Use of Therapeutic RNAs to Accelerate Wound Healing in Diabetic Rabbit Wounds.

Introduction: Diabetes mellitus (DM) affects over 422 million people globally. Patients with DM are subject to a myriad of complications, of which diabetic foot ulcers (DFUs) are the most common with ∼25% chance of developing these wounds throughout their lifetime. Innovation: Currently there are no therapeutic RNAs approved for use in DFUs. Use of dressings containing novel layer-by-layer (LbL)-formulated therapeutic RNAs that inhibit PHD2 and miR-210 can significantly improve diabetic wound healing. These dressings provide sustained release of therapeutic RNAs to the wounds locally without systemic side effects. Clinical Problem Addressed: Diabetic foot wounds are difficult to heal and often result in significant patient morbidity and mortality. Materials and Methods: We used the diabetic neuroischemic rabbit model of impaired wound healing. Diabetes was induced in the rabbits with alloxan, and neuroischemia was induced by ligating the central neurovascular bundle of each ear. Four 6-mm full-thickness wounds were created on each ear. A LbL technique was used to conformally coat the wound dressings with chemically modified RNAs, including an antisense oligonucleotide (antimiR) targeting microRNA-210 (miR-210), an short synthetic hairpin RNA (sshRNA) targeting PHD2, or both. Results: Wound healing was improved by the antimiR-210 but not the PHD2-sshRNA. Specific knockdown of miR-210 in tissue as measured by RT-qPCR was ∼8 Ct greater than nonspecific controls, and this apparent level of knockdown (>99%) suggests that delivery to the tissue is highly efficient at the administered dose. Discussion: Healing of ischemic/neuropathic wounds in diabetic rabbits was accelerated upon inhibition of miR-210 by LbL delivery to the wound bed. miR-210 inhibition was achieved using a chemically modified antisense RNA.

Inferior mesenteric artery revascularization can supplement salvage of mesenteric ischemia.

The inferior mesenteric artery (IMA) has often been overlooked in favor of the celiac or superior mesenteric artery in arterial mesenteric ischemia, owing to the typically robust visceral collateral networks. In the present report, we have described a case series of patients in whom "salvage" revascularization of the IMA was performed after attempted celiac or superior mesenteric artery revascularization had been unsuccessful. The restored IMA inflow had resolved the symptoms for three patients. However, sole IMA revascularization was insufficient to reverse the course for two other patients with severe acute-on-chronic mesenteric ischemia. The IMA should be considered for salvage revascularization in the appropriate clinical scenario.

Greater Patient Travel Distance is Associated with Perioperative and One-Year Cost Increases After Complex Aortic Surgery.

BACKGROUND: With increasing regionalization of complex aortic surgery within fewer US centers, patients may face increased travel burden when accessing aortic surgery. Longer travel distances have been associated with inferior outcomes after major surgery; however, the impacts of distance on reinterventions and costs have not been described. This study aims to assess the association between patient travel distance and longer-term outcomes including costs and reinterventions after complex aortic surgery. METHODS: A retrospective review was conducted of all patients in the Vascular Implant Surveillance and Interventional Outcomes Network database undergoing complex endovascular aortic repair including internal iliac or visceral vessel involvement, complex thoracic endovascular aortic repair including Zone 0-2 proximal extent or branched devices, and complex open abdominal aortic aneurysm repair including suprarenal or higher clamp sites. Travel distance was stratified by Rural-Urban Commuting Area population-density category. Multinomial logistic regression models, negative-binomial models, and zero-inflated Poisson models were used to assess the association between travel distance and index procedural and comprehensive first-year costs, long-term imaging, and long-term reinterventions, respectively. RESULTS: Between 2011 and 2018, 8,782 patients underwent complex aortic surgery in the Vascular Implant Surveillance and Interventional Outcomes Network database, including 4,822 complex endovascular aortic repairs, 2,672 complex thoracic endovascular aortic repairs, and 1,288 complex open abdominal aortic aneurysm repairs. Median travel distance was 22.8 miles (interquartile range 8.6-54.8 miles, range 0-2,688.9 miles). Median age was 75 years for all distance quintiles. Patients traveling farther were more likely to be female (26.8% in quintile 5 [Q5] vs. 19.9% in Q1, P < 0.001) and to have had a prior aortic surgery (20.8% for Q5 vs. 5.9% for Q1, P < 0.001). Patients traveling farther had higher index procedural costs, with adjusted odds ratio (OR) 2.34 (95% confidence interval [CI] 1.86-2.94, P < 0.0001) of being in the highest cost tertile versus lowest for patients in Q5 vs. Q1. For patients with ≥ 1-year follow-up, those traveling farther had higher imaging costs, with adjusted Q5 OR 1.55 (95% CI 1.22-1.95, P = 0.0002), and comprehensive first-year costs, with adjusted Q5 OR 2.06 (95% CI 1.57-2.70, P < 0.0001). In contrast, patients traveling farther had similar numbers of reinterventions and imaging studies postoperatively. CONCLUSIONS: Patients traveling farther for complex aortic surgery have higher procedural costs, postoperative imaging costs, and comprehensive first-year costs. These patients should be targeted for increased care coordination for improved outcomes and healthcare system burden.

Utility of Hook Sign in the Diagnosis of Median Arcuate Ligament Syndrome.

BACKGROUND: Median arcuate ligament syndrome (MALS) is a clinical syndrome caused by compression of the celiac artery by the median arcuate ligament that often manifests with nonspecific abdominal pain. Identification of this syndrome is often dependent on imaging of compression and upward bending of the celiac artery by lateral computed tomography angiography, the so-called "hook sign." The purpose of this study was to assess the relationship of radiologic characteristics of the celiac artery to clinically relevant MALS. METHODS: An institutional review board-approved retrospective chart review from 2,000 to 2,021 of 293 patients at a tertiary academic center diagnosed with celiac artery compression (CAC) was performed. Patient demographics and symptoms of 69 patients who were diagnosed with symptomatic MALS were compared to 224 patients without MALS (but with CAC) per electronic medical record review. Computed tomography angiography images were reviewed and the fold angle (FA) was measured. The presence of a hook sign (defined as a visual FA < 135°), as well as stenosis (defined as >50% of luminal narrowing on imaging) were recorded. Wilcoxon rank-sum test and Chi-squared test were used for comparative analysis. Logistic model was run to relate the presence of MALS with comorbidities and radiographic findings. RESULTS: Imaging was available in 59 patients (25 males, 34 females) and 157 patients (60 males, 97 females) with and without MALS, respectively. Patients with MALS were more likely to have a more severe FA (120.7 ± 33.6 vs. 134.8 ± 27.9, P = 0.002). Males with MALS were also more likely to have a more severe FA compared with males without MALS (111.1 ± 33.7 vs. 130.4 ± 30.4, P = 0.015). In patients with body mass index (BMI) >25, MALS patients also had narrower FA compared with patients without MALS (112.6 ± 30.5 vs. 131.7 ± 30.3, P = 0.001). The FA was negatively correlated with BMI in patients with CAC. The hook sign and stenosis were associated with diagnosis of MALS (59.3% vs. 28.7%, P < 0.001, and 75.7% vs. 45.2%, P < 0.001, respectively). In logistic regression, pain, stenosis, and a narrow FA were statistically significant predictors of the presence of MALS. CONCLUSIONS: The upward deflection of the celiac artery in patients with MALS is more severe compared with patients without MALS. Consistent with prior literature, this bending of the celiac artery is negatively correlated with BMI in patients with and without MALS. When demographic variables and comorbidities are considered, a narrow FA is a statistically significant predictor of MALS. Regardless of MALS diagnosis, a hook sign was associated with narrower FA. While demographics and imaging findings may inform MALS diagnosis, clinicians should not rely on a visual assessment of a hook sign but should quantitatively measure the anatomic bending angle of the celiac artery to assist with the diagnosis and understand the outcomes.

Experimental treatments in clinical trials for diabetic foot ulcers: wound healers in the pipeline.

INTRODUCTION: Diabetes affects 400 million people globally and patients and causes nephropathy, neuropathy, and vascular disease. Amongst these complications, diabetic foot ulcers remain a substantial problem for patients and clinicians. Aggressive wound care and antibiotics remain important for the healing of these chronic wounds, but even when treated these chronic ulcers can lead to infection and amputations. AREAS COVERED: This paper reviews the pathophysiology of diabetic foot ulcers and the current management strategies. Then, it discusses novel therapeutics such as topical oxygen therapy as well as autologous patches and macrophage creams. EXPERT OPINION: Diabetic foot ulcers are a substantial problem for patients and clinicians. Early identification, aggressive wound care, and normoglycemia remain the standard of care, however when these fail it is important to adapt. Since each patient and wound vary drastically we believe they should be treated as such. For patient with intact perfusion, topical ON101 and sucrose octasulfate creams can help. While patient with peripheral arterial disease should consider topical oxygen therapy as an adjunct. However, as scientists gain a better understanding of the pathophysiology behind DFUs, the hope is that this new wave of therapeutics will emerge.

Longer patient travel distance is associated with increased non-index readmission after complex aortic surgery.

