Real World Application of WIfI Scores in Peripheral Arterial Disease Patients.

OBJECTIVE: The Society for Vascular Surgery wound, ischemia, and foot infection (WIfI) classification system aims to risk stratify patients with chronic limb threatening ischemia (CLTI), predicting both amputation rates and the need for revascularization. However, real-world utilization of the system and whether it accurately predicts outcomes following open revascularization and peripheral interventions is unclear. Therefore, we sought to determine the adoption of the WIfI classification system within a contemporary statewide collaborative as well as the impact of patient factor, and WIfI risk assessment on short- and long-term outcomes. METHODS: Using data from a large statewide collaborative, we identified patients with CLTI undergoing open surgical revascularization or peripheral vascular intervention (PVI) between 2016 - 2022. The primary exposure was preoperative clinical WIfI stage. Patients were categorized according to the SVS Lower Extremity Threatened Limb Classification System into clinical WIfI stages1, 2, 3, or 4. The primary outcomes were 30-day and 1-year amputation and mortality. Multivariable logistic regression was performed to estimate the association of WIfI stage on post-revascularization outcomes. RESULTS: In the cohort of 17,417 patients, 83.4% (n=14,529) had WIfI stage documented. Peripheral vascular interventions (PVIs) were performed on 57.6% of patients, and 42.4% underwent an open surgical revascularization (OSR). 49.5% of patients were classified as stage 1, 19.3% stage 2, 12.8% stage 3 and 18.3% of patients met stage 4 criteria. Stage 3 and 4 patients had higher rates of diabetes, congestive heart failure, and renal failure, and were less likely to be current or former smokers. One-half of stage 3 patients underwent OSR, while stage 1 patients were most likely to have received a PVI (64%). As WIfI stage increased from 1 to 4, 1-year mortality increased from 12% to 21% (p<0.001), 30-day amputation rates increased from 5% to 38% (p<0.001), and 1-year amputation rates increased from 15% to 55% (p<0.001). Finally, patients who did not have WIfI scores classified had significantly higher 30-day and 1-year mortality, as well as higher 30-day and 1-year amputation rates. CONCLUSION: The Society for Vascular Surgery WIfI clinical stage is significantly associated with 1-year amputation rates in patients with CLTI following lower extremity revascularization. As nearly 55% of stage 4 patients require a major amputation within one year of intervention, this study supports use of the WIfI classification system in clinical decision making for patients with CLTI.

Developmental or Procedural Vena Cava Interruption and Venous Thromboembolism: A Review.

The inferior vena cava (IVC) and superior vena cava are the main conduits of the systemic venous circulation into the right atrium. Developmental or procedural interruptions of vena cava might predispose to stasis and deep vein thrombosis (DVT) distal to the anomaly and may impact the subsequent rate of pulmonary embolism (PE). This study aimed to review the various etiologies of developmental or procedural vena cava interruption and their impact on venous thromboembolism. A systematic search was performed in PubMed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines per each clinical question. For management questions with no high-quality evidence and no mutual agreements between authors, Delphi methods were used. IVC agenesis is the most common form of congenital vena cava interruption, is associated with an increased risk of DVT, and should be suspected in young patients with unexpected extensive bilateral DVT. Surgical techniques for vena cava interruption (ligation, clipping, and plication) to prevent PE have been largely abandoned due to short-term procedural risks and long-term complications, although survivors of prior procedures are occasionally encountered. Vena cava filters are now the most commonly used method of procedural interruption, frequently placed in the infrarenal IVC. The most agreed-upon indication for vena cava filters is for patients with acute venous thromboembolism and coexisting contraindications to anticoagulation. Familiarity with different forms of vena cava interruption and their local and systemic adverse effects is important to minimize complications and thrombotic events.

Venous Thromboembolism: Review of Clinical Challenges, Biology, Assessment, Treatment, and Modeling.

Venous thromboembolism (VTE) is a massive clinical challenge, annually affecting millions of patients globally. VTE is a particularly consequential pathology, as incidence is correlated with extremely common risk factors, and a large cohort of patients experience recurrent VTE after initial intervention. Altered hemodynamics, hypercoagulability, and damaged vascular tissue cause deep-vein thrombosis and pulmonary embolism, the two permutations of VTE. Venous valves have been identified as likely locations for initial blood clot formation, but the exact pathway by which thrombosis occurs in this environment is not entirely clear. Several risk factors are known to increase the likelihood of VTE, particularly those that increase inflammation and coagulability, increase venous resistance, and damage the endothelial lining. While these risk factors are useful as predictive tools, VTE diagnosis prior to presentation of outward symptoms is difficult, chiefly due to challenges in successfully imaging deep-vein thrombi. Clinically, VTE can be managed by anticoagulants or mechanical intervention. Recently, direct oral anticoagulants and catheter-directed thrombolysis have emerged as leading tools in resolution of venous thrombosis. While a satisfactory VTE model has yet to be developed, recent strides have been made in advancing in silico models of venous hemodynamics, hemorheology, fluid-structure interaction, and clot growth. These models are often guided by imaging-informed boundary conditions or inspired by benchtop animal models. These gaps in knowledge are critical targets to address necessary improvements in prediction and diagnosis, clinical management, and VTE experimental and computational models.

Natural history of visceral branch artery dissections and the influence of concurrent aortic dissection on overall and intervention-free survival.

OBJECTIVE: Visceral branch artery dissection (VBAD) is uncommon and may occur with or without an associated aortic dissection (AD). We hypothesized that isolated VBAD would have a more benign clinical course than those with concurrent AD and compared survival outcomes stratified based on aortic involvement. METHODS: VBAD over a 5-year period were identified using International Classification of Diseases codes. Data related to patient demographics, comorbid conditions, clinical presentation, management (including procedural interventions), and survival were obtained from medical records. Anatomic imaging studies were reviewed to characterize anatomy, including the presence or absence of concurrent AD. Overall survival and intervention-free survival were evaluated using Kaplan-Meier and Cox proportional hazards models. RESULTS: A total of 299 VBAD were identified, 174 of which were isolated VBAD and 125 were associated with concurrent AD. Seventy-one percent of patients were men, 77% were White, and 85% were non-Hispanic. The mean age was 61.1 ± 14.4 years. The mean follow-up was 53.2 ± 50.0 months. The estimated overall survival was 88.2% and the estimated overall intervention-free survival was 55.6% at 12 months. Isolated VBAD had better overall survival than those with concurrent AD (69.2% vs 32.4%; P < .001). Concurrent AD was also associated with inferior intervention-free survival (57.5% vs 7.3%; P < .001). Acute presentation was associated with decreased intervention-free survival (86.1% vs 13.4%; P < .001). Acute presentation was also associated with decreased overall survival in patients with isolated VBAD (60.8% vs 80.0% at 180 months; P < .001) and inferior intervention-free survival (48.4% vs 69.5% at 180 months; P < .001) in the subgroup of patients with isolated VBAD. Multivariable Cox models identified that age (hazard ratio [HR]: 1.05, standard deviation [SD]: 0.02; P = .001) was associated with inferior survival and renal dissections (HR: 3.08, SD: 0.99; P = .001) or mesenteric and renal dissections (HR: 3.39, SD: 1.44; P = .004) were associated with inferior intervention-free survival. CONCLUSIONS: Isolated VBAD has superior overall and intervention-free survival to those associated with concurrent AD. The absence vs presence of aortic involvement is useful for risk stratification and may support tailored approaches to the frequency of imaging surveillance.

Carotid and Renal Vascular Disease.

This article review covers carotid artery disease, abdominal aortic aneurysm, and atherosclerotic renal artery disease. It overviews each condition's clinical presentation, diagnosis, medical management, and interventional approach. Carotid artery disease is characterized by hemispheric and neuropsychological manifestations, which can help detect this condition. Screening for carotid artery stenosis is recommended in high-risk individuals and can be performed using different methods, with carotid duplex ultrasonography being the preferred option. Carotid endarterectomy and carotid artery stenting are indicated based on specific criteria and patient characteristics. An abdominal aortic aneurysm is often asymptomatic, but abdominal, back, or flank pain may sometimes be present. Ultrasonography is an effective method for screening and monitoring abdominal aortic aneurysms, with high sensitivity and specificity. Smoking cessation is a crucial intervention for preventing further enlargement of small aortic aneurysms. Repair of abdominal aortic aneurysm is recommended based on the aneurysm size, growth rate, and the presence of symptoms. Endovascular repair is preferred when suitable anatomy is present. Atherosclerotic renal artery disease is associated with resistant hypertension, renal failure, and occasionally pulmonary edema. Doppler ultrasonography is a valuable diagnostic tool for detecting it, while the renal resistive index provides additional insights into disease severity and treatment response. Revascularization is not routinely recommended for atherosclerotic renal artery disease, but it may be considered in specific cases, such as renal arterial fibromuscular dysplasia or unexplained congestive heart failure.

