Evaluating the Effectiveness of Systemic Heparin During Arteriovenous Fistula Creation by Emulating a Target Trial.

Most of the 800,000 people living with end-stage kidney disease in the United States rely on a functioning vascular access to provide life-sustaining hemodialysis, yet one-third of arteriovenous fistulas experience early failures. Determining the safety and effectiveness of systemic heparin during fistula creation could improve the quality and quantity of life for these vulnerable patients. In this paper, a pragmatic randomized trial was emulated to assess the effect of systemic heparin administration (vs. none) during radiocephalic arteriovenous fistula creation on early bleeding and thrombosis using data from two international multicenter randomized trials performed between 2014 and 2019. Marginal risks were estimated using inverse probability weighted parametric survival analysis and confidence intervals were generated with bootstrapping. A total of 914 patients were enrolled and 61% received systemic heparin; median (IQR) age was 58 (49, 67) years and 45% were on hemodialysis at enrollment. No difference in the risk of bleeding events was observed, with a risk difference (95% CI) at 14 days of -0.1% (-1.6, 1.4). The risk of access thrombosis was lower in the heparin group, with a risk of 3.7% (2.6, 4.8) after heparin and 5.3% (3.4, 7.4) without heparin at 14 days (risk ratio 0.72, 95% CI 0.50, 0.98).

Descriptive Analysis of Amputation-Free Survival After First Time Infra-Inguinal Bypass Occlusion.

INTRODUCTION: Occlusion after infra-inguinal bypass surgery for peripheral artery disease is a major complication with potentially devastating consequences. In this descriptive analysis, we sought to describe the natural history and explore factors associated with long-term major amputation-free survival following occlusion of a first-time infra-inguinal bypass. METHODS: Using a prospective database from a tertiary care vascular center, we conducted a retrospective cohort study of all patients with peripheral artery disease who underwent a first-time infra-inguinal bypass and subsequently suffered a graft occlusion (1997-2021). The primary outcome was longitudinal rate of major amputation-free survival after bypass occlusion. Cox proportional hazard models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) to explore predictors of outcomes. RESULTS: Of the 1318 first-time infra-inguinal bypass surgeries performed over the study period, 255 bypasses occluded and were included in our analysis. Mean age was 66.7 (12.6) years, 40.4% were female, and indication for index bypass was chronic limb threatening ischemia (CLTI) in 89.8% (n = 229). 48.2% (n = 123) of index bypass conduits used great saphenous vein, 29.0% (n = 74) prosthetic graft, and 22.8% (n = 58) an alternative conduit. Median (interquartile range) time to bypass occlusion was 6.8 (2.3-19.0) months, and patients were followed for median of 4.3 (1.7-8.1) years after bypass occlusion. Following occlusion, 38.04% underwent no revascularization, 32.94% graft salvage procedure, 25.1% new bypass, and 3.92% native artery recanalization. Major amputation-free survival following occlusion was 56.9% (50.6%-62.8%) at 1 y, 37.1% (31%-43.3%) at 5 y, and 17.2% (11.9%-23.2%) at 10 y. In multivariable analysis, factors associated with lower amputation-free survival were older age, female sex, advanced cardiorenal comorbidities, CLTI at index procedure, CLTI at time of occlusion, and distal index bypass outflow. Initial treatment after occlusion with both a new surgical bypass (HR 0.44, CI: 0.29-0.67) or a graft salvage procedure (HR 0.56, CI: 0.38-0.82) showed improved amputation-free survival. One-year rate of major amputation or death were 59.8% (50.0%-69.6%) for those who underwent no revascularization, 37.9% (28.7%-49.0%) for graft salvage, and 26.7% (17.6%-39.5%) for new bypass. CONCLUSIONS: Long-term major amputation-free survival is low after occlusion of a first-time infra-inguinal bypass. While several nonmodifiable risk factors were associated with lower amputation-free survival, treatment after graft occlusion with either a new bypass or a graft salvage procedure may improve longitudinal outcomes.

Temporal trends in hemodialysis access creation during the fistula first era.

