Association Between Endoscopic vs Open Vein-Graft Harvesting and Mortality, Wound Complications, and Cardiovascular Events in Patients Undergoing CABG Surgery FREE

In the mid-1990s, surgeons began using endoscopic vein-graft harvesting techniques as an alternative to large, incision-based open vein-graft harvesting to improve postoperative discomfort and incision-site complications.^1- 3 The endoscopic vein-graft harvesting technique uses devices cleared by the US Food and Drug Administration (FDA) based on substantial equivalence to devices currently in use without the need for clinical trials of the new device. The perceived advantages of endoscopic vein-graft harvesting led to widespread adoption of the technique, and the devices have been used in the majority of the more than 400 000 coronary artery bypass graft (CABG) surgery procedures performed at US surgical centers each year.⁴

Carefully conducted randomized controlled trials demonstrated the short-term safety and efficacy of endoscopic vein-graft harvesting, but did not assess the long-term outcomes following the endoscopic technique. In 2009, a large observational study called into question the safety of the endoscopic vein-graft harvesting technique.⁵ That study examined 3000 patients undergoing CABG surgery enrolled in the PREVENT IV (PRoject of Ex-vivo Vein graft ENgineering via Transfection IV) trial, which investigated the effect of edifoligide delivered under pressure to vein grafts during CABG surgery procedures. Those patients receiving endoscopic vein-graft harvesting had a higher risk of 1-year angiographic vein-graft failure and higher 3-year mortality than those receiving open vein-graft harvesting technique.⁵ Proposed biological mechanisms for endoscopic technique harm included potentially greater vessel manipulation, venous stasis during harvest caused by the pressurized subcutaneous tunnel, and larger caliber segments of harvested vein with endoscopic techniques. The PREVENT IV findings of increased risk associated with the endoscopic technique were not confirmed in 1 regional study.⁶

The US FDA asked for an analysis of the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) to further assess endoscopic vein-graft harvesting technique use in CABG surgery for the risk of death, myocardial infarction (MI), and repeat revascularization.

The STS ACSD is the largest specialty-specific clinical data registry in the world. The STS ACSD currently houses data from 1091 participants, representing nearly 90% of the cardiac surgery centers in the United States. Participating centers report more than 300 data elements for each episode of cardiac surgery using a standardized data collection form. Race/ethnicity data were collected by open-ended patient designation and used based on previous literature reporting differences in surgical procedure utilization and outcomes associated with these variables. In collaboration with the Duke Clinical Research Institute's outcomes research group, the STS has developed mortality, morbidity, and length-of-stay risk models for CABG surgery and other major adult cardiac surgery procedures.^4,7 The quality of the STS ACSD data has been assessed in a regional independent chart abstraction study, which documented a 96% correlation between submitted and reabstracted data elements.⁸

The STS ACSD has previously been limited to perioperative episodes of care with outcomes truncated at 30 days or hospital discharge. For the purposes of our study, we used the capability to link STS ACSD registry files with the Centers for Medicare & Medicaid Services (CMS) Parts A and B claims database.⁹ The STS ACSD records were matched with Medicare inpatient claims data using previously validated deterministic matching techniques and indirect identifiers, including admission date, discharge date, patient age, and hospital center.¹⁰ Linkage with Medicare Part A data afforded the measurement of mid-term to long-term outcomes.

Institutional review board approval and the processing of data sharing agreements were achieved before proceeding with any analyses. A waiver of patient informed consent was applied for and obtained from the Duke University institutional review board.

Because the STS ACSD only began collecting information on harvest technique (endoscopic vs open) on January 1, 2008, linkage to Medicare Part B data (professional billing) was used to determine whether CABG surgery cases used endoscopic vein-graft harvest technique. Endoscopic vein-graft harvest technique is coded in Medicare Part B claims with current procedural terminology (CPT) code 33508.

The study population consisted of patients with primary isolated CABG surgery having at least 1 vein graft and enrolled in the STS ACSD between 2003 and 2008 (Figure 1). Exclusions included (1) emergent/salvage procedure, (2) prior CABG surgery, (3) radial artery or right internal mammary artery grafting, and (4) patients without an internal mammary artery graft. Presence of at least 1 vein graft was confirmed by STS ACSD records and CMS Part B CPT codes 33510 to 33523 occurring on the same day as the CABG surgery procedure in the corresponding CMS Part A claim.