A mapping review of Pacific Vascular Symposium 6 initiatives.

OBJECTIVE: The 2010 Pacific Vascular Symposium 6 (PVS6) brought venous disease content experts together with a goal of addressing critical issues collated together in the next decade with concrete plans to achieve these goals. This mapping review aims to provide a broader representation of how progress in critical issues of chronic venous disease has been made by extrapolating scientific publications related to the PVS6 initiatives. METHODS: We performed a mapping review identifying original or systematic review/meta-analysis articles related to PVS 6 initiatives (aims) that addressed one of the following key objectives: scales to measure chronic venous disease, effectiveness of interventional deep venous thrombus removal, development of a deep venous valve, and biomarkers related to venous disease. Searches were undertaken in PubMed, Ovid Medline, Cochrane Library, Embase (Elsevier), CINAHL (EBSCO), and Scopus. We extracted descriptive information about the studies and predefined variables for each specific aim, showing what and where research exists on the aims included. RESULTS: A total of 2138 articles were screened from 3379 retrieved articles from six electronic databases. We mapped 186 included articles, finding that the total number of publications significantly increased after the 2010 PVS6 meeting. Aim results were visually summarized. The largest body of data addressed catheter-based thrombus removal strategies for acute iliofemoral deep venous thrombosis. Primary research on artificial venous valves and venous biomarkers remained limited. No new post-thrombotic syndrome (PTS) score has been developed. CONCLUSIONS: This mapping review identified and characterized the available evidence and gaps in our knowledge of chronic venous disease that exist visually, which may guide where more significant investments for the future should be targeted.

Non-Coronary Atherosclerotic Arterial Disease: Where Are We Now?

Lower extremity peripheral artery and upper extremity artery disease are significant vascular conditions with distinct clinical presentations and diagnostic and therapeutic approaches. The lower extremity peripheral artery is associated with worse major adverse cardiovascular events compared with coronary artery disease, but often remains underdiagnosed and undertreated. Upper extremity artery disease encompasses a range of clinical presentations resulting from atherosclerosis and other obstructive lesions in arteries such as the subclavian artery and brachiocephalic trunk. While atherosclerosis is a common cause, non-atherosclerotic factors can also influence distal lesions. This review aims to synthesize existing knowledge on both conditions, encompassing risk factors, clinical manifestations, diagnostic modalities, and treatment options. Improved awareness and early intervention can mitigate complications and enhance patient outcomes for lower extremity peripheral artery and upper extremity artery disease.

The Histone Methyltransferase SETDB2 Modulates Tissue Inhibitors of Metalloproteinase-Matrix Metalloproteinase Activity During Abdominal Aortic Aneurysm Development.

OBJECTIVE: To determine macrophage-specific alterations in epigenetic enzyme function contributing to the development of abdominal aortic aneurysms (AAAs). BACKGROUND: AAA is a life-threatening disease, characterized by pathologic vascular remodeling driven by an imbalance of matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). Identifying mechanisms regulating macrophage-mediated extracellular matrix degradation is of critical importance to developing novel therapies. METHODS: The role of SET Domain Bifurcated Histone Lysine Methyltransferase 2 (SETDB2) in AAA formation was examined in human aortic tissue samples by single-cell RNA sequencing and in a myeloid-specific SETDB2 deficient murine model induced by challenging mice with a combination of a high-fat diet and angiotensin II. RESULTS: Single-cell RNA sequencing of human AAA tissues identified SETDB2 was upregulated in aortic monocyte/macrophages and murine AAA models compared with controls. Mechanistically, interferon-ß regulates SETDB2 expression through Janus kinase/signal transducer and activator of transcription signaling, which trimethylates histone 3 lysine 9 on the TIMP1-3 gene promoters thereby suppressing TIMP1-3 transcription and leading to unregulated matrix metalloproteinase activity. Macrophage-specific knockout of SETDB2 ( Setdb2f/fLyz2Cre+ ) protected mice from AAA formation with suppression of vascular inflammation, macrophage infiltration, and elastin fragmentation. Genetic depletion of SETDB2 prevented AAA development due to the removal of the repressive histone 3 lysine 9 trimethylation mark on the TIMP1-3 gene promoter resulting in increased TIMP expression, decreased protease activity, and preserved aortic architecture. Lastly, inhibition of the Janus kinase/signal transducer and activator of the transcription pathway with an FDA-approved inhibitor, Tofacitinib, limited SETDB2 expression in aortic macrophages. CONCLUSIONS: These findings identify SETDB2 as a critical regulator of macrophage-mediated protease activity in AAAs and identify SETDB2 as a mechanistic target for the management of AAAs.

