Search

Introduction: Evaluation of limb hemodynamics using the ankle–brachial index (ABI) may be difficult due to skin lesions, extensive necrosis, and obesity, such as commonly present in patients with diabetes with chronic limb-threatening ischemia (CLTI). We hypothesized that the pedal acceleration time (PAT) correlates with ABI and Wound, Ischemia, and foot Infection (WIfI) scores in patients with diabetes to serve as a new modality to accurately stage CLTI. Methods: A single-center, cross-sectional study included patients with and without diabetes > 18 years with CLTI. Limbs were categorized in three grades of ischemia based on the ABI (ABI < 0.8, < 0.6, and < 0.4) and in two classes based on WIfI stages of amputation risk. Receiver operator characteristic (ROC) curves were used to determine PAT sensitivity, specificity, and accuracy to predict lower-limb ischemia. Results: A total of 141 patients (67 nondiabetic and 74 diabetic) and 198 lower limbs (94 nondiabetic and 104 diabetic) met the inclusion criteria. In patients without diabetes, the accuracy of PAT for detecting an ABI < 0.8 was 85%; for detecting an ABI < 0.6 was 85%; and for detecting an ABI < 0.4 was 87%. In patients with diabetes, the accuracy of PAT in detecting an ABI < 0.8 was 91%; for detecting an ABI < 0.6 was 79%; and for detecting an ABI < 0.4 was 88%. In patients without diabetes, the accuracy for detecting WIfI stages of moderate and high amputation risk was 77% and for patients with diabetes was also 77%. Conclusions: PAT shows high correlation with the ABI as well as with the WIfI stages of amputation risk and the grades of ischemia, with high accuracy.

Patients with abdominal aortic aneurysm (AAA) can choose open repair or endovascular repair (EVAR). While EVAR is less invasive, it requires lifelong surveillance and more frequent aneurysm-related reinterventions than open repair. A decision aid may help patients receive their preferred type of AAA repair.To determine the effect of a decision aid on agreement between patient preference for AAA repair type and the repair type they receive.In this cluster randomized trial, 235 patients were randomized at 22 VA vascular surgery clinics. All patients had AAAs greater than 5.0 cm in diameter and were candidates for both open repair and EVAR. Data were collected from August 2017 to December 2020, and data were analyzed from December 2020 to June 2021.Presurgical consultation using a decision aid vs usual care.The primary outcome was the proportion of patients who had agreement between their preference and their repair type, measured using χ2 analyses, κ statistics, and adjusted odds ratios.Of 235 included patients, 234 (99.6%) were male, and the mean (SD) age was 73 (5.9) years. A total of 126 patients were enrolled in the decision aid group, and 109 were enrolled in the control group. Within 2 years after enrollment, 192 (81.7%) underwent repair. Patients were similar between the decision aid and control groups by age, sex, aneurysm size, iliac artery involvement, and Charlson Comorbidity Index score. Patients preferred EVAR over open repair in both groups (96 of 122 [79%] in the decision aid group; 81 of 106 [76%] in the control group; P = .60). Patients in the decision aid group were more likely to receive their preferred repair type than patients in the control group (95% agreement [93 of 98] vs 86% agreement [81 of 94]; P = .03), and κ statistics were higher in the decision aid group (κ = 0.78; 95% CI, 0.60-0.95) compared with the control group (κ = 0.53; 95% CI, 0.32-0.74). Adjusted models confirmed this association (odds ratio of agreement in the decision aid group relative to control group, 2.93; 95% CI, 1.10-7.70).Patients exposed to a decision aid were more likely to receive their preferred AAA repair type, suggesting that decision aids can help better align patient preferences and treatments in major cardiovascular procedures.ClinicalTrials.gov Identifier: NCT03115346.

Background: Arteriovenous fistulae (AVF) are the gold standard for vascular access for hemodialysis. Although the vein must thicken and dilate for successful hemodialysis, excessive wall thickness leads to stenosis causing AVF failure. Since TGF-β (transforming growth factor-beta) regulates ECM (extracellular matrix) deposition and smooth muscle cell (SMC) proliferation—critical components of wall thickness—we hypothesized that disruption of TGF-β signaling prevents excessive wall thickening during venous remodeling. Methods: A mouse aortocaval fistula model was used. SB431542—an inhibitor of TGF-β receptor I—was encapsulated in nanoparticles and applied to the AVF adventitia in C57BL/6J mice. Alternatively, AVFs were created in mice with conditional disruption of TGF-β receptors in either SMCs or endothelial cells. Doppler ultrasound was performed serially to confirm patency and to measure vessel diameters. AVFs were harvested at predetermined time points for histological and immunofluorescence analyses. Results: Inhibition of TGF-β signaling with SB431542-containing nanoparticles significantly reduced p-Smad2–positive cells in the AVF wall during the early maturation phase (days 7–21) and was associated with decreased AVF wall thickness that showed both decreased collagen density and decreased SMC proliferation. SMC-specific TGF-β signaling disruption decreased collagen density but not SMC proliferation or wall thickness. Endothelial cell–specific TGF-β signaling disruption decreased both collagen density and SMC proliferation in the AVF wall and was associated with reduced wall thickness, increased outward remodeling, and improved AVF patency. Conclusions: Endothelial cell–targeted TGF-β inhibition may be a translational strategy to improve AVF patency.

ImportanceSurgeon-scientists are uniquely positioned to facilitate translation between the laboratory and clinical settings to drive innovation in patient care. However, surgeon-scientists face many challenges in pursuing research, such as increasing clinical demands that affect their competitiveness to apply for National Institutes of Health (NIH) funding compared with other scientists.ObjectiveTo examine how NIH funding has been awarded to surgeon-scientists over time.Design, Setting, and ParticipantsThis cross-sectional study used publicly available data from the NIH RePORTER (Research Portfolio Online Reporting Tools Expenditures and Results) database for research project grants awarded to departments of surgery between 1995 and 2020. Surgeon-scientists were defined as NIH-funded faculty holding an MD or MD-PhD degree with board certification in surgery; PhD scientists were NIH-funded faculty holding a PhD degree. Statistical analysis was performed from April 1 to August 31, 2022.Main OutcomeNational Institutes of Health funding to surgeon-scientists compared with PhD scientists, as well as NIH funding to surgeon-scientists across surgical subspecialties.ResultsBetween 1995 and 2020, the number of NIH-funded investigators in surgical departments increased 1.9-fold from 968 to 1874 investigators, corresponding to a 4.0-fold increase in total funding (1995, $214 million; 2020, $861 million). Although the total amount of NIH funding to both surgeon-scientists and PhD scientists increased, the funding gap between surgeon-scientists and PhD scientists increased 2.8-fold from a $73 million difference in 1995 to a $208 million difference in 2020, favoring PhD scientists. National Institutes of Health funding to female surgeon-scientists increased significantly at a rate of 0.53% (95% CI, 0.48%-0.57%) per year from 4.8% of grants awarded to female surgeon-scientists in 1995 to 18.8% in 2020 (P P Conclusion and RelevanceThis study suggests that research performed by surgeon-scientists continues to be underrepresented in the NIH funding portfolio, highlighting a fundamental need to support and fund more surgeon-scientists.

Arteriovenous fistulae (AVF) fail to mature in female patients compared with male patients, leading to inferior outcomes and decreased utilization. As our mouse AVF model recapitulates sex differences in human AVF maturation, we hypothesized that sex hormones mediate these differences during AVF maturation. C57Bl/6 mice (9-11 week) underwent aortocaval AVF surgery and gonadectomy. AVF hemodynamics were measured via ultrasound (days 0-21). Blood was collected for FACS, and tissue for immunofluorescence and ELISA (days 3,7); wall thickness was assessed using histology (day 21). Inferior vena cava (IVC) shear stress was higher in male mice (p=0.0028) after gonadectomy, and they had increased wall thickness (22.0 ± 1.8 um vs. 12.7 ± 1.2; p

