Clinician perspectives regarding CYP2C19 genotype testing in patients with critical limb ischemia: A Delphi approach.

OBJECTIVES: Antiplatelet therapy is an essential element in the management of patients with arterial vascular disease. In peripheral arterial disease (PAD), dual antiplatelet therapy (DAPT), primarily clopidogrel and aspirin, is routinely prescribed following intervention. There is sparse data regarding the need for DAPT, the appropriate duration, or the heterogeneity of treatment effects for antiplatelet regimens across patients, leading to potential uncertainty and heterogeneity around treatment practices. An example of heterogeneity of treatment effects is a patients' metabolizer status for the use of clopidogrel. The aim of the study was to (1) assess clinicians' knowledge of and attitudes toward managing patients with CYP2C19 mutations, (2) identify barriers to implementation of CYP2C19 testing and management policies, and (3) reach consensus for CYP2C19 testing and management strategies for patients with PAD who undergo peripheral vascular interventions (PVI). METHODS: A modified Delphi method was used to establish consensus amongst PAD interventionalists around CYP2C19 testing. All practicing Yale New Haven Hospital PAD interventionalists with backgrounds in interventional cardiology, vascular surgery, or interventional radiology were approached by email for participation. Round 1 included the collection of baseline demographic questions, knowledge questions, and three statements for consensus. Knowledge questions were rated on a 0-10 Likert scale with the following anchors: 0 ("Not at all"), 5 ("Neutral), and 10 ("Very Much"). Participants were asked to rate the importance of the three consensus statements on a 9-point Likert scale from 1 ("Strongly Disagree") to 10 ("Strongly Agree"). In Round 2, participants were shown the same consensus statements, the median response of the group from the previous round, and their previous answers. Participants were instructed to revise their rating using the results from the previous round. This process was repeated for Round 3. RESULTS: Of the 28 experts invited to participate, 13 agreed (46%). Participants were predominantly male (92.3%) and white (61.5%) with representation from interventional cardiology (46.2%) and vascular surgery (53.8%). Most participants reported more than 10+ years in practice (61.5%). PAD interventionalists felt they would benefit from more education regarding CYP2C19 mutations (median score 8.0, interquartile range 5.0-8.5). They indicated some familiarity with CYP2C19 mutations (7.0, 6.0-9.5) but did not feel strongly that CYP2C19 was important to their practice (6.0, 5.5-7.5). In each round, the median responses for the three consensus statements were 5, 6, and 9, respectively. With each successive round the interquartile range narrowed indicative of evolving consensus but did not reach the prespecified interquartile range for consensus of 1 for any of the statements. CONCLUSIONS: PAD interventionalists practicing at an academic health system recognize the heterogenous response of their patients to clopidogrel therapy but are unsure when to leverage genetic testing to improve outcomes for their patients. Our study identified gaps regarding PAD interventionalists' knowledge, perceived barriers, and attitudes toward CYP2C19 testing in PAD. This information highlights the need for randomized data on genetic testing for clopidogrel responsiveness in peripheral vascular disease following intervention to help guide antiplatelet management.

Reduced Muscle Mass and Muscle Quality in Patients with Intermittent Claudication due to Peripheral Artery Disease.

BACKGROUND: Peripheral arterial disease (PAD) is associated with reduced muscle mass and quality, but the effects of leg ischemia caused by PAD on muscle quality remain poorly understood. The purpose of this study was to evaluate leg muscle mass and muscle quality in patients with intermittent claudication due to PAD using bioelectrical impedance analysis (BIA). METHODS: One hundred forty-one patients with intermittent claudication due to PAD who visited Tokyo Medical University Hospital from April 2019 to April 2020 were retrospectively analyzed. Leg ischemia was assessed using ankle-brachial pressure index (ABI). The skeletal muscle mass (SMM) assessed leg muscle mass, while the phase angle (PhA) assessed leg muscle quality using BIA. RESULTS: A total of 282 legs in 141 patients were included in the analysis. Leg PhA and SMM showed a decreasing trend according to the severity of leg ischemia (borderline/no ischemia: 2.80 ± 0.50 kg/m2, 4.38 ± 0.94°; mild ischemia: 2.83 ± 0.49 kg/m2, 4.33 ± 1.03°; moderate/severe ischemia: 2.50 ± 0.40 kg/m2, 3.89 ± 0. 88°; P < 0.001 and P = 0.020, respectively). The ABI was moderately correlated with leg SMM (B = 0.347, ß = 0.134, P < 0.001) and leg PhA (B = 0.577, ß = 0.111, P = 0.013) after adjustment for all significant covariates. Leg PhA was moderately correlated with leg SMM (r = 0.318, P < 0.001). CONCLUSIONS: Leg ischemia, especially when moderate or severe, has an adverse effect on both muscle mass and quality in the lower extremities and is associated with skeletal muscle myopathy.

