Mahmoud B. Malas

Age and Outcomes After Carotid Stenting and Endarterectomy The Carotid Revascularization Endarterectomy Versus Stenting Trial

Background and Purpose— High stroke event rates among carotid artery stenting (CAS)-treated patients in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) lead-in registry generated an a priori hypothesis that age may modify the relative efficacy of CAS versus carotid endarterectomy (CEA). In the primary CREST report, we previously noted significant effect modification by age. Here we extend this investigation by examining the relative efficacy of the components of the primary end point, the treatment-specific impact of age, and contributors to the increasing risk in CAS-treated patients at older ages. Methods— Among 2502 CREST patients with high-grade carotid stenosis, proportional hazards models were used to examine the impact of age on the CAS-to-CEA relative efficacy, and the impact of age on risk within CAS-treated and CEA-treated patients. Results— Age acted as a treatment effect modifier for the primary end point (P interaction=0.02), with the efficacy of CAS and CEA approximately equal at age 70 years. For CAS, risk for the primary end point increased with age (P<0.0001) by 1.77-times (95% confidence interval, 1.38–2.28) per 10-year increment; however, there was no evidence of increased risk for CEA-treated patients (P=0.27). Stroke events were the primary contributor to the overall effect modification (P interaction=0.033), with equal risk at ≈64 years. The treatment-by-age interaction for CAS and CEA was not altered by symptomatic status (P=0.96) or by sex (P=0.45). Conclusions— Outcomes after CAS versus CEA were related to patient age, attributable to increasing risk for stroke after CAS at older ages. Patient age should be an important consideration when choosing between the 2 procedures for treating carotid stenosis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732.

Trends in Incident Hemodialysis Access and Mortality

IMPORTANCE Based on evidence of survival benefit when initiating hemodialysis (HD) via arteriovenous fistula (AVF) or arteriovenous graft (AVG) vs hemodialysis catheter (HC), the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative published practice guidelines in 1997 recommending 50% or greater AVF rates in incident HD patients. A decade after, lapses exist and the impact on HD outcomes is uncertain. OBJECTIVE To assess the achievement of the practice goals for incident vascular access and the effects on HD outcomes. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study was conducted using the US Renal Data System. All patients with end-stage renal disease in the United States without prior renal replacement therapy who had incident vascular access for HD created between January 1, 2006, and December 31, 2010 (N = 510 000) were included. MAIN OUTCOMES AND MEASURES Incident vascular access use rates and mortality. Relative mortality was quantified using multivariable Cox proportional hazard models. Coarsened exact matching and propensity score-matching techniques were used to better account for confounding by indication. RESULTS Of 510 000 patients included in this study, 82.6% initiated HD via HC, 14.0% via AVF, and 3.4% via AVG. Arteriovenous fistula use increased only minimally, from 12.2% in 2006 to 15.0% in 2010. Patients initiating HD with AVF had 35% lower mortality than those with HC (adjusted hazard ratio, 0.65; 95% CI, 0.64-0.66; P < .001). Those initiating HD with AVF had 23% lower mortality than those initiating with an HC while awaiting maturation of an AVF (adjusted hazard ratio, 0.77; 95% CI, 0.76-0.79; P < .001). CONCLUSIONS AND RELEVANCE Current incident AVF practice falls exceedingly short years after recommendations were made in 1997. The impact of this shortcoming on mortality for patients with end-stage renal disease is enormous. Functioning permanent access at initiation of HD confers lower mortality even compared with patients temporized with an HC while awaiting maturation of permanent access. A change of current policies and structured multidisciplinary efforts are required to establish matured fistulae prior to HD to ameliorate this deficit in delivering care.

Perioperative mortality following repair of abdominal aortic aneurysms: Application of a randomized clinical trial to real-world practice using a validated nationwide data set

IMPORTANCE Because of the restrictions applied to the conduct of randomized clinical trials, the risks reported in their comparison of open and endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAA) may not be applicable to real-world vascular surgical practice. The magnitude of this deviation is indeterminate. OBJECTIVES To compare 30-day mortality from the recent Open Vs Endovascular Repair (OVER) Veterans Affairs Cooperative trial with results obtained from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) and to assess temporal trends in perioperative mortality. DESIGN, SETTING, AND PARTICIPANTS We analyzed data from 21,115 patients who received elective EVAR or open repair for asymptomatic infrarenal AAA between January 1, 2005, and December 31, 2011, in the NSQIP database. We used χ2 and t tests to compare perioperative mortality between groups. Logistic regression was used to analyze perioperative mortality, adjusting for age, sex, race, and comorbidities. The outcomes of the OVER trial were then compared with the national estimates obtained from the NSQIP. MAIN OUTCOMES AND MEASURES Death within 30 days of surgery. RESULTS Perioperative mortality was 3.7% (95% CI, 3.2%-4.3%) after open repair and 1.3% (95% CI, 1.2%-1.5%) after EVAR. There was a 70% reduction in operative mortality after EVAR compared with open repair (adjusted odds ratio [aOR], 0.30; 95% CI, 0.25-0.38; P < .001). Mortality was significantly lower in men compared with women (aOR, 0.73; 95% CI, 0.57-0.92; P = .009). Thirty-day mortality in the NSQIP cohort was higher than that reported in the OVER trial for both EVAR and open repair (EVAR, 1.3% vs 0.2%; open, 3.7% vs 2.3%). There was an increase in the proportion of patients who received EVAR during the 7 years studied (65% in 2005 and 80% in 2011). There has been no significant decrease in perioperative mortality during these years (P > .05). CONCLUSIONS AND RELEVANCE Perioperative mortality reported by the OVER trial is significantly lower than outcomes from practices outside the restriction of randomized clinical trials. We attribute this difference to the fact that the OVER trial excluded high-risk patients deemed unfit for open repair. This finding supports the need for individualized assessment of risk and treatment selection for patients with infrarenal AAA. There has been no change in perioperative mortality after EVAR in recent years despite improvements in techniques, devices, and proficiency.

Outcome-based anatomic criteria for defining the hostile aortic neck

OBJECTIVE There is abundant evidence linking hostile proximal aortic neck anatomy to poor outcome after endovascular aortic aneurysm repair (EVAR), yet the definition of hostile anatomy varies from study to study. This current analysis was undertaken to identify anatomic criteria that are most predictive of success or failure at the aortic neck after EVAR. METHODS The study group comprised 221 patients in the Aneurysm Treatment using the Heli-FX Aortic Securement System Global Registry (ANCHOR) clinical trial, a population enriched with patients with challenging aortic neck anatomy and failure of sealing. Imaging protocols were not protocol specified but were performed according to the institutions standard of care. Core laboratory analysis assessed the three-dimensional centerline-reformatted computed tomography scans. Failure at the aortic neck was defined by type Ia endoleak occurring at the time of the initial endograft implantation or during follow-up. Receiver operating characteristic curve analysis was used to assess the value of each anatomic measure in the classification of aortic neck success and failure and to identify optimal thresholds of discrimination. Binary logistic regression was performed after excluding highly intercorrelated variables, creating a final model with significant predictors of outcome after EVAR. RESULTS Among the 221 patients, 121 (54.8%) remained free of type Ia endoleak and 100 (45.2%) did not. Type Ia endoleaks presented immediately after endograft deployment in 58 (58.0%) or during follow-up in 42 (42.0%). Receiver operating characteristic curve analysis identified 12 variables where the classification of patients with type Ia endoleak was significantly more accurate than chance alone. Increased aortic neck diameter at the lowest renal artery (P = .013) and at 5 mm (P = .008), 10 mm (P = .008), and 15 mm (P = .010) distally; aneurysm sac diameter (P = .001), common iliac artery diameters (right, P = .012; left, P = .032), and a conical (P = .049) neck configuration were predictive of endoleak. By contrast, increased aortic neck length (P = .050), a funnel-shaped aortic neck (P = .036), and neck mural thrombus content, as measured by average thickness (P = .044) or degrees of circumferential coverage (P = .029), were protective against endoleak. Binary logistic regression identified three variables independently predictive of type Ia endoleak. Neck diameter at the lowest renal artery (P = .002, cutpoint 26 mm) and neck length (P = .017, cutpoint 17 mm) were associated with endoleak, whereas some mural neck thrombus content was protective (P = .001, cutpoint 11° of circumferential coverage). CONCLUSIONS A limited number of independent anatomic variables are predictive of type Ia endoleak after EVAR, including aortic neck diameter and aortic neck length, whereas mural thrombus in the neck is protective. This study suggests that anatomic measures with identifiable threshold cutpoints should be considered when defining the hostile aortic neck and assessing the risk of complications after EVAR.