Background: There is uncertainty whether elderly patients with symptomatic carotid stenosis have higher rates of adverse events following carotid endarterectomy. In trials, recurrent stroke risk on medical therapy alone increased with age, whereas operative stroke risk was not related. Few octogenarians were included in trials and there has been no systematic analysis of all study types. We aimed to evaluate the safety of carotid endarterectomy in symptomatic elderly patients, particularly in octogenarians. Methods: We did a systematic review and meta-analysis of studies (from January 1, 1980 through March 1, 2022) reporting post carotid endarterectomy risk of stroke, myocardial infarction, and death in patients with symptomatic carotid stenosis. We included observational studies and interventional arms of randomized trials if the outcome rates (or the raw data to calculate these) were provided. Individual patient data from 4 prospective cohorts enabled multivariate analysis. Results: Of 47 studies (107 587 patients), risk of perioperative stroke was 2.04% (1.94–2.14) in octogenarians (390 strokes/19 101 patients) and 1.85% (1.75–1.95) in nonoctogenarians (1395/75 537); P =0.046. Perioperative death was 1.09% (0.94–1.25) in octogenarians (203/18 702) and 0.53% (0.48–0.59) in nonoctogenarians (392/73 327); P P =0.04 to 0.002. However, during the last 3 decades, perioperative stroke±death has declined significantly in octogenarians (7.78% [5.58–10.55] before year 2000 to 2.80% [2.56–3.04] after 2010); P P P =0.005). Yet, survival was similar for octogenarians versus nonoctogenarians at 1-year (95.0% [93.2–96.5] versus 97.5% [96.4–98.6]; P =0.08), as was 5-year stroke risk (11.93% [9.98–14.16]) versus 12.78% [11.65–13.61]; P =0.24). Conclusions: We found a modest increase in perioperative risk with age in symptomatic patients undergoing carotid endarterectomy. As stroke risk increases with age when on medical therapy alone, our findings support selective urgent intervention in symptomatic elderly patients.

© 2022 Elsevier B.V. All rights reserved., Jolobe supports that screening for asymptomatic carotid stenosis (AsxCS) should be extended to patients with non-valvular atrial fibrillation (NVAF). Indeed, a 2021 meta-analysis (n = 20 studies; 49,070 patients) demonstrated that the pooled prevalence of >50% AsxCS inpatients with NVAF was 12.4% (range: 4.4–24.3%). Although this issue was not discussed in our manuscript, the optimal management of patients presenting with a recent transient ischemic attack [TIA]/ischemic stroke with an ipsilateral 50–99% carotid stenosis and concomitant NVAF was addressed by the 2023 European Society for Vascular Surgery (ESVS) carotid guidelines. It was recognized that although no guidelines have provided recommendations regarding the management of these patients, a pragmatic approach is warranted.

Objective: Patients with end-stage renal disease depend on hemodialysis for survival. Although arteriovenous fistulae (AVF) are the preferred vascular access for hemodialysis, the primary success rate of AVF is only 30% to 50% within 6 months, showing an urgent need for improvement. PD-L1 (programmed death ligand 1) is a ligand that regulates T-cell activity. Since T cells have an important role during AVF maturation, we hypothesized that PD-L1 regulates T cells to control venous remodeling that occurs during AVF maturation. Approach and results: In the mouse aortocaval fistula model, anti-PD-L1 antibody (200 mg, 3×/wk intraperitoneal) was given to inhibit PD-L1 activity during AVF maturation. Inhibition of PD-L1 increased T-helper type 1 cells and T-helper type 2 cells but reduced regulatory T cells to increase M1-type macrophages and reduce M2-type macrophages; these changes were associated with reduced vascular wall thickening and reduced AVF patency. Inhibition of PD-L1 also inhibited smooth muscle cell proliferation and increased endothelial dysfunction. The effects of anti-PD-L1 antibody on adaptive venous remodeling were diminished in nude mice; however, they were restored after T-cell transfer into nude mice, indicating the effects of anti-PD-L1 antibody on venous remodeling were dependent on T cells. Conclusions: Regulation of PD-L1 activity may be a potential therapeutic target for clinical translation to improve AVF maturation.