Leveraging Artificial Intelligence to Optimize the Care of Peripheral Artery Disease Patients.

Peripheral artery disease is a major atherosclerotic disease that is associated with poor outcomes such as limb loss, cardiovascular morbidity, and death. Artificial intelligence (AI) has seen increasing integration in medicine, and its various applications can optimize the care of peripheral artery disease (PAD) patients in diagnosis, predicting patient outcomes, and imaging interpretation. In this review, we introduce various AI applications such as natural language processing, supervised machine learning, and deep learning, and we analyze the current literature in which these algorithms have been applied to PAD.

Why selective screening for asymptomatic carotid stenosis is currently appropriate: a special report.

INTRODUCTION: Two of the main reasons recent guidelines do not recommend routine population-wide screening programs for asymptomatic carotid artery stenosis (AsxCS) is that screening could lead to an increase of carotid revascularization procedures and that such mass screening programs may not be cost-effective. Nevertheless, selective screening for AsxCS could have several benefits. This article presents the rationale for such a program. AREAS COVERED: The benefits of selective screening for AsxCS include early recognition of AsxCS allowing timely initiation of preventive measures to reduce future myocardial infarction (MI), stroke, cardiac death and cardiovascular (CV) event rates. EXPERT OPINION: Mass screening programs for AsxCS are neither clinically effective nor cost-effective. Nevertheless, targeted screening of populations at high risk for AsxCS provides an opportunity to identify these individuals earlier rather than later and to initiate a number of lifestyle measures, risk factor modifications, and intensive medical therapy in order to prevent future strokes and CV events. For patients at 'higher risk of stroke' on best medical treatment, a prophylactic carotid intervention may be considered.

Recent advances and controversial issues in the optimal management of asymptomatic carotid stenosis.

OBJECTIVE: The optimal management of patients with asymptomatic carotid stenosis (AsxCS) is enduringly controversial. We updated our 2021 Expert Review and Position Statement, focusing on recent advances in the diagnosis and management of patients with AsxCS. METHODS: A systematic review of the literature was performed up to August 1, 2023, using PubMed/PubMed Central, EMBASE and Scopus. The following keywords were used in various combinations: "asymptomatic carotid stenosis," "carotid endarterectomy" (CEA), "carotid artery stenting" (CAS), and "transcarotid artery revascularization" (TCAR). Areas covered included (i) improvements in best medical treatment (BMT) for patients with AsxCS and declining stroke risk, (ii) technological advances in surgical/endovascular skills/techniques and outcomes, (iii) risk factors, clinical/imaging characteristics and risk prediction models for the identification of high-risk AsxCS patient subgroups, and (iv) the association between cognitive dysfunction and AsxCS. RESULTS: BMT is essential for all patients with AsxCS, regardless of whether they will eventually be offered CEA, CAS, or TCAR. Specific patient subgroups at high risk for stroke despite BMT should be considered for a carotid revascularization procedure. These patients include those with severe (≥80%) AsxCS, transcranial Doppler-detected microemboli, plaque echolucency on Duplex ultrasound examination, silent infarcts on brain computed tomography or magnetic resonance angiography scans, decreased cerebrovascular reserve, increased size of juxtaluminal hypoechoic area, AsxCS progression, carotid plaque ulceration, and intraplaque hemorrhage. Treatment of patients with AsxCS should be individualized, taking into consideration individual patient preferences and needs, clinical and imaging characteristics, and cultural, ethnic, and social factors. Solid evidence supporting or refuting an association between AsxCS and cognitive dysfunction is lacking. CONCLUSIONS: The optimal management of patients with AsxCS should include BMT for all individuals and a prophylactic carotid revascularization procedure (CEA, CAS, or TCAR) for some asymptomatic patient subgroups, additionally taking into consideration individual patient needs and preference, clinical and imaging characteristics, social and cultural factors, and the available stroke risk prediction models. Future studies should investigate the association between AsxCS with cognitive function and the role of carotid revascularization procedures in the progression or reversal of cognitive dysfunction.

