Cost-effectiveness analysis of endovascular vs surgical arteriovenous fistula creation in the United States.

OBJECTIVE: In the United States, an estimated $2.8 billion annually is spent on vascular access and its complications. Endovascular arteriovenous fistula (endoAVF) creation is a novel, minimally invasive alternative to traditional surgical AV fistula (sAVF) creation in ≤60% of patients. Although cost effective in single-payer systems, the clinical and financial impact of endoAVF in the United States remains uncertain. METHODS: We constructed a decision tree followed by a probabilistic cohort state-transition model to study the cost effectiveness of endoAVF vs sAVF creation. We conducted a systematic review to obtain input parameters including technical success, maturation, patency, and utility values. We derived costs from the Medicare 2022 fee schedule and from the literature. We used a 5-year time horizon, an annual discount rate of 3% for costs and utilities (measured in quality-adjusted life-years [QALYs]), and the common willingness-to-pay threshold of $50,000. One-way and Monte Carlo probabilistic sensitivity analyses were performed varying technical success, patency, reintervention, cost, and utility parameters. RESULTS: In the base-case scenario, endoAVF ($30,129 average per-person costs, 2.19 QALYs gained, 65% patent at 5 years) was not cost effective compared with sAVF ($12.987 average per-person costs, 2.11 QALYs gained, 66% patent at 5 years), generating an incremental cost-effectiveness ratio of $227,504 per QALY gained. In one-way sensitivity analyses, endoAVF becomes cost effective when the initial cost of sAVF creation exceeds endoAVF by ≥$600 (eg, if endoAVF creation costs ≤$3000 relative to the base-case sAVF cost of $3600), the additional QALYs gained from endoAVF exceeds 0.12 QALYs/year (eg, 0.81 QALYs gained/year from endoAVF compared with base-case sAVF 0.69 QALYs/year), the endoAVF maturation rate is >90% (base case 78%), or the sAVF maturation rate is <65% (base case 78%). Probabilistic sensitivity analysis demonstrated that sAVF remained the optimal strategy in 71% of iterations. CONCLUSIONS: EndoAVF is not cost effective compared with sAVF when modeling 5-year outcomes. The main driver of sAVF remaining cost effective is the four times higher up-front cost for endoAVF creation, as well as a relatively low additional increase in quality of life for endoAVF. It will be important to establish how the endoAVF learning curve contributes to upfront costs and, given the annual cost attributed to vascular access nationally, a randomized controlled trial is warranted.

Association of Frailty and the Expanded Operative Stress Score with Preoperative Acute Serious Conditions, Complications, and Mortality in Males Compared to Females: A Retrospective Observational Study.

OBJECTIVE: The aim of this study was to expand Operative Stress Score (OSS) increasing procedural coverage and assessing OSS and frailty association with Preoperative Acute Serious Conditions (PASC), complications and mortality in females versus males. SUMMARY BACKGROUND DATA: Veterans Affairs male-dominated study showed high mortality in frail veterans even after very low stress surgeries (OSS1). METHODS: Retrospective cohort using NSQIP data (2013-2019) merged with 180-day postoperative mortality from multiple hospitals to evaluate PASC, 30-day complications and 30-, 90-, and 180-day mortality. RESULTS: OSS expansion resulted in 98.2% case coverage versus 87.0% using the original. Of 82,269 patients (43.8% male), 7.9% were frail/very frail. Males had higher odds of PASC [adjusted odds ratio (aOR) = 1.31, 95% confidence interval (CI) = 1.21-1.41, P < 0.001] and severe/life-threatening Clavien-Dindo IV (CDIV) complications (aOR = 1.18, 95% CI = 1.09-1.28, P < 0.001). Although mortality rates were higher (all time-points, P < 0.001) in males versus females, mortality was similar after adjusting for frailty, OSS, and case status primarily due to increased male frailty scores. Additional adjustments for PASC and CDIV resulted in a lower odds of mortality in males (30-day, aOR = 0.81, 95% CI = 0.71-0.92, P = 0.002) that was most pronounced for males with PASC compared to females with PASC (30-day, aOR = 0.75, 95% CI = 0.56-0.99, P = 0.04). CONCLUSIONS: Similar to the male-dominated Veteran population, private sector, frail patients have high likelihood of postoperative mortality, even after low-stress surgeries. Preoperative frailty screening should be performed regardless of magnitude of the procedure. Despite males experiencing higher adjusted odds of PASC and CDIV complications, females with PASC had higher odds of mortality compared to males, suggesting differences in the aggressiveness of care provided to men and women.

Most privately insured patients do not receive federally recommended abdominal aortic aneurysm screening.

OBJECTIVE: Since 2005, the United States Preventative Services Task Force has recommended abdominal aortic aneurysm (AAA) ultrasound screening for 65- to 75-year-old male ever-smokers. Integrated health systems such as Kaiser Permanente and the Veterans Affairs (VA) health care system report 74% to 79% adherence, but compliance rates in the private sector are unknown. METHODS: The IBM Marketscan Commercial and Medicare Supplemental databases (2006-2017) were queried for male ever-smokers continuously enrolled from age 65 to 75 years. Exclusion criteria were previous history of AAA, connective tissue disorder, and aortic surgery. Patients with abdominal computed tomographic or magnetic resonance imaging from ages 65 to 75 years were also excluded. Screening was defined as a complete abdominal, retroperitoneal, or aortic ultrasound. A logistic mixed-effects model utilizing state as a random intercept was used to identify patient characteristics associated with screening. RESULTS: Of 35,154 eligible patients, 13,612 (38.7%) underwent screening. Compliance varied by state, ranging from 24.4% in Minnesota to 51.6% in Montana (P < .05). Screening activity increased yearly, with 0.7% of screening activity occurring in 2008 vs 22.2% in 2016 (P <.05). In a logistic mixed-effects model adjusting for state as a random intercept, history of hypertension (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.03-1.13), coronary artery disease (OR, 1.17; 95% CI, 1.10-1.22), congestive heart failure (OR, 1.14; 95% CI, 1.01-1.22), diabetes (OR, 1.1; 95% CI, 1.06-1.16), and chronic kidney disease (OR, 1.4; 95% CI, 1.24-1.53) were associated with screening. Living outside of a census-designated metropolitan area was negatively associated with screening (OR, 0.92; 95% CI, 0.87-0.97). CONCLUSIONS: In a private claims database representing 250 million claimants, 38.7% of eligible patients received United States Preventative Services Task Force-recommended AAA screening. Compliance was nearly one-half that of integrated health systems and was significantly lower for patients living outside of metropolitan areas. Efforts to improve early detection of AAA should include targeting non-metropolitan areas and modifying Medicare reimbursement and incentivization strategies to improve guideline adherence.

Female sex is independently associated with reduced inpatient mortality after endovascular repair of blunt thoracic aortic injury.

BACKGROUND: Female sex has been associated with decreased mortality after blunt trauma, but whether sex influences the outcomes of thoracic endovascular aortic repair (TEVAR) for traumatic blunt thoracic aortic injury (BTAI) is unknown. METHODS: In this retrospective study of a prospectively maintained database, the Vascular Quality Initiative registry was queried from 2013 to 2020 for patients undergoing TEVAR for BTAI. Univariate Student's t-tests and χ2 tests were performed, followed by multivariate logistic regression for variables associated with inpatient mortality. RESULTS: Of 806 eligible patients, 211 (26.2%) were female. Female patients were older (47.9 vs 41.8 years, P < .0001) and less likely to smoke (38.3% vs 48.2%, P = .044). Most patients presented with grade III BTAI (54.5% female, 53.6% male), followed by grade IV (19.0% female, 19.5% male). Mean Injury Severity Scores (30.9 + 20.3 female, 30.5 + 18.8 male) and regional Abbreviated Injury Score did not vary by sex. Postoperatively, female patients were less likely to die as inpatients (3.8% vs 7.9%, P = .042) and to be discharged home (41.4% vs 52.2%, P = .008). On multivariate logistic regression, female sex (odds ratio [OR]: 0.05, P = .002) was associated with reduced inpatient mortality. Advanced age (OR: 1.06, P < .001), postoperative transfusion (OR: 1.05, P = .043), increased Injury Severity Score (OR: 1.03, P = .039), postoperative stroke (OR: 9.09, P = .016), postoperative myocardial infarction (OR: 9.9, P = .017), and left subclavian coverage (OR: 2.7, P = .029) were associated with inpatient death. CONCLUSIONS: Female sex is associated with lower odds of inpatient mortality after TEVAR for BTAI, independent of age, injury severity, BTAI grade, and postoperative complications. Further study of the influence of sex on postdischarge outcomes is needed.

Precocious Rupture of Abdominal Aortic Aneurysms Below Size Criteria for Repair: Risk Factors and Outcomes.

BACKGROUND: Practice guidelines recommend elective repair for abdominal aortic aneurysms (AAAs) ≥ 5.5 cm in men and ≥ 5 cm in women to prevent rupture; however, some rupture at smaller diameters. We identify risk factors for rupture AAA (rAAA) below this threshold and compare outcomes following rAAA repair above/below size criteria. METHODS: The Vascular Quality Initiative (2013-2019) was queried for patients undergoing repair for rAAA and stratified based on diameter into small and large cohorts [Small: < 5.5 cm (men), < 5.0 cm (women)]. Univariate analysis was performed, and Kaplan-Meier analysis compared overall survival, aneurysm-related mortality, and reintervention at 12 months. RESULTS: Five thousand one hundred sixty two rAAA were identified. Small rAAA patients [n = 588] were more likely to have hypertension (81.3% vs. 77.0%, P < 0.02), diabetes (18.2% vs. 14.9%, P < 0.04), and end-stage renal disease (2.9% vs. 0.9%, P < 0.01) and be on optimal medical therapy (32.1% vs. 26.8%, P < 0.01). Women were more likely to rupture at smaller diameters compared to men (P < 0.01). Small rAAA patients were more likely to undergo endovascular aortic repair (EVAR) (70.2% vs. 56.0%, P < 0.01) and had lower in-hospital mortality (17.7% vs. 27.7%, P < 0.01) and fewer perioperative complications across all categories. At 12 months, small rAAA patients had better overall survival, freedom from aneurysm-related mortality, and freedom from reintervention, largely driven by EVAR approach. CONCLUSIONS: More than 11% of patients presenting with ruptured AAA were below the recommended size threshold for repair, and they tended to be younger, non-White, and have hypertension, diabetes, and/or renal failure. Patients with small rAAA experienced lower in-hospital morbidity and mortality and improved 1-year survival, and EVAR was associated with better outcomes than open repair. However, women more frequently rupture at smaller diameters compared to men. Given contemporary elective outcomes for women, a randomized controlled trial for EVAR versus surveillance at a sex-specific size threshold is needed.

Simplifying Hospital Quality Comparisons for Vascular Surgery Using Center-Level Frailty Burden Rather Than Comorbidities.

BACKGROUND: Failure to rescue (FtR), or inpatient death following complication, is a publicly reported hospital quality measure. Previous work has demonstrated significant variation in the proportion of frail patients across hospitals. However, frailty is not incorporated into risk-adjustment algorithms for hospital quality comparisons and risk adjustment is made by comorbidity scores. Our aim was to assess the impact of frailty on FtR quality measurement and as a means of risk adjustment. METHODS: Patients undergoing open or endovascular aneurysm repair or lower extremity bypass in the Vascular Quality Initiative (VQI) at centers performing ≥ 25 vascular procedures annually (2003-2019) were included. Multivariable logistic regression evaluated in-hospital death using scaled hierarchical modeling clustering at the center level. Center FtR observed/expected ratios were compared with expected values adjusted for either standard comorbidity profiles or frailty as measured by the VQI Risk Analysis Index. Centers were divided into quartiles using VQI-linked American Hospital Association data to describe the hospital characteristics of centers whose ranks changed. RESULTS: A total of 63,143 patients (213 centers) were included; 1,630 patients (2.58%) were classified as FtR. After accounting for center-level variability, frailty was associated with FtR [scaled odds ratio 1.9 (1.8-2.0), P < 0.001]. The comorbidity-centric and frailty-based models performed similarly in predicting FtR with C-statistics of 0.85 (0.84-0.86) and 0.82 (0.82-0.84), respectively. Overall changes in ranking based on observed/expected ratios were not statistically significant (P = 0.48). High and low performing centers had similar ranking using comorbidity-centric and frailty-based methods; however, centers in the middle of the performance spectrum saw more variability in ranking alterations. Forty nine (23%) of hospitals improved their ranking by five or more positions when using frailty versus comorbidity risk adjustment. The centers in Quartile 4, those who performed the highest number of vascular procedures annually, experience on average a significant improvement in hospital ranking when frailty was used for risk adjustment, whereas centers performing the fewest number of vascular procedures and the lowest proportion of vascular surgery cases annually (Quartile 1) saw a significant worsening of ranking position (all P < 0.05). However, total number of surgical procedures annually, total hospital beds, for-profit status, and teaching hospital status were not significantly associated with changes in rank. CONCLUSIONS: A simple frailty-adjusted model has similar predictive abilities as a comorbidity-focused model for predicting a common quality metric that influences reimbursement. In addition to distilling the risk-adjustment algorithm to a few variables, frailty can be assessed preoperatively to develop quality improvement efforts for rescuing frail patients. Centers treating a greater proportion of frail patients and those who perform higher volumes of vascular surgery benefit from a risk adjustment strategy based on frailty.

Trends in annual open abdominal aortic surgical volumes for vascular trainees compared with annual national volumes in the endovascular era.

OBJECTIVE: A prior analysis predicted a shortfall in open abdominal aortic repair (OAR) experience for vascular trainees resulting from the rapid adoption, and increased anatomic suitability, of endovascular aortic aneurysm repair (EVAR) technology. We explored how EVAR has transformed contemporary open aortic surgical education for vascular trainees. METHODS: We examined the Accreditation Council for Graduate Medical Education case volumes of open abdominal aortic aneurysm (AAA) repair and reconstruction for aortoiliac occlusive disease via aortoiliac or femoral bypass (AFB) from integrated vascular surgery residents (VSRs) and fellows (VSFs) graduating from 2006 to 2017 and compared them to the national estimates of total OAR (open AAA repair plus AFB) in the Agency for Healthcare Research and Quality National Inpatient Sample using the International Classification of Diseases, 9th and 10th revision, procedural codes. Changes over time were assessed using the χ2 test, Student's t test, and linear regression. RESULTS: During the 12-year study period, the national annual total OAR and open AAA repair estimates had decreased: total OAR by 72.5% (estimate ± standard error: 2006, 24,255 ± 1185; vs 2017, 6690 ± 274; P < .001) and open AAA repair by 84.7% (estimate ± standard error: 2006, 18,619 ± 924; vs 2017, 2850 ± 168; P < .001). The AFB estimates had decreased by 33.0% (P < .001). The percentage of total OAR, open AAA repair, and AFB performed at teaching hospitals had significantly increased, from ∼55% to 80% (P < .001 for all). A 40.9% decrease was found for open AAA repairs performed by graduating VSFs (mean, 18.6 vs 11) but only a 6.9% decrease in total OAR cases (mean, 27.6 vs 25.7) owing to increasing AFB volumes (mean, 9.0 vs 14.7). The VSR graduates had consistently logged an average of ∼10 open AAA repairs, with a 31.0% increase in total OARs (mean, 23.2 vs 30.4), again secondary to increasing AFB volumes (mean, 11.4 vs 17.5). Although an absolute decrease was found in open aortic experience for VSFs, the rate of decline for the total OAR case volumes was not significantly different after VSR programs had been established (P = .40). CONCLUSIONS: As the incidence has decreased nationally, the use of OAR has been shifting toward teaching hospitals. Although open AAA procedures for trainees have been declining with the increased use of EVAR, open aortic reconstruction for aortoiliac occlusive disease has been increasing, playing an important role in ensuring that vascular trainees continue to have satisfactory OAR experience sufficient for meeting minimum graduation requirements. Strategies to maintain and maximize the education and experience from these cases should be the top priority for vascular surgery program directors.

CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing's sarcoma.

The post-genomic era has seen many advances in our understanding of cancer pathways, yet resistance and tumor heterogeneity necessitate multiple approaches to target even monogenic tumors. Here, we combine phenotypic screening with chemical genetics to identify pre-messenger RNA endonuclease cleavage and polyadenylation specificity factor 3 (CPSF3) as the target of JTE-607, a small molecule with previously unknown target. We show that CPSF3 represents a synthetic lethal node in a subset of acute myeloid leukemia (AML) and Ewing's sarcoma cancer cell lines. Inhibition of CPSF3 by JTE-607 alters expression of known downstream effectors in AML and Ewing's sarcoma lines, upregulates apoptosis and causes tumor-selective stasis in mouse xenografts. Mechanistically, it prevents the release of newly synthesized pre-mRNAs, resulting in read-through transcription and the formation of DNA-RNA hybrid R-loop structures. This study implicates pre-mRNA processing, and specifically CPSF3, as a druggable target providing an avenue to therapeutic intervention in cancer.

Author Correction: CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing's sarcoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Female sex is independently associated with in-hospital mortality after endovascular aortic repair for ruptured aortic aneurysm.

BACKGROUND: Endovascular aortic repair (EVAR) can treat anatomically compatible ruptured abdominal aortic aneurysms (rAAA), but registry data suggests that women undergo more open abdominal aneurysm repairs than men. We evaluate in-hospital outcomes of EVAR for rAAA by sex. METHODS: The Vascular Quality Initiative (VQI) registry was queried from 2013 to 2019 for rAAA patients treated with EVAR. Univariate analysis was performed with Student's t-test and chi-squared tests. Multivariable logistic regression was then performed to assess the association between female sex and inpatient mortality. RESULTS: A total of 1775 patients were included (23.8% female). Female rAAA patients were older (P< 0.01) and weighed less (P < 0.01). They were less likely to have smoked (P <.0 001) and had lower creatinine (1.29 vs. 1.43, P < 0.01) and hemoglobin (10.7 vs. 11.7, P < 0.01). Women had smaller maximum aortic diameters (74 vs. 66 mm, P < 0.01) and were less likely to have iliac aneurysms (P < 0.001). Women were more likely to have concomitant femoral endarterectomy (8.5% vs. 4.6%, P = 0.03). Despite having no significant difference in complication or reintervention rates, women had higher rates of in-hospital mortality (45.9% vs. 34.5%, P < 0.01). In a logistic regression model for predictors of in-hospital mortality (χ2 < .01), increased age (OR 1.08, P < 0.01), female sex (OR 1.7, P = 0.02), preoperative cardiac arrest (OR 5.29, P < 0.01), concurrent iliac stenting (OR 2.38, P = 0.02), postoperative mesenteric ischemia (OR 2.51, P < 0.01) and postoperative transfusion (OR 1.06, P < 0.01) were independently associated with in-hospital mortality. Increased preoperative hemoglobin was protective (OR 0.89, P < 0.01) CONCLUSIONS: Female sex is independently associated with in-hospital mortality after EVAR for rAAA, suggesting a relationship beyond anatomical, biochemical, and procedural covariates.

The Correlation Between Case Total Work Relative Value Unit, Operative Stress, and Patient Frailty: Retrospective Cohort Study.

OBJECTIVE: Assess the relationships between case total work relative value units (wRVU), patient frailty, and the physiologic stress of surgical interventions. SUMMARY OF BACKGROUND DATA: Surgeon reimbursement is frequently apportioned by wRVU. These subjective, procedure-specific valuations generated by physician survey estimate the intensity and time for typical patient care services. We hypothesized wRVU would not adequately account for patient-specific factors, such as frailty, that modify the required physician work, regardless of procedural complexity. METHODS: Using National and Veterans Affairs Surgical Quality Improvement Programs (2015-2018), we evaluated the correlation between case total wRVU, patient frailty (risk analysis index) and physiologic surgical stress (operative stress score). RESULTS: Of 4,111,371 (86%) cases, the correlation between total wRVU and operative stress was moderate [ρs = 0.587 (95% confidence interval, 0.586-0.587)], but negligible with frailty ρ = 0.177 (95% confidence interval, 0.176-0.178)]. Very high operative stress procedures [n = 34,047 (1%)] generated a mean total wRVU of 55.1 (standard deviation, 12.9), comprising 7%, 2%, and 1% of thoracic, vascular, and general surgical cases, respectively. Very frail patients [n = 152,535 (4%)] accounted for 9% of thoracic, 9% of vascular, 4% of general, 5% of urologic, and 4% of neurologic surgical cases, generating 21.0 (standard deviation, 12.4) mean total wRVU. Some nonfrail patients undergoing low operative stress procedures [n = 60,128 (2%)] nonetheless generated the highest quintile wRVU; these comprised >15% of plastic, gynecologic, and urologic surgical cases. CONCLUSIONS: Surgeon reimbursement correlates with operative stress but not patient frailty. The total wRVU does not adequately reflect patient-specific factors that increase the physician workload required to render optimal care to complex patients.

Cost-effectiveness analysis of ankle-brachial index screening in patients with coronary artery disease to optimize medical management.

INTRODUCTION: Screening for peripheral artery disease (PAD) with the ankle-brachial index (ABI) test is currently not recommended in the general population; however, previous studies advocate screening in high-risk populations. Although providers may be hesitant to prescribe low-dose rivaroxaban to patients with coronary artery disease (CAD) alone, given the reduction in cardiovascular events and death associated with rivaroxaban, screening for PAD with the ABI test and accordingly prescribing rivaroxaban may provide additional benefits. We sought to describe the cost-effectiveness of screening for PAD in patients with CAD to optimize this high-risk populations' medical management. METHODS: We used a Markov model to evaluate the ABI test in patients with CAD. We assumed that all patients screened would be candidates for low-dose rivaroxaban. We assessed the cost of ABI screening at $100 per patient and added additional charges for physician visits ($100) and rivaroxaban cost ($470 per month). We used a 30-day cycle and performed analysis over 35 years. We evaluated quality-adjusted life years (QALYs) from previous studies and determined the incremental cost-effectiveness ratio (ICER) according to our model. We performed a deterministic and probabilistic sensitivity analyses of variables with uncertainty and reported them in a Tornado diagram showing the variables with the greatest effect on the ICER. RESULTS: Our model estimates decision costs to screen or not screen at $94,953 and $82,553, respectively. The QALYs gained from screening was 0.060, generating an ICER of $207,491 per QALY. Factors most influential on the ICER were the reduction in all-cause mortality associated with rivaroxaban and the prohibitively high cost of rivaroxaban. If rivaroxaban cost less than $95 per month, this would make screening cost-effective based on a willingness to pay threshold of $50,000 per QALY. CONCLUSIONS: According to our model, screening patients with CAD for PAD to start low-dose rivaroxaban is not currently cost-effective due to insufficient reduction in all-cause mortality and high medication costs. Nevertheless, vascular surgeons have a unique opportunity to prescribe or advocate for low-dose rivaroxaban in patients with PAD to improve cardiovascular outcomes.

Intraoperative heparin use is associated with reduced mortality without increasing hemorrhagic complications after thoracic endovascular aortic repair for blunt aortic injury.

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) is an effective treatment of blunt thoracic aortic injury (BTAI). However, the risks and benefits of administering intraoperative heparin in trauma patients are not well-defined, especially with regard to bleeding complications. METHODS: The Vascular Quality Initiative registry was queried from 2013 to 2019 to identify patients who had undergone TEVAR for BTAI with or without the administration of intraoperative heparin. Univariate analyses were performed with the Student t test, Fisher exact test, or χ2 test, as appropriate. Multivariable logistic regression was then performed to assess the association of heparin with inpatient mortality. RESULTS: A total of 655 patients were included, of whom most had presented with grade III (53.3%) or IV (20%) BTAI. Patients receiving heparin were less likely to have an injury severity score (ISS) of ≥15 (70.2% vs 90.5%; P < .0001) or major head or neck injury (39.6% vs 62.9%; P < .0001). Patients receiving heparin also had a lower incidence of inpatient death (5.1% vs 12.9%; P < .01). Across all injury grades, heparin use was not associated with the need for intraoperative transfusion or postoperative transfusion or the development of hematoma. In patients with grade III BTAI, the nonuse of heparin was associated with an increased risk of lower extremity embolization events (7.4% vs 1.8%; P < .05). On multivariable logistic regression analysis for inpatient mortality, intraoperative heparin use (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.11-0.86; P < .05) and female gender (OR, 0.11; 95% CI, 0.11-0.86; P < .05) were associated with better survival, even after controlling for head and neck trauma and injury grade. In contrast, increased age (OR, 1.06; 95% CI, 1.03-1.1; P < .001), postoperative transfusion (OR, 1.06; 95% CI, 1.02-1.11; P < .01), higher ISS (OR, 1.04; 95% CI, 1.01-1.07; P < .05), postoperative dysrhythmia (OR, 4.48; 95% CI, 1.10-18.18; P < .05), and postoperative stroke or transient ischemic attack (OR, 5.54; 95% CI, 1.11-27.67; P < .05) were associated with increased odds of inpatient mortality. CONCLUSIONS: Intraoperative heparin use was associated with reduced inpatient mortality for patients undergoing TEVAR for BTAI, including those with major head or neck trauma and high ISSs. Heparin use did not increase the risk of hemorrhagic complications across all injury grades. Also, in patients with grade III BTAI, heparin use was associated with a reduced risk of lower extremity embolic events. Heparin appears to be safe during TEVAR for BTAI and should be administered when no specific contraindication exists.

Discovery of a ZIP7 inhibitor from a Notch pathway screen.

The identification of activating mutations in NOTCH1 in 50% of T cell acute lymphoblastic leukemia has generated interest in elucidating how these mutations contribute to oncogenic transformation and in targeting the pathway. A phenotypic screen identified compounds that interfere with trafficking of Notch and induce apoptosis via an endoplasmic reticulum (ER) stress mechanism. Target identification approaches revealed a role for SLC39A7 (ZIP7), a zinc transport family member, in governing Notch trafficking and signaling. Generation and sequencing of a compound-resistant cell line identified a V430E mutation in ZIP7 that confers transferable resistance to the compound NVS-ZP7-4. NVS-ZP7-4 altered zinc in the ER, and an analog of the compound photoaffinity labeled ZIP7 in cells, suggesting a direct interaction between the compound and ZIP7. NVS-ZP7-4 is the first reported chemical tool to probe the impact of modulating ER zinc levels and investigate ZIP7 as a novel druggable node in the Notch pathway.

Gender Disparity in Surgical Society Leadership and Annual Meeting Programs.

INTRODUCTION: Prior work suggests women surgical role models attract more female medical students into surgical training. We investigate recent trends of women in surgical society leadership and national conference moderator and plenary speaker roles. METHODS: Gender distribution was surveyed at 15 major surgical societies and 14 conferences from 2014 to 2018 using publicly reported data. Roles were categorized as leadership (executive council), moderator, or plenary speaker. Data were cross-checked from online profiles and by contacting societies. Logistic regression with Huber-White clustering by society was utilized to evaluate proportions of women in each role over time and determine associations between the proportion of women in executive leadership, and scientific session moderators and plenary speakers. RESULTS: The proportion of leadership positions held by women increased slightly from 2014 to 2018 (20.6%-26.6%, P = 0.23), as did the proportion of moderators (26.2%-30.6%, P = 0.027) and plenary speakers (26.2%-30.9%, P = 0.058). The proportion of women in each role varied significantly across societies (all P < 0.001): leaders (range 0.0%-52.0%), moderators (12.5%-58.8%), and plenary speakers (11.3%-60.0%). Three patterns of change were observed: eight societies (53.3%) demonstrated increases in representation of women over time, four societies (26.6%) showed stable moderate-to-good gender balance, and three societies (20.0%) had consistent underrepresentation of women. CONCLUSION: There is significant variability in the representation of women at the leadership level of national surgical societies and participating at national surgical conferences as moderators and plenary speakers. Over the past 5 years some societies have achieved advances in gender equity, but many societies still have substantial room for improvement.

Contemporary Practices and Complications of Surgery for Thoracic Outlet Syndrome in the United States.

BACKGROUND: Thoracic outlet syndrome (TOS) surgery is relatively rare and controversial, given the challenges in diagnosis as well as wide variation in symptomatic and functional recovery. Our aims were to measure trends in utilization of TOS surgery, complications, and mortality rates in a nationally representative cohort and compare higher versus lower volume centers. METHODS: The National Inpatient Sample was queried using International Classification of Diseases, Ninth Revision, codes for rib resection and scalenectomy paired with axillo-subclavian aneurysm (arterial [aTOS]), subclavian deep vein thrombosis (venous [vTOS]), or brachial plexus lesions (neurogenic [nTOS]). Basic descriptive statistics, nonparametric tests for trend, and multivariable hierarchical regression models with random intercept for center were used to compare outcomes for TOS types, trends over time, and higher and lower volume hospitals, respectively. RESULTS: There were 3,547 TOS operations (for an estimated 18,210 TOS operations nationally) performed between 2010 and 2015 (89.2% nTOS, 9.9% vTOS, and 0.9% aTOS) with annual case volume increasing significantly over time (P = 0.03). Higher volume centers (≥10 cases per year) represented 5.2% of hospitals and 37.0% of cases, and these centers achieved significantly lower overall major complication (defined as neurologic injury, arterial or venous injury, vascular graft complication, pneumothorax, hemorrhage/hematoma, or lymphatic leak) rates (adjusted odds ratio [OR] 0.71 [95% confidence interval 0.52-0.98]; P = 0.04], but no difference in neurologic complications such as brachial plexus injury (aOR 0.69 [0.20-2.43]; P = 0.56) or vascular injuries/graft complications (aOR 0.71 [0.0.33-1.54]; P = 0.39). Overall mortality was 0.6%, neurologic injury was rare (0.3%), and the proportion of patients experiencing complications decreased over time (P = 0.03). However, vTOS and aTOS had >2.5 times the odds of major complication compared with nTOS (OR 2.68 [1.88-3.82] and aOR 4.26 [1.78-10.17]; P < 0.001), and ∼10 times the odds of a vascular complication (aOR 10.37 [5.33-20.19] and aOR 12.93 [3.54-47.37]; P < 0.001], respectively. As the number of complications decreased, average hospital charges also significantly decreased over time (P < 0.001). Total hospital charges were on average higher when surgery was performed in lower volume centers (<10 cases per year) compared with higher volume centers (mean $65,634 [standard deviation 98,796] vs. $45,850 [59,285]; P < 0.001). CONCLUSIONS: The annual number of TOS operations has increased in the United States from 2010 to 2015, whereas complications and average hospital charges have decreased. Mortality and neurologic injury remain rare. Higher volume centers delivered higher value care: less or similar operative morbidity with lower total hospital charges.

Racial and Sex Disparities in Catheter Use and Dialysis Access in the United States Medicare Population.

BACKGROUND: Despite efforts to increase arteriovenous fistula and graft use, 80% of patients in the United States start hemodialysis on a central venous catheter (CVC). METHODS: To better understand in incident hemodialysis patients how sex and race/ethnicity are associated with time on a central venous catheter and transition to an arteriovenous fistula and graft, our observational cohort study analyzed US Renal Data System data for patients with incident ESKD aged ≥66 years who started hemodialysis on a CVC in July 2010 through 2013. RESULTS: At 1 year, 32.7% of 74,194 patients transitioned to an arteriovenous fistula, 10.8% transitioned to an arteriovenous graft, 32.1% stayed on a CVC, and 24.5% died. Women spent a significantly longer time on a CVC than men. Compared with white patients, patients who were black, Hispanic, or of another racial/ethnicity minority spent significantly more days on a CVC. In competing risk regression, women were significantly less likely than men to transition to a fistula and more likely to transition to a graft. Compared with white patients, blacks were significantly less likely to transition to a fistula but more likely to transition to a graft, Hispanics were significantly more likely to transition to a fistula, and other races/ethnicities were significantly more likely to transition to either a fistula or a graft. CONCLUSIONS: Female patients spend a longer time on a CVC and are less likely to transition to permanent access. Compared with white patients, minorities also spend longer time on a CVC, but are more likely to eventually transition to permanent access. Strategies to speed transition to permanent access should target groups that currently lag in this area.

Frailty as measured by the Risk Analysis Index is associated with long-term death after carotid endarterectomy.

OBJECTIVE: The role of carotid endarterectomy (CEA) continues to be debated in the age of optimal medical therapy, particularly for patients with limited life expectancy. The Risk Analysis Index (RAI) measures frailty, a syndrome of decreased physiologic reserve, which increases vulnerability to adverse outcomes. The RAI better predicts surgical complications, nonhome discharge, and death than age or comorbidities alone. We sought to measure the association of frailty, as measured by the RAI, with postoperative in-hospital stroke, long-term stroke, and long-term survival after CEA. We also sought to determine how postoperative stroke interacts with frailty to alter survival trajectory after CEA. METHODS: We queried the Vascular Quality Initiative CEA procedure and long-term data sets (2003-2017) for elective CEAs with complete RAI case information. For all analyses, the cohort was divided into asymptomatic and symptomatic carotid stenosis. Scoring was defined as not frail (RAI <30), frail (RAI 30-34), and very frail (RAI ≥35). Mortality information through December 2017 was obtained from the Social Security Death Index. Multivariable models (logistic and Cox proportional hazards regressions) were used to study the association of frail and very frail patients with the outcomes of interest. In a post hoc analysis, we created Kaplan-Meier curves to analyze patient mortality after CEA as well as after postoperative stroke. RESULTS: Of the 42,869 included patients, 17,092 (39.9%) were female, and 38,395 (89.6%) were white. There were 25,673 (59.9%) patients assigned to the asymptomatic stenosis group and 17,196 (40.1%) patients in the symptomatic stenosis group. Frailty was not associated with perioperative or long-term postoperative stroke. The risk of long-term mortality was significantly higher for frail (hazard ratio, 1.9 [1.7-2.3]) and very frail (hazard ratio, 3.1 [2.6-3.7]) asymptomatic patients; symptomatic frail and very frail patients also had a two to three times increased risk of long-term mortality. Frail and very frail patients had two to three times the risk for long-term mortality compared with patients who were not frail. Postoperative stroke negatively affected the mortality trajectory for all patients in the cohort, regardless of frailty status. CONCLUSIONS: RAI score is not associated with postoperative stroke; however, frail and very frail status is associated with decreased long-term survival in an incremental fashion based on increasing RAI. RAI assessment should be considered in the preoperative decision-making for patients undergoing CEA to ensure long-term survival and optimal surgical outcomes vs medical management.

Variation in center-level frailty burden and the impact of frailty on long-term survival in patients undergoing elective repair for abdominal aortic aneurysms.

OBJECTIVE: Frailty is increasingly recognized as a key determinant in predicting postoperative outcomes. Centers that see more frail patients may not be captured in risk adjustment, potentially accounting for poorer outcomes in hospital comparisons. We aimed to (1) determine the effect of frailty on long-term mortality in patients undergoing elective abdominal aortic aneurysm (AAA) repair and (2) evaluate the variability in frailty burden among centers in the Vascular Quality Initiative (VQI) database. METHODS: Patients undergoing elective open and endovascular AAA repair (2003-2017) were identified, and those with complete data on component variables of the VQI-derived Risk Analysis Index (VQI-RAI) and centers with ≥10 AAA repairs were included. VQI-RAI characteristics are sex, age, body mass index, renal failure, congestive heart failure, dyspnea, preoperative ambulation, and functional status. Frailty was defined as VQI-RAI ≥35 based on prior work in surgical patients using other quality improvement databases. This corresponds to the top 12% of patients at risk in the VQI. Center-level VQI-RAI differences were assessed by analysis of variance test. Relationships between frailty and survival were compared by Kaplan-Meier analysis and the log-rank test for open and endovascular procedures. Multivariable hierarchical Cox proportional hazards regression models were calculated with random intercepts for center, controlling for frailty, race, insurance, AAA diameter, procedure type, AAA case mix, and year. RESULTS: A total of 15,803 patients from 185 centers were included. Mean VQI-RAI scores were 27.6 (standard deviation, 5.9; range, 4-56) and varied significantly across centers (F = 2.41, P < .001). The percentage of frail patients per center ranged from 0% to 40.0%. In multivariable analysis, frailty was independently associated with long-term mortality (hazard ratio, 2.88; 95% confidence interval, 2.6-3.2) after accounting for covariates and center-level variance. Open AAA repair was not associated with long-term mortality after adjusting for frailty (hazard ratio, 0.98; 95% confidence interval, 0.86-1.13). There was a statistically significant difference in the percentage of frail patients compared with nonfrail patients who were discharged to a rehabilitation facility or nursing home after both open (40.5% vs 17.8%; P < .0001) and endovascular repair (17.7% vs 4.6%; P < .0001). CONCLUSIONS: There is considerable variability of preoperative frailty among VQI centers performing elective AAA repair. Adjusting for center-level variation, frailty but not procedure type had a significant association with long-term mortality; however, frailty and procedure type were both associated with nonhome discharge. Routine measurement of frailty preoperatively by centers to identify high-risk patients may help mitigate procedural and long-term outcomes and improve shared decision-making regarding AAA repair.

Comparison of Surgeon Assessment to Frailty Measurement in Abdominal Aortic Aneurysm Repair.

BACKGROUND: Endovascular abdominal aortic aneurysm repair (EVAR) allows us to intervene on patients otherwise considered poor candidates for open repair. Despite its importance in determining operative approach, no comparison has been made between the subjective "eyeball test" and an objective measurement of preoperative frailty for EVAR patients. MATERIALS AND METHODS: Patients undergoing elective EVAR were identified in the Vascular Quality Initiative (VQI) database (2003-2017). Patients were classified "unfit" based on a surgeon-reported variable. Frailty was defined using the VQI-derived Risk Analysis Index, which includes sex, age, BMI, renal failure, congestive heart failure, dyspnea, preoperative ambulation, and functional status. The association between fitness and/or frailty and adverse outcomes was determined by logistic regression. RESULTS: A total of 11,694 patients undergoing elective EVAR were included of which only 18.1% were "unfit," whereas 34.6% were "frail" and overall 43.6% "unfit or frail." Patients deemed "unfit" or "frail" had significantly increased odds of mortality, complications, and nonhome discharge (P < 0.001), and both frailty and unfitness generated negative predictive values for these outcomes greater than 93%. In adjusted logistic regression, the addition of objective frailty significantly improved model performance in predicting nonhome discharge (C-statistic 0.65 versus 0.71, P < 0.001) and complications (0.59 versus 0.61, P = 0.01), but similarly predicted mortality (0.74 versus 0.73, P = 0.99). CONCLUSIONS: Preoperative frailty assessment provides a useful objective measure of risk stratification as an adjunct to a physician's clinical intuition. The addition of frailty expands the pool of high-risk patients who are more likely to experience adverse postoperative events after elective EVAR and may benefit from uniquely tailored perioperative interventions.