be associated with a reduced number of grafts performed (class I, LOE A) and with diminished graft patency (class IIa, LOE A, with increased coronary reintervention at 1 year and beyond (class IIa, LOE A), as well as increased mortality at a median follow-up of 5 years (class IIb, LOE A).
OPCAB compared with CCAB may improve outcomes in the short-term (stroke, renal dysfunction, blood transfusion, respiratory failure, atrial fibrillation, wound infection, ventilation time, and length of stay). However, over the longer-term, OPCAB may be associated with reduced graft patency, and increased risk of cardiac re-intervention and death.
Tranexamic acid (TA) reduces blood loss and blood transfusion during heart surgery with cardiopulmonary bypass (CPB). TA dosing has been empiric because only limited pharmacokinetic studies have been ...reported, and CPB effects have not been characterized. We hypothesized that many of the published TA dosing techniques would prove, with pharmacokinetic modeling and simulation, to yield unstable TA concentrations.
Thirty adult patients undergoing elective coronary artery bypass grafting, valve surgery, or repair of atrial septal defect received after induction of anesthesia: TA 50 mg/kg (n = 11), TA 100 mg/kg (n = 10), or TA 10 mg/kg (n = 10) over 15 min, with 1 mg x kg(-1) x hr(-1) maintenance infusion for 10 h. TA was measured in plasma using high performance liquid chromatography. Pharmacokinetic modeling was accomplished using a mixed effects technique. Models of increasing complexity were compared using Schwarz-Bayesian Criterion (SBC).
Tranexamic acid concentrations rapidly fell in all three groups. Data were well fit to a 2-compartment model, and adjustments for CPB were supported by SBC. Assuming a body weight of 80 kg, our model estimates V1 = 10.3 l before CPB and 11.9 l during and after CPB; V2 = 8.5 l before CPB and 9.8 l during and after CPB; Cl1 = 0.15 l/s before CPB, 0.11 l/s during CPB, and 0.17 l/s after CPB; and Cl2 = 0.18 l/s before CPB and 0.21 l/s during and after CPB. Based on simulation of previous studies of TA efficacy, we estimate that a 30-min loading dose of 12.5 mg/kg with a maintenance infusion of 6.5 mg x kg(-1) x hr(-1) and 1 mg/kg added to the pump prime will maintain TA concentration greater than 334 microm, and a higher dose based on 30 mg/kg loading dose plus 16 mg x kg(-1) x h(-1) continuous infusion and 2 mg/kg added to the pump prime would maintain TA concentrations greater than 800 microm.
Tranexamic acid pharmacokinetics are influenced by CPB. Our TA pharmacokinetic model does not provide support for the wide range of TA dosing techniques that have been reported. Variation in TA efficacy from study to study and confusion about the optimal duration of TA treatment may be the result of dosing techniques that do not maintain stable, therapeutic TA concentrations.
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