Purpose: The optimal treatment for isolated abdominal aortic dissection (IAAD) is currently unknown. We compared the effects of straight and bifurcated aortic stent grafts on postoperative aortic remodeling in patients with IAAD. Materials and Methods: From February 2012 to December 2019, 57 patients with IAAD were treated using endovascular methods, including either a bifurcated or a straight aortic stent graft. The clinical features, risk factors, computed tomography angiograms, midterm follow-up results, and aortic remodeling of these patients were reviewed and analyzed. Results: In total, 44 (77%) patients were treated with a bifurcated graft and 13 (23%) patients were treated with a straight graft. Patients treated with straight grafts had fewer common iliac arteries involved (38% vs 73%, p=0.023), the dissection length was shorter (76.3 ± 40.0 vs 116.2 ± 56.7 mm, p=0.011), and the preoperative aortic diameter (26.0 ± 5.6 vs 35.2 ± 12.1 mm) and the false lumen diameter (13.1 ± 5.2 vs 21.2 ± 11.3 mm) were smaller. During the procedure, there were 3 (5.3%) type I endoleaks, 1 (1.8%) surgical conversion and 1 (1.8%) partial renal artery coverage without perioperative mortality. Patients with straight grafts had shorter operative time (96.5 ± 24.4 vs 144.2 ± 49.0 minutes, pConclusions: Endovascular treatment provides a safe, minimally invasive treatment for IAAD in midterm follow-up. Compression of the true lumen at the aortic bifurcation is the main concern after treatment with a bifurcated graft. Straight grafts are an excellent alternative for some patients, with the benefit of reduced procedural time, effective aortic remodeling, and excellent clinical prognosis. More experience is needed to offer clear recommendations for making treatment decisions as well as determine long-term effectiveness and durability.

Aims: Discuss the clinical value, technique characteristics, and early follow-up results of a newly designed gutter-free chimney stent-graft system for aortic arch pathology. Methods and Results: About 13 patients with aortic arch dissection were enrolled in a clinical trial testing a novel gutter-free stent-graft between February 2019 and December 2020. All 13 patients were male, age 52.6±10.4 years. The implantation time was 14.0±6.9 minutes; total procedure time was 89.5±19.8 minutes. The volume of contrast was 79.6±7.2 ml. And 15 aortic stent-grafts were implanted, and all 13 patients had chimney branch stent-grafts implanted into the left subclavian artery (LSA). There were 3 (23.1%) cases of immediate type Ιa endoleak after thoracic endovascular aortic repair (TEVAR), and 7.7% type Ιa endoleaks occurred in delayed fashion. Survival at 2 years was 100%, and the 2-year patency of chimney stent-grafts was 100%. Conclusions: This study reports early success with good freedom from endoleak using a novel stent-graft designed for chimney TEVAR to treat aortic arch dissection. Postoperative survival and patency of the branch stent-grafts were excellent. Additional data from this multicenter clinical trial will be forthcoming.

Background: The optimal antithrombotic (antiplatelet or anticoagulant) treatment of patients undergoing extracranial carotid artery interventions is a subject of debate. The aim of this multidisciplinary document was to critically review the recommendations of current guidelines, taking into consideration the results of recently published studies. Methods: The various antithrombotic strategies reported were evaluated for asymptomatic and symptomatic patients undergoing extracranial carotid artery interventions (endarterectomy, transfemoral carotid artery stenting [CAS] or transcarotid artery revascularization [TCAR]). Based on a critical review, a series of recommendations were formulated by an international expert panel. Results: For asymptomatic patients, we recommend low-dose aspirin (75–100 mg/day) or clopidogrel (75 mg/day) with the primary goal to reduce the risk of myocardial infarction and cardiovascular event rates rather than to reduce the risk of stroke. For symptomatic patients, we recommend dual antiplatelet treatment (DAPT) initiated within 24 h of the index event to reduce the risk of recurrent events. We suggest that following transfemoral CAS or TCAR, patients continue DAPT for 1 month after which a single antiplatelet agent is used. High level of evidence to support anticoagulant treatment for patients with carotid artery disease is lacking. Conclusions: The antithrombotic treatment offered to carotid patients should be individualized, taking into account the presence of symptoms, the type of intervention and the goal of the treatment. The duration and type of DAPT (ticagrelor instead of clopidogrel) should be evaluated in future trials.

