A miRNA cassette reprograms smooth muscle cells into endothelial cells.

Cellular reprogramming through targeting microRNAs (miRNAs) holds promise for regenerative therapy due to their profound regulatory effects in proliferation, differentiation, and function. We hypothesized that transdifferentiation of vascular smooth muscle cells (SMCs) into endothelial cells (ECs) using a miRNA cassette may provide a novel approach for use in vascular disease states associated with endothelial injury or dysfunction. miRNA profiling of SMCs and ECs and iterative combinatorial miRNA transfections of human coronary SMCs revealed a 4-miRNA cassette consisting of miR-143-3p and miR-145-5p inhibitors and miR-146a-5p and miR-181b-5p mimics that efficiently produced induced endothelial cells (iECs). Transcriptome profiling, protein expression, and functional studies demonstrated that iECs exhibit high similarity to ECs. Injected iECs restored blood flow recovery even faster than conventional ECs in a murine hindlimb ischemia model. This study demonstrates that a 4-miRNA cassette is sufficient to reprogram SMCs into ECs and shows promise as a novel regenerative strategy for endothelial repair.

Subclavian to carotid artery bypass for a case of ocular ischemic syndrome.

BACKGROUND: Ocular Ischemic Syndrome (OIS) is a rare, vision threatening condition associated with severe carotid artery disease. There are few cases of OIS reported in the literature. METHODS: We present the case of a 54-year-old male with history of multiple previous carotid interventions including a right carotid stent, who presented with right-sided OIS. RESULTS: CTA and angiogram showed a severe calcific plaque causing restenosis of the right carotid stent, with a patent right internal carotid artery (ICA) in the very distal neck. The right common carotid artery (CCA) was patent but diseased with ulcerated plaque extending proximally to below the level of the clavicle. The left CCA was chronically occluded from its origin all the way to the bifurcation. Given our patient's surgical history, the imperative to revascularize the ipsilateral carotid, and a diffusely diseased ipsilateral CCA, he was successfully treated with an ipsilateral subclavian to internal carotid bypass. CONCLUSION: There is paucity of data regarding the best approach for carotid revascularization in OIS. This case report discusses our unique perioperative decision making as well as relevant literature.

Socioeconomic characteristics of those with peripheral artery disease in the chronic renal insufficiency cohort.

BACKGROUND: The association between socioeconomic factors and peripheral arterial disease (PAD) has not been as well characterized as other cardiovascular conditions. We sought to define how annual income and education level are associated with PAD in a well-characterized diverse set of adults with chronic kidney disease (CKD). METHODS: The Chronic Renal Insufficiency Cohort Study (CRIC) is a multi-center, prospective cohort study designed to examine risk factors for progression of CKD and cardiovascular disease. Demographic, income, and education-level data, as well as clinical data including ankle-brachial index (ABI) were collected at baseline. Annual income was categorized as < $25,000, $25,000-50,000, $50,000-100,000, or above $100,000; educational level was categorized as some high school, high school graduate, some college, or college graduate. Participants with missing income data or incompressible ABI (>1.4) were excluded from initial analysis. Logistic regression was used to estimate the association of income and/or education level with PAD, defined as an enrollment ABI of <0.90, history of PAD, or history of PAD intervention. RESULTS: A total of 4122 were included, mean age of participants was 59.5 years, 56% were male, and 44% were Black. There were 763 CRIC participants with PAD at study enrollment (18.5%). In the final multivariable logistic regression model, Black race (OR = 1.3, 95% CI 1.1-1.6, p = 0.004) and level of annual household income remained independently associated with PAD at the time of enrollment (income <$25,000 OR = 1.9, 95% CI 1.3-2.8, p < 0.001; income $25,000-50,000 OR = 1.6, 95% CI 1.1-2.3, p = 0.011; income $50,000-100,000 OR = 1.2, 95% CI 0.9-1.8, p = 0.246), relative to a baseline annual income of >$100,000 (overall p-value <0.001). Decreasing level of educational attainment was not independently associated with increased PAD at enrollment, but lower level of educational attainment was associated with increased PAD when income data was not adjusted for (p = 0.001). Interestingly, Black race (OR = 0.7, 95% CI 0.6-0.8, p < 0.001), female gender (OR = 0.8, 95% CI 0.7-0.9, p = 0.007), and income <$25,000 (OR = 0.7, 95% CI 0.5-0.9, p = 0.008) were significantly associated with decreased statin use even after controlling for cardiovascular conditions. CONCLUSIONS: In this prospectively followed CKD cohort, lower annual household income and Black race were significantly associated with increased PAD at study enrollment. In contrast, educational level was not associated with PAD when adjusted for patient income data. Black race, female gender, and low income were independently associated with decreased statin use, populations which could be targets of future public health programs.

