APPENDIX Supplemental Methods Literature Search Strategy Electronic searches were performed using Ovid Medline, Pubmed, Cochrane Central Register of Controlled Trials (CCTR), Cochrane Database of Systematic Reviews (CDSR), ACP Journal Club, and Database of Abstracts of Review of Effectiveness (DARE), from their dates of inception to April 2016. To achieve maximum sensitivity of the search strategy, we combined the terms “anaortic”, “no-touch”, “aorta”, “off-pump”, “coronary artery bypass grafting”, “proximal anastomosis”, “stroke”, “neurological complications”, “cerebral ischemia”, and “cerebrovascular accident” as both text keywords and exploded MeSH headings where possible. For an additional review of randomized and non-randomized studies comparing the use of single versus double aortic clamp in on-pump CABG, the terms “single”, “double”, “multiple”, “partial-occluding”, “clamp”, “cross-clamp”, “clamping”, “on-pump”, “coronary artery bypass grafting”, “stroke”, “neurological complications”, “cerebral ischemia”, and “cerebrovascular accident” were combined as both text keywords and exploded MeSH headings where possible. Two authors (D.F.Z and M.S) performed the search independently, and any discrepancies were resolved by discussion. The reference lists of all retrieved articles were reviewed for further identification of potentially relevant studies, assessed using the inclusion and exclusion criteria. Selection Criteria Studies specifying the use of single or double (partial-occluding) aortic clamp in onpump CABG were included in separate network and pairwise meta-analyses. Minimally invasive direct CABG, often indicated in single-vessel disease, and on-pump beating-heart CABG were 1 excluded. When institutions published duplicate studies with accumulating numbers of patients or increased lengths of follow-up, only the most complete reports were included for quantitative assessment. All publications were limited to those involving human subjects. Abstracts, case reports, conference presentations, editorials, reviews, and expert opinions were excluded. Data Extraction and Critical Appraisal Because quality scoring is controversial in meta-analyses of observational studies, two reviewers (D.F.Z and M.S) independently appraised each article included in our analysis according to a critical review checklist of the Dutch Cochrane Centre proposed by MOOSE (1). The key points of this checklist include: (I) clear definition of study population; (II) clear definition of outcomes and outcome assessment; (III) independent assessment of outcome parameters; (IV) sufficient duration of follow-up; (V) no selective loss during follow-up; and (VI) important confounders and prognostic factors identified. Outcomes Stroke was defined as cerebrovascular events occurring in the postoperative period unresolved within 24 hours (2). Where available, stroke was diagnosed by a neurologist and confirmed by computed tomographic (CT) scanning or nuclear magnetic resonance imaging (MRI) (3). Operative mortality was defined as any death occurring within 30 days of the procedure (4,5). Peri-operative myocardial infarction was identified by the presence of a new Q wave on the electrocardiogram, a maximal serum creatine kinase MB isoenzyme level of >100 IU/L, or new wall motion abnormalities on echocardiography (4,5). Renal failure was defined as a >50 mM post-operative increase serum creatinine, doubling or greater increase in creatinine over the pre-operative value, or new requirement for dialysis (4,5). Bleeding complication was defined as the need for redo-sternotomy in the presence of more than 500 mL of blood from 2 chest tubes within the first hour, more than 400mLwithin the second hour, more than 300 mL within the third hour, or total bleeding greater than 1000 mL within four hours (6). Postoperative atrial fibrillation was defined as new-onset atrial fibrillation following the operation (7,8). Statistical Analysis Both random and fixed effects analyses were conducted for the Bayesian Markov chain Monte-Carlo model. Predictive distributions (informative priors) for between-study heterogeneity were applied to random effects analyses (9). All-cause mortality informative priors were chosen based on non-pharmacological interventions with objective outcomes (10). The random effects model was adopted for final interpretation of results for its more conservative estimates. Convergence was achieved at 20,000 iterations for all outcomes and lack of autocorrelation was checked and confirmed. A further 30,000 iterations were taken after discarding the burn-in simulation. The variability of results across trials over and above chance (heterogeneity [τ2]) was evaluated, with an τ2 estimate of 0.04 interpreted as a low, 0.14 as a moderate, and 0.40 as a high degree of heterogeneity (11). Comparison with conventional pairwise meta-analysis was also performed for evaluation of model consistency. Relative risk was chosen as a summary statistic with both fixed and random effects models tested. The Mantel–Haenszel test was used to combine discrete data. Inverse variance-weighted averages were used for continuous data and logarithmic risk ratios (RR). The random effects model was used to take into account the possible clinical diversity and methodological variation amongst studies. All P values were two-sided. Additional tests include: χ2 to test heterogeneity between trials; I2 to estimate the percentage of total variation across studies due to heterogeneity rather than chance. I2 can be calculated as follows: I2 = 3 100%×(Q−df)/Q (where Q represents Cochrane’s measure of heterogeneity and df the degrees of freedom). Heterogeneity is substantial when I2 > 50%. Analysis for potential confounding factors was not performed due to the lack of raw data. Statistical analysis was conducted using Review Manager Version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen). The Egger regression asymmetry test was performed for quantitative assessment of publication bias (12). Regression of the standardized effect estimates was tested against precision to determine whether the gradient significantly deviates from zero. Logarithmic summary estimate (risk ratio) and standard error were analyzed. Publication bias is significant when P < 0.05. Statistical analysis was conducted using Stata Statistical Software 14 (College Station, TX) with the metabias module. Supplemental Results Additional analyses Five studies with 15254 patients were included in a subgroup analysis evaluating anOPCABG (2910 patients), OPCABG-PC (3756 patients), single-aortic clamp on-pump CABG (2512 patients), and double-clamp on-pump CABG (6076 patients). Definitions of aortic clamping technique are reported in Online Table 3. Three studies (6,13,14) utilized the singleclamp technique, three studies (14-16) utilized the double-clamp technique (with partialoccluding clamp). Four studies (2,4,17,18) did not specify the aortic clamping strategy and were excluded from the subgroup analysis. The evidence network for the subgroup analysis of postoperative stroke outcomes following anOPCABG, OPCABG-PC, and on-pump CABG with single or double aortic clamp is shown in Online Figure 6A. anOPCABG was associated with a reduction of 81% in the 30-day risk of stroke compared with on-pump CABG using a double-clamping technique (OR 0.19, 95% CI 0.08 – 4 0.38), 77% compared with on-pump CABG using a single-clamping technique (OR 0.23, 95% CI 0.09 – 0.50), and 66% compared with OPCABG-PC (OR 0.34, 95% CI 0.15 – 0.71) (Online Figure 6B). OPCABG-PC was associated with a 43% reduction in stroke risk compared with onpump CABG using a double-clamping technique (OR 0.57, 95% CI 0.32 – 0.87). There were no significant differences between single versus double aortic clamping techniques in on-pump CABG (OR 0.70, 95% CI 0.30 – 1.39) or between OPCABG-PC and onpump CABG with a single aortic cross-clamp (OR 0.81, 95% CI 0.41 – 1.68). Heterogeneity was moderate (τ2 = 0.16). The league table is shown in Online Figure 6C. Bayesian Markov chain Monte-Carlo modeling demonstrated that anOPCABG had the highest probability of having the lowest rate of stroke (SUCRA 99.9%), followed by OPCABG-PC (61.3%), on-pump CABG using a single-clamping technique (29.6%), and on-pump CABG using a double-clamping technique (9.2%) (Online Figure 6D). To confirm model consistency and further evaluate the outcome comparing single versus double-clamping techniques in on-pump CABG, an additional review of all randomized and nonrandomized studies was performed. After application of the inclusion and exclusion criteria, nine (19-27) relevant articles were included in this additional pairwise meta-analysis, including five matched or randomized (19,21,24,26,27) and four unmatched (20,22,23,25) trials. A total of 5153 patients undergoing on-pump CABG were included for analysis with 2559 receiving single and 2594 receiving double aortic clamps. No significant differences were detected between single or double aortic clamp use in the overall pairwise meta-analysis (1.1% vs 1.7%; RR 0.7, 95% CI 0.5–1.2; P = 0.19; I2 = 0%) (Online Figure 7), in matched or randomized studies only (1.2% vs 1.5%; RR 0.8, 95% CI 0.5–1.5; P = 0.52; I2 = 0%) (Online Figure 7.1), or in unmatched studies only (1.1% vs 1.9%; RR 0.6, 95% CI 0.3–1.3; P = 0.19; I2 = 0%) (Online Figure 7.2). 5 The outcome following single versus double-clamping techniques in on-pump CABG was comparable between the subgroup network analysis (OR 0.70, 95% CI 0.30 – 1.39) and additional review and pairwise analysis (RR 0.7, 95% CI 0.5–1.2). 6 Supplemental References 1. Stroup DF, Berlin JA, Morton SC et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283:2008-12. 2. Moss E, Puskas JD, Thourani VH et al. Avoiding aortic clamping during coronary artery bypass grafting reduces postoperative stroke. J Thorac Cardiovasc Surg 2015;149:17580. 3. Matsuura K, Mogi K, Sakurai M, Kawamura T, Takahara Y. Medium-term neurological complications after off-pump coronary artery bypass grafting with and without aortic manipulation. Coron Artery Dis 2013;24:475-80. 4. Misfeld M, Potger K, Ross DE et al. "Anaortic" off-pump coronary artery bypass grafting significantly reduces neurological complications compared to off-pump and conventional on-pump surgery with aortic manipulation. Thorac Cardiovasc Surg 2010;58:408-14. 5. Leacche M, Carrier M, Bouchard D et al. Improving neurologic outcome in off-pump surgery: the "no touch" technique. Heart Surg Forum 2003;6:169-75. 6. Lemma MG, Coscioni E, Tritto FP et al. On-pump versus off-pump coronary artery bypass surgery in high-risk patients: operative results of a prospective randomized trial (on-off study). J Thorac Cardiovasc Surg 2012;143:625-31. 7. Manabe S, Fukui T, Miyajima K et al. Impact of proximal anastomosis procedures on stroke in off-pump coronary artery bypass grafting. J Card Surg 2009;24:644-9. 8. Frendl G, Sodickson AC, Chung MK et al. 2014 AATS guidelines for the prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures. J Thorac Cardiovasc Surg 2014;148:e153-93. 7 9. Turner RM, Jackson D, Wei Y, Thompson SG, Higgins JPT. Predictive distributions for between-study heterogeneity and simple methods for their application in Bayesian metaanalysis. Stat Med 2015;34:984-998. 10. Turner RM, Davey J, Clarke MJ, Thompson SG, Higgins JPT. Predicting the extent of heterogeneity in meta-analysis, using empirical data from the Cochrane Database of Systematic Reviews. Int J Epidemiol 2012. 11. Stettler C, Allemann S, Wandel S et al. Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis. BMJ 2008;337. 12. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-34. 13. Kim KB, Kang CH, Chang WI et al. Off-pump coronary artery bypass with complete avoidance of aortic manipulation. Ann Thorac Surg 2002;74:S1377-82. 14. Calafiore AM, Di Mauro M, Teodori G et al. Impact of aortic manipulation on incidence of cerebrovascular accidents after surgical myocardial revascularization. Ann Thorac Surg 2002;73:1387-93. 15. Kapetanakis EI, Stamou SC, Dullum MK et al. The impact of aortic manipulation on neurologic outcomes after coronary artery bypass surgery: a risk-adjusted study. Ann Thorac Surg 2004;78:1564-71. 16. Patel NC, Deodhar AP, Grayson AD et al. Neurological outcomes in coronary surgery: independent effect of avoiding cardiopulmonary bypass. Ann Thorac Surg 2002;74:4005; discussion 405-6. 8 17. Emmert MY, Seifert B, Wilhelm M, Grunenfelder J, Falk V, Salzberg SP. Aortic notouch technique makes the difference in off-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg 2011;142:1499-506. 18. Izumoto H, Oka T, Kawazoe K, Ishibashi K, Yamamoto F. Individualized off-pump all internal thoracic artery revascularization. Ann Thorac Cardiovasc Surg 2009;15:155-9. 19. Araque JC, Greason KL, Li Z et al. On-pump coronary artery bypass graft operation: Is one crossclamp application better than two? J Thorac Cardiovasc Surg 2015;150:145-9. 20. Gasparovic H, Borojevic M, Malojcic B, Gasparovic K, Biocina B. Single aortic clamping in coronary artery bypass surgery reduces cerebral embolism and improves neurocognitive outcomes. Vasc Med 2013;18:275-81. 21. Hammon JW, Stump DA, Butterworth JF et al. Single crossclamp improves 6-month cognitive outcome in high-risk coronary bypass patients: the effect of reduced aortic manipulation. J Thorac Cardiovasc Surg 2006;131:114-21. 