Racial/Ethnic Disparities Associated With Initial Hemodialysis Access

IMPORTANCE Superior outcomes have been established with the use of an arteriovenous fistula (AVF) at first hemodialysis. However, considering the influence of comorbidities, medical insurance, and specialist care, racial/ethnic differences in the patterns of utilization of AVFs are unknown and deserve evaluation. OBJECTIVE To assess national trends in initial hemodialysis access with respect to race/ethnicity stratified by comorbid disease, nephrology care, and medical insurance status within the US Renal Data System. DESIGN, SETTING, AND PARTICIPANTS A retrospective analysis of all patients with end-stage renal disease in the US Renal Data System who initiated hemodialysis between January 1, 2006, and December 31, 2010. Univariable statistics (χ² test and analysis of variance) and logistic regression were used to compare racial/ethnic groups (white vs black vs Hispanic). Multivariable logistic regression and propensity score-matching techniques were used to evaluate hemodialysis access rates between patients of different races/ethnicities with comparable characteristics. MAIN OUTCOMES AND MEASURES Utilization rates of AVF, arteriovenous graft, and intravascular hemodialysis catheter. RESULTS In this cohort of 396,075 patients, more white patients initiated hemodialysis with an AVF than black patients or Hispanic patients (18.3% vs 15.5% and 14.6%, respectively; P < .001). Black patients and Hispanic patients initiated hemodialysis with an AVF less frequently despite being younger and having less coronary artery disease, chronic obstructive pulmonary disease, and cancer than white patients with an AVF. When stratified by medical insurance status, black patients (odds ratios, 0.90 [95% CI, 0.82-0.98] for uninsured and 0.85 [95% CI, 0.84-0.87] for insured) and Hispanic patients (odds ratios, 0.72 [95% CI, 0.65-0.81] for uninsured and 0.81 [95% CI, 0.79-0.84] for insured) persistently initiated hemodialysis with an AVF less frequently than white patients (P < .05 for all). Arteriovenous fistula utilization at initial hemodialysis was lower among black patients (odds ratio, 0.81 [95% CI, 0.78-0.84]) and Hispanic patients (odds ratio, 0.86 [95% CI, 0.82-0.90]) compared with white patients within the category of patients who had nephrology care for longer than 1 year (P < .001 for all). CONCLUSIONS AND RELEVANCE Black patients and Hispanic patients tend to initiate hemodialysis with an AVF less frequently than white patients despite being younger and having fewer comorbidities. These disparities persisted independent of factors that drive health access for fistula placement, such as medical insurance status and nephrology care. The sociocultural underpinnings of these disparities deserve investigation and redress to maximize the benefits of initiating hemodialysis via fistula in patients with end-stage renal disease irrespective of race/ethnicity.

Chronic venous leg ulcer treatment: Future research needs

The prevalence and costs of chronic venous ulcer care in the US are increasing. The Johns Hopkins University Evidence‐Based Practice Center recently completed a systematic review of the comparative effectiveness of advanced wound dressings, antibiotics, and surgical management of chronic venous ulcers. Of 10,066 citations identified in the literature search, only 66 (0.06%) met our liberal inclusion criteria for providing evidence on the effectiveness of interventions for chronic venous ulcers. Based on review of those studies, members of our team and a panel of informed stakeholders identified important research gaps and methodological deficiencies and prioritized specific future research needs. Based on that review, we provide the results of our assessment of future research needs for chronic venous ulcer care. Advanced wound dressings were considered to have the highest priority for future research, followed by venous surgery and antibiotics. An imperative from our assessment is that future research evaluating interventions for chronic venous ulcers meet quality standards. In a time of increasing cost pressure, the wound care community needs to develop high‐quality evidence to justify the use of present and future therapeutic modalities.

Mortality benefits of different hemodialysis access types are age dependent.

OBJECTIVE Risk of death in dialysis patients is lowest with arteriovenous fistulas (AVFs), followed by arteriovenous grafts (AVGs) and then intravenous hemodialysis catheters (HCs). Our aim was to analyze the effects of age at hemodialysis initiation on mortality across different access types. METHODS All patients ≥18 years in the United States Renal Data System between the years 2006 and 2010 were analyzed. Spline modeling and risk-adjusted Cox proportional hazard models were used to analyze the effect of age on mortality for first dialysis access with AVF vs AVG vs HC. RESULTS The study analyzed 507,791 patients (63.4 ± 0.02 years; 56.5% male; 40.9% mortality; follow-up, 1.57 ± 1.36 years). Increasing age was a significant predictor of overall mortality (adjusted hazard ratio [aHR], 1.03; P < .001). Compared with patients with HCs (n = 418,932), overall risk-adjusted mortality was lowest in patients with AVFs (n = 71,316; aHR, 0.63; P < .001) followed by AVGs (n = 17,543; aHR, 0.83; P < .001). AVF was superior to both HC and AVG for all age groups (P < .001). However, there was a significant change in the relative efficacy of AVG at ages 48 years and 89 years based on spline modeling; there were no significant differences comparing adjusted mortality with AVG vs HC for patients aged 18 to 48 years or for patients >89 years, but AVG was superior to HC for patients 49 to 89 years of age (aHR, 0.811; P < .001). The mortality benefit of AVF was consistently superior to that of AVG and HC for patients of all ages (all, P < .001). CONCLUSIONS AVF is superior to AVG and HC regardless of the patients age, including in octogenarians. In contrast, the mortality benefit of AVG over HC may not apply to younger (18-48 years) or older (>89 years) age groups. All patients 18 to 48 years should receive AVF for dialysis access whenever possible.