Smart thrombosis inhibitors without bleeding side effects via charge tunable ligand design.

Current treatments to prevent thrombosis, namely anticoagulants and platelets antagonists, remain complicated by the persistent risk of bleeding. Improved therapeutic strategies that diminish this risk would have a huge clinical impact. Antithrombotic agents that neutralize and inhibit polyphosphate (polyP) can be a powerful approach towards such a goal. Here, we report a design concept towards polyP inhibition, termed macromolecular polyanion inhibitors (MPI), with high binding affinity and specificity. Lead antithrombotic candidates are identified through a library screening of molecules which possess low charge density at physiological pH but which increase their charge upon binding to polyP, providing a smart way to enhance their activity and selectivity. The lead MPI candidates demonstrates antithrombotic activity in mouse models of thrombosis, does not give rise to bleeding, and is well tolerated in mice even at very high doses. The developed inhibitor is anticipated to open avenues in thrombosis prevention without bleeding risk, a challenge not addressed by current therapies.

Direct and Indirect Effects of Race and Socioeconomic Deprivation on Outcomes After Lower Extremity Bypass.

OBJECTIVE: To evaluate the potential pathway, through which race and socioeconomic status, as measured by the social deprivation index (SDI), affect outcomes after lower extremity bypass chronic limb-threatening ischemia (CLTI), a marker for delayed presentation. BACKGROUND: Racial and socioeconomic disparities persist in outcomes after lower extremity bypass; however, limited studies have evaluated the role of disease severity as a mediator to potentially explain these outcomes using clinical registry data. METHODS: We captured patients who underwent lower extremity bypass using a statewide quality registry from 2015 to 2021. We used mediation analysis to assess the direct effects of race and high values of SDI (fifth quintile) on our outcome measures: 30-day major adverse cardiac event defined by new myocardial infarction, transient ischemic attack/stroke, or death, and 30-day and 1-year surgical site infection (SSI), amputation and bypass graft occlusion. RESULTS: A total of 7077 patients underwent a lower extremity bypass procedure. Black patients had a higher prevalence of CLTI (80.63% vs 66.37%, P < 0.001). In mediation analysis, there were significant indirect effects where Black patients were more likely to present with CLTI, and thus had increased odds of 30-day amputation [odds ratio (OR): 1.11, 95% CI: 1.068-1.153], 1-year amputation (OR: 1.083, 95% CI: 1.045-1.123) and SSI (OR: 1.052, 95% CI: 1.016-1.089). There were significant indirect effects where patients in the fifth quintile for SDI were more likely to present with CLTI and thus had increased odds of 30-day amputation (OR: 1.065, 95% CI: 1.034-1.098) and SSI (OR: 1.026, 95% CI: 1.006-1.046), and 1-year amputation (OR: 1.068, 95% CI: 1.036-1.101) and SSI (OR: 1.026, 95% CI: 1.006-1.046). CONCLUSIONS: Black patients and socioeconomically disadvantaged patients tended to present with a more advanced disease, CLTI, which in mediation analysis was associated with increased odds of amputation and other complications after lower extremity bypass compared with White patients and those that were not socioeconomically disadvantaged.

Characterizing geographic variation in postoperative venous thromboembolism.

OBJECTIVE: Venous thromboembolism (VTE) after major surgery remains an important contributor to morbidity and mortality. Despite significant quality improvement efforts in prevention and prophylaxis strategies, the degree of hospital and regional variation in the United States remains unknown. METHODS: Medicare beneficiaries undergoing 13 different major surgeries at U.S. hospitals between 2016 and 2018 were included in this retrospective cohort study. We calculated the rates of 90-day VTE. We adjusted for a variety of patient and hospital covariates and used a multilevel logistic regression model to calculate the rates of VTE and coefficients of variation across hospitals and hospital referral regions (HRRs). RESULTS: A total of 4,115,837 patients from 4116 hospitals were included, of whom 116,450 (2.8%) experienced VTE within 90 days. The 90-day VTE rates varied substantially by procedure, from 2.5% for abdominal aortic aneurysm repair to 8.4% for pancreatectomy. Across the hospitals, there was a 6.6-fold variation in index hospitalization VTE and a 5.3-fold variation in the rate of postdischarge VTE. Across the HRRs, there was a 2.6-fold variation in 90-day VTE, with a 12.1-fold variation in the coefficient of variation. A subset of HRRs was identified with both higher VTE rates and higher variance across hospitals. CONCLUSIONS: Substantial variation exists in the rate of postoperative VTE across U.S. hospitals. Characterizing HRRs with high overall rates of VTE and those with significant variation across the hospitals will allow for targeted quality improvement efforts.

A Novel Preoperative Risk Assessment Tool to Identify Patients at Risk of Contrast-Associated Acute Kidney Injury After Endovascular Abdominal Aortic Aneurysm Repair.

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) after endovascular abdominal aortic aneurysm repair (EVAR) is associated with mortality and morbidity. Risk stratification remains a vital component of preoperative evaluation. We sought to generate and validate a preprocedure CA-AKI risk stratification tool for elective EVAR patients. METHODS: We queried the Blue Cross Blue Shield of Michigan Cardiovascular Consortium database for elective EVAR patients and excluded those on dialysis, with a history of renal transplant, death during procedure, and without creatinine measures. Association with CA-AKI (rise in creatinine > 0.5 mg/dL) was tested using mixed-effects logistic regression. Variables associated with CA-AKI were used to generate a predictive model via a single classification tree. The variables selected by the classification tree were then validated by fitting a mixed-effects logistic regression model into the Vascular Quality Initiative dataset. RESULTS: Our derivation cohort included 7,043 patients, 3.5% of whom developed CA-AKI. After multivariate analysis, age (odds ratio [OR] 1.021, 95% confidence interval [CI] 1.004-1.040), female sex (OR 1.393, CI 1.012-1.916), glomerular filtration rate (GFR) < 30 mL/min (OR 5.068, CI 3.255-7.891), current smoking (OR 1.942, CI 1.067-3.535), chronic obstructive pulmonary disease (OR 1.402, CI 1.066-1.843), maximum abdominal aortic aneurysm (AAA) diameter (OR 1.018, CI 1.006-1.029), and presence of iliac artery aneurysm (OR 1.352, CI 1.007-1.816) were associated with increased odds of CA-AKI. Our risk prediction calculator demonstrated that patients with a GFR < 30 mL/min, females, and patients with a maximum AAA diameter of > 6.9 cm are at a higher risk of CA-AKI after EVAR. Using the Vascular Quality Initiative dataset (N = 62,986), we found that GFR < 30 mL/min (OR 4.668, CI 4.007-5.85), female sex (OR 1.352, CI 1.213-1.507), and maximum AAA diameter > 6.9 cm (OR 1.824, CI 1.212-1.506) were associated with an increased risk of CA-AKI after EVAR. CONCLUSIONS: Herein, we present a simple and novel risk assessment tool that can be used preoperatively to identify patients at risk of CA-AKI after EVAR. Patients with a GFR < 30 mL/min, maximum AAA diameter > 6.9 cm, and females who are undergoing EVAR may be at risk for CA-AKI after EVAR. Prospective studies are needed to determine the efficacy of our model.

Guideline-Directed Medical Therapy and Long-Term Mortality and Amputation Outcomes in Patients Undergoing Peripheral Vascular Interventions.

BACKGROUND: Lack of guideline-directed medical therapy (GDMT) in patients undergoing peripheral vascular interventions (PVIs) may increase mortality and amputation risk. OBJECTIVES: The authors sought to study the association between GDMT and mortality/amputation and to examine GDMT variability among providers and health systems. METHODS: We performed an observational study using patients in the Vascular Quality Initiative registry undergoing PVI between 2017 and 2018. Two-year all-cause mortality and major amputation data were derived from Medicare claims data. Compliance with GDMT was defined as receiving a statin, antiplatelet therapy, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker if hypertensive. Propensity 1:1 matching was applied for GDMT vs no GDMT and survival analyses were performed to compare outcomes between groups. RESULTS: Of 15,891 patients undergoing PVIs, 48.8% received GDMT and 6,120 patients in each group were matched. Median follow-up was 9.6 (IQR: 4.5-16.2) months for mortality and 8.4 (IQR: 3.5-15.4) for amputation. Mean age was 72.0 ± 9.9 years. Mortality risk was higher among patients who did not receive GDMT versus those on GDMT (31.2% vs 24.5%; HR: 1.37, 95% CI: 1.25-1.50; P < 0.001), as well as, risk of amputation (16.0% vs 13.2%; HR: 1.20; 95% CI: 1.08-1.35; P < 0.001). GDMT rates across sites and providers ranging from 0% to 100%, with lower performance translating into higher risk. CONCLUSIONS: Almost one-half of the patients receiving PVI in this national quality registry were not on GDMT, and this was associated with increased risk of mortality and major amputation. Quality improvement efforts in vascular care should focus on GDMT in patients undergoing PVI.

Experimental venous thrombus resolution is driven by IL-6 mediated monocyte actions.

Deep venous thrombosis and residual thrombus burden correlates with circulating IL-6 levels in humans. To investigate the cellular source and role of IL-6 in thrombus resolution, Wild type C57BL/6J (WT), and IL-6-/- mice underwent induction of VT via inferior vena cava (IVC) stenosis or stasis. Vein wall (VW) and thrombus were analyzed by western blot, immunohistochemistry, and flow cytometry. Adoptive transfer of WT bone marrow derived monocytes was performed into IL6-/- mice to assess for rescue. Cultured BMDMs from WT and IL-6-/- mice underwent quantitative real time PCR and immunoblotting for fibrinolytic factors and matrix metalloproteinase activity. No differences in baseline coagulation function or platelet function were found between WT and IL-6-/- mice. VW and thrombus IL-6 and IL-6 leukocyte-specific receptor CD126 were elevated in a time-dependent fashion in both VT models. Ly6Clo Mo/MØ were the predominant leukocyte source of IL-6. IL-6-/- mice demonstrated larger, non-resolving stasis thrombi with less neovascularization, despite a similar number of monocytes/macrophages (Mo/MØ). Adoptive transfer of WT BMDM into IL-6-/- mice undergoing stasis VT resulted in phenotype rescue. Human specimens of endophlebectomized tissue showed co-staining of Monocyte and IL-6 receptor. Thrombosis matrix analysis revealed significantly increased thrombus fibronectin and collagen in IL-6-/- mice. MMP9 activity in vitro depended on endogenous IL-6 expression in Mo/MØ, and IL-6-/- mice exhibited stunted matrix metalloproteinase activity. Lack of IL-6 signaling impairs thrombus resolution potentially via dysregulation of MMP-9 leading to impaired thrombus recanalization and resolution. Restoring or augmenting monocyte-mediated IL-6 signaling in IL-6 deficient or normal subjects, respectively, may represent a non-anticoagulant target to improve thrombus resolution.

A vein wall cell atlas of murine venous thrombosis determined by single-cell RNA sequencing.

Deep vein thrombosis (DVT) is a common clinical problem, but its cellular and molecular mechanisms remain incompletely understood. In this study, we performed single-cell RNA sequencing on mouse inferior vena cava (IVC) 24 h after thrombus-inducing IVC ligation or sham operation. 9 cell types composed of multiple subpopulations were identified. Notable transcriptomic changes induced by DVT included a marked inflammatory response, elevated hypoxia, and globally reduced myogenesis. Analysis of individual cell populations revealed increased inflammation and reduced extracellular matrix production across smooth muscle cells and fibroblasts, juxtaposed against an early phenotypic shift in smooth muscle cell populations away from a contractile state. By characterizing the transcriptomic changes in the vein wall during acute venous thrombosis at the single-cell level, this work provides novel insights into early pathological events in the vein wall that may potentiate thrombus formation and result in long term adverse venous remodeling.

Race and outcomes after percutaneous coronary intervention: Insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium.

BACKGROUND: Current studies show similar in-hospital outcomes following percutaneous coronary intervention (PCI) between Black and White patients. Long-term outcomes and the role of individual and community-level socioeconomic factors in differential risk are less understood. METHODS: We linked clinical registry data from PCIs performed between January, 2013 and March, 2018 at 48 Michigan hospitals to Medicare Fee-for-service claims. We analyzed patients of Black and White race. We used propensity score matching and logistic regression models to estimate the odds of 90-day readmission and Cox regression to evaluate the risk of postdischarge mortality. We used mediation analysis to evaluate the proportion of association mediated by socioeconomic factors. RESULTS: Of the 29,317 patients included in this study, 10.28% were Black and 89.72% were White. There were minimal differences between groups regarding post-PCI in-hospital outcomes. Compared with White patients, Black patients were more likely to be readmitted within 90-days of discharge (adjusted OR 1.62, 95% CI [1.32-2.00]) and had significantly higher risk of all-cause mortality (adjusted HR 1.45, 95% CI 1.30-1.61) when adjusting for age and gender. These associations were significantly mediated by dual eligibility (proportion mediated [PM] for readmission: 11.0%; mortality: 21.1%); dual eligibility and economic well-being of the patient's community (PM for readmission: 22.3%; mortality: 43.0%); and dual eligibility, economic well-being of the community, and baseline clinical characteristics (PM for readmission: 45.0%; mortality: 87.8%). CONCLUSIONS: Black patients had a higher risk of 90-day readmission and cumulative mortality following PCI compared with White patients. Associations were mediated by dual eligibility, community economic well-being, and traditional cardiovascular risk factors. Our study highlights the need for improved upstream care and streamlined postdischarge care pathways as potential strategies to improve health care disparities in cardiovascular disease.

