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The antitubulin drugs, paclitaxel (PX) and colchicine (COL), inhibit cell growth and are therapeutically valuable. PX stabilizes microtubules, while COL promotes their depolymerization. But, the drug concentrations that alter tubulin polymerization are hundreds of times higher than their clinically useful levels. To map genetic targets for drug action at single-gene resolution, we used a human radiation hybrid panel. We identified loci that affected cell survival in the presence of five compounds of medical relevance. For PX and COL, the zinc and ring finger 3 (ZNRF3) gene dominated the genetic landscape at therapeutic concentrations. ZNRF3 encodes an R-spondin regulated receptor that inhibits Wingless/Int (Wnt) signaling. Overexpression of the ZNRF3 gene shielded cells from antitubulin drug action, while small interfering RNA knockdowns resulted in sensitization. Further a potent pharmacological inhibitor of Wnt signaling, Wnt-C59, protected cells from PX and COL. Our results suggest that the antitubulin drugs perturb microtubule dynamics, thereby influencing Wnt signaling.

Introduction: Firearm-related injuries (FRIs) are serious but a preventable public health issue. The objective of this study was to describe FRI inpatient costs by (1) patient insurance payer type and (2) hospital safety-net mix., Methods: FRIs were identified using International Classification of Disease diagnosis codes in the National Inpatient Sample. All admissions between 2003 and 2020 were included. The primary outcome was consumer-price index adjusted inpatient stay costs. Mixed effects generalized linear regressions, with a random intercept at the hospital level, were used to describe costs. Analyses were sample weighted and performed between 2023 and 2024., Results: Among 538,795 FRIs, the median age was 27 years (interquartile range: 21-37 years). Injuries by payer type were highest among self-pay (280,161; 39%), followed by Medicaid (182,716; 34%), private (113,650; 21%), and Medicare (30,110; 6%). Inflation-adjusted costs of FRI stays totaled $15.2 billion, with $6.2 billion from Medicaid and $5 billion from the self-pay group. After 2014, FRI incidence declined among self-pay/no-charge patients and increased among Medicaid-covered patients-representing a 127% total increase in Medicaid costs from $169 million in 2003 to $753 million in 2020. Among moderate-high and high safety-net mix hospitals, costs increased from $257 million in 2003 to $567 million in 2020., Conclusions: The incidence and costs of FRIs among Medicaid-insured has substantially increased since 2003. Importantly, these increased costs are disproportionately placed on disadvantaged patients and safety-net hospitals., (Published by Elsevier Inc.)

Background: Transcatheter aortic valve replacement has become an accepted alternative to surgical aortic valve replacement. We examined the trends and predictors in inflation-adjusted costs of transcatheter aortic valve replacement and surgical aortic valve replacement., Methods: National Inpatient Sample identified patients who underwent aortic valve replacement for severe aortic stenosis by International Classification of Diseases, Ninth and Tenth Revisions, codes. Hospitalization costs were inflation-adjusted using the Federal Reserve's consumer price index to reflect current valuation. Outcomes of interest were unadjusted trend in annual cost for each procedure and predictors of in-patient cost. Generalized linear models with a log link function identified predictors of adjusted costs. Interaction terms determined where cost predictors were different by operation type., Results: Between 2011 and 2019, the mean annual inflation-adjusted cost of surgical aortic valve replacement increased from $62,853 to $63,743, in contrast to decreasing cost of transcatheter aortic valve replacement from $64,913 to $56,042 ($1,854 per year; P = .004). Significant independent predictors of patient-level cost included operation type (transcatheter aortic valve replacement associated with $9,625 increase; P < .001), incidence of in-hospital mortality ($28,836 increase; P < .001), elective status ($2,410 decrease; P < .001), Elixhauser Index ($995 increase; P < .001), and postoperative length of stay ($2,014 per day increase; P < .001). Compared to discharges with Medicare, discharges with private insurance and Medicaid paid $736 less (P = .004) and $1,863 less (P = .01), respectively. Increasing hospital volume was a significant predictor of decreasing patient level cost (P < .001)., Conclusion: Annual cost of transcatheter aortic valve replacement has decreased significantly and has been a more cost-effective modality compared to surgical aortic valve replacement since 2017. Predictors of patient-level costs allow for mindful preparation of healthcare systems for aortic valve replacement., (Published by Elsevier Inc.)

Background: Previous studies report that patients of racial/ethnic minorities more frequently present with ruptured abdominal aortic aneurysms (rAAAs) than their counterparts. The distribution of rAAA treatment modality, whether open aneurysm repair (OAR) or endovascular aneurysm repair (EVAR), by race/ethnicity classification remains uncertain. This study aims to investigate disparities, as represented by race/ethnic classification, median income, and insurance status, in the management of rAAA in a national cohort., Methods: We conducted a retrospective analysis of patients admitted with rAAA managed with either OAR or EVAR from 2002 to 2020 using the National Inpatient Sample, comparing repair type by race/ethnicity group. Multilevel mixed effects logistic regression models, adjusted for patient- and system-level factors, were used to calculate difference in use of OAR or EVAR dependent on race/ethnicity classification., Results: We identified 10,788 admissions for rAAA repairs, of which 9506 (88.1%) were White, 605 (5.6%) were Black, 424 (3.9%) were Hispanic, and 253 (2.4%) were Asian/Native American. Asians/Native Americans underwent the highest frequency of OAR as compared with EVAR (61.7% vs 38.3%). In the adjusted model, there was no statistically significant difference in the use of OAR vs EVAR by race/ethnicity classification. In total, primary payer and median income were also not statistically significant predictors of AAA treatment modality., Conclusions: Our study found no statistical evidence of disparities with respect to race, insurance, or median income and use of OAR or EVAR for the management of rAAA., Competing Interests: Disclosures None., (Published by Elsevier Inc.)

Objective: Observational studies demonstrate reduced mortality after endovascular (EVAR) compared with open aneurysm repair (OAR) for ruptured abdominal aortic aneurysms (rAAAs). We sought to determine national trends in repair type and in-hospital mortality rates for rAAAs., Methods: We analyzed patients with rAAAs managed with OAR or EVAR from 2002 to 2020 in the National Inpatient Sample and evaluated annual trends in volume and in-hospital mortality by repair type. Multilevel mixed effects logistic regression model was fit for patient and system-level risk adjustment. We assessed interactions between time, sex, and Elixhauser index with repair type., Results: We examined 13,376 patients with rAAAs. Of these, 8357 (62.5%) underwent OAR. Patients receiving EVAR were slightly older (73.7 vs 72.5 years; P < .001) with slightly higher mean Elixhauser index (4.0 vs 3.8; P < .001). Unadjusted in-hospital mortality was 37.4% vs 22.4% for OAR and EVAR, respectively. EVAR offered a risk-adjusted survival advantage (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.32-0.46). There was a statistically significant reduction of in-hospital mortality over time in the EVAR group (interaction OR, 0.96; 95% CI, 0.95-0.98). The interaction between Elixhauser index and repair was not statistically significant (interaction OR, 0.95; 95% CI, 0.87-1.05)., Conclusions: Survival rates for OAR and EVAR improved over time. EVAR persistently provided a substantial survival advantage over OAR in patients with rAAAs over the past 2 decades., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. All rights reserved.)

Objective: The objective of this study was to compare postoperative 90-day mortality between (1) fully vaccinated patients with COVID-19-positive and negative diagnosis, and (2) vaccinated and unvaccinated patients with COVID-19 positive diagnosis., Background: Societal guidelines recommend postponing elective operations for at least 7 weeks in unvaccinated patients with preoperative coronavirus disease 2019 (COVID-19) infection. The role of vaccination in this infection-operation time risk is unclear., Methods: We conducted a national US multicenter retrospective, matched cohort study spanning July 2021 to October 2022. Participants were included if they underwent a high-risk general, vascular, orthopedic, neurosurgery, or genitourinary surgery. All-cause mortality occurring within 90 days of the index operation was the primary outcome. Inverse probability treatment weighted propensity scores were used to adjust logistic regression models examining the independent and interactive associations between mortality, exposure status, and infection proximity., Results: Of 3401 fully vaccinated patients in the 8-week preoperative period, 437 (12.9%) were COVID-19-positive. Unadjusted mortality rates were not significantly different between vaccinated patients with COVID-19 (22, 5.0%) and vaccinated patients without COVID-19 (99, 3.3%; P = 0.07). After inverse probability treatment weighted adjustment, mortality risk was not significantly different between vaccinated COVID-19-positive patients compared to vaccinated patients without COVID-19 (adjusted odds ratio = 1.38, 95% CI: 0.70, 2.72). The proximity of COVID-19 diagnosis to the index operation did not confer added mortality risk in either comparison cohort., Conclusions: Contrary to risks observed among unvaccinated patients, postoperative mortality does not differ between patients with and without COVID-19 when vaccinated against the severe acute respiratory syndrome coronavirus 2 virus and receiving a high-risk operation within 8 weeks of the diagnosis, regardless of operation timing relative to diagnosis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The need for right ventricular outflow tract reconstruction is common and growing in congenital heart surgery given expanding indications for the repair of congenital as well as acquired heart disease. Various valved conduit options currently exist including homografts, xenograft pulmonary valved conduits (Contegra™), and porcine valved conduits. The major limitation for all conduits is implant durability, which requires reoperation. Currently, cryopreserved homografts are often used given their superiority shown in long-term data. Significant limitations remain in the cost and availability of the graft, particularly for smaller sizes. Contegra conduits are available in a variety of sizes. Nonetheless, the data regarding long-term durability are less robust and studies comparing durability with homografts have been conflicting. Additionally, there is concern for increased rates of late endocarditis in this conduit. Porcine valved conduits offer a reliable option but are limited by structural valve degeneration associated with all types of bioprosthetic heart valve replacements. New developments in the field of tissue engineering have produced promising bio-restorative valved conduits that may overcome many of the limitations of previous conduit technologies. These remain in the early stages of clinical testing. This review summarizes the clinical data surrounding the conduits used most commonly in clinical practice today and explores emerging technologies that may bring us closer to developing the ideal conduit., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Vasospasm following aneurysmal subarachnoid hemorrhage (SAH) contributes significant morbidity and mortality after brain aneurysm rupture. However, the association between vascular territory of vasospasm and clinical outcome has not been studied. We present a hypothesis-generating study to determine whether the location of vasospasm within the intracranial circulation is associated with functional outcome after SAH., Methods: A retrospective analysis of a prospective, intention-to-treat trial for aneurysmal SAH was performed to supplement trial outcomes with in-hospital angiographic imaging and treatment variables regarding vasospasm. The location of vasospasm and the position on the vessel (distal vs proximal) were evaluated. Modified Rankin scale (mRS) outcomes were assessed at discharge and 6 months, and predictive models were constructed., Results: A total of 406 patients were included, 341 with follow-up data at 6 months. At discharge, left-sided vasospasm was associated with poor outcome (odds ratio (OR), 2.37; 95% CI, 1.25 to 4.66; P=0.01). At 6 months, anterior cerebral artery (ACA) vasospasm (OR, 3.87; 95% CI, 1.29 to 11.88; P=0.02) and basilar artery (BA) vasospasm (OR, 6.22; 95% CI, 1.54 to 27.11; P=0.01) were associated with poor outcome after adjustment. A model predicting 6-month mRS score and incorporating vasospasm variables achieved an area under the curve of 0.85 and a net improvement in reclassification of 13.2% (P<0.01) compared with a previously validated predictive model for aneurysmal SAH., Conclusions: In aneurysmal SAH, left-sided vasospasm is associated with worse discharge functional status. At 6 months, both ACA and BA vasospasm are associated with unfavorable functional status., Competing Interests: Competing interests: AFD is a consultant for Medtronic (Dublin, Ireland), Penumbra (Alameda, CA), Cerenovus (Johnson & Johnson, New Brunswick, NJ), Stryker (Kalamazoo, MI), Koswire (Flowery Branch, GA), and Oculus (Menlo Park, CA). AFD also has an ownership interest in Aneuvas Technologies, Inc. (Flagstaff, AZ). FCA and AFD are on the editorial board of Journal of NeuroInterventional Surgery., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The clinical impact of vascular invasion in Papillary Thyroid Carcinoma (PTC) is not well understood. Our aim was to determine if there was an association between vascular invasion and other tumor characteristics and patient outcomes in PTC., Methods: A retrospective chart review was performed of 536 patients with PTC between January 2007-December 2011. Patient demographics, comorbidities, tumor characteristics, and outcomes were collected., Results: Vascular invasion was associated with lymphatic invasion, capsular invasion, extrathyroidal extension, and the presence of positive lymph nodes. Logistic regression revealed that tumor size was a predictor of vascular invasion. Vascular invasion in PTC tumors was associated with higher tumor recurrence rates, but there were no differences in mortality., Conclusion: This study indicates that vascular invasion in PTC is associated with other aggressive pathologic features and an increased recurrence rate. For these reasons, vascular invasion should be an important tumor characteristic when determining extent of treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)