The Differential Impact of Medicaid Expansion on Disparities in Outcomes Following Peripheral Vascular Intervention.

BACKGROUND: Peripheral artery disease (PAD) disproportionately affects nonwhite, Hispanic/Latino, and low socioeconomic status patients, who are less likely to have insurance and routine healthcare visits. Medicaid expansion (ME) has improved insurance rates and access to care, potentially benefitting these patients. We sought to assess the impact of ME on disparities in outcomes after peripheral vascular intervention (PVI) for PAD. METHODS: A retrospective analysis of prospectively-collected Vascular Quality Initiative PVI procedures between 2011 and 2019 was conducted. The sample was restricted to first-record procedures in adults under the age 65 in states that expanded Medicaid on January 1, 2014 (ME group) or had not expanded before January 1, 2019 (non-expansion [NE] group). ME and NE groups were compared between pre-expansion (2011-2013) and post-expansion (2014- 2019) time periods to assess baseline demographic and operative differences. We used difference-in-differences multivariable logistic regression adjusted for patient factors and clinical center and year fixed effects. Our primary outcome was 1-year major amputation. Secondary outcomes included trends in presentation, 30-day mortality, 1-year mortality, and 1-year primary and secondary patency. Outcomes were stratified by race and ethnicity. RESULTS: We examined 34,313 PVI procedures, including 20,378 with follow-up data. Rates of Medicaid insurance increased post-expansion in ME and NE states (ME 16.7% to 23.0%, P < 0.001; NE 10.0% to 11.9%, P = 0.013) while rates of self-pay decreased in ME states only (ME 4.6% to 1.8%, P < 0.001; NE 8.1% to 8.4%, P = 0.620). Adjusted difference-in-differences analysis revealed lower odds of urgent/emergent PVI among all patients and all nonwhite patients in ME states post-expansion compared to NE states (all: odds ratio [OR] 0.53 [95% confidence interval 0.33-0.87], P = 0.011; nonwhite: OR 0.41 [0.19-0.88], P = 0.023). No differences were observed for 1-year major amputation (OR 0.70 [0.43-1.14], P = 0.152), primary patency (OR 0.93 [0.63-1.38], P = 0.726), or secondary patency (OR 1.29 [0.69-2.41], P = 0.431). Odds of 1-year mortality were higher in ME states post-expansion compared to NE states (OR 2.50 [1.07-5.87], P = 0.035), although 30-day mortality was not different (OR 2.04 [0.60-6.90], P = 0.253). Notably, odds of 1-year major amputation among Hispanic/Latino patients decreased in ME states post-expansion compared to NE states (OR 0.11 [0.01-0.86], P = 0.036). CONCLUSIONS: ME was associated with lower odds of 1-year major amputation among Hispanic/Latino patients who underwent PVI for PAD. ME was also associated with lower odds of urgent/emergent procedures among patients overall and nonwhite patients specifically. However, 1-year mortality increased in the overall cohort. Further study is needed to corroborate our findings that ME may have benefits for certain underserved populations with PAD.

The Association Between Socioeconomic Factors and Incident Peripheral Artery Disease in the Chronic Renal Insufficiency Cohort (CRIC).

BACKGROUND: The association between socioeconomic factors and development of peripheral artery disease (PAD) has not been as well characterized compared to other cardiovascular diseases. We sought to define how annual income, sex, race, and education level are associated with newly diagnosed PAD in a well-characterized, diverse set of adults with CKD. METHODS: The Chronic Renal Insufficiency Cohort Study (CRIC) is a multicenter, prospective cohort study designed to examine risk factors for progression of CKD and cardiovascular disease. Demographic and clinical data including ankle brachial index (ABI) and interventions were collected at baseline, as well as yearly during follow-up visits. Annual income was categorized as: <$25,000, $25,000-50,000, $50,000-100,000, or above $100,000. We excluded those with pre-existing PAD, defined as enrollment ABI of <0.9 or >1.4, or missing income data. Cox proportional hazards regression was used to estimate the risk for incident PAD during CRIC enrollment, defined as a drop in ABI to <0.90 or a confirmed PAD intervention, including revascularization or amputation. RESULTS: A total of 3,313 patients met inclusion criteria, the mean age was 58.7 years, 56% were male, and 42% were Black. Over a median follow-up of 10.1 years, 639 participants (19%) were newly diagnosed with PAD. After adjusting for cardiovascular risk factors, all lower levels of annual household income were associated with increased incidence of PAD (income <$25,000 HR 1.7, 95% CI 1.1-2.4, P = 0.008; income $25,000-50,000 HR 1.5, 95% CI 1.1-2.3, P = 0.009; income $50,000-100,000 HR 1.6, 95% CI 1.2-2.4, P = 0.004), relative to a baseline annual income of >$100,000 (overall P-value = 0.02). In the multivariable model, there was no association between education level and PAD incidence (P = 0.80). Black race (HR 1.2, 95% CI 1.0-1.5, P = 0.023) and female sex (HR 1.7, 95% CI 1.4-2.0, P < 0.001) were independently associated with PAD incidence. Multiple imputation analysis provided similar results. CONCLUSIONS: In the CRIC, a multi-center cohort of prospectively followed CKD patients undergoing yearly CVD surveillance, lower annual household income, female sex, and Black race were significantly associated with the PAD incidence. In contrast, level of education was not independently associated with incident PAD.