The development of a novel endovascular grasper for challenging inferior vena cava filter retrieval.

OBJECTIVE: Although inferior vena cava (IVC) filters are commonly retrieved using a snare, lateral tilt and fibrosis around struts can complicate the procedure and sometimes require the use of off-label devices. We describe the development of a novel articulating endovascular grasper designed to remove permanent and retrievable IVC filters in any configuration. METHODS: For in vitro testing, the IVC filters were anchored to the inner wall of a flexible tube in a centered or tilted configuration. A high-contrast backlit camera view simulated the two-dimensional fluoroscopy projection during retrieval. The time from the retrieval device introduction into the camera field to complete filter retrieval was measured in seconds. The control experiment involved temporary IVC filter retrieval with a snare. There were four comparative groups: (1) retrievable filter in centered configuration; (2) retrievable filter in tilted configuration; (3) permanent filter in centered configuration; and (4) permanent filter in tilted configuration. Every experiment was repeated five times, with median retrieval time compared with the control group. For in vivo testing in a porcine model, six tilted infrarenal IVC filters were retrieved with grasper via right jugular approach. Comparison analysis between animal and patient procedures was performed for the following variables: total procedure time, the retrieval time, and fluoroscopy time. RESULTS: The in vitro experiments showed comparable retrieval times between the experimental groups 1, 2, and 4 and the control. However, grasper removal of a centered permanent filter (group 3) required significantly less time than in the control (29 vs 79 seconds; P = .009). In the animal model, all IVC filters were retrieved using the grasper with no adverse events. The total procedure time (21.2 vs 43.5 minutes; P = .01) and the fluoroscopy time (4.3 vs 10 minutes; P = .044) were significantly shorter in the animal model compared with the patient group. Moreover, in the patient group, 16.7% of retrievals required advanced endovascular techniques, and one IVC filter could not be retrieved (success rate = 91.7%), whereas all the IVC filters were successfully retrieved in the animal model without the use of additional tools. CONCLUSIONS: The novel endovascular grasper is effective in retrieving different types of IVC filters in different configurations and compared favorably with the snare in the in vitro model. In vivo experiments demonstrated more effective retrieval when compared with matched patient retrievals.

An international, multispecialty, expert-based Delphi Consensus document on controversial issues in the management of patients with asymptomatic and symptomatic carotid stenosis.

OBJECTIVE: Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear. METHODS: Fourteen controversial topics were identified. A three-round Delphi Consensus process was performed including 61 experts. The aim of Round 1 was to investigate the differing views and opinions regarding these unresolved topics. In Round 2, clarifications were asked from each participant. In Round 3, the questionnaire was resent to all participants for their final vote. Consensus was reached when ≥75% of experts agreed on a specific response. RESULTS: Most experts agreed that: (1) the current periprocedural/in-hospital stroke/death thresholds for performing a carotid intervention should be lowered from 6% to 4% in patients with SxCS and from 3% to 2% in patients with AsxCS; (2) the time threshold for a patient being considered "recently symptomatic" should be reduced from the current definition of "6 months" to 3 months or less; (3) 80% to 99% AsxCS carries a higher risk of stroke compared with 60% to 79% AsxCS; (4) factors beyond the grade of stenosis and symptoms should be added to the indications for revascularization in AsxCS patients (eg, plaque features of vulnerability and silent infarctions on brain computed tomography scans); and (5) shunting should be used selectively, rather than always or never. Consensus could not be reached on the remaining topics due to conflicting, inadequate, or controversial evidence. CONCLUSIONS: The present international, multi-specialty expert-based Delphi Consensus document attempted to provide responses to several unanswered/unresolved issues. However, consensus could not be achieved on some topics, highlighting areas requiring future research.

Association of Socioeconomic Status, Sex, Racial, and Ethnic Identity With Sustained and Cultivated Careers in Surgery.

OBJECTIVE: Examine the association between sex, race, ethnicity, and family income, and the intersectionality between these identities, and sustained or cultivated paths in surgery in medical school. METHODS: This retrospective cohort study examines US medical students who matriculated in academic years 2014-2015 and 2015-2016. Data were provided by the Association of American Medical Colleges, including self-reported sex, race, ethnicity, family income, interest in surgery at matriculation, and successful placement into a surgical residency at graduation. This study examined 2 outcomes: (1) sustained path in surgery between matriculation and graduation for students who entered medical school with an interest in surgery and (2) cultivated path in surgery for students who entered medical school not initially interested in surgery and who applied to and were successfully placed into a surgical residency at graduation. RESULTS: Among the 5074 students who reported interest in surgery at matriculation, 2108 (41.5%) had sustained path in surgery. Compared to male students, female students were significantly less likely to have sustained path in surgery [adjusted relative risk (aRR): 0.92 (0.85-0.98)], while Asian (aRR: 0.82, 95% CI: 0.74-0.91), Hispanic (aRR: 0.70, 95% CI: 0.59-0.83), and low-income (aRR: 0.85, 95% CI: 0.78-0.92) students were less likely to have a sustained path in surgery compared to their peers. Among the 17,586 students who reported an initial interest in a nonsurgical specialty, 1869 (10.6%) were placed into a surgical residency at graduation. Female students, regardless of race/ethnic identity and income, were significantly less likely to have cultivated paths in surgery compared to male students, with underrepresented in medicine female students reporting the lowest rates. CONCLUSIONS AND RELEVANCE: This study demonstrates the significant disparity in sustained and cultivated paths in surgery during undergraduate medical education. Innovative transformation of the surgical learning environment to promote surgical identity development and belonging for females, underrepresented in medicine, and low-income students is essential to diversify the surgical workforce.

The Preoperative Lymphocyte-To-Monocyte Ratio Predicts Mortality Among Patients Undergoing Endovascular Aortic Repair for Abdominal Aortic Aneurysm.

PURPOSE: The purpose of this study was to investigate the preoperative lymphocyte-to-monocyte ratio (LMR) as a potential surrogate biomarker predictive of overall mortality in patients undergoing endovascular aortic repair (EVAR) for abdominal aortic aneurysm (AAA). METHODS: Data on patients with AAA treated by EVAR between March 2012 and December 2016 were obtained from a prospectively maintained EVAR database at Tokyo Medical University Hospital, Tokyo, Japan. The LMR was calculated by dividing the absolute lymphocyte count by the absolute monocyte count. RESULTS: One hundred seventy-six patients were included in this study after selection based on the exclusion criteria. The subjects consisted of 148 males and 28 females with a mean age of 78.5 years (range, 51-89 years). The median follow-up period was 4.98 years (range, .03-9.28). A receiver operating characteristic curve analysis determined the optimal cut-off value of the preoperative LMR for predicting overall mortality with 3.21 (area under the curve, .71; 95% confidence interval [CI], .62-.79; sensitivity, 57.4%; specificity, 77.0%; P < .001). On univariable and multivariable analyses, octogenarian (hazard ratio [HR], 1.89; 95%CI, 1.10-3.22; P = .020), poor nutritional status (HR, 2.95; 95%CI, 1.73-5.03; P < .001), chronic obstructive pulmonary disease (HR, 1.79; 95%CI, 1.06-3.03; P = .031), active cancer (HR, 2.60; 95%CI, 1.53-4.41; P < .001), and low preoperative LMR (HR, 2.56; 95%CI, 1.53-4.30; P < .001) were identified as independent predictors for overall mortality. CONCLUSION: This study showed that a low preoperative LMR (<3.21) is an independent predictor of overall mortality after EVAR for AAA. The LMR may help in decision-making regarding the prediction of poor prognosis after EVAR.

Anatomic patterns in claudicants who fail supervised exercise therapy.

OBJECTIVE: Patients with intermittent claudication (IC) from peripheral arterial disease (PAD) have significant improvement with supervised exercise therapy (SET). However, many patients have progressive disease that will ultimately require revascularization. We sought to determine whether the anatomic patterns of PAD were associated with response to SET. METHODS: We prospectively enrolled patients with IC at the West Haven, Connecticut Veterans Health Administration between June 2019 and June 2022. Patients were classified based on the level of their arterial disease with >50% obstruction. SET failure was defined as progressive symptoms or development of critical limb-threatening ischemia (CLTI) requiring revascularization. RESULTS: Thirty-eight patients with PAD were included. Thirteen patients (34.2%) had significant common femoral artery (CFA) disease, and 25 (65.8%) had non-CFA disease. Over a median follow-up of 1407 days, 11 patients (84.6%) with CFA disease failed SET as compared with three patients (12.0%) with non-CFA disease (P < .001). Patients with CFA disease were more likely to develop CLTI (46.2% vs 4.0%; P = .001) and have persistent symptoms (38.5% vs 8.0%; P = .02). Patients with CFA disease had significantly lower post-SET ankle-brachial index (0.58 ± 0.14 vs 0.77 ± 0.19; P = .03). In multivariate analysis, the only variable associated with SET failure was CFA disease location (odds ratio, 68.75; 95% confidence interval, 5.05-936.44; P = .001). CONCLUSIONS: Patients with IC from high-grade CFA atherosclerosis are overwhelmingly likely to fail SET, potentially identifying a subset of patients who benefit from upfront revascularization.

Computer Science meets Vascular Surgery: Keeping a pulse on artificial intelligence.

Artificial intelligence (AI)-based technologies have garnered interest across a range of disciplines in the past several years, with an even more recent interest in various health care fields, including Vascular Surgery. AI offers a unique ability to analyze health data more quickly and efficiently than could be done by humans alone and can be used for clinical applications such as diagnosis, risk stratification, and follow-up, as well as patient-used applications to improve both patient and provider experiences, mitigate health care disparities, and individualize treatment. As with all novel technologies, AI is not without its risks and carries with it unique ethical considerations that will need to be addressed before its broad integration into health care systems. AI has the potential to revolutionize the way care is provided to patients, including those requiring vascular care.

2023 Vascular Research Initiatives Conference: Structural and Immune Cells in Vascular Disease.

The 2023 Vascular Research Initiatives Conference (VRIC) was held in Boston, Massachusetts, and coincided with the first day of Vascular Discovery 2023, hosted by the American Heart Association. VRIC attracts vascular clinicians, surgeon-scientists, and basic science researchers to a common arena to facilitate the exchange of basic and translational science to stimulate and inspire participants to study and find solutions to vascular conditions. The theme of the conference this year was "Structural and Immune Cells in Vascular Disease." Abstract sessions focused on venous disease, vascular regeneration, stem cells and wound healing, aortopathies, and the role of the immune system in atherosclerosis. A moderated translational science panel included talks from Dr Chiara Giannarelli and Dr Bhama Ramkhelawon. Recipients of Society for Vascular Surgery partner grants and National Institutes of Health K08 awardees presented their progress reports, and the Resident Research and VRIC Trainee Awardees were acknowledged. The Alexander W. Clowes Distinguished Lecture, entitled "Co-stimulatory Immune Checkpoints in Atherosclerosis: Novel Immunotherapeutic Targets to Combat Atherosclerotic Cardiovascular Disease" was given by Dr Ester Lutgens. VRIC continues to foster interdisciplinary collaborations across the translational field of vascular disease.

Systematic review of inferior vena cava atresia.

OBJECTIVE: Inferior vena cava (IVC) atresia is a rare venous anomaly characterized by absence of the IVC. It has been associated with deep vein thrombosis (DVT) and other congenital anomalies. The aim of the present study is to provide a comprehensive summary of the literature on IVC atresia and discuss the presentation and outcomes of patients with IVC atresia. METHODS: A systematic review of the English literature up to April 2020 was performed. The presentations and treatments reported were noted and compared between the two sexes. The IVC atresia cases were further stratified into isolated IVC atresia and IVC atresia associated with other congenital anomalies. RESULTS: A total of 412 abstracts were screened, with 178 reports included. A total of 376 patients were analyzed. Overall, males seem to be more affected than females, with a ratio of almost 2:1 (male, 227 [64.1%]; vs female, 127 [35.8%]). However, females were more likely to have congenital IVC atresia compared with males (46.1% vs 21.3%; P < .001). The mean age at presentation was 27.9 ± 18.0 years (range, 0-77 years), with no differences between the sexes. Most patients with IVC atresia presented with DVT (n = 242 of 376; 64.3%), with the iliac veins most often affected (n = 159 of 242; 65.7%). No difference was found in the reported proportion of patients presenting with DVT between the two sexes. The symptom presentation was similar, with leg pain and swelling the most common in both sexes. The patients were treated either medically with anticoagulation or surgically (open or endovascular). No mortality was reported with isolated IVC atresia in either treatment group. However, the mortality of patients with IVC atresia associated with other congenital anomalies was 11.7%. CONCLUSIONS: IVC atresia is more common in males but seems to have a predilection for females in the setting of other congenital anomalies. Most patients present with leg pain and swelling related to the development of DVT. Open and endovascular surgical interventions to treat IVC atresia have been reported in 18.3% of patients reviewed, with acceptable mid-term results in terms of patency and symptomatic relief.

Sclerotherapy Improves Symptoms in Patients with Small and Moderate Diameter Low-Flow Vascular Malformations: A Prospective Cohort Study.

BACKGROUND: Vascular malformations are rare diseases and treatment remains controversial. Sclerotherapy is accepted as a minimally invasive treatment with good results; however, some patients do not report good response to sclerotherapy, and it is not clear which variables influence treatment outcome, preventing optimal patient selection. We hypothesized that large diameter lesions have reduced efficacy and satisfaction with sclerotherapy. Therefore, we prospectively evaluated the clinical response of low-flow vascular malformations treated with 1% polidocanol foam sclerotherapy and determined the correlation of symptom improvement with clinical variables. METHODS: Prospective cohort study of patients with symptomatic low flow vascular malformations treated at the Hospital das Clínicas between December 2016 and November 2018. Lesions were classified according to location, extension, diameter, type of vessels, margins, and symptoms. Sclerotherapy was performed by direct injection of 1% polidocanol foam, with a maximum volume of 10 ml per session. Symptom improvement was evaluated using the visual analog scale and patient-reported quality of life was assessed by the Short-form 6 dimensions (SF-6D) questionnaire. Follow-up was performed every 3 months after treatment. RESULTS: Forty lesions were treated in 38 patients, with 19 women and 19 men; median age was 20.5 years (range 4 months to 63 years). Most lesions (80%) were venous, and most commonly in the lower limbs (47.5%); 27.5% were superficial, 35% were deep, and 37.5% affected both compartments. The most common clinical presentations were deformity (95%), pain (78%), and functional limitation (58%); deep compartment lesions were more associated with functional limitation (69% vs. 27%; P = 0.030). Fifty-three per cent of lesions were >10 cm and were associated with increased numbers of psychosocial symptoms (P = 0.038). Two-hundred and forty-two sessions of sclerotherapy were performed, with 6 mean treatments per lesion (range 1-15). The mean follow-up time was 23 months (range 2-23 months). The most common complications were pain and local edema, without any major complications; some patients reported symptom recurrence (15% pain, 10% deformity, and 12% functional limitation). Sclerotherapy was associated with significant improvement of all symptoms (P < 0.001). However, lesions >10 cm were associated with poor improvement in deformity (P = 0.003). Quality of life improved for most patients (60%) and treatment satisfaction was high (82%). CONCLUSIONS: Treatment of low-flow vascular malformations with 1% polidocanol foam is safe and effective; sclerotherapy improves symptoms and quality of life. Large diameter lesions (>10 cm) are associated with increased treatment failure. A small percentage of patients reported recurrent symptoms and require other modalities for successful treatment.

Prognostic Value of Nutritional Markers for Long-Term Mortality in Patients Undergoing Endovascular Aortic Repair.

Objective: The relationship between nutritional status and morbidity and death in a number of diseases and disorders has garnered considerable attension. In patients having endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAA), we assessed the prognostic value of nutritional markers of albumin (ALB), body mass index (BMI), and geriatric nutritional risk index (GNRI) for long-term mortality. Materials and Methods: Retrospective data analysis was done on patients who had undergone elective EVAR for AAA more than 5 years earlier. Results: A total of 176 patients underwent EVAR for AAA between March 2012 and April 2016. The optimal cutoff value of ALB, BMI, and GNRI for predicting long-term mortality was calculated as 3.75 g/dL (area under the curve [AUC] 0.64), 21.4 kg/m2 (AUC 0.65), and 101.4 (AUC 0.70), respectively. Low ALB, low BMI, and low GNRI as well as age ≥75 years, chronic obstructive pulmonary disease, chronic kidney disease, and active cancer were independent risk factors for long-term mortality. Conclusion: Malnutrition, which is measured by ALB, BMI, and GNRI, is an independent risk factor for long-term mortality in patients receiving EVAR for AAA. Of the nutritional markers, the GNRI can be the most reliable nutritional indicator to identify a potentially high-risk group of mortality after EVAR.

Sex hormones impact early maturation and immune response in the arteriovenous fistula mouse model.

Arteriovenous fistulae (AVF) fail to mature more frequently in female patients compared with male patients, leading to inferior outcomes and decreased utilization. Since 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 wk) were treated with aortocaval AVF surgery and/or gonadectomy. AVF hemodynamics were measured via ultrasound (days 0-21). Blood was collected for FACS and tissue for immunofluorescence and ELISA (days 3 and 7); wall thickness was assessed by histology (day 21). Inferior vena cava shear stress was higher in male mice (P = 0.0028) after gonadectomy, and they had increased wall thickness (22.0 ± 1.8 vs. 12.7 ± 1.2 µm; P < 0.0001). Conversely, female mice had decreased wall thickness (6.8 ± 0.6 vs. 15.3 ± 0.9 µm; P = 0.0002). Intact female mice had higher proportions of circulating CD3+ T cells on day 3 (P = 0.0043), CD4+ (P = 0.0003) and CD8+ T cells (P = 0.005) on day 7, and CD11b+ monocytes on day 3 (P = 0.0046). After gonadectomy, these differences disappeared. In intact female mice, CD3+ T cells (P = 0.025), CD4+ T cells (P = 0.0178), CD8+ T cells (P = 0.0571), and CD68+ macrophages (P = 0.0078) increased in the fistula wall on days 3 and 7. This disappeared after gonadectomy. Furthermore, female mice had higher IL-10 (P = 0.0217) and TNF-α (P = 0.0417) levels in their AVF walls than male mice. Sex hormones mediate AVF maturation, suggesting that hormone receptor signaling may be a target to improve AVF maturation.NEW & NOTEWORTHY After arteriovenous fistula creation, females have lower rates of maturation and higher rates of failure than males. In a mouse model of venous adaptation that recapitulates human fistula maturation, sex hormones may be mechanisms of the sexual dimorphism: testosterone is associated with reduced shear stress, whereas estrogen is associated with increased immune cell recruitment. Modulating sex hormones or downstream effectors suggests sex-specific therapies and could address disparities in sex differences in clinical outcomes.

Rates of National Institutes of Health Funding for Surgeon-Scientists, 1995-2020.

Importance: Surgeon-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. Objective: To examine how NIH funding has been awarded to surgeon-scientists over time. Design, Setting, and Participants: This 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 Outcome: National Institutes of Health funding to surgeon-scientists compared with PhD scientists, as well as NIH funding to surgeon-scientists across surgical subspecialties. Results: Between 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 < .001). However, substantial disparity remained, with female surgeon-scientists receiving less than 20% of NIH grants and funding dollars in 2020. In addition, although there was increased NIH funding to neurosurgeons and otolaryngologists, funding to urologists decreased significantly from 14.9% of all grants in 1995 to 7.5% in 2020 (annual percent change, -0.39% [95% CI, -0.47% to -0.30%]; P < .001). Despite surgical diseases making up 30% of the global disease burden, representation of surgeon-scientists among NIH investigators remains less than 2%. Conclusion and Relevance: This 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.