22. Ates M, Yangel M, Gullu AU, Sensoz Y, Kizilay M, Akcar M. Is single or double aortic clamping safer in terms of cerebral outcome during coronary bypass surgery? Int Heart J 2006;47:185-92. 23. Sinatra R, Capuano F, Santaniello E, Tonelli E, Roscitano A. Occluding clamp technique during coronary artery bypass grafting: single or double-clamp technique? Ital Heart J 2004;5:450-2. 24. Tsang JC, Morin JF, Tchervenkov CI, Platt RW, Sampalis J, Shum-Tim D. Single aortic clamp versus partial occluding clamp technique for cerebral protection during coronary artery bypass: a randomized prospective trial. J Card Surg 2003;18:158-63. 9 25. Grega MA, Borowicz LM, Baumgartner WA. Impact of single clamp versus double clamp technique on neurologic outcome. Ann Thorac Surg 2003;75:1387-91. 26. Dar MI, Gillott T, Ciulli F, Cooper GJ. Single aortic cross-clamp technique reduces S100 release after coronary artery surgery. Ann Thorac Surg 2001;71:794-6. 27. Bertolini PS, F.; Montalbano, G., Pessotto, R., Mazzucco, A. Single aortic cross-clamp technique in coronary surgery: a prospective randomized study. Eur J Cardiothorac Surg 1997;12:413-418. 10 Supplemental Figure 1: Funnel plot for assessment of publication bias in network metaanalysis of coronary artery bypass grafting with and without manipulation of the aorta. Outcomes shown for (A) anOPCABG vs CABG; (B) anOPCABG vs OPCABG-PC. The logit event rate for outcomes (horizontal axis) is presented against the standard error (SE) of the log of logit event rate (vertical axis). SE inversely corresponds to study size. Asymmetry of the plot may indicate publication bias. RR, risk ratio. 11 Supplemental Figure 2: Forest plots for coronary artery bypass grafting with and without manipulation of the aorta. Outcomes shown for (2.1) stroke, (2.2) mortality, (2.3) myocardial infarction, (2.4) renal failure, (2.5) bleeding complications, and (2.6) atrial fibrillation following anOPCABG vs CABG in pairwise meta-analysis of coronary artery bypass grafting with and without manipulation of the aorta. anOPCABG, anaortic off-pump coronary artery bypass grafting; CABG, coronary artery bypass grafting; RR, risk ratio; CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel. 12 13 Supplemental Figure 3: Forest plots for coronary artery bypass grafting with and without manipulation of the aorta. Outcomes shown for (3.1) stroke, (3.2) mortality, (3.3) myocardial infarction, (3.4) renal failure, (3.5) bleeding complications, and (3.6) atrial fibrillation risk following anOPCABG vs OPCABG-PC in pairwise meta-analysis of coronary artery bypass grafting with and without manipulation of the aorta. anOPCABG, anaortic off-pump coronary artery bypass grafting; OPCABG-PC, off-pump coronary artery bypass grafting with partial clamp; RR, risk ratio; CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel. 14 15 Supplemental Figure 4: Forest plots for coronary artery bypass grafting with and without manipulation of the aorta. Outcomes showing stroke risk following OPCABG-HS vs CABG in pairwise meta-analysis of off-pump coronary artery bypass grafting with and without manipulation of the aorta. OPCABG-HS, off-pump coronary artery bypass grafting with the Heartstring system; CABG, coronary artery bypass grafting; RR, risk ratio; CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel. 16 Supplemental Figure 5: Forest plots for coronary artery bypass grafting with and without manipulation of the aorta. Outcomes shown for (5.1) ICU length of stay after anOPCABG vs CABG, (5.2) hospital length of stay after anOPCABG vs OPCABG-PC, and (5.3) ICU length of stay after anOPCABG vs OPCABG-PC. ICU, intensive care unit; anOPCABG, anaortic offpump coronary artery bypass grafting; OPCABG-PC, off-pump coronary artery bypass grafting with partial clamp; CABG, coronary artery bypass grafting; RR, risk ratio; CI, confidence interval; df, degrees of freedom; IV, inverse variance. 