OBJECTIVE: Recently evolving practice patterns in complex aortic surgery have led to regionalization of care within fewer centers in the United States, and thus patients may have to travel farther for complex aortic care. Travel distance has been associated with inferior outcomes after non-vascular surgery, particularly non-index readmission. This study aims to assess the impact of patient travel distance on perioperative outcomes and readmissions after complex aortic surgery. METHODS: A retrospective review was conducted of all patients in the Vascular Quality Initiative and Vascular Implant Surveillance and Interventional Outcomes Network databases undergoing complex endovascular aortic repair (EVAR) including internal iliac or visceral vessel involvement, complex thoracic endovascular aortic repair (TEVAR) including zone 0 to 2 proximal extent or branched devices, and complex open abdominal aortic aneurysm (AAA) repair including suprarenal or higher clamp sites. Travel distance was stratified by rural/urban commuting area (RUCA) population-density category. Wilcoxon and χ2 tests were used to assess relationships between travel distance quintiles and baseline characteristics, mortality, and readmission. Travel distance and other factors were included in multivariable Cox models for survival and Fine-Gray competing risk models for freedom from readmission. RESULTS: Between 2011 and 2018, 8782 patients underwent complex aortic surgery in the Vascular Quality Initiative and Vascular Implant Surveillance and Interventional Outcomes Network databases, including 4822 complex EVARs, 2672 complex TEVARs, and 1288 complex open AAA repairs. Median travel distance was 22.8 miles (interquartile range [IQR], 8.6-54.8 miles). Median age was 75 years for all distance quintiles, but patients traveling longer distances were more likely female (26.8% in quintile 5 [Q5] vs 19.9% in Q1; P < .001), white (93.8% of Q5 vs 83.8% of Q1; P < .001), to have larger-diameter AAAs (median 59 mm for Q5 vs 55 mm for Q1; P < .001), and to have had prior aortic surgery (20.8% for Q5 vs 5.9% for Q1; P < .001). Overall 30-day readmission was more common at farther distances (18.1% for Q5 vs 14.8% for Q1; P = .003), with higher non-index readmission (11.2% for Q5 vs 2.7% for Q1; P < .001) and conversely lower index readmission (6.9% for Q5 vs 12.0% for Q1; P < .001). Multivariable-adjusted Fine-Gray models confirmed greater hazard of non-index readmission with farther distance, with a Q5 hazard ratio of 3.02 (95% confidence interval, 2.12-4.30; P < .001). Multivariable-adjusted Cox models demonstrated no association between travel distance and long-term survival but found that non-index readmission was associated with increased long-term mortality (hazard ratio, 1.46; 95% confidence interval, 1.20-1.78; P = .0001). CONCLUSIONS: Patients traveling farther for complex aortic surgery demonstrate higher non-index readmission, which, in turn, is associated with increased long-term mortality risk. Aortic centers of excellence should consider targeting these patients for more comprehensive follow-up and care coordination to improve outcomes.

Hyperspectral imaging in systemic sclerosis-associated Raynaud phenomenon.

BACKGROUND/PURPOSE: Lack of robust, feasible, and quantitative outcomes impedes Raynaud phenomenon (RP) clinical trials in systemic sclerosis (SSc) patients. Hyperspectral imaging (HSI) non-invasively measures oxygenated and deoxygenated hemoglobin (oxyHb and deoxyHb) concentrations and oxygen saturation (O2 sat) in the skin and depicts data as oxygenation heatmaps. This study explored the potential role of HSI in quantifying SSc-RP disease severity and activity. METHODS: Patients with SSc-RP (n = 13) and healthy control participants (HC; n = 12) were prospectively recruited in the clinic setting. Using a hand-held camera, bilateral hand HSI (HyperMed™, Waltham, MA) was performed in a temperature-controlled room (22 °C). OxyHb, deoxyHb, and O2 sat values were calculated for 78-mm2 regions of interest for the ventral fingertips and palm (for normalization). Subjects underwent a cold provocation challenge (gloved hand submersion in 15 °C water bath for 1 min), and repeated HSI was performed at 0, 10, and 20 min. Patients completed two patient-reported outcome (PRO) instruments: the Raynaud Condition Score (RCS) and the Cochin Hand Function Scale (CHFS) for symptom burden assessment. Statistical analyses were performed using the Mann-Whitney U test and a mixed effects model (Stata, College Station, TX). RESULTS: Ninety-two percent of participants were women in their 40s. For SSc-RP patients, 69% had limited cutaneous SSc, the mean ± SD SSc duration was 11 ± 5 years, and 38% had prior digital ulcers-none currently. Baseline deoxyHb was higher, and O2 sat was lower, in SSc patients versus HC (p < 0.05). SSc patients had a greater decline in oxyHb and O2 sat from baseline to time 0 (after cold challenge) with distinct rewarming oxyHb, O2 sat, and deoxyHb trajectories versus HCs (p < 0.01). There were no significant correlations between oxyHb, deoxyHb, and O2 sat level changes following cold challenge and RCS or CHFS scores. CONCLUSION: Hyperspectral imaging is a feasible approach for SSc-RP quantification in the clinic setting. The RCS and CHFS values did not correlate with HSI parameters. Our data suggest that HSI technology for the assessment of SSc-RP at baseline and in response to cold provocation is a potential quantitative measure for SSc-RP severity and activity, though longitudinal studies that assess sensitivity to change are needed.

Future Directions in Research in Transcriptomics in the Healing of Diabetic Foot Ulcers.

Diabetic foot ulcers are a health crisis that affect millions of individuals worldwide. Current standard of care involves diligent wound care with adjunctive antibiotics and surgical debridement. However, despite this, the majority will still become infected and fail to heal. Recent efforts using bioengineered skin initially appeared promising, but randomized clinical trials have disappointed. Scientists have now begun to understand that the normal wound healing physiology does not apply to diabetic foot ulcers as they maintain a chronic state of inflammation and fail to progress in a linear pathway. Using transcriptomics, research over the past decade has started identifying master genes and protein pathways that are dysregulated in patients with diabetes. This review paper discusses those genes involved and how novel advancements are using this information to create new biologically based compounds to accelerate wound healing in patients with diabetic foot ulcers.

Prevalence and Characteristics of Patients with Median Arcuate Ligament Syndrome in a Cohort Diagnosed with Celiac Artery Compression.

BACKGROUND: Median arcuate ligament syndrome (MALS) is a frequent differential diagnosis in patients with postprandial abdominal symptoms, but diagnosis remains challenging. The aim of this study was to identify characteristics of patients who had MALS compared with non-MALS patients among a cohort of patients diagnosed with celiac artery compression (CAC). STUDY DESIGN: An IRB-approved retrospective chart review (2000 to 2021) of patients at our institution with a discharge diagnosis of CAC was performed. Medical record review for clinical symptoms and findings consistent with MALS was performed. RESULTS: Two hundred ninety-three patients with a diagnosis of CAC were identified; 59.7% were women, and average age was 63.9 ± 20.2 years. Sixty-nine (23.5%) patients with CAC had MALS. There were no significant differences in sex or race between MALS and non-MALS patients, but MALS patients were younger (55.7 vs 68.1, p < 0.001). There was no significant difference in gastrointestinal comorbidities between the 2 groups. Patients with MALS were less likely to have diabetes (12.5% vs 26.9%), renal disease (4.6% vs 8.2%), hypertension (41.5% vs 70.3%), mesenteric atherosclerotic disease (14% vs 61.9%), and peripheral artery disease (15.0% vs 39.7%). CONCLUSIONS: We demonstrate a novel observation that MALS patients tend to have fewer atherosclerotic characteristics than non-MALS patients with CAC. Patients in our study with MALS were more likely to be younger, women, and presenting with epigastric pain. MALS patients had a significantly lower incidence of diabetes, hypertension, renal disease, mesenteric artery disease, and peripheral arterial disease compared with the non-MALS group. An important clinically relevant feature of MALS patients may be their lack of atherosclerotic phenotype compared with non- MALS patients with CAC.

Partial and complete explantation of aortic endografts in the modern era.

OBJECTIVE: Despite the progressive advancement of devices for endovascular aortic repair (EVAR), endografts continue to fail, requiring explant. We present a single-institutional experience of EVAR explants, characterizing modern failure modes, presentation, and outcomes for partial and complete EVAR explantation. METHODS: A retrospective analysis was performed of all EVARs explanted at an urban quaternary center from 2001 to 2020, with one infected endograft excluded. Patient and graft characteristics, indications, and perioperative and long-term outcomes were analyzed. Partial versus complete explants were performed per surgeon discretion without a predefined protocol. This process was informed by patient risk factors; asymptomatic, symptomatic, or ruptured aneurysm presentation; and anatomical or intraoperative factors, including endoleak type. RESULTS: From 2001 to 2020, 52 explants met the inclusion and exclusion criteria. More than one-half (57.7%) were explants of EVAR devices placed at outside institutions, designated nonindex explants. Most patients were male (86.5%), the median age was 74 years (interquartile range, 70-78 years). More than one-half (61.5%) were performed in the second decade of the study period. The most commonly explanted grafts were Gore Excluder (n = 9 grafts), Cook Zenith (n = 8), Endologix AFX (n = 7), Medtronic Endurant (n = 5), and Medtronic Talent (n = 5). Most grafts (78.8%) were explanted for neck degeneration or sac expansion. Five were explanted for initial seal failure, five for symptomatic expansion, and seven for rupture. The median implant duration was 4.2 years, although ranging widely (interquartile range, 2.6-5.1 years), but similar between index and nonindex explants (4.2 years vs 4.1 years). Partial explantation was performed in 61.5%, with implant duration slightly lower, 3.2 years versus 4.4 years for complete explants. Partial explantation was more frequent in index explants (68.2% vs 56.7%). The median length of stay was 8 days. The median intensive care unit length of stay was 3 days, without significant differences in nonindex explants (4 days vs 3 days) and partial explants (4 days vs 3 days). Thirty-day mortality occurred in two nonindex explants (one partial and one complete explant). Thirty-day readmission was similar between partial and complete explants (9.7% vs 5.0%), without accounting for nonindex readmissions. Long-term survival was comparable between partial and complete explants in Cox regression (hazard ratio, 2.45; 95% confidence interval, 0.79-7.56; P = .12). CONCLUSIONS: Explants of EVAR devices have increased over time at our institution. Partial explant was performed in more than one-half of cases, per operating surgeon discretion, demonstrating higher blood loss, more frequent acute kidney injury, and longer intensive care unit stays, however with comparable short-term mortality and long-term survival.

Reassuring Intraoperative Parameters Do Not Obviate the Need for Infrainguinal Bypass Completion Angiograms.

OBJECTIVE: To determine if routine completion angiography for lower extremity bypasses using vein conduit results in lower rates of postoperative bypass occlusion. SUMMARY OF BACKGROUND DATA: With the increasing availability of on-table angiography and significant advancements in endovascular techniques, some operators routinely perform completion angiograms. The effect of this surgical paradigm has yet to be rigorously compared to the more widespread selective use of completion imaging in the modern era. METHODS: This retrospective cohort study included infrainguinal arterial bypass procedures utilizing vein conduit completed at a single hospital system from 2001 to 2018 and compared postoperative outcomes between bypasses that underwent routine completion angiography versus selective completion angiography. Notably, any bypasses that underwent completion angiography due to intraoperative concerns were excluded from this analysis. RESULTS: 666 bypasses that were performed in 589 patients met inclusion criteria. 126 (16.9%) bypasses were classified into the routine completion angiogram group compared to 540 (81.0%) into the selective completion angiogram group. Patients who underwent routine completion angiograms had a rate of intraoperative reintervention of 22.2%. The routine angiogram group had lower rates of reintervention (3.9% vs 10.0%, P = 0.03) and graft occlusion (2.3% vs 9.2%, P = 0.01) at 1-month postoperatively. CONCLUSION: Lower extremity bypasses using vein conduit that undergo routine completion angiography are associated with lower rates of graft occlusion at 30-days postoperatively. Completion angiography should thus be routinely performed in infrainguinal bypasses that utilize venous conduit.

Natural history of penetrating atherosclerotic ulcers in aortic branch vessels.

OBJECTIVE: Penetrating atherosclerotic ulcers (PAUs) in aortic branch vessels are rare. There is a paucity of data regarding their long-term natural history and associated management. This study aimed to determine the prevalence and natural history of aortic branch PAUs. METHODS: Institutional data on all patients with an aortic branch PAU from 2005 to 2020 were retrospectively reviewed. Branch PAUs were defined as any PAU in the iliac, mesenteric, or arch vessels. End points included symptoms, end-organ events, and interventions. All computed tomography angiographies (CTAs) for each patient were reviewed, and total diameter, ulcer width, and ulcer depth were recorded on each computed tomography scan for the branch PAUs. Rate of change was compared between groups (iliac vs arch and visceral vessels) using a linear mixed-effects model. RESULTS: Among 58,800 patients who underwent a CTA, 367 patients had an aortic PAU (prevalence: 0.6%) and 58 patients had a branch PAU (prevalence: 0.1%). Among those 58 patients, there were 66 ulcerated branches. There were 50 iliac (42 common iliac, 7 internal, and 1 external), 11 arch (8 left subclavian, 3 innominate), and 5 visceral ulcers (3 superior mesenteric artery, 1 celiac, and 1 renal). Mean age was 74.0 ± 8.8 years, and 86% of patients were male; 74% had hypertension, 79% had hyperlipidemia, and 59% had a concomitant aortic aneurysm. There were 45 PAU vessels with >1 CTA (total of 167 CTAs) with a median follow-up of 4.0 years (interquartile range: 2.0-6.2 years). Total vessel diameter increased in size by 0.27 mm/y but did not differ between groups (iliac vs visceral/arch vessels). PAU width and depth also did not significantly change over time, nor did it differ between groups. No branch PAUs caused symptoms, end-organ events, or rupture, nor required intervention due to symptoms and/or progression. Four PAUs spontaneously resolved (2 iliac, 2 other), and 1 iliac PAU progressed to a saccular aneurysm. CONCLUSIONS: This is one of the largest studies evaluating the natural history of branched PAUs objectively via CTA. Branch PAUs are rare-the prevalence was one-sixth that of aortic PAUs. There was minimal growth noted in a median follow-up of 4 years, and no PAUs required intervention for symptoms or progression. Asymptomatic branch PAUs may be safely observed.

Defining the human and health care costs of chronic venous insufficiency.