Factors associated with successful median arcuate ligament release in an international, multi-institutional cohort.

OBJECTIVE: Prior research on median arcuate ligament syndrome has been limited to institutional case series, making the optimal approach to median arcuate ligament release (MALR) and resulting outcomes unclear. In the present study, we compared the outcomes of different approaches to MALR and determined the predictors of long-term treatment failure. METHODS: The Vascular Low Frequency Disease Consortium is an international, multi-institutional research consortium. Data on open, laparoscopic, and robotic MALR performed from 2000 to 2020 were gathered. The primary outcome was treatment failure, defined as no improvement in median arcuate ligament syndrome symptoms after MALR or symptom recurrence between MALR and the last clinical follow-up. RESULTS: For 516 patients treated at 24 institutions, open, laparoscopic, and robotic MALR had been performed in 227 (44.0%), 235 (45.5%), and 54 (10.5%) patients, respectively. Perioperative complications (ileus, cardiac, and wound complications; readmissions; unplanned procedures) occurred in 19.2% (open, 30.0%; laparoscopic, 8.9%; robotic, 18.5%; P < .001). The median follow-up was 1.59 years (interquartile range, 0.38-4.35 years). For the 488 patients with follow-up data available, 287 (58.8%) had had full relief, 119 (24.4%) had had partial relief, and 82 (16.8%) had derived no benefit from MALR. The 1- and 3-year freedom from treatment failure for the overall cohort was 63.8% (95% confidence interval [CI], 59.0%-68.3%) and 51.9% (95% CI, 46.1%-57.3%), respectively. The factors associated with an increased hazard of treatment failure on multivariable analysis included robotic MALR (hazard ratio [HR], 1.73; 95% CI, 1.16-2.59; P = .007), a history of gastroparesis (HR, 1.83; 95% CI, 1.09-3.09; P = .023), abdominal cancer (HR, 10.3; 95% CI, 3.06-34.6; P < .001), dysphagia and/or odynophagia (HR, 2.44; 95% CI, 1.27-4.69; P = .008), no relief from a celiac plexus block (HR, 2.18; 95% CI, 1.00-4.72; P = .049), and an increasing number of preoperative pain locations (HR, 1.12 per location; 95% CI, 1.00-1.25; P = .042). The factors associated with a lower hazard included increasing age (HR, 0.99 per increasing year; 95% CI, 0.98-1.0; P = .012) and an increasing number of preoperative diagnostic gastrointestinal studies (HR, 0.84 per study; 95% CI, 0.74-0.96; P = .012) Open and laparoscopic MALR resulted in similar long-term freedom from treatment failure. No radiographic parameters were associated with differences in treatment failure. CONCLUSIONS: No difference was found in long-term failure after open vs laparoscopic MALR; however, open release was associated with higher perioperative morbidity. These results support the use of a preoperative celiac plexus block to aid in patient selection. Operative candidates for MALR should be counseled regarding the factors associated with treatment failure and the relatively high overall rate of treatment failure.

The histone methyltransferase MLL1/KMT2A in monocytes drives coronavirus-associated coagulopathy and inflammation.

Coronavirus-associated coagulopathy (CAC) is a morbid and lethal sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. CAC results from a perturbed balance between coagulation and fibrinolysis and occurs in conjunction with exaggerated activation of monocytes/macrophages (MO/Mφs), and the mechanisms that collectively govern this phenotype seen in CAC remain unclear. Here, using experimental models that use the murine betacoronavirus MHVA59, a well-established model of SARS-CoV-2 infection, we identify that the histone methyltransferase mixed lineage leukemia 1 (MLL1/KMT2A) is an important regulator of MO/Mφ expression of procoagulant and profibrinolytic factors such as tissue factor (F3; TF), urokinase (PLAU), and urokinase receptor (PLAUR) (herein, "coagulopathy-related factors") in noninfected and infected cells. We show that MLL1 concurrently promotes the expression of the proinflammatory cytokines while suppressing the expression of interferon alfa (IFN-α), a well-known inducer of TF and PLAUR. Using in vitro models, we identify MLL1-dependent NF-κB/RelA-mediated transcription of these coagulation-related factors and identify a context-dependent, MLL1-independent role for RelA in the expression of these factors in vivo. As functional correlates for these findings, we demonstrate that the inflammatory, procoagulant, and profibrinolytic phenotypes seen in vivo after coronavirus infection were MLL1-dependent despite blunted Ifna induction in MO/Mφs. Finally, in an analysis of SARS-CoV-2 positive human samples, we identify differential upregulation of MLL1 and coagulopathy-related factor expression and activity in CD14+ MO/Mφs relative to noninfected and healthy controls. We also observed elevated plasma PLAU and TF activity in COVID-positive samples. Collectively, these findings highlight an important role for MO/Mφ MLL1 in promoting CAC and inflammation.

Development of open-source software for free-hand 3D vascular ultrasound: Dialysis fistula application.

BACKGROUND: The arteriovenous fistula (AVF) is the preferred vascular access for End Stage Renal Disease, having superior patency and lower infection risks than prosthetic graft and catheter access. When AVF dysfunction or delayed maturation does occur, the gold standard for diagnosis is the fistula angiogram (a.k.a. fistulogram). 3D ultrasound is available for obstetrical and other specialized uses, but it is cost prohibitive and has a field of view that is too small to cover the region of interest for the dialysis fistula application. We sought to develop a point of care 3D solution using freehand 2D ultrasound data acquisition. METHODS: We developed open-source software for 3D image reconstruction and projection of an angiogram-like image of the vascular access using a 2D freehand ultrasound scanner. We evaluated this software by comparing the ultrasound "sono-angiogram" images to fistulogram images in five subjects, using visual inspection and by applying the Percent of Exact Match (PEM) as a statistic test. RESULTS: The sono-angiograms showed identifiable characteristics that matched the fistulogram results in all five subjects. The PEM ranged between 42.8% and 77.0%, with Doppler and grayscale ultrasound data, showing complementary advantages and disadvantages when used for sono-angiogram image construction. Motion from freehand ultrasound acquisition was a significant source of mismatch. 3D image generation is a potential advantage with ultrasound data. CONCLUSIONS: While further work is needed to improve the accuracy with free hand scanning, fistulogram-like "sono-angiograms" can be generated using point of care 2D ultrasound. Methods such as these may be able to assist in point-of-care diagnosis in the future. The software is open-source, and importantly, the ultrasound data used are non-proprietary and available from any standard ultrasound machine. The simplicity and accessibility of this approach warrant further study.

Assessment of Determinants of Value in Carotid Endarterectomy.

BACKGROUND: Over 150,000 carotid endarterectomies (CEA) are performed annually worldwide, accounting for $900 million in the United States alone. How cost/spending and quality are related is not well understood but remain essential components in maximizing value. We sought to identify determinants of variability in hospital 90-day episode value for CEA. METHODS: Medicare and private-payer admissions for CEA from January 2, 2014 to August 28, 2020 were linked to retrospective clinical registry data for hospitals in Michigan performing vascular surgery. Hospital-specific, risk-adjusted, 30-day composite complications (defined as reoperation, new neurologic deficit, myocardial infarction, additional procedure including CEA or carotid artery stenting, readmission, or mortality) and 30-day risk-adjusted, price-standardized total episode payments were used to categorize hospitals into low or high value by defining the intersection between complications and spending. RESULTS: A total of 6,595 patients across 39 hospitals were identified across both datasets. Patients at low-value hospitals had a higher rate of 30-day composite complications (17.9% vs. 10.1%, P < 0.001) driven by a significantly higher rate of reoperation (3.0% vs. 1.4%, P = 0.016), readmission (10.7% vs. 6.2%, P = 0.012), new neurologic deficit (4.6% vs. 2.3%, P = 0.017), and mortality (1.6% vs. 0.6%, P < 0.049). Mean total episode payments were $19,635 at low-value hospitals compared to $15,709 at high-value hospitals driven by index hospitalization ($10,800 vs. $9,587, P = 0.002), professional ($3,421 vs. $2,827, P < 0.001), readmission ($3,011 vs. $1,826, P < 0.001), and post-acute care payments ($2,335 vs. $1,486, P < 0.001). Findings were similar when only including patients who did not suffer a complication. CONCLUSIONS: There is tremendous variation in both quality and payments across hospitals included for CEA. Importantly, costs were higher at low-value hospitals independent of postoperative complication. There appears to be little to no relationship between total episode spending and surgical quality, suggesting that improvements in value may be possible by decreasing total episode cost without affecting surgical outcomes.