© 2022 Elsevier B.V. All rights reserved., ackground: Current guidelines do not recommend screening for asymptomatic carotid artery stenosis (AsxCS). The rationale behind this recommendation is that detection of AsxCS may lead to an unnecessary carotid intervention. In contrast, screening for abdominal aortic aneurysms is strongly recommended. Methods: A critical analysis of the literature was performed to evaluate the implications of detecting AsxCS. Results: Patients with AsxCS are at high risk for future stroke, myocardial infarction and vascular death. Population-wide screening for AsxCS should not be recommended. Additionally, screening of high-risk individuals for AsxCS with the purpose of identifying candidates for a carotid intervention is inappropriate. Instead, selective screening for AsxCS should be considered and should be viewed as an opportunity to identify individuals at high risk for atherosclerotic cardiovascular disease and future cardiovascular events for the timely initiation of intensive medical therapy and risk factor modification. Conclusions: Although mass screening should not be recommended, there are several arguments suggesting that selective screening for AsxCS should be considered. The rationale supporting such selective screening is to optimize risk factor control and to initiate intensive medical therapy for prevention of future cardiovascular events, rather than to identify candidates for an intervention.

Introduction Incomplete hemostasis after vascular cannulation can cause a hematoma or pseudoaneurysm. We hypothesized that a hydrogel-coated needle would effectively and rapidly stop bleeding after vascular cannulation.Methods: A hydrogel composed of sodium alginate, hyaluronic acid, and calcium carbonate was coated onto the surface of suture needles. Needles were observed using scanning electronic microscopy (SEM) and immunofluorescence. Cannulation was performed in both mouse and rat models; the liver, kidney, jugular vein, inferior vena cava and aorta were punctured using uncoated and hydrogel-coated needles. Needles coated with a hydrogel with and without CD34 antibody were used to puncture the rat jugular vein and aorta. Tissues were examined by histology and immunofluorescence.Results: The hydrogel was successfully coated onto the surface of 22G and 30G needles and confirmed by SEM. Hydrogel-coated needles rapidly stopped bleeding after cannulation of the liver, kidney, jugular vein, inferior vena cava and aorta. Hydrogel-coated needles that contained CD34 antibody attracted vascular progenitor cells near the puncture site; there were fewer M1-type macrophages and more M2-type macrophages.Conclusion: Hydrogel-coated needles can effectively and rapidly stop puncture-site bleeding. The hydrogel that contains CD34 antibody attracted vascular progenitor cells, potentially promoting healing of the site after cannulation. Statement of significance Incomplete hemostasis after vascular cannulation can cause a hematoma or pseudoaneurysm and remains a significant clinical problem. We developed a hydrogel composed of sodium alginate, hyaluronic acid, and calcium carbonate; hydrogel-coated needles effectively and rapidly stopped bleeding after vascular cannulation. Interestingly, the hydrogel can also serve as a carrier for drugs that are delivered to the puncture site during the short time of cannulation that could additionally promote puncture site healing. Hydrogel-coated needles may be a new method for rapid hemostasis with application to patients especially at risk for bleeding.

Background Arteriovenous fistulae (AVF) are the preferred mode of vascular access for hemodialysis. Before use, AVF remodel by thickening and dilating to achieve a functional conduit via an adaptive process characterized by expression of molecular markers characteristic of both venous and arterial identity. Although signaling via EphB4, a determinant of venous identity, mediates AVF maturation, the role of its counterpart EphrinB2, a determinant of arterial identity, remains unclear. We hypothesize that EphrinB2 signaling is active during AVF maturation and may be a mechanism of venous remodeling. Methods Aortocaval fistulae were created or sham laparotomy was performed in C57Bl/6 mice, and specimens were examined on Days 7 or 21. EphrinB2 reverse signaling was activated with EphB4-Fc applied periadventitially in vivo and in endothelial cell culture medium in vitro. Downstream signaling was assessed using immunoblotting and immunofluorescence. Results Venous remodeling during AVF maturation was characterized by increased expression of EphrinB2 as well as Akt1, extracellular signal-regulated kinases 1/2 (ERK1/2), and p38. Activation of EphrinB2 with EphB4-Fc increased phosphorylation of EphrinB2, endothelial nitric oxide synthase, Akt1, ERK1/2, and p38 and was associated with increased diameter and wall thickness in the AVF. Both mouse and human endothelial cells treated with EphB4-Fc increased phosphorylation of EphrinB2, endothelial nitric oxide synthase, Akt1, ERK1/2, and p38 and increased endothelial cell tube formation and migration. Conclusions Activation of EphrinB2 signaling by EphB4-Fc was associated with adaptive venous remodeling in vivo while activating endothelial cell function in vitro. Regulation of EphrinB2 signaling may be a new strategy to improve AVF maturation and patency.

Secondary aortoenteric fistula is a potentially lethal complication after aortic surgery. Traditional treatment consists of open graft excision with extra-anatomic bypass or in situ reconstruction. Patients who present in extremis, however, are generally poor candidates for re-do open aortic surgery. Endovascular repair has emerged as an alternative treatment modality for patients who would otherwise be unable to tolerate an extended operation. We report here a case of urgent endovascular repair of a juxtarenal secondary aortoenteric fistula via endovascular aneurysm repair with a renal artery chimney in a patient with a solitary kidney who presented in hemorrhagic and septic shock.

Peripheral vascular interventions (PVI) utilize iodinated contrast medium (ICM) to visualize intravascular lesions and guide therapy. The use of ICM carries a risk of postcontrast acute kidney injury (PC-AKI), which is increased in the elderly and in patients with chronic kidney disease (CKD). Furthermore, the risk of PC-AKI increases with the volume of ICM used. This paper reports a 94-year-old patient with CKD stage 4 who presented with chronic limb threatening ischemia. He underwent successful endovascular revascularization using a combination of CO2 and dilute ICM (total volume = 6.5 mL). The case demonstrates strategies to minimize ICM during PVIs.

The objectives of the study were to quantitatively evaluate leg edema in patients undergoing endovenous radiofrequency ablation (RFA) for saphenous varicose veins using bioelectrical impedance analysis (BIA) and to elucidate the time course of leg edema after RFA.The data of 87 patients with 128 limbs undergoing RFA for saphenous varicose veins in Eniwa Midorino Clinic from April 2018 to November 2019 were retrospectively analyzed. Saphenous vein reflux was evaluated by duplex scan. Extracellular water/total body water ratio (ECW/TBW) of the leg was measured by BIA. Moderate to severe leg edema (ECW/TBW ≥ 0.400) was defined as significant leg edema. Venous reflux was evaluated as a venous filling index (VFI) using air plethysmography.BIA revealed that 26 legs (20.3%) had significant edema and 102 legs (79.7%) did not before RFA. The proportion of patients with significant leg edema increased significantly from preoperative to 1 week after RFA (P 0.05) and decreased 1 month after RFA (P 0.01). The ECW/TBW increased significantly from preoperative (0.393 ± 0.008) to 1 week after RFA (0.394 ± 0.008, P 0.05), whereas it decreased significantly before or 1 week to 1 month after RFA (0.391 ± 0.008, P 0.05). There was a significant, moderate correlation between the decrease of the VFI and that of ECW/TBW (r = 0.34, P 0.001).This is the first study to quantitatively elucidate the time course of leg edema after RFA. Leg edema worsens one week after RFA, but it is improved one month after RFA, compared with that preoperatively.