Chronic venous insufficiency (CVI) affects more than 25 million adults in the United States alone, and more 6 million with advanced stages of venous disease. The high incidence of CVI and the increasing costs of care, place a heavy financial burden on the US health care system. Recent studies estimate the total cost of care at more than $3 billion per year. These staggering numbers highlight the importance of timely diagnosis, treatment, and prevention of CVI. In this article, we review the epidemiology and prevalence of CVI, and its financial impact on national health care budget. Racial disparities in CVI and the impact of socioeconomic status on access to care are also discussed. Finally, we discuss CVI-related screening programs and the importance of preventative measures in venous disease.

Venous mesenteric ischemia carries high procedural burden and elevated mortality in patients with severe presentation.

OBJECTIVE: Venous mesenteric ischemia (VMI) presents with variable severity resulting in a spectrum of outcomes. This study sought to characterize the natural history of VMI and identify drivers of intervention and adverse outcomes. METHODS: All patients who presented to our institution with acute and subacute VMI between 1993 and 2016 were identified. Images were reviewed to determine thrombosis location and charts were reviewed to identify clinical factors and outcomes. Univariate analysis was performed for demographics, comorbidities, and presenting characteristics, with primary outcomes of intervention, readmission, and 30-day mortality. A survival analysis was performed with log-rank difference testing for demographics, comorbidities, and presenting characteristics. RESULTS: We identified 103 patients with acute and subacute VMI. The locations of the thrombosis included the superior mesenteric vein (SMV) (31.1%); SMV and portal vein (35.9%); SMV, portal, and splenic veins (15.5%); and other combinations of portomesenteric veins (17.4%), without correlation between the location and outcomes. Most patients were male (60.6%), 22.3% were actively smoking, and the median Charlson comorbidity score was 4 (interquartile range, 2-7). The mean patient age was 61.3 years. More than one-half had a known hypercoagulability (52.4%), 22.3% had prior bowel resection, and 8.7% had prior mesenteric venous intervention, including transjugular intrahepatic portosystemic shunt procedures. Thirty-five patients underwent 83 procedures during their hospitalization, and 23 patients underwent surgical intervention specifically. Prior mesenteric venous procedure, abdominal tenderness, and lactatemia of more than 1.5 mmol/L were associated with an increased need for surgical intervention (P < .05). Patients with leukocytosis of greater than 10K/µL had increased surgical intervention (P = .10), although without statistical significance. However, symptoms for less than 2 weeks (P < .05) were associated with decreased surgical intervention. The 30-day mortality was low in this cohort (6.8%), but was increased in patients requiring intervention (11.4%). For those undergoing procedures, a shorter time to intervention was associated with an improved 30-day mortality (8.7% for procedures on hospital days 0-1 vs 16.7% for hospital day 2 or later; P = .01). Abdominal tenderness and lactatemia were associated with increased 30-day mortality (6.8% vs 3.6% [P < .01] and 16.0% vs 3.8% [P = .03], respectively). A Kaplan-Meier survival analysis revealed a median survival of 7.1 years, with a 1-year survival rate of 74.9%, a 3-year survival rate of 67.1%, and a 5-year survival rate of 57.9%. Negative predictors of survival included a higher Charlson comorbidity index (hazard ratio, 3.7; P < .01) and malignancy (hazard ratio, 3.1; P < .01). CONCLUSIONS: The 30-day mortality of VMT is low, but more than one-third of patients required an intervention beyond anticoagulation. Comorbidity, a prior mesenteric vessel or intestinal operation, and presentation with tenderness or relevant laboratory abnormalities portend worse outcomes. Early intervention is associated with improved outcomes.

Utility of unilateral versus bilateral venous reflux studies for venous insufficiency.

OBJECTIVE: Duplex ultrasonography is the reference standard for diagnosing chronic venous insufficiency. Bilateral venous reflux ultrasound studies are among the most time-consuming and physically demanding tests for vascular ultrasound technologists to perform. Furthermore, if a venous procedure is required, many insurance policies require that a diagnostic venous ultrasound scan for reflux must be performed within 1 year of the procedure. If the intervention is scheduled for >1 year after the ultrasound scan, the insurance company might require a repeat venous ultrasound scan before granting insurance authorization. Hence, ordering bilateral venous duplex ultrasound scans to evaluate for reflux when an intervention might only be performed on one limb within the year could be a waste of time and resources. The aim of the present study was to determine the utility of ordering bilateral vs unilateral studies to evaluate for reflux in patients with suspected chronic venous insufficiency and to determine whether a resource-saving potential exists for vascular laboratories through optimization of the process of ordering venous duplex ultrasound studies. METHODS: A retrospective review of all patients who had undergone bilateral lower extremity ultrasound scanning to evaluate for reflux from January 1, 2016 to December 31, 2016 at the Massachusetts General Hospital vascular laboratory was performed. The demographics, indications for ultrasound scanning, comorbidities, time required to perform the ultrasound study, and interval to intervention were documented. The data were analyzed using SPSS statistical software (IBM Corp, Armonk, NY). RESULTS: During the study period, 13,854 ultrasound studies had been performed in our vascular laboratory, of which 606 (4.4%) had been bilateral ultrasound scans for venous insufficiency. The time allotted for a bilateral study was 2 hours. Of the 606 studies evaluated, 152 (25.1%) showed no evidence of reflux, 284 (46.9%) showed bilateral lower extremity reflux, and 170 (28.1%) showed only venous insufficiency in one leg. Venous ablation, phlebectomy, and/or sclerotherapy were performed for 28.7% of the patients. However only 6.2% of patients had undergone venous procedures on both legs within 1 year after the ultrasound studies. Ablation was the most common procedure performed (54.6%), followed by phlebectomy (27.%) and sclerotherapy (17.9%). Overall, 94.7% of patients had not undergone a venous procedure on both legs within 1 year after the ultrasound studies and, hence, would have required a repeat duplex ultrasound scan to ensure insurance coverage for future procedures. CONCLUSIONS: Most bilateral ultrasound scans for venous insufficiency will not result in an intervention. Thus, most patients (95%) could have undergone a unilateral scan before the initial intervention instead of bilateral duplex ultrasound scanning.

