Comparison of open thoracoabdominal repair for chronic aortic dissections and aneurysms.

OBJECTIVE: Aortic dissection is common in patients undergoing open surgical repair of thoracoabdominal aortic aneurysms (TAAAs). Most often, dissection is chronic and is associated with progressive aortic dilatation. Because contemporary outcomes in chronic dissection are not clearly understood, we compared patient characteristics and outcomes after open TAAA repair between patients with chronic dissection and those with non-dissection aneurysm. METHODS: We retrospectively analyzed data from 3470 open TAAA repairs performed in a single practice. Operations were for non-dissection aneurysm in 2351 (67.8%) and chronic dissection in 1119 (32.2%). Outcomes included operative mortality and adverse events, a composite variable comprising operative death and persistent (present at discharge) stroke, paraplegia, paraparesis, and renal failure necessitating dialysis. Logistic regression identified predictors of operative mortality and adverse events. Time-to-event analyses examined survival, death, repair failure, subsequent progressive repair, and survival free of failure or subsequent repair. RESULTS: Compared with patients with non-dissection aneurysm, those with chronic dissection were younger, had fewer atherosclerotic risk factors, and were more likely to have heritable thoracic aortic disease and undergo extent II repair. The operative mortality rate was 8.5% (n = 296) overall and was higher in non-dissection aneurysm patients (n = 217; 9.2%) than in chronic dissection patients (n = 79; 7.1%; P = .03). Adverse events were less frequent (P = .01) in patients with chronic dissection (n = 145; 13.0%), 22 (2.0%) of whom had persistent paraplegia. Chronic dissection was not predictive of operative mortality (P = .5) or adverse events (P = .6). Operative mortality and adverse events, respectively, were independently predicted by emergency repair (odds ratio [OR], 3.46 and 2.87), chronic kidney disease (OR, 1.74 and 1.81), extent II TAAA repair (OR, 1.44 and 1.73), increasing age (OR, 1.04/year and 1.04/year), and increasing aortic cross-clamp time (OR, 1.02/minutes and 1.02/minutes). Patients with chronic dissection had lower 10-year unadjusted mortality (42% vs 69%) but more frequent repair failure (5% vs 3%) and subsequent repair for progressive aortic disease (11% vs 5%) than patients with non-dissection aneurysm (P < .001); these differences were no longer statistically significant after adjustment. CONCLUSIONS: Outcomes of open TAAA repair vary by aortic disease type. Emergency repairs and atherosclerotic diseases most commonly occur in patients with non-dissection aneurysm and independently predict operative mortality. Repair of chronic dissection is associated with low rates of adverse events, including operative mortality and persistent paraplegia, along with reasonable late survival and good durability. However, patients with chronic dissection tend to more commonly undergo subsequent repair to treat progressive aortic disease, which emphasizes the need for robust long-term imaging surveillance protocols.

A Review of WIfI Clinical Staging to Predict Outcomes in Patients With Threatened Limbs.

The Society for Vascular Surgery Wound, Ischemia, and foot Infection's (WIfI's) threatened limb classification system serves to comprehensively assess the severity of disease in patients with chronic limb-threatening ischemia by identifying and grading the main factors that place the threatened limb at greatest risk: wound severity, ischemic burden, and presence of infection. Each of these 3 factors is graded and the limb placed into a clinical stage, with increasing stage associated with severity of limb threat and predicted risk of major limb amputation at 1 year. Globally, there is a growing body of evidence reported from multiple institutions that has assessed amputation rates and wound-healing outcomes following revascularization in patients with WIfI clinical staging. Risk of major amputation at 1 year is low in clinical stage 1, moderate in stages 2 and 3, and high in stage 4. Higher clinical stages are associated with prolonged time to wound healing, while 1-year wound healing rates consistently decrease with increasing clinical stage. Additional avenues of investigation utilizing WIfI as an objective clinical staging tool have yielded new insights into which patients benefit from revascularization, complexity of care, hospital length of stay, quality of life, ethnic and socioeconomic disparities, as well as spurred interest in other modalities of assessing limb perfusion and their possible clinical utility. Ongoing study and refinement of WIfI grading and clinical staging will continue to improve its prognostic utility.

Contemporary Medical Management of Peripheral Arterial Disease.

PURPOSE: Peripheral arterial disease (PAD) is characterized by atherosclerotic arterial occlusive disease of the lower extremities and is associated with an increased risk of major adverse cardiovascular events (MACE) in addition to disabling clinical sequelae, including intermittent claudication and chronic limb-threatening ischemia (CLTI). Given the growing burden of disease, knowledge of modern practices to prevent MACE and major adverse limb events (MALE) is essential. This review article examines evidence for medical management of PAD and its associated risk factors, as well as wound prevention and care. METHODS: A thorough review of the literature was performed, with attention to evidence for the management of modifiable atherosclerotic risk factors, claudication symptoms, wound prevention, and wound care. RESULTS: Contemporary management of PAD requires a multi-faceted approach to care, with medical optimization of smoking, hypertension, hyperlipidemia, and diabetes mellitus. The use of supervised exercise therapy for intermittent claudication is highlighted. The anatomic disease patterns of smoking and diabetes mellitus are discussed further, and best practices for diabetic foot ulcer prevention, including offloading footwear, are described. Quality wound care is essential in this patient population and involves strategic use of debridement, wound-healing adjuncts, and skin substitutes, when appropriate. CONCLUSION: The objective of medical management of PAD is to reduce the risk of MACE and MALE. Atherosclerotic risk factor optimization, appropriate wound care, and management of diabetic foot ulcers, foot infections, gangrene, and chronic, non-healing wounds are critical components of PAD care. Interdisciplinary care is essential to coordinate care, leverage expertise, and improve outcomes.

Human microvascular pericyte basement membrane remodeling regulates neutrophil recruitment.

OBJECTIVE: Neutrophil extravasation at post-capillary venules, consisting of EC, PC, and the shared ECM, increases following fibrotic remodeling in the lung, liver, and skin. The role of fibrotic pericyte-derived ECM in regulating EC activation and neutrophil recruitment remains unexplored. METHODS: To elucidate the role of human pericyte-derived ECM in EC activation, we characterized PC-derived ECM following transforming growth factor-ß1, IL-1ß, CCL2, or bleomycin activation, and examined surface adhesion molecule expression and neutrophil recruitment by EC cultured on PC-ECM. RESULTS: Pro-inflammatory activation of PC-induced deposition of compositionally distinct ECM compared with non-activated control. Bleomycin activation induced fibronectin-rich and collagen-poor ECM remodeling by PC, facilitating increased neutrophil transendothelial migration when compared with non-activated pericyte ECM (49.9 ± 3.4% versus 29.7 ± 1.4%). Increases in fibronectin compared to collagen I, are largely responsible for ECM-regulated neutrophil recruitment, as EC cultured on fibronectin supported increased neutrophil transmigration compared to collagen I (51.6 ± 6.2% versus 28.0 ± 4.8%). We attribute this difference to increased expression of ICAM-1 and its redistribution to EC borders. CONCLUSIONS: This is the first demonstration of human pericyte sensitivity to inflammatory stimuli, inducing fibrotic matrix deposition that regulates EC adhesion molecule expression and neutrophil recruitment.

The severity of chronic obstructive pulmonary disease is associated with adverse outcomes after open thoracoabdominal aortic aneurysm repair.

OBJECTIVE: We assessed associations between outcomes after open thoracoabdominal aortic aneurysm (TAAA) repair and preoperative airflow limitation stratified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric classification of chronic obstructive pulmonary disease (COPD) severity. METHODS: Among 2368 open elective TAAA repairs in patients with spirometric data, 1735 patients had COPD and 633 did not. Those with COPD were stratified by preoperative respiratory dysfunction as GOLD 1 (forced expiratory volume in the first second of expiration [FEV1] ≥80% of predicted; n = 228), GOLD 2 (50% ≤ FEV1 < 80% of predicted; n = 1215), GOLD 3 (30% ≤ FEV1 < 50% of predicted; n = 260), or GOLD 4 (FEV1 < 30% of predicted; n = 32). Early outcomes included operative mortality and adverse events (operative death or persistent stroke, spinal cord deficit, or renal failure requiring dialysis); associations of outcomes were determined using logistic regression models. Kaplan-Meier analysis compared late survival by the log-rank test. RESULTS: Pulmonary complications occurred in 38.4% of patients with COPD versus 30.0% without COPD (P < .001). Operative mortality and adverse events were more frequent in patients with COPD than without COPD (7.9% vs 3.8% [P < .001] and 14.9% vs 9.8% [P = .001], respectively). Worsening GOLD severity was independently associated with operative death and adverse event. Survival was poorer in patients with COPD than in those without (61.9% ± 1.2% vs 73.6% ± 1.8% at 5 years; P < .001), particularly in patients with increasing GOLD severity (68.7% ± 3.2% vs 63.7% ± 1.4% vs 51.4% ± 3.2% vs 31.3% ± 8.2% at 5 years; P < .001). CONCLUSIONS: Patients with COPD are at elevated risk for operative death and adverse events. Staging by GOLD severity aids preoperative risk stratification. Patients with airflow limitations may benefit from optimization before TAAA repair.

A 30-year analysis of National Institutes of Health-funded cardiac transplantation research: Surgeons lead the way.

OBJECTIVES: Obtaining National Institutes of Health funding for heart transplant research is becoming increasingly difficult, especially for surgeons. We sought to determine the impact of National Institutes of Health-funded cardiac transplantation research over the past 30 years. METHODS: National Institutes of Health Research Portfolio Online Reporting Tools Expenditures and Results was queried for R01s using 10 heart transplant-related terms. Principal Investigator, total grant funding amount, number of publications, and citations of manuscripts were collected. A citation-based Grant Impact Metric was assigned to each grant: sum of citations for each manuscript normalized by the funding of the respective grant (per $100K). The department and background degree(s) (MD, PhD, MD/PhD) for each funded Principal Investigator were identified from institutional faculty profiles. RESULTS: A total of 321 cardiac transplantation R01s totaling $723 million and resulting in 6513 publications were analyzed. Surgery departments received more grants and more funding dollars to study cardiac transplantation than any other department (n = 115, $249 million; Medicine: n = 93, $208 million; Pathology: 26, $55 million). Surgeons performed equally well compared with all other Principal Investigators with respect to Grant Impact Metric (15.1 vs 20.6; P = .19) and publications per $1 million (7.5 vs 6.8; P = .75). Finally, all physician-scientists (MDs) have a significantly higher Grant Impact Metric compared with nonclinician researchers (non-MDs) (22.3 vs 16.3; P = .028). CONCLUSIONS: Surgeon-scientists are equally productive and impactful compared with nonsurgeons despite decreasing funding rates at the National Institutes of Health and greater pressure from administrators to increase clinical productivity.

Comprehensive National Institutes of Health funding analysis of academic cardiac surgeons.

OBJECTIVE: To determine trends in National Institutes of Health (NIH) funding for cardiac surgeons, hypothesizing they are at a disadvantage in obtaining funding owing to intensive clinical demands. METHODS: Cardiac surgeons (adult/congenital) currently at the top 141 NIH-funded institutions were identified using institutional websites. The NIH funding history for each cardiac surgeon was queried using the NIH Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER). Total grant funding, publications, and type was collected. Academic rank, secondary degrees, and fellowship information was collected from faculty pages. Grant productivity was calculated using a validated grant impact metric. RESULTS: A total of 818 academic cardiac surgeons were identified, of whom 144 obtained 293 NIH grants totaling $458 million and resulting in 6694 publications. We identified strong associations between an institution's overall NIH funding rank and the number of cardiac surgeons, NIH grants to cardiac surgeons, and amount of NIH funding to cardiac surgeons (P < .0001 for all). The majority of NIH funding to cardiac surgeons is concentrated in the top quartile of institutions. Cardiac surgeons had a high conversion rates from K awards (mentored development awards) to R01s (6 of 14; 42.9%). Finally, we demonstrate that the rate of all NIH grants awarded to cardiac surgeons has increased, driven primarily by P and U (collaborative project) grants. CONCLUSIONS: NIH-funded cardiac surgical research has had a significant impact over the last 3 decades. Aspiring cardiac surgeon-scientists may be more successful at top quartile institutions owing to better infrastructure and mentorship.