Background Claudication has a relatively benign natural history, associated with a low risk of limb loss. However, rates of progression to chronic limb-threatening ischemia (CLTI) following lower extremity revascularization (LER) for claudication remain unclear. This study examines the long-term outcomes and risk factors associated with progression to CLTI after LER for claudication. Methods A single-center retrospective review of patients undergoing LER for claudication was performed from 2013–2016. Patients were stratified based on whether they progressed to CLTI or not. Results There were 448 patients (502 limbs) treated for claudication, and 57 (12.7%) progressed to CLTI with a mean follow up time of 3.7 ± 1.5 years. Among patients who progressed, 23 (5.1%) developed tissue loss, 34 (7.6%) developed rest pain, and 6 (1.2%) underwent major amputation. The mean time of progression to CLTI was 1.6 ± 1.5 years after index LER. Patients who progressed to CLTI were more likely to have a history of congestive heart failure and prior open revascularizations compared with those who did not progress. There was no difference in type or level of index revascularization between the two groups and no difference in perioperative complications. Patients who developed CLTI had significantly higher rates of reinterventions and a mean number of reinterventions after index LER prior to developing CLTI compared to those who did not progress. Multivariable logistic regression demonstrated that history of congestive heart failure (OR = 2.8 [1.2–6.6]), stroke (OR = 2.6 [1.1–6.1]), prior open procedure (OR = 2.8 [1.3–5.9]) and increasing number of reinterventions after index LER (OR = 2.9 [1.5–5.7]) were independently associated with disease progression to CLTI. Conclusions Multiple reinterventions and previous open revascularization are associated with progression to CLTI following LER for claudication. Patients with atherosclerosis in the coronary and cerebrovascular beds are also more likely to have a progression of claudication to CLTI after LER.

ImportanceSurgical diseases account for approximately 30% of the global burden of disease. Gender diversity in biomedical research is critical to generate innovative patient-centered research in surgery.ObjectiveTo examine the distribution of biomedical research funding by the National Institutes of Health (NIH) among women and men surgeon-scientists during a 25-year period.Design, Setting, and ParticipantsThis cross-sectional study used publicly available data from the NIH RePORTER (Research Portfolio Online Reporting Tools: Expenditures and Results) database for research project grants awarded to women and men surgeon-scientists who were principal investigators between 1995 and 2020. Data were retrieved between January 20 and March 20, 2022. The representation of women surgeon-scientists among academic surgeons was compared with the representation of men surgeon-scientists over time.Main Outcomes and MeasuresDistribution of NIH funding to women and men surgeon-scientists was examined via 2 metrics: holding a large-dollar (ie, R01-equivalent) grant and being a super principal investigator (SPI) with $750 000 or more in total annual research funding. Statistical analysis was performed between April 1 and August 31, 2022.ResultsBetween 1995 and 2020, 2078 principal investigator surgeons received funding from the NIH. The proportion of women academic surgeons who were surgeon-scientists remained unchanged during this same period (1995, 14 of 792 [1.8%] vs 2020, 92 of 3834 [2.4%]; P = .10). Compared with their men counterparts, women surgeon-scientists obtained their first NIH grant earlier in their career (mean [SD] years after first faculty appointment, 8.8 [6.2] vs 10.8 [7.9] years; P Conclusions and RelevanceThe findings of this cross-sectional study of NIH-funded surgeons suggest that women surgeons remained underrepresented among surgeon-scientists over a 25-year period despite early career success in receiving NIH funding. This is concerning and warrants further investigation to increase the distribution of NIH funding among women surgeon-scientists.

Objectives Restenosis after stenting for superficial femoral artery atherosclerotic disease remains a significant clinical problem, especially for long-segment lesions. We assessed predictors of in-stent restenosis in patients with long-segment superficial femoral artery disease and hypothesized that pre-procedural ultrasound assessment would predict in-stent restenosis. Methods This single-center study retrospectively analyzed 283 limbs in 243 patients who treated with superficial femoral artery nitinol stent placement for long-segment (≥15 cm) lesions between 2015 and 2018. Color duplex ultrasound was performed pre-procedure and post-procedure at 3, 6, 12, 24, and 36 months. The endpoint was ≥50% in-stent restenosis in the superficial femoral artery. Primary patency rates were analyzed with Kaplan–Meier survival analysis and compared using the log-rank test. A multivariable Cox proportional hazards model was used to evaluate the risk factors for in-stent restenosis. Results The median length of lesions was 25.8 ± 8.1 cm. The cumulative freedom from ≥50% in-stent restenosis at 3, 6, 12, 24, and 36 months was 95.3%, 78.3%, 56.0%, 30.6%, and 15.9%, respectively. Univariate and multivariate Cox regression analysis showed that cumulative lesion length ≥ 25 cm (hazard ratio 1.681; p = 0.003), calcified plaque (hazard ratio 1.549, p = 0.006), poor runoff scores >10 (hazard ratio 1.870, p = 0.003), and chronic renal failure (hazard ratio 2.075, p = 0.009) were independent risk factors for in-stent restenosis. The agreement rate between ultrasound and angiography was 92.6% for cumulative lesion length ( κ 0.851) and 91.9% for runoff score ( κ 0.872). Conclusions The results indicate that pre-procedural color duplex ultrasound evaluation is helpful for the selection of appropriate candidates for superficial femoral artery stent placement. Cumulative lesion length ≥25 cm, plaque calcification, poor distal runoff, and chronic renal failure independently predicted in-stent restenosis.

Objective Arteriovenous fistulae (AVF) placed for hemodialysis have high flow rates that can stimulate left ventricular (LV) hypertrophy. LV hypertrophy generally portends poor cardiac outcomes, yet clinical studies point to superior cardiac-specific outcomes for patients with AVF when compared with other dialysis modalities. We hypothesize that AVF induce physiologic cardiac hypertrophy with cardioprotective features. Methods We treated 9- to 11-week-old C57Bl/6 male and female mice with sham laparotomy or an aortocaval fistula via a 25G needle. Cardiac chamber size and function were assessed with serial echocardiography, and cardiac computed tomography angiography. Hearts were harvested at 5 weeks postoperatively, and the collagen content was assessed with Masson's trichrome. Bulk messenger RNA sequencing was performed from LV of sham and AVF mice at 10 days. Differentially expressed genes were analyzed using Ingenuity Pathway Analysis (Qiagen) to identify affected pathways and predict downstream biological effects. Results Mice with AVF had similar body weight and wet lung mass, but increased cardiac mass compared with sham-operated mice. AVF increased cardiac output while preserving LV systolic and diastolic function, as well as indices of right heart function; all four cardiac chambers were enlarged, with a slight decrement in the relative LV wall thickness. Histology showed preserved collagen density within each of the four chambers without areas of fibrosis. RNA sequencing captured 19 384 genes, of which 857 were significantly differentially expressed, including transcripts from extracellular matrix-related genes, ion channels, metabolism, and cardiac fetal genes. The top upstream regulatory molecules predicted include activation of angiogenic (Vegf, Akt1), procardiomyocyte survival (Hgf, Foxm1, Erbb2, Lin9, Areg), and inflammation-related (CSF2, Tgfb1, TNF, Ifng, Ccr2, IL6) genes, as well as the inactivation of cardiomyocyte antiproliferative factors (Cdkn1a, FoxO3, α-catenin). The predicted downstream effects include a decrease in heart damage, and increased arrhythmia, angiogenesis, and cardiogenesis. There were no significant sex-dependent differences in the AVF-stimulated cardiac adaptation. Conclusions AVF stimulate adaptive cardiac hypertrophy in wild-type mice without heart failure or pathologic fibrosis. Transcriptional correlates suggest AVF-induced cardiac remodeling has some cardioprotective, although also arrhythmogenic features. (JVS–Vascular Science 2021;2:110-28.) Clinical Relevance Arteriovenous fistulae (AVF) are commonly used as access for hemodialysis in patients with end-stage renal disease. AVF induce a high-output state that is associated with long-term structural cardiac remodeling, including left ventricle hypertrophy, but this element has uncertain clinical significance. Although left ventricle hypertrophy has traditionally been associated with an increased risk of cardiovascular disease, clinical studies have suggested that cardiac-specific outcomes of patients with end-stage renal disease were better with AVF compared with other dialysis modalities. This study uses a mouse model of AVF to study the structural, functional, and molecular correlates of AVF-induced cardiac remodeling. It finds that AVF causes an adaptive cardiac hypertrophy without functional decline or fibrosis. Transcriptional correlates suggest an electrical remodeling and the upregulation of proangiogenic, procardiogenic, and prosurvival factors, implying that AVF-induced cardiac hypertrophy is potentially cardioprotective, but also arrhythmogenic.