Effect of occult malignancy on femoropopliteal bypass graft thrombosis.

OBJECTIVE: The presence of cancer increases arterial thromboembolic events, specifically myocardial infarction and stroke, before a formal diagnosis of cancer. To the best of our knowledge, this increase in thrombotic risk has not been studied in patients with lower extremity bypass grafts. In the present study, we aimed to determine the effect of occult cancer on femoropopliteal bypass patency. METHODS: A retrospective review of femoropopliteal bypass procedures completed from 2001 to 2018 was performed. International Classification of Diseases, 9th and 10th revision, codes corresponding to breast, lung, prostate, colorectal, skin, brain, and hematologic cancer were used to identify patients who had had occult cancer. Occult cancer was defined as cancer diagnosed within ≤1 year after the bypass procedure. The demographics, comorbidities, bypass configuration and conduit, 1-month, 3-month, 6-month, and 1-year occlusion rates, major adverse limb events, and mortality rates were analyzed. Statistical analysis included t tests, χ2 tests, and Cox regression analysis. RESULTS: A total of 621 procedures in 517 patients met the inclusion criteria. Of the 621 procedures, 36 (5.8%) were classified as procedures in patients with occult cancer. The patients with occult cancer had had higher occlusion rates at 3 months (27.8% vs 8.0%; P < .001), 6 months (30.5% vs 15.1%; P < .01), and 1 year (44.4% vs 19.8%; P < .001). In Cox regression analysis for bypass thrombosis at 1 year, the only significant predictors were occult cancer (hazard ratio [HR], 2.03; P = .01), below-the-knee distal target (HR, 1.88; P < .01), and a compromised conduit (HR, 2.14; P < .001). CONCLUSIONS: We found an increase in bypass graft thrombosis rates in patients who had undergone femoropopliteal bypass who had had occult cancer. Thrombosis of the graft within 1 year postoperatively might be a sign of occult cancer.

Higher Inpatient Mortality for Women after Intervention for Lifestyle Limiting Claudication.

BACKGROUND: Sex-related differences in outcomes have been identified in patients with peripheral artery disease (PAD). We hypothesized that women with PAD would have equivalent inpatient mortality with men after vascular intervention. METHODS: Patients with a primary diagnosis of critical limb ischemia (CLI) or lifestyle-limiting claudication (LLC) receiving endovascular (EV) or open surgical repair from 2003-2012 were identified from the Nationwide Inpatient Sample. Demographics, comorbidities, and inpatient mortality were analyzed by chi-squared tests of independence and independent-samples t-tests. Logistic regression analysis was performed to identify predictors of inpatient mortality. SPSS 24 software was used with P < 0.05 considered statistically significant. RESULTS: We identified 139,435 (59,432 women and 80,003 men) individuals meeting the aforementioned criteria. Women were older than men (71.5 years vs. 68.2, P < 0.001). There were no differences in racial distribution but women had lower rates of diabetes (38.6% vs. 39.7%, P < 0.001), chronic obstructive pulmonary disease (17.9% vs. 19.5%, P < 0.001), and coronary artery disease (38.6% vs. 47.4%, P < 0.001), while having a higher rate of hypertension (60.0% vs. 56.1%, P < 0.001). There was no sex-related difference in the rate of chronic renal failure. Women had higher inpatient mortality than men after vascular intervention (1.3% vs. 1.1%, P < 0.001). When stratified by surgical technique, women also had higher inpatient mortality after EV repair (1.0% vs. 0.8%, P < 0.05) and open repair (1.9% vs 1.3%, P < 0.001). When separated by admitting diagnosis, women with CLI had higher inpatient mortality than men after open surgery (2.3% vs. 1.9%, P < 0.05) but not after EV intervention. Women with LLC had higher inpatient mortality after both open (0.6% vs. 0.3%, P < 0.05) and EV surgery (0.3% vs. 0.1%, P < 0.05). Regression analysis revealed female sex as an independent predictor of inpatient mortality in patients with LLC (OR, 1.74; 95% CI 1.30-2.32, P < 0.001) but not CLI. CONCLUSIONS: Women had higher inpatient mortality than men after vascular intervention for PAD. Women were also older and more likely to have EV intervention than men. Subgroup analysis suggests that these sex-related differences in inpatient mortality are more pronounced in patients with LLC than with CLI. Furthermore, regression analysis shows that sex is a significant predictor for patients diagnosed with LLC but not with CLI. Treatment guidelines should include consideration of sex in their indications for revascularization, particularly for patients diagnosed with LLC.

Incisional Negative Pressure Wound Therapy Augments Perfusion and Improves Wound Healing in a Swine Model Pilot Study.

BACKGROUND: A commonly used treatment for open wounds, negative pressure wound therapy (NPWT) has recently been used to optimize wound healing in the setting of surgically closed wounds; however, the specific mechanisms of action by which NPWT may benefit patients after surgery remain unknown. Using a swine wound healing model, the current study investigates angiogenesis as a candidate mechanism. METHODS: Multiple excisional wounds were created on the dorsa of 10 male Yorkshire pigs and closed by primary suture. The closed wounds underwent treatment with either NPWT dressing or control dressings in the absence of negative pressure. Dressings were maintained for 8 days followed by euthanasia of the animal. Scar evaluation of the wounds by photographic analysis was performed, and wounds were analyzed for angiogenesis markers by enzyme-linked immunosorbent assay and immunohistochemistry. RESULTS: Scar evaluation scores were observed to be significantly higher for the NPWT-treated sites compared with the control sites (P < 0.05). The enzyme-linked immunosorbent assay results demonstrated increases for vascular endothelial growth factor (VEGF) staining at the incision site treated with NPWT compared with other treatment groups (P < 0.05). In addition, an approximately 3-fold elevation in VEGF expression was observed at the NPWT-treated sites (2.8% vs. 1%, respectively; P < 0.0001).). However, there was no significant difference in immunohistochemistry staining. CONCLUSIONS: The use of NPWT improves the appearance of wounds and appears to increase VEGF expression after 8 days in the setting of a closed excisional wound model, suggesting that improved angiogenesis is one mechanism by which NPWT optimizes wound healing when applied to closed surgical wound sites.

Use of Closed-Incision Negative-Pressure Therapy: Cardiothoracic and Vascular Surgery.

Vascular groin wound and median sternotomy infections are challenging complications that may lead to serious sequela. Traditional gauze dressings have poor bacteria barrier properties, and so there has been a recent enthusiasm for the use of closed-incision negative-pressure therapy as an effective closed environment, which controls exudate and helps hold the incision edges together. Studies suggest that it may reduce surgical site infection in cardiothoracic and vascular surgery.

Regulation of Yes-Associated Protein by Laminar Flow.

BACKGROUND: The cells lining the endothelium of blood vessels are recognized as playing critical roles in vascular health and disease. The mechanisms that regulate endothelial cells (ECs) proliferation and release of mediators remain poorly understood but represent a potential source of disease modulation. Actin-cytoskeleton remodeling and cell shape have been suggested as key regulators of phosphorylation of yes-associated protein (YAP) which controls cellular growth and proliferation. Because different types of flow have been shown to affect cell shape and cytoskeleton differently, we hypothesized that the level of phosphorylated yes-associated protein (pYAP; serine 127) decreases in EC exposed to pulsatile uniform flow or steady laminar flow, whereas exposure to pulsatile disturbed flow causes an increase or no change. METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to pulsatile uniform flow, pulsatile disturbed flow, or steady laminar flow and analyzed by immunoblotting. RESULTS: Exposure of HUVECs to steady laminar flow caused a significant decrease in the levels of pYAP (69.7 + 2.6%, P < 0.05), whereas total YAP levels remained nearly unchanged. Conversely, exposure to either pulsatile uniform or disturbed flow caused a significant decrease in the levels of both pYAP (63.2 + 10.9% and 69.8 + 11.9%, respectively; P < 0.05) and total YAP (57.1 + 17.8% and 58.4 + 16.3%, respectively; P < 0.05). Addition of MG132, a ubiquitin-proteasome system inhibitor, failed to significantly inhibit the decrease in the levels of total YAP in HUVECs exposed to either pulsatile uniform or disturbed flow. CONCLUSIONS: Flow causes a decrease in pYAP. The observed decrease in total YAP levels with pulsatile flow is due to degradation via a proteasome-independent mechanism. This may be a potential target for intervention for disease states such as atherosclerosis and intimal hyperplasia.