OBJECTIVE: Although forearm arteriovenous fistulas (AVFs) are the preferred initial vascular access for hemodialysis based on national guidelines, there are no population-level studies evaluating trends in creation of forearm vs upper arm AVFs and arteriovenous grafts (AVGs). The purpose of this study was to report temporal trends in first-time permanent hemodialysis access type, and to assess the effect of national initiatives on rates of AVF placement. METHODS: Retrospective cross-sectional study (2012-2022) utilizing the Vascular Quality Initiative database. All patients older than 18 years with creation of first-time upper extremity surgical hemodialysis access were included. Anatomic location of the AVF or AVG (forearm vs upper arm) was defined based on inflow artery, outflow vein, and presumed cannulation zone. Primary analysis examined temporal trends in rates of forearm vs upper arm AVFs and AVGs using time series analyses (modified Mann-Kendall test). Subgroup analyses examined rates of access configuration stratified by age, sex, race, dialysis, and socioeconomic status. Interrupted time series analysis was performed to assess the effect of the 2015 Fistula First Catheter Last initiative on rates of AVFs. RESULTS: Of the 52,170 accesses, 57.9% were upper arm AVFs, 25.2% were forearm AVFs, 15.4% were upper arm AVGs, and 1.5% were forearm AVGs. From 2012 to 2022, there was no significant change in overall rates of forearm or upper arm AVFs. There was a numerical increase in upper arm AVGs (13.9 to 18.2 per 100; P = .09), whereas forearm AVGs significantly declined (1.8 to 0.7 per 100; P = .02). In subgroup analyses, we observed a decrease in forearm AVFs among men (33.1 to 28.7 per 100; P = .04) and disadvantaged (Area Deprivation Index percentile ≥50) patients (29.0 to 20.7 per 100; P = .04), whereas female (17.2 to 23.1 per 100; P = .03), Black (15.6 to 24.5 per 100; P < .01), elderly (age ≥80 years) (18.7 to 32.5 per 100; P < .01), and disadvantaged (13.6 to 20.5 per 100; P < .01) patients had a significant increase in upper arm AVGs. The Fistula First Catheter Last initiative had no effect on the rate of AVF placement (83.2 to 83.7 per 100; P=.37). CONCLUSIONS: Despite national initiatives to promote autogenous vascular access, the rates of first-time AVFs have remained relatively constant, with forearm AVFs only representing one-quarter of all permanent surgical accesses. Furthermore, elderly, Black, female, and disadvantaged patients saw an increase in upper arm AVGs. Further efforts to elucidate factors associated with forearm AVF placement, as well as potential physician, center, and regional variation is warranted.

Short-term Pre-operative Methionine Restriction Induces Browning of Perivascular Adipose Tissue and Improves Vein Graft Remodeling in Mice.

Short-term preoperative methionine restriction (MetR) shows promise as a translatable strategy to modulate the body's response to surgical injury. Its application, however, to improve post-interventional vascular remodeling remains underexplored. Here, we find that MetR protects from arterial intimal hyperplasia in a focal stenosis model and adverse vascular remodeling after vein graft surgery. RNA sequencing reveals that MetR enhances the brown adipose tissue phenotype in arterial perivascular adipose tissue (PVAT) and induces it in venous PVAT. Specifically, PPAR-α was highly upregulated in PVAT-adipocytes. Furthermore, MetR dampens the post-operative pro-inflammatory response to surgery in PVAT-macrophages in vivo and in vitro . This study shows for the first time that the detrimental effects of dysfunctional PVAT on vascular remodeling can be reversed by MetR, and identifies pathways involved in browning of PVAT. Furthermore, we demonstrate the potential of short-term pre-operative MetR as a simple intervention to ameliorate vascular remodeling after vascular surgery.

Comparative effectiveness of bovine carotid artery xenograft and polytetrafluoroethylene in hemodialysis access revision.

BACKGROUND: When hemodialysis arteriovenous accesses fail, autogenous options are often limited. Non-autogenous conduit choices include bovine carotid artery xenografts (BCAG) and expanded polytetrafluoroethylene (PTFE), yet their comparative effectiveness in hemodialysis access revision remains largely unknown. METHODS: A cohort study was performed from a prospectively collected institutional database from August 2010 to July 2021. All patients undergoing an arteriovenous access revision with either BCAG or PTFE were followed for up to 3 years from their index access revision. Revision was defined as graft placement to address a specific problem of an existing arteriovenous access while maintaining one or more of the key components of the original access (e.g. inflow, outflow, and cannulation zone). Outcomes were measured starting at the date of the index revision procedure. The primary outcome was loss of secondary patency at 3 years. Secondary outcomes included loss of post-intervention primary patency, rates of recurrent interventions, and 30-day complications. Pooled logistic regression was used to estimate inverse probability weighted marginal structural models for the time-to-event outcomes of interest. RESULTS: A total of 159 patients were included in the study, and 58% received access revision with BCAG. Common indications for revision included worn out cannulation zones (32%), thrombosis (18%), outflow augmentation (16%), and inflow augmentation (13%). Estimated risk of secondary patency loss at 3 years was lower in the BCAG group (8.6%, 3.9-15.1) compared to the PTFE group (24.8%, 12.4-38.7). Patients receiving BCAG experienced a 60% decreased relative risk of secondary patency loss at 3 years (risk ratio 0.40, 0.14-0.86). Recurrent interventions occurred at similar rates in the BCAG and PTFE groups, with 1.86 (1.31-2.43) and 1.60 (1.07-2.14) interventions at 1 year, respectively (hazard ratio 1.22, 0.74-1.96). CONCLUSIONS: Under the conditions of this contemporary cohort study, use of BCAG in upper extremity hemodialysis access revision decreased access abandonment when compared to PTFE.

Cystathionine-γ-lyase overexpression modulates oxidized nicotinamide adenine dinucleotide biosynthesis and enhances neovascularization.

Objective: Hydrogen sulfide is a proangiogenic gas produced primarily by the transsulfuration enzyme cystathionine-γ-lyase (CGL). CGL-dependent hydrogen sulfide production is required for neovascularization in models of peripheral arterial disease. However, the benefits of increasing endogenous CGL and its mechanism of action have not yet been elucidated. Methods: Male whole body CGL-overexpressing transgenic (CGLTg) mice and wild-type (WT) littermates (C57BL/6J) were subjected to the hindlimb ischemia model (age, 10-12 weeks). Functional recovery was assessed via the treadmill exercise endurance test. Leg perfusion was measured by laser Doppler imaging and vascular endothelial-cadherin immunostaining. To examine the angiogenic potential, aortic ring sprouting assay and postnatal mouse retinal vasculature development studies were performed. Finally, comparative metabolomics analysis, oxidized/reduced nicotinamide adenine dinucleotide (NAD+/NADH) analysis, and quantitative real-time polymerase chain reaction were performed on CGLWT and CGLTg gastrocnemius muscle. Results: The restoration of blood flow occurred more rapidly in CGLTg mice. Compared with the CGLWT mice, the median ± standard deviation running distance and time were increased for the CGLTg mice after femoral artery ligation (159 ± 53 m vs 291 ± 74 m [P < .005] and 17 ± 4 minutes vs 27 ± 5 minutes [P < .05], respectively). Consistently, in the CGLTg ischemic gastrocnemius muscle, the capillary density was increased fourfold (0.05 ± 0.02 vs 0.20 ± 0.12; P < .005). Ex vivo, the endothelial cell (EC) sprouting length was increased in aorta isolated from CGLTg mice, especially when cultured in VEGFA (vascular endothelial growth factor A)-only media (63 ± 2 pixels vs 146 ± 52 pixels; P < .05). Metabolomics analysis demonstrated a higher level of niacinamide, a precursor of NAD+/NADH in the muscle of CGLTg mice (61.4 × 106 ± 5.9 × 106 vs 72.4 ± 7.7 × 106 area under the curve; P < .05). Similarly, the NAD+ salvage pathway gene expression was increased in CGLTg gastrocnemius muscle. Finally, CGL overexpression or supplementation with the NAD+ precursor nicotinamide mononucleotide improved EC migration in vitro (wound closure: control, 35% ± 9%; CGL, 55% ± 11%; nicotinamide mononucleotide, 42% ± 13%; P < .05). Conclusions: Our results have demonstrated that CGL overexpression improves the neovascularization of skeletal muscle on hindlimb ischemia. These effects correlated with changes in the NAD pathway, which improved EC migration.

Staged autogenous to prosthetic hemodialysis access creation strategy to maximize forearm options.