The primary outcome measure was all-cause mortality, obtained through the linkage of STS registry data to the Medicare denominator file. Myocardial infarction and revascularization requiring rehospitalization were identified using Medicare Part A data. The International Classification of Diseases, Ninth Revision (ICD-9) codes 410.x1 were used to identify MI following hospital discharge. For revascularization, ICD-9 codes 36.10-19 (CABG surgery) and 0066, 36.01-09, 3602 (percutaneous coronary intervention) were used.

Wound complication was identified in-hospital following CABG surgery using the STS ACSD. The STS ACSD defines harvest site wound complication by the presence of any of the following: wound opened with excision of tissue (incision and drainage), positive culture, or treated with antibiotics. Furthermore, suspected leg wound complications occurring following hospital discharge and within the first postoperative month were identified through Medicare Part A data (disruption of operative wound, 998.32; postoperative infection, 998.5x; nonhealing surgical wound, 998.83). Any episode of systemic sepsis occurring following hospital discharge and within the first postoperative month was considered surgery related and was identified through Medicare Part A data (sepsis/systemic inflammatory response syndrome, 995.90-995.92 and 998.59; septicemia, 038.0x-038.9x).

Baseline demographic and operative characteristics were summarized as percentages for categorical variables and as medians with interquartile ranges for continuous variables. Baseline characteristics were also summarized for STS ACSD patients meeting study inclusion criteria who were successfully linked vs not linked to Medicare files.

Propensity scores with inverse probability weights (IPW) were developed to adjust for differences in baseline characteristics between the 2 treatment groups. The propensity score represents the estimated probability of patients receiving endoscopic vs direct vein harvest as a function of the covariates in the propensity model.¹¹ Propensity scores were estimated using a nonparsimonious logistic regression model, including each of the variables shown in Table 1.

The ability of the propensity model to balance the 2 treatment groups was assessed in 2 ways. First, we compared the distribution of estimated propensity scores in the 2 treatment groups to ensure that there was a high degree of overlap. The 5-number summaries (minimum, 25th, 50th, 75th, maximum) of the propensity distributions in each treatment group were similar (endoscopic: 14.5%, 48.6%, 58.7%, 65.8%, 84.7%; and open: 14.2%, 35.7%, 49.1%, 59.8%, 80.0%), suggesting that comparisons based on the propensity score were statistically appropriate. To further increase the comparability between the 2 groups, patients with propensity scores that were not in the range of overlapping propensity distributions (ie, <14.5% or >80.0%) were removed from the risk-adjusted analysis. Second, we compared the distribution of patient characteristics across the 2 treatment groups before and after weighting the observations based on the propensity score. After propensity weighting, the observed differences in covariates were small and in all cases were less than 1% of the estimated SD.¹²

For comparison of wound complications within the first postoperative month, the unadjusted odds ratio (OR) was estimated using generalized estimating equation models to account for potential clustering of similar patients within sites and using a logit link function having a single covariate for treatment group.¹³ The adjusted OR was estimated by fitting a similar generalized estimating equation model and weighting each observation by the inverse of the estimated propensity score.¹⁴ Robust sandwich variance estimates were used to obtain 95% CIs. Statistical tests were 2-sided and performed at the 5% level of significance.

The difference between treatment groups in long-term all-cause mortality and the composite of death, MI, and revascularization were compared with time-to-event analyses. Patient follow-up was considered to be censored at the end of the study period (December 31, 2008). The unadjusted hazard ratio (HR) for endoscopic vs open vein-graft harvesting was estimated in a Cox proportional hazard regression model with a single treatment group indicator, stratified by surgical year to allow year-specific baseline hazard. The risk-adjusted HR was estimated by fitting the similar model and weighting each observation by the inverse of the estimated propensity score.¹⁵ To account for the correlation of patients' failure time within the same participant site (cluster), a robust sandwich covariance estimator with an independent working covariance matrix was used to obtain 95% CIs of coefficients under the assumption of a common baseline hazard within a cluster.¹⁶ The unadjusted mortality cumulative incidence rate was estimated for each treatment group using the product-limit method of Kaplan and Meier¹⁷; the propensity-adjusted incidence rate was calculated for each treatment group using a weighted version of the Breslow estimator.¹⁸

Because the STS ACSD only began collecting information on harvest technique (endoscopic vs open) on January 1, 2008, the 2008 data have endoscopic vein-graft harvest coding from both CMS carrier claim and STS ACSD. For each individual center performing CABG surgery, the sensitivity and specificity of Medicare Part B capture of endoscopic vs open vein-graft harvest techniques were calculated using 2008 STS ACSD reporting of endoscopic as the reference standard. Centers having more than 80% sensitivity and specificity for endoscopic coding, which included 44 423 patients at 165 sites, were also identified for a planned sensitivity analysis to evaluate the potential effect of endoscopic data collection error. Among these 165 sites, the sensitivity and specificity of identifying endoscopic technique were 93% and 96%, respectively.

Because our primary Cox proportional hazard regression model analysis did not account for measurement error in the Medicare-derived endoscopic variable, we refit the model using the estimation technique of corrected score estimation as described by Zucker and Spiegelman.¹⁹ The published corrected score estimation method was modified to allow for tied observations, stratum variables, and center-level clustering, and the simplifying assumption was made so that measurement error was nondifferential and could be modeled by 2 parameters, sensitivity and specificity. The association of interest was then estimated across a range of plausible estimates for sensitivity (0.60% to 1.00%) and specificity (0.85% to 1.00%) based on our previous study of endoscopic coding accuracy using the PREVENT IV database and 2008 STS data.

The influence of unmeasured confounders on the estimated HR of death or the composite of death, MI, or revascularization for the endoscopic vs open vein-graft harvest groups was further evaluated using the method of Lin et al.²⁰ This method uses a regression model, including the exposure of interest (vein harvest method) as well as measured and unmeasured confounders to make statistical inferences about the true exposure effect by specifying distributions of an unmeasured confounder in the study groups along with effects of an unmeasured confounder on outcomes. The effect of departure from randomization due to unbalanced prevalence of an unmeasured confounder was assessed on a range of possible HR values of that confounder for the exposure variable.

Subpopulations were identified using STS data files, including diabetes mellitus (yes or no), body mass index (BMI, calculated as weight in kilograms divided by height in meters squared; <30, 30-34, and ≥35), and number of vein grafts (1, 2, and ≥3). Separate propensity models were fit within these subgroups. To estimate strata-specific treatment effects, the IPW Cox proportional hazard regression and logistic models were applied, as previously described, within each stratum of these 3 prespecified subpopulations.

A cohort of 235 394 patients from 934 US sites met study inclusion criteria and was available for analysis, including 122 899 endoscopic and 112 495 open vein-graft harvest cases (Figure 1). Table 1 shows demographic and operative characteristics before and after propensity score adjustment among these patients. The mean age was 74 years for both the endoscopic and open vein-graft harvest groups, an age typical for a Medicare population given we only included patients eligible for Medicare insurance at the time of their CABG surgery. Baseline patient characteristics were generally balanced across the treatment groups, including age (endoscopic: 74 years [95% CI, 69-78 years] vs open: 74 years [95% CI, 69-78 years]), BMI (28.5 [95% CI, 25-31] vs 28.4 [95% CI, 25-31]), prevalence of peripheral vascular disease (17.9% vs 18.0%), active smoking (13.9% vs 13.5%), diabetes mellitus requiring insulin (10.1% vs 9.9%), and urgent case status (48.9% vs 49.2%). The year of surgery (2003 to 2008) was imbalanced between treatment groups, with later years of study reporting more endoscopic vein-graft harvest cases than earlier years. The year 2003 accounted for 9% of the endoscopic cases captured in the study, and the proportion increased each year with 21% of the endoscopic cases being performed in 2008. This trend was reversed for open cases, with 24% of the open cases being performed in 2003 vs only 11% in 2008. Overall, in 2008, 70% of the vein-graft harvests captured in our study were performed endoscopically. Following propensity score adjustment, all observed covariates were balanced across treatment groups (Table 1). The complete list of all patient demographic and operative characteristics before and after propensity score adjustment using IPW is shown in eTable 1).