Interpretation of the Results of OVER in the Context of EVAR Trial, DREAM, and the EUROSTAR Registry

Several early studies have shown the benefit of endovascular aneurysm repair in reducing procedure-related mortality and morbidity of open aneurysm repair. Three prospective randomized trials have addressed the advantages and disadvantages of the two procedures. These studies had shown some conflicting findings in survival and complications. We reviewed the largest registry for endovascular abdominal aortic repair and the three randomized trials to evaluate the similarities and differences in their outcomes. Cross-comparison of operative, aneurysm-related and all-cause mortality is presented. Patient characteristics, device specifications, procedure morbidity and reintervention rate of each study are evaluated.

Closed incision negative pressure therapy: international multidisciplinary consensus recommendations

Surgical site occurrences (SSOs) affect up to or over 25% of patients undergoing operative procedures, with the subset of surgical site infections (SSIs) being the most common. Commercially available closed incision negative pressure therapy (ciNPT) may offer surgeons an additional option to manage clean, closed surgical incisions. We conducted an extensive literature search for studies describing ciNPT use and assembled a diverse panel of experts to create consensus recommendations for when using ciNPT may be appropriate. A literature search of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials using key words ‘prevention’, ‘negative pressure wound therapy (NPWT)’, ‘active incisional management’, ‘incisional vacuum therapy’, ‘incisional NPWT’, ‘incisional wound VAC’, ‘closed incisional NPWT’, ‘wound infection’, and ‘SSIs’ identified peer‐reviewed studies published from 2000 to 2015. During a multidisciplinary consensus meeting, the 12 experts reviewed the literature, presented their own ciNPT experiences, identified risk factors for SSOs and developed comprehensive consensus recommendations. A total of 100 publications satisfied the search requirements for ciNPT use. A majority presented data supporting ciNPT use. Numerous publications reported SSI risk factors, with the most common including obesity (body mass index ≥30 kg/m2); diabetes mellitus; tobacco use; or prolonged surgical time. We recommend that the surgeon assess the individual patients risk factors and surgical risks. Surgeons should consider using ciNPT for patients at high risk for developing SSOs or who are undergoing a high‐risk procedure or a procedure that would have highly morbid consequences if an SSI occurred.

Performance of the Aorfix endograft in severely angulated proximal necks in the PYTHAGORAS United States clinical trial.

OBJECTIVE This study compared the performance of the Aorfix endograft (Lombard Medical, Oxfordshire, United Kingdom) in standard (<60°), highly angled (60°-90°), and severely angled (>90°) aortic necks in the PYTHAGORAS study and evaluated changes in neck morphology over time. METHODS PYTHAGORAS is a prospective nonrandomized clinical trial of the Aorfix endograft. We divided the endovascular aneurysm repair (EVAR) cohort into groups by standard, high, and severe neck angle. The primary control group was patients concurrently undergoing open repair. Mortality at 30 days, 1 year, and 2 years and 30-day freedom from Society for Vascular Surgery major adverse events for the EVAR groups was compared with the open control. Aneurysm sac change, type I and III endoleaks, graft migration, and the reintervention rate at 1 and 2 years was compared between the standard, highly, and severely angled populations. The relative risk of graft complications with a neck diameter increase >10% was also calculated. At predetermined anatomic points, the effect of oversizing on aortic diameter was evaluated by calculating oversize percentage ([1 - outer aortic diameter measured at a given time/stent graft diameter] × 100%) preoperatively and at 3 years. In addition, the average oversizing percentage at 30 days and annually at 1 to 5 years was compared with the preoperative oversizing percentage. Finally, complication rates with ≥30% vs <30% planned oversizing were compared. RESULTS The adverse event rate was lower for every EVAR group than the open control. In addition, the mortality rates at 30 days, 1 year, and 2 years were similar between the standard-angle (1.5%, 3.0%, 4.5%), high-angle (0.9%, 7.3%, 13.8%), and severe-angle (4.8%, 9.5%, 14.3%) EVAR groups and the open control groups (1.3, 6.6%, 10.5%). At 1 and 2 years, there was no difference in graft complications among the EVAR groups. However, with neck dilatation of >10% at 5 mm above the proximal renal and 1 mm below the distal renal, there was an increased risk of graft migration (relative risk, 4.38 [P = .01] and 4.33 [P = .002], respectively). For all predetermined anatomic points, the oversizing percentage decreased over time. The rate of oversize percentage decrease was faster at more distal aortic locations, reaching <10% at 30 days 15 mm below the renal, at 2 years 7 mm below the renal, and at 5 years 1 mm below the renal (P < .001 for all). Half the oversize percentage achieved at the index procedure remained at 3 years (Pearson correlation coefficient = 0.5). However, there was no difference in complications between the ≥30% and <30% planned oversize groups. CONCLUSIONS The Aorfix endograft has performed well in excluding aneurysms with standard and highly angled aortic neck anatomy.