OBJECTIVE: When an adequate cephalic vein is not available for fistula construction, surgeons often turn to basilic vein or prosthetic constructions. Single-stage forearm prosthetic hemodialysis accesses are associated with poor durability, and upper arm non-autogenous access options are often limited by axillary outflow failure, which inevitably drives transition to the contralateral arm or lower extremity. We hypothesized that initial creation of a modest flow proximal forearm arterial-venous anastomosis to dilate ("develop") inflow and outflow vessels, followed by a planned second-stage procedure to create a cannulation zone with a prosthetic graft in the forearm, would result in reliable and durable hemodialysis access in patients with limited options. METHODS: We performed an institutional cohort study from 2017 to 2021 using a prospectively maintained database supplemented with adjudicated chart review. Patients without traditional autogenous hemodialysis access options in the forearm underwent an initial non-wrist arterial-venous anastomosis creation in the forearm as a first stage, followed by a second-stage interposition graft sewn to the existing inflow and venous outflow segments to create a useable cannulation zone in the forearm while leveraging vascular development. Outcomes included time from second-stage access creation to loss of primary and secondary patency, frequency of subsequent interventions, and perioperative complications. RESULTS: The cohort included 23 patients; first-stage radial artery-based (74%) configurations were more common than brachial artery-based (26%). Mean age was 63 years (standard deviation, 14 years), and 65% were female. Median follow-up was 340 days (interquartile range [IQR], 169-701 days). Median time to cannulation from second-stage procedure was 28 days (IQR, 18-53 days). Primary, primary assisted, and secondary patency at 1 year was 16.7% (95% confidence interval [CI], 5.3%-45.8%), 34.6% (95% CI, 15.2%-66.2%), and 95.7% (95% CI, 81.3%-99.7%), respectively. Subsequent interventions occurred at a rate of 3.02 (IQR, 1.0-4.97) per person-year, with endovascular thrombectomy with or without angioplasty/stenting (70.9%) being the most common. There were no cases of steal syndrome. Infection occurred in two cases and were managed with antibiotics alone. CONCLUSIONS: For patients without adequate distal autogenous access options, staged prosthetic graft placement in the forearm offers few short-term complications and excellent durability with active surveillance while strategically preserving the upper arm for future constructions.

Evaluating national guideline concordance of recurrent interventions after radiocephalic arteriovenous fistula creation.

OBJECTIVE: Radiocephalic arteriovenous fistulas have been historically perceived as requiring multiple follow-up procedural interventions to achieve maturation and maintain patency. Recent clinical practice guidelines from the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) emphasize a patient-centered hemodialysis access strategy with new maximum targets for intervention rates, potentially conflicting with concomitant recommendations to prioritize autogenous forearm hemodialysis access creation. The present descriptive study seeks to assess whether radiocephalic fistulas can meet the KDOQI guideline benchmarks for interventions following access creation, and to elucidate clinical and anatomic characteristics associated with the timing and frequency of interventions following radiocephalic arteriovenous fistula creation. METHODS: Prospective patient-level data from the multicenter PATENCY-1 and PATENCY-2 randomized trials, which enrolled patients undergoing new radiocephalic arteriovenous fistula creation, was analyzed (ClinicalTrials.govNCT02110901 and NCT02414841). The primary outcome was the rate of interventions at 1 year postoperatively. Incidence rates were calculated, and time to surgical or endovascular intervention following fistula creation was modeled using recurrent event extensions of the Cox proportional hazards model. Confidence intervals at the 95% level were calculated using nonparametric bootstrapping. RESULTS: The cohort consisted of 914 patients; mean age was 57 years (standard deviation, 13 years), and 22% were female. Median follow-up was 707 days (interquartile range, 447-1066 days). The incidence of interventions per person-year was 1.04 (95% confidence interval [CI], 0.95-1.13) overall; 1.10 (95% CI, 0.98-1.21) before fistula use, and 0.96 (95% CI, 0.82-1.11) after fistula use. The most common interventions overall were balloon angioplasty (54.9% of all interventions), venous side-branch ligation (16.4%), and open revisions (eg, proximalization from snuffbox to wrist, 16.4%). The locations requiring balloon angioplasty included the juxta-anastomotic segment (51.7% of angioplasties), the outflow vein (29.2%), the inflow artery (14.8%), the central veins (3.8%), and the cephalic arch (0.5%). Common indications were to restore or maintain patency (75.6% of all interventions), assist maturation (14.9%), improve depth (4.4%), or improve augmentation (3.0%). In the multivariable regression analysis, female sex (adjusted hazard ratio [HR], 1.21; 95% CI, 1.05-1.45), diabetes (HR, 1.21; 95% CI, 1.01-1.46), and intraoperative vein diameter <3.0 mm (vs ≥4.0 mm: HR, 1.33; 95% CI, 1.02-1.66) were associated with earlier and more frequent interventions. Patients not on hemodialysis at the time of fistula creation underwent less frequent interventions (HR, 0.69; 95% CI, 0.59-0.81). CONCLUSIONS: Patients with radiocephalic arteriovenous fistulas can expect to undergo one intervention, on average, in the first year after creation, which aligns with current KDOQI guidelines. Patients already requiring hemodialysis, female patients, patients with diabetes, and patients with intraoperative vein diameters <3.0 mm were at increased risk for repeated intervention. No subgroup exceeded guideline-suggested maximum thresholds for recurrent interventions. Overall, the results demonstrate that creation of radiocephalic arteriovenous fistula remains a guideline-concordant strategy when part of an end-stage kidney disease life-plan in appropriately selected patients.