A comparison of demographic characteristics and in-hospital outcomes for Medicare linked vs not-linked STS ACSD patients meeting study inclusion criteria revealed these groups of patients to be generally similar with regard to most variables of interest. However, the successfully linked STS to Medicare patients were less likely to be urgently (vs electively) operated (49.2% linked vs 53.9% not-linked, P < .001) and less likely to experience in-hospital MI (0.99% vs 1.1%, P < .001), wound complication (3.0% vs 3.6%, P < .001), and death (2.3% vs 2.5%, P = .001). A summary of pertinent baseline variables and short-term outcomes according to Medicare linkage for all STS ACSD patients meeting study inclusion criteria is shown in eTable 2.

Median follow-up was 3 years (range, 0-6 years). Table 2 shows the cumulative incidence rates for death, the composite of death, MI, or revascularization, and wound complications for endoscopic vs open vein-graft harvest technique among the 235 394 study patients. There were no significant differences between the unadjusted cumulative incidence rate for mortality through 3 years for the endoscopic (13.2% [12 429/122 899 events]) and open (13.4% [13 096/112 495 events]) vein-graft harvest groups. There were no significant differences between the cumulative incidence through 3 years for the composite of death, MI, or revascularization among the endoscopic vs open vein-graft harvest groups (19.5% [18 419/122 899 events] vs 19.7% [19 232/112 495 events]). The unadjusted 30-day rate for wound complication was 3.0% (3654/122 899) for endoscopic vs 3.6% (4047/112 495) for open vein-graft harvest groups. Figure 2 shows the unadjusted and risk-adjusted mortality curves comparing CABG surgery with endoscopic vs open vein-graft harvesting techniques. The risk-adjusted HR for long-term mortality was 1.00 (95% CI, 0.97-1.04; P > .99). Figure 3 shows unadjusted and risk-adjusted event curves for the composite end point of death, MI, or revascularization. The adjusted HR for the composite of death, MI, or revascularization was 1.00 (95% CI, 0.98-1.05; P = .34).

Endoscopic vein-graft harvesting was associated with a significantly lower rate of wound complications (adjusted HR, 0.83; 95% CI, 0.77-0.89; P < .001) for the endoscopic vs open vein-graft harvest groups (Table 3). Confining the analysis to STS ACSD–captured leg wound infections, the adjusted OR was 0.65 (95% CI, 0.55-0.76; P < .001) for endoscopic (547 events) vs open (796 events) vein-graft harvest techniques.

To evaluate the effect of treatment misclassification resulting from underreporting of the endoscopic CPT code, we replicated our primary analysis in a center-level subgroup of the overall cohort. We examined the cohort of sites having more than 80% sensitivity and specificity for endoscopic vein-graft harvest reporting. Among 44 423 patients at 165 sites, the unadjusted incidence of mortality, the composite of death, MI, or revascularization, and wound complications were 14%, 20%, and 3.3%, respectively. No risk-adjusted difference was observed between patients undergoing endoscopic vs open vein-graft harvest in mortality (adjusted HR, 0.95; 95% CI, 0.89-1.01; P = .10) or the composite of death, MI, and revascularization (adjusted HR, 1.00; 95% CI, 0.94-1.06; P = .88), but lower rates of wound complications were observed among patients in the endoscopic vein-graft harvest group (adjusted HR, 0.75; 95% CI, 0.64-0.89; P < .001). Table 3 shows the results of the marginal common baseline hazard model, before and after risk adjustment, for endoscopic vs open vein-graft harvesting techniques for the overall population as well as for the sensitivity cohort.

Sensitivity analysis for measurement error in the coding of endoscopic findings revealed no possibility of a large difference between the treatment groups for the mortality end point. Point estimates for the HR of endoscopic vs open vein-graft harvesting techniques ranged across scenarios from 1.00 to 1.02. The upper limit of the 95% CI was 1.05 or lower for 19 of 36 scenarios tested, 1.10 or lower for 31 of 36 scenarios, and 1.16 or lower for all 36 scenarios.

No difference in study end points was observed when comparing open vs endoscopic vein-graft harvest groups among patients with (n = 41 745) or without (n = 70 698) diabetes mellitus. Similarly, within 3 BMI strata (<30, 30-34, and ≥35), there was no difference in mortality or the composite outcome between the open and endoscopic vein-graft harvest groups, and no difference was observed based on the number of vein grafts used.

In 2009, the FDA issued a request for proposal to evaluate the safety of endoscopic vein-graft harvesting technique for CABG surgery. Investigators from the STS and the Duke Clinical Research Institute answered this request and, in partnership with the FDA, we conducted this nationally representative observational comparison of the long-term outcomes of endoscopic vein-graft harvesting technique in CABG surgery. Our study found that endoscopic vein-graft harvesting was the most commonly used technique for vein-graft harvesting, with approximately 70% of CABG surgery cases in the STS ACSD using this technique in 2008, the most recent year examined. After adjustment for baseline clinical factors, no evidence was found of increased long-term mortality or the composite of death, MI, or revascularization associated with endoscopic vs open vein-graft harvesting in isolated patients undergoing CABG surgery. Consistent with previous randomized comparisons, use of endoscopic vein-graft harvesting was associated with a significant reduction in wound complications relative to the open procedures (risk-adjusted HR, 0.83; 95% CI, 0.77-0.89).

Since the introduction of endoscopic vein-graft harvesting techniques and device systems in the 1990s,^1,21 multiple randomized controlled trials have demonstrated the short-term advantages of endoscopic harvesting with respect to morbidities (predominantly wound infections) and patient satisfaction.^3,22- 26 The wound complication rates reported in these randomized comparisons are generally higher than those observed in our study, likely due to protocol-driven inspection of harvest sites and more liberal definitions of wound complications in the prospective trial setting. One small randomized controlled trial by Allen et al²⁷ reported that 112 patients undergoing CABG surgery randomized to endoscopic vs open vein-graft harvesting technqiues had similar 5-year likelihood of death, MI, or recurrent angina (75% for endoscopic vs 74% for open; P = .85). In 2005, based on these limited data, a consensus statement from the International Society for Minimally Invasive Cardiothoracic Surgery recommended that endoscopic vein-graft harvesting be the preferred technique given its proven benefit in wound-related complications, postoperative pain, and consumption of outpatient wound-management resources.²⁸

In 2009, an observational study by Lopes et al⁵ challenged the use of endoscopic vein-graft harvesting as the preferred technique for vein-graft harvest and generated considerable debate in the cardiovascular community.^6,29- 33 Looking at patients undergoing first-time isolated CABG surgery as part of a multicenter PREVENT IV trial, Lopes et al compared outcomes of 1753 endoscopic vs 1247 open vein-graft harvesting procedures.³⁴ All veins harvested in the PREVENT IV trial underwent ex-vivo manipulation with pressurized delivery of study drug or placebo, and overall vein-graft failure rates were higher than for other CABG surgery trials. Nonetheless, the post hoc analysis by Lopes et al using propensity adjustment found endoscopic vein-graft harvesting was associated with a higher adjusted risk of death (HR, 1.5; 95% CI, 1.1-2.0; P < .005) as well as higher risk for death, MI, or repeat revascularization (HR, 1.22; P = .04). Based on this finding, the UK National Institute for Health and Clinical Excellence published new recommendations relating to the use of endoscopic vein-graft harvesting for CABG surgery, advising that this procedure should only be used with special arrangements for “clinical governance, consent and audit or research.”³⁵ The UK National Institute for Health and Clinical Excellence group recommends in this statement that clinicians ensure that their patients understand the uncertain balance regarding the known benefits of endoscopic vein-graft harvesting vs the potential risks of inferior cardiovascular clinical outcomes.

In contrast with the findings from Lopes et al, the Northern New England study group found no safety concerns with endoscopic vein-graft harvesting. The Northern New England group included 8542 patients having isolated CABG surgery between 2001 and 2004, including 53% with endoscopic vein-graft harvesting.⁶ Endoscopic vein-graft harvesting was associated with a 20% reduced risk of mortality at 4 years following CABG surgery (adjusted HR, 0.74; 95% CI, 0.60-0.92; for those patients surviving 90 days). Endoscopic vein-graft harvesting was not found to be associated with a higher rate of repeat revascularization (adjusted HR, 1.10; 95% CI, 0.96-1.74).

In a predetermined secondary analysis of the Randomized On/Off Bypass (ROOBY) trial,³⁶ short-term and 1-year clinical composite outcomes (death or major perioperative complication defined as reoperation, new mechanical support, cardiac arrest, coma, stroke, or renal failure requiring dialysis) were compared between patients who underwent endoscopic vein-graft harvesting and those who underwent open vein-graft harvesting.³⁷ This ROOBY substudy captured 1471 patients enrolled between 2003 (the first year the trial began recording vein harvest technique) and 2007. Endoscopic vein-graft harvesting was used in only 38% of the cases among the 18 US Veterans Affairs medical centers studied. There were no significant differences in both short-term and 1-year composite outcomes between the endoscopic and open vein-graft harvesting groups. No interaction was found between endoscopic vein-graft harvesting and off-pump CABG treatment.

Our current analysis from the STS ACSD extends the findings of the Northern New England study for reduced wound complications.⁶ However, unlike the Northern New England study, our results do not suggest an associated survival advantage with endoscopic vein-graft harvesting. On the other hand, unlike the Lopes et al⁵ study, our analysis did not identify harm associated with endoscopic vein-graft harvesting (Figure 4). Several differences exist between our study and the preceding clinical studies. Compared with the studies by Lopes et al and the Northern New England group, our study included patients 65 years or older and a more contemporary cohort, perhaps further along the endoscopic vein-graft harvesting learning curve with fewer traction or electrocautery injuries in recent years. Our study was also 10-fold greater in size than the Lopes et al and the Northern New England group analyses combined (Figure 4). Our study included a diverse, more representative group of large and small community programs and university and nonuniversity affiliated centers.

As with both the Lopes et al and the Northern New England studies, our analysis was unable to account for differences in conduit caliber between the endoscopic and open vein-graft harvesting groups, a potentially critical confounding variable in comparing endoscopic and open vein-graft harvesting techniques. Several trials have compared blinded tissue specimens between segments of vein harvested conventionally and endoscopically and found no histological difference.^23,25 Vein grafts harvested endoscopically are commonly taken above the knee, whereas vein grafts harvested by open techniques are commonly taken beginning from the ankle (where the vein is smallest) and then upwards as needed. The diameter of the vein grows along its cephalad course up the lower extremity when it is harvested. Several articles have shown that large vein caliber is associated with poorer patency,^22,38- 39 likely the result of reduced flow velocity within a larger diameter conduit. Thus, the exact level from which the saphenous vein is harvested might be important. In addition, no study has specifically addressed the effect of the use of carbon dioxide insufflation (either the carbon dioxide itself or the gas pressure) on the quality of saphenous vein grafts. All endoscopic vein harvests are not the same. Our observational study, as with previous studies, is unable to assess for particulars of technique such as carbon dioxide insufflations, use of electro-cautery, or the experience of the endoscopic harvester.

Our study has other important limitations. First, the median follow-up was only 3 years and no direct clinical identification of endoscopic vein-graft harvesting use in the STS before 2008. Surgeons may have converted an endoscopic harvest to an open harvest during the course of an operation. This happens when speed is required or a vein is difficult to harvest endoscopically. In our analysis, if conversion from endoscopic to open vein-graft harvest occurred, the procedure would be identified as endoscopic by our case identification methods. Some of the harvested vessel would have been exposed to the risks of endoscopic vein-graft harvesting and therefore properly allocated in the analysis. We used billing (professional fees) to identify endoscopic vein-graft harvesting. Misclassification of endoscopic vs open vein-graft harvest could have biased our results toward the finding of no treatment effect with regards to mortality or ischemic outcomes. We performed sensitivity analyses using only hospitals with more than 80% sensitivity and specificity for endoscopic vein-graft harvesting reporting to address this potential bias, finding that mortality and revascularization rates remained similar between groups. Consequently, it seems unlikely that the similar outcomes we observed between groups were caused by misclassification of endoscopic vein-graft harvesting as open cases. The significant and consistent finding of an association of endoscopic vein-graft harvesting with improved wound complications, an expected effect confirmed by multiple randomized studies, also supports a reasonable degree of sensitivity to our analytic assay. ICD-9 codes were also used to capture wound complications, and the true association of endoscopic vein-graft harvesting with reduced wound complications may have been greater than that estimated by our analysis due to their lack of diagnostic specificity. In addition, information regarding the type of device used for endoscopic vein-graft harvesting was lacking for this analysis.

In conclusion, our observational study found no evidence of an association of endoscopic vein-graft harvest with long-term mortality or a composite of death, MI, or repeat revascularization. Endoscopic technique was found to be associated with significantly reduced wound complications.