17 Supplemental Figure 6: Network meta-analysis of postoperative stroke following coronary artery bypass grafting with different on-pump aortic clamping techniques. (A) Network diagram. The number of patients in each group is proportional to the size of the circle. The number of direct comparisons is represented by the width of the connecting line. A, anaortic offpump coronary artery bypass grafting; PC, off-pump coronary artery bypass grafting with partial clamp; CS, on-pump coronary artery bypass grafting with single clamp; CD, on-pump coronary artery bypass grafting with double clamp. (B) Forest plot. anOPCABG, anaortic off-pump coronary artery bypass grafting; OPCABG-PC, off-pump coronary artery bypass grafting with partial clamp; CABG-Single, on-pump coronary artery bypass grafting with single clamp; CABG-Double, on-pump coronary artery bypass grafting with double clamp; OR, odds ratio; CI, confidence interval; Inform, informative prior. (C) League table (odds ratios and 95% confidence intervals). Odds ratio <1 means the treatment in top left is better. (D) Rankogram showing the likelihood of reducing postoperative stroke. SUCRA, surface under the cumulative ranking. 18 19 Supplemental Figure 7: Forest plots for on-pump coronary artery bypass grafting with single or double aortic clamp. Stroke outcomes shown for (7.1) matched or randomized trials, (7.2) unmatched trials. CS, on-pump coronary artery bypass grafting with single clamp; CD, onpump coronary artery bypass grafting with double clamp.; RR, risk ratio; CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel. 20 Supplemental Figure 8: Forest plots for coronary artery bypass grafting with and without manipulation of the aorta. Outcomes shown for (8.1) stroke, (8.2) mortality, (8.3) myocardial infarction, (8.4) renal failure, (8.5) bleeding, and (8.6) atrial fibrillation risk following combined off-pump techniques vs on-pump CABG in pairwise meta-analysis of coronary artery bypass grafting with and without manipulation of the aorta. Off-pump, combined off-pump coronary artery bypass grafting techniques; On-pump, on-pump coronary artery bypass grafting; RR, risk ratio; CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel. 21 22 Supplemental Table 1. MOOSE quality assessment for included studies in network meta-analysis of coronary artery bypass grafting with and without manipulation of the aorta. Important Clear definition Clear definition of Independent Sufficient Sufficient No selective confounders and of study outcomes and assessment of duration of sample loss during prognostic factors First author population outcome assessment outcome parameters follow-up size follow-upd identified Moss Yes Yes Nod Yes Yes Yes Yes Lemma Noa Yes Yes Yes Nof Yes Yes Matsuura Yes Yes Yes Yes Yes Yes Yes Emmert Yes Yes Yes Yes Yes Yes Yes Misfield Yes Yes Yes Yes Yes Yes Yes Manabe Yes Yes Yes Yes Yes Yes Yes Izumoto Yes Noc Nod Yes Nof Yes Yes Lev-Ran Yes Yes Yes Yes Yes Yes Yes Kapetanakis Yes Yes Yes Yes Yes Yes Yes Leacche Yes Nod Yes Nof Yes Yes Yes 23 Patel Yes Yes Nod Yes Yes Yes Yes Kim Yes Yes Yes Yes Yes Yes Yes Calafiore Yes Yes Yes Yes Yes Yes Yes a anOPCABG population not explicitly stated in article – data acquired from correspondence with author; bdetailed definition and assessment of stroke shown in Supplementary Table 2; cdefinition of stroke not adequately described; ddiagnosis of stroke not independently confirmed by a neurologist; eall outcomes were 30-day or post-operative; fnumber of patients in anOPCABG is less than 100 24 Supplemental Table 2. Usage of epi-aortic ultrasonography and definition of stroke for network meta-analysis of coronary artery bypass grafting with and without manipulation of the aorta. Epi-aortic ultrasound First author Moss (mean grade ) Stroke definition and assessment Performed in majority Any confirmed neurologic deficit of abrupt onset caused by a disturbance in blood of patientsa supply to the brain that did not resolve within 24 hours anOPCABG 2.13 CABG 1.44 OPCABGPC HS 1.35 2.38 A neurological deficit confirmed by brain MRI or CT; diagnosed by neurologist and Matsuura NR radiologist 25 Lemma NR Neurologic deficit lasting>24 hours with positive computed tomography findings A new neurologic deficit that appears and remains evident for more than 24 hours after on-set and occurs during or after the CABG procedure; diagnosed before discharge; diagnosis confirmed by neurologist and brain imaging; transient ischemic attacks, Emmert Not implemented intellectual impairment, confusion, or irritation excluded Focal or global neurological deficits evident after emergence from anesthesia and diagnosed by neurologist and confirmed by computed tomographic scanning (CT) or nuclear magnetic resonance imaging (MRI); a prolonged or permanent neurological Misfield Manabe anOPCABG OPCABG- Routinely performed deficit persisting for more than 72 hours Conducted in patients Any new global or focal neurological deficit; confirmed by computed tomography or receiving aortic magnetic resonance imaging (MRI); diagnosed definitively by an attending neurologist; proximal anastomosisb reversible ischemic events excluded Severe Moderate 26 PC HS Izumoto Less than mild NR NR Any global or focal neurologic deficit evident after emergence from anesthesia and categorized as either permanent or reversible (transient ischemic attacks and prolonged reversible ischemic neurologic deficit); all neurologic events were evaluated by Lev-Ran Performed selectively neurologist and further assessed by computed tomographic scan Postoperatively occurring new focal neurologic deficit; persisting for longer than 72 hours after onset; diagnosed by clinical findings; confirmed by neurologist or brain imaging (head computed tomography or magnetic resonance imaging); noted before Not performed Kapetanakis discharge or death; transient neurologic events, intellectual impairment, and confusional or irritable states excluded A new focal neurologic deficit confirmed by clinical findings and computed Leacche Not routinely used tomographic scan; stroke defined as postoperative if occurred after a normal 27 postoperative period A new focal neurologic deficit or a comatose state occurring postoperatively that persisted for more than 24 hours after onset; noted before discharge or death; transient neurologic events, confusional states, or intellectual impairment excluded; resident and Patel Not performed consultant medical staff made the diagnosis of focal neurologic deficit An interview and neurologic evaluation by a neurologist, carotid duplex ultrasonography, and transcranial Doppler or magnetic resonance angiography; stroke defined as a new and sudden onset of neurologic deficits lasting more than 24 hours Kim NR with no apparent nonvascular causes A focal or global cerebral dysfunction of presumed vascular origin lasting more than 24 hours; diagnosed by a neurologist and confirmed by a brain computed tomographic Calafiore a Not performed scan or nuclear magnetic resonance image Aortic grading ranges from 1 to 5: 1, normal (<2 mm thickness); 2, minimal disease (2-3 mm thickness); 3, moderate disease (3-5 mm thickness); 4, severe disease (>5mm thickness); 5, mobile plaque present in the ascending aorta; bascending aortic atherosclerotic 28 disease was defined as normal/mild (intimal thickness <3 mm), moderate (intimal thickness 3 mm to 5 mm), and severe (intimal thickness >5 mm; or the presence of marked calcification, protruding mobile intraluminal atheromatous portions, and ulcerated plaques) anOPCABG, anaortic off-pump coronary artery bypass grafting; OPCABG-PC, off-pump coronary artery bypass grafting with partial clamp; OPCABG-HS, off-pump coronary artery bypass grafting with the Heartstring system; CABG, coronary artery bypass grafting 29 Supplemental Table 3. On-pump CABG aortic cross-clamping techniques and definitions in network meta-analysis of coronary artery bypass grafting with and without manipulation of the aorta. Aortic cross-clamping First author technique N Definition Calafiore Single 2233 Cardiopulmonary bypass with aortic cannulation and crossclamping, with no side-clamping Double 597 Cardiopulmonary bypass with aortic cannulation and crossclamping, with side-clamping Kim Single 76 Proximal anastomosis of free grafts was performed during a single cross-clamp period Lemma Single 203 Cardiopulmonary bypass performed with single crossclamping of the ascending aorta Patel Double 1210 Following completion of distal anastomoses, aortic cross- 30 clamp removed and proximal anastomoses made with single application of side-biting clamp Kapetanakis Double 4269 Full plus tangential (side-biting) aortic clamp application Izumoto NR NR All distal anastomoses performed with cardiopulmonary bypass, aortic cross clamp, and cardioplegic arrest Misfeld NR NR 37.0% received side-biting clamps Emmert NR NR Conventional on-pump approach with aortic cross-clamping Moss NR NR 1 or 2 (cross-clamp and partial-occluding clamp) aortic clamps were used Single, on-pump coronary artery bypass grafting with single aortic cross-clamp; Double, on-pump coronary artery bypass grafting with double aortic-clamping technique; NR, not reported. 31
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