Radiocephalic Arteriovenous Fistula Patency and Use: A Post Hoc Analysis of Multicenter Randomized Clinical Trials.

We sought to confirm and extend the understanding of clinical outcomes following creation of a common distal autogenous access, the radiocephalic arteriovenous fistula (RCAVF). Background: Interdisciplinary guidelines recommend distal autogenous arteriovenous fistulae as the preferred hemodialysis (HD) access, yet uncertainty about durability and function present barriers to adoption. Methods: Pooled data from the 2014-2019 multicenter randomized-controlled PATENCY-1 and PATENCY-2 trials were analyzed. New RC-AVFs were created in 914 patients, and outcomes were tracked prospectively for 3-years. Cox proportional hazards and Fine-Gray regression models were constructed to explore patient, anatomic, and procedural associations with access patency and use. Results: Mean (SD) age was 57 (13) years; 45% were on dialysis at baseline. Kaplan-Meier estimates of 3-year primary, primary-assisted, and secondary patency were 27.6%, 56.4%, and 66.6%, respectively. Cause-specific 1-year cumulative incidence estimates of unassisted and overall RC-AVF use were 46.8% and 66.9%, respectively. Patients with larger baseline cephalic vein diameters had improved primary (per mm, hazard ratio [HR] 0.89, 95% confidence intervals 0.81-0.99), primary-assisted (HR 0.75, 0.64-0.87), and secondary (HR 0.67, 0.57-0.80) patency; and higher rates of unassisted (subdistribution hazard ratio 1.21, 95% confidence intervals 1.02-1.44) and overall RCAVF use (subdistribution hazard ratio 1.26, 1.11-1.45). Similarly, patients not requiring HD at the time of RCAVF creation had better primary, primary-assisted, and secondary patency. Successful RCAVF use occurred at increased rates when accesses were created using regional anesthesia and at higher volume centers. Conclusions: These insights can inform patient counseling and guide shared decision-making regarding HD access options when developing an individualized end-stage kidney disease life-plan.

Predicting radiocephalic arteriovenous fistula success with machine learning.

After creation of a new arteriovenous fistula (AVF), assessment of readiness for use is an important clinical task. Accurate prediction of successful use is challenging, and augmentation of the physical exam with ultrasound has become routine. Herein, we propose a point-of-care tool based on machine learning to enhance prediction of successful unassisted radiocephalic arteriovenous fistula (AVF) use. Our analysis includes pooled patient-level data from 704 patients undergoing new radiocephalic AVF creation, eligible for hemodialysis, and enrolled in the 2014-2019 international multicenter PATENCY-1 or PATENCY-2 randomized controlled trials. The primary outcome being predicted is successful unassisted AVF use within 1-year, defined as 2-needle cannulation for hemodialysis for ≥90 days without preceding intervention. Logistic, penalized logistic (lasso and elastic net), decision tree, random forest, and boosted tree classification models were built with a training, tuning, and testing paradigm using a combination of baseline clinical characteristics and 4-6 week ultrasound parameters. Performance assessment includes receiver operating characteristic curves, precision-recall curves, calibration plots, and decision curves. All modeling approaches except the decision tree have similar discrimination performance and comparable net-benefit (area under the ROC curve 0.78-0.81, accuracy 69.1-73.6%). Model performance is superior to Kidney Disease Outcome Quality Initiative and University of Alabama at Birmingham ultrasound threshold criteria. The lasso model is presented as the final model due to its parsimony, retaining only 3 covariates: larger outflow vein diameter, higher flow volume, and absence of >50% luminal stenosis. A point-of-care online calculator is deployed to facilitate AVF assessment in the clinic.

Plasma Gut Microbe-Derived Metabolites Associated with Peripheral Artery Disease and Major Adverse Cardiac Events.

Cardiovascular diseases are associated with gut dysbiosis, but the role of microbe-derived metabolites as biomarkers or modulators of cardiovascular disease are not well understood. This is a targeted metabolomics study to investigate the association of nine microbe-derived metabolites with lower extremity peripheral artery disease (PAD), a form of atherosclerosis, and major adverse cardiac events (MACE). The study cohort consists of individuals with intermittent claudication and ankle-brachial index (ABI) < 0.9 (N = 119) and controls without clinically-apparent atherosclerosis (N = 37). The primary endpoint was MACE, a composite endpoint of myocardial infarction, coronary revascularization, stroke, transient ischemic attack, or cardiac-related death. Plasma metabolite concentrations differed significantly between the PAD and control groups. After adjustment for traditional atherosclerosis risk factors, kynurenine, hippuric acid, indole-3-propionic acid (IPA), and indole-3-aldehyde (I3A) concentrations were negatively associated with PAD, whereas indoxyl sulfate and 3-hydroxyanthranilic acid were positively associated. Hippuric acid, IPA, and I3A correlated with ABI, a surrogate for atherosclerotic disease burden. Those in the highest I3A concentration quartile had significantly improved freedom from MACE during follow-up compared to those in the lowest quartile. This study identifies specific indole- and phenyl-derived species impacted by gut microbial metabolic pathways that could represent novel microbiome-related biomarkers of PAD.

Microfluidic bioprinting of tough hydrogel-based vascular conduits for functional blood vessels.

Three-dimensional (3D) bioprinting of vascular tissues that are mechanically and functionally comparable to their native counterparts is an unmet challenge. Here, we developed a tough double-network hydrogel (bio)ink for microfluidic (bio)printing of mono- and dual-layered hollow conduits to recreate vein- and artery-like tissues, respectively. The tough hydrogel consisted of energy-dissipative ionically cross-linked alginate and elastic enzyme-cross-linked gelatin. The 3D bioprinted venous and arterial conduits exhibited key functionalities of respective vessels including relevant mechanical properties, perfusability, barrier performance, expressions of specific markers, and susceptibility to severe acute respiratory syndrome coronavirus 2 pseudo-viral infection. Notably, the arterial conduits revealed physiological vasoconstriction and vasodilatation responses. We further explored the feasibility of these conduits for vascular anastomosis. Together, our study presents biofabrication of mechanically and functionally relevant vascular conduits, showcasing their potentials as vascular models for disease studies in vitro and as grafts for vascular surgeries in vivo, possibly serving broad biomedical applications in the future.

Multiomics assessment of dietary protein titration reveals altered hepatic glucose utilization.

Dietary protein restriction (PR) has rapid effects on metabolism including improved glucose and lipid homeostasis, via multiple mechanisms. Here, we investigate responses of fecal microbiome, hepatic transcriptome, and hepatic metabolome to six diets with protein from 18% to 0% of energy in mice. PR alters fecal microbial composition, but metabolic effects are not transferable via fecal transplantation. Hepatic transcriptome and metabolome are significantly altered in diets with lower than 10% energy from protein. Changes upon PR correlate with calorie restriction but with a larger magnitude and specific changes in amino acid (AA) metabolism. PR increases steady-state aspartate, serine, and glutamate and decreases glucose and gluconeogenic intermediates. 13C6 glucose and glycerol tracing reveal increased fractional enrichment in aspartate, serine, and glutamate. Changes remain intact in hepatic ATF4 knockout mice. Together, this demonstrates an ATF4-independent shift in gluconeogenic substrate utilization toward specific AAs, with compensation from glycerol to promote a protein-sparing response.

Contemporary indications for open abdominal aortic aneurysm repair in the endovascular era.

OBJECTIVE: Despite the emergence of endovascular aneurysm repair (EVAR) as the most common approach to abdominal aortic aneurysm repair, open aneurysm repair (OAR) remains an important option. This study seeks to define the indications for OAR in the EVAR era and how these indicatioxns effect outcomes. METHODS: A retrospective cohort study was performed of all OAR at a single institution from 2004 to 2019. Preoperative computed tomography scans and operative records were assessed to determine the indication for OAR. These reasons were categorized into anatomical contraindications, systemic factors (connective tissue disorders, contraindication to contrast dye), and patient or surgeon preference (patients who were candidates for both EVAR and OAR). Perioperative and long-term outcomes were compared between the groups. RESULTS: We included 370 patients in the analysis; 71.6% (265/370) had at least one anatomic contraindication to EVAR and 36% had two or more contraindications. The most common anatomic contraindications were short aortic neck length (51.6%), inadequate distal seal zone (19.2%), and inadequate access vessels (15.7%). The major perioperative complication rate was 18.1% and the 30-day mortality was 3.0%. No single anatomic factor was identified as a predictor of perioperative complications. Sixty-one patients (16.5%) underwent OAR based on patient or surgeon preference; these patients were younger, had lower incidences of coronary artery disease and chronic obstructive pulmonary disease, and were less likely to require suprarenal cross-clamping compared with patients who had anatomic and/or systemic contraindications to EVAR. The patient or surgeon preference group had a lower incidence of perioperative major complications (8.2% vs 20.1%; P = .034), shorter length of stay (6 days vs 8 days; P < .001) and no 30-day mortalities. The multivariable adjusted risk for 15-year mortality was lower for patient or surgeon preference patients (adjusted hazard ratio, 0.44; 95% confidence interval, 0.24-0.80; P = .007) compared with those anatomic or systemic contraindications. CONCLUSIONS: Within a population of patients who did not meet instruction for use criteria for EVAR, no single anatomic contraindication was a marker for worse outcomes with OAR. Patients who were candidates for both aortic repair approaches but elected to undergo OAR owing to patient or surgeon preference have very low 30-day mortality and morbidity, and superior long-term survival rates compared with those patients who underwent OAR owing to anatomic and/or systemic contraindications to EVAR.

Comparative analysis of open abdominal aortic aneurysm repair outcomes across national registries.

OBJECTIVE: In a recent analysis, we discovered lower mortality after open abdominal aortic aneurysm repair (OAAA) in the Society for Vascular Surgery Vascular Quality Initiative (VQI) database when compared with previously published reports of other national registries. Understanding differentials in these registries is essential for their utility because such datasets increasingly inform clinical guidelines and health policy. METHODS: The VQI, American College of Surgeons National Surgical Quality Improvement Program (NSQIP), and National Inpatient Sample (NIS) databases were queried to identify patients who had undergone elective OAAA between 2013 and 2016. χ2 tests were used for frequencies and analysis of variance for continuous variables. RESULTS: In total, data from 8775 patients were analyzed. Significant differences were seen across the baseline characteristics included. Additionally, the availability of patient and procedural data varied across datasets, with VQI including a number of procedure-specific variables and NIS with the most limited clinical data. Length of stay, primary insurer, and discharge destination differed significantly. Unadjusted in-hospital mortality also varied significantly between datasets: NIS, 5.5%; NSQIP, 5.2%; and VQI, 3.3%; P < .001. Similarly, 30-day mortality was found to be 3.5% in VQI and 5.9% in NSQIP (P < .001). CONCLUSIONS: There are fundamental important differences in patient demographic/comorbidity profiles, payer mix, and outcomes after OAAA across widely used national registries. This may represent differences in outcomes between institutions that elect to participate in the VQI and NSQIP compared with patient sampling in the NIS. In addition to avoiding direct comparison of information derived from these databases, it is critical these differences are considered when making policy decisions and guidelines based on these "real-world" data repositories.

Plasma Hydrogen Sulfide Is Positively Associated With Post-operative Survival in Patients Undergoing Surgical Revascularization.

Objective: Hydrogen sulfide (H2S) is a gaseous signaling molecule and redox factor important for cardiovascular function. Deficiencies in its production or bioavailability are implicated in atherosclerotic disease. However, it is unknown if circulating H2S levels differ between vasculopaths and healthy individuals, and if so, whether H2S measurements can be used to predict surgical outcomes. Here, we examined: (1) Plasma H2S levels in patients undergoing vascular surgery and compared these to healthy controls, and (2) the association between H2S levels and mortality in a cohort of patients undergoing surgical revascularization. Methods: One hundred and fifteen patients undergoing carotid endarterectomy, open lower extremity revascularization or lower leg amputation were enrolled at a single institution. Peripheral blood was also collected from a matched control cohort of 20 patients without peripheral or coronary artery disease. Plasma H2S production capacity and sulfide concentration were measured using the lead acetate and monobromobimane methods, respectively. Results: Plasma H2S production capacity and plasma sulfide concentrations were reduced in patients with PAD (p < 0.001, p = 0.013, respectively). Patients that underwent surgical revascularization were divided into high vs. low H2S production capacity groups by median split. Patients in the low H2S production group had increased probability of mortality (p = 0.003). This association was robust to correction for potentially confounding variables using Cox proportional hazard models. Conclusion: Circulating H2S levels were lower in patients with atherosclerotic disease. Patients undergoing surgical revascularization with lower H2S production capacity, but not sulfide concentrations, had increased probability of mortality within 36 months post-surgery. This work provides insight on the role H2S plays as a diagnostic and potential therapeutic for cardiovascular disease.

Short-Term Pre-Operative Protein Caloric Restriction in Elective Vascular Surgery Patients: A Randomized Clinical Trial.

(1) Background: Vascular surgery operations are hampered by high failure rates and frequent occurrence of peri-operative cardiovascular complications. In pre-clinical studies, pre-operative restriction of proteins and/or calories (PCR) has been shown to limit ischemia-reperfusion damage, slow intimal hyperplasia, and improve metabolic fitness. However, whether these dietary regimens are feasible and safe in the vascular surgery patient population remains unknown. (2) Methods: We performed a randomized controlled trial in patients scheduled for any elective open vascular procedure. Participants were randomized in a 3:2 ratio to either four days of outpatient pre-operative PCR (30% calorie, 70% protein restriction) or their regular ad-libitum diet. Blood was drawn at baseline, pre-operative, and post-operative day 1 timepoints. A leukocyte subset flow cytometry panel was performed at these timepoints. Subcutaneous/perivascular adipose tissue was sampled and analyzed. Follow-up was one year post-op. (3) Results: 19 patients were enrolled, of whom 11 completed the study. No diet-related reasons for non-completion were reported, and there was no intervention group crossover. The PCR diet induced weight loss and BMI decrease without malnutrition. Insulin sensitivity was improved after four days of PCR (p = 0.05). Between diet groups, there were similar rates of re-intervention, wound infection, and cardiovascular complications. Leukocyte populations were maintained after four days of PCR. (4) Conclusions: Pre-operative PCR is safe and feasible in elective vascular surgery patients.

Total protein, not amino acid composition, differs in plant-based versus omnivorous dietary patterns and determines metabolic health effects in mice.

Plant-based dietary patterns are associated with improved cardiometabolic health, but causal dietary components are unclear. Protein has been proposed to play a role, but the importance of protein quantity versus quality remains unknown. We investigated the contributions of total protein amount, amino acid (AA) composition, and plant versus animal source. Analysis of total protein and AA composition of food items and dietary patterns revealed differences between individual food items, but few differences between AA profiles of vegan versus omnivorous dietary patterns. Effects of protein quantity, but not quality, on cardiometabolic health markers were observed in mice using semi-purified diets with crystalline AAs in plant versus animal-based ratios and naturally sourced diets with whole-food ingredients. Our data show relatively little difference in protein quality between plant-based and omnivorous dietary patterns and that reduced total protein intake in plant-based dietary patterns may be a contributor to the benefits of plant-based diets.