Effects of dual antiplatelet therapy on graft patency after lower extremity bypass.

OBJECTIVE: Current guidelines recommend single-agent antiplatelet therapy for patients with symptomatic peripheral artery disease and consideration of dual antiplatelet therapy (DAPT) after surgical revascularization. The objective of this study was both to explore prescribing patterns of single antiplatelet therapy vs DAPT after lower extremity bypass surgery and to investigate the effects of antiplatelet therapy on bypass graft patency. METHODS: A retrospective analysis of prospectively collected nonemergent infrainguinal lower extremity bypass operations entered in the national Vascular Quality Initiative (2003-2018) with captured long-term follow-up was performed. Patients discharged on aspirin monotherapy or DAPT were identified. Linear regression investigated temporal trends in antiplatelet use. Multivariable Cox regression investigated predictors of primary, primary assisted, and secondary patency. RESULTS: Of the 13,020 patients investigated, 52.2% were discharged on aspirin monotherapy and 47.8% on DAPT. The proportion of patients discharged on DAPT increased from 10.6% in 2003 to 60.6% in 2018 (P < .001). The DAPT cohort was younger, had higher rates of medical (hypertension, diabetes, congestive heart failure, chronic obstructive pulmonary disease) and atherosclerotic (coronary artery disease, prior coronary artery bypass graft or percutaneous coronary intervention, prior lower extremity intervention) comorbidities, and had higher risk bypass procedures (more distal targets, prior inflow bypass procedure, prosthetic conduit use). Multivariable Cox regression analysis did not show any difference between the DAPT and aspirin cohorts in primary patency (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.88-1.10; P = .78), primary assisted patency (HR, 0.93; 95% CI, 0.80-1.07; P = .30), or secondary patency (HR, 0.88; 95% CI, 0.74-1.06; P = .18). On subgroup analysis based on bypass conduit, DAPT was found to have a protective effect on patency only in the prosthetic bypass cohort (primary patency: HR, 0.81 [95% CI, 0.66-1.00; P = .05]; primary assisted patency: HR, 0.74 [95% CI, 0.58-0.94; P = .01]; and secondary patency: HR, 0.60 [95% CI, 0.44-0.82; P < .001]). No patency differences were observed on adjusted subgroup analysis for the other bypass conduits. CONCLUSIONS: A significant and increasing proportion of patients are discharged on DAPT after lower extremity bypass revascularization. These patients represent a higher risk cohort with more medical comorbidities and higher risk bypass features. After controlling for these differences, DAPT therapy had no beneficial effect on overall bypass graft patency or major adverse limb events. However, on subgroup analysis, DAPT was associated with improved bypass graft patency in patients receiving prosthetic bypass conduits. Further study is warranted to investigate optimal duration of DAPT therapy and its possible bleeding complications in prosthetic bypass patients.

The use of intravascular ultrasound in the treatment of type B aortic dissection with thoracic endovascular aneurysm repair is associated with improved long-term survival.

OBJECTIVE: Intravascular ultrasound (IVUS) examination is an integral technique used for treating type B aortic dissection (TBAD) because it verifies true lumen access. The purpose of this study was to evaluate the use of IVUS, to determine factors associated with IVUS use, and to investigate the potential survival benefit associated with IVUS in the treatment of TBAD. METHODS: A retrospective review of TEVARs performed for TBAD in the national Vascular Quality Initiative was performed from January 2010 to August 2018. Data collected included demographics, intraoperative and postoperative variables, and long-term mortality. Multivariable logistic regression evaluated variables associated with IVUS the use and mortality, and Cox regression was performed for adjusted survival analysis. RESULTS: In this study of 2686 patients, the average age was 60.4 years, 69.3% were male, and IVUS examination was used in 74.6% of cases. IVUS patients were younger (60.0 years vs 61.7 years; P = .004), more often male (72.1% vs 61.3%; P < .001), exhibited less coronary disease, but had higher preoperative creatinine (1.27 ± 0.89 mg/dL vs 1.14 ± 0.68 mg/dL; P < .001) and were more often treated in the acute setting (55.2% vs 49.7%; P = .03). Interestingly, there were no differences in contrast use (117.4 ± 77.6 mL vs 123.0 ± 81.90.1 mL; P = .11) or fluoroscopy time (20.3 ± 16.5 minutes vs 19.0 ± 22.1 minutes; P = .10). However, IVUS cases had a greater number of devices implanted (1.84 vs 1.65; P < .001), higher rates of Zone 0 to 2 proximal seal (43.9% vs 30.7%; P < .001), higher rates of distal seal zones beyond the diaphragm (53.9% vs 37.4%; P = .001), and larger proximal and distal graft diameters, with no differences in postoperative renal function. IVUS patients notably also had higher rates of follow-up imaging (61.3% vs 54.8%; P = .003), larger maximum aortic diameters at follow-up, and more reinterventions over time. The number of aortic devices (odds ratio [OR] 1.56; 95% confidence interval [CI], 1.24-1.97; P < .001), malperfusion indication (OR, 1.68; 95% CI, 1.17-2.42; P = .005) and distal seal zone beyond the diaphragm (OR, 1.64; 95% CI, 1.30-2.07; P < .001) were independently associated with IVUS use, whereas female gender showed a trend towards less IVUS use (OR, 0.79; 95% CI, 0.62-1.01; P = .063). Even after controlling for age, preoperative comorbidities, and postoperative complications like spinal cord ischemia, IVUS was associated with a 61% decrease in the odds of mortality (OR, 0.39; 95% CI, 0.20-0.78; P = .008), with a clear survival advantage shown in adjusted survival curves. CONCLUSIONS: IVUS examination was used in the majority of TBAD, although not universally. IVUS examination was used more often in acute TBAD and more complex aortic repairs, and was independently associated with improved long-term survival. Further study is needed to understand these patterns.

Length of Stay after Thoracic Endovascular Aortic Repair Depends on Indication and Acuity.

BACKGROUND: Length of stay (LOS) is a commonly used metric to optimize value in medical care. Although pathways have been developed for some procedures in vascular surgery to reduce LOS, they do not yet exist for thoracic endovascular aortic repair (TEVAR). The purpose of this study is to identify and define the risk factors for prolonged LOS in patients undergoing TEVAR to facilitate pathway development. METHODS: We included TEVAR patients in the National Surgical Quality Improvement Program database from 2005 to 2015. Prolonged LOS was defined as LOS > 75th percentile of the overall cohort (11 days). Because initial analysis revealed the distinct clinical differences between dissection and aneurysm patients, further analysis was stratified by aortic pathology. Student's t-test and Chi-square tests were used to compare demographic and perioperative variables between dissection and aneurysm patients, respectively. Multivariable logistic regression was used to evaluate the predictors for prolonged LOS. RESULTS: A total of 3,021 patients underwent TEVAR, with 858 patients (28.4%) undergoing TEVAR for dissection and 2,163 (71.6%) undergoing TEVAR for aneurysm. An initial analysis with logistic regression identified dissection indication (odds ratio [OR], 2.87; 95% confidence interval [CI], 1.1-7.3) as an independent predictor of prolonged LOS. Further analysis for prolonged LOS was subsequently performed separating dissection and aneurysm patients. Aneurysm patients were older (71.2 ± 11.7 vs. 63.1 ± 13.6 years, P < 0.001), more often Caucasian (76.8% vs. 61.8%, P < 0.001), and had more medical comorbidities (chronic obstructive pulmonary disease, cardiac history, diabetes, peripheral vascular disease, transient ischemic attack [TIA], P < 0.001). In contrast, dissection patients had higher American Society of Anesthesiology (ASA) classification score (58.5% had >3 ASA vs. 45.5%, P < 0.001), longer hospitalizations (10.2 ± 9.3 vs. 8.5 ± 10.4 days, P < 0.001), were more likely to have been transferred from another hospital or emergency room (58.4% vs. 48.3%, P < 0.001), and were more often emergent (32.4% vs. 15.4%, P < 0.001). In dissection patients, ASA classification score (OR, 1.49; 95% CI, 1.1-2.1) and dialysis (OR, 1.98; 95% CI, 1.0-3.9) were independent predictors for prolonged LOS. In aneurysm patients, dependent functional status (OR, 2.03; 95% CI, 1.4-2.8), diabetes (OR, 1.75; 95% CI, 1.1-2.8), cardiac history (OR, 1.37; 95% CI, 1.0-1.9), emergency status (OR, 1.98; 95% CI, 1.4-2.8), and dialysis (OR, 2.08; 95% CI, 1.2-3.7) predicted prolonged LOS. Postoperative complications including stroke/TIA; failure to wean from ventilator, sepsis, and pneumonia; and need for reoperation similarly increased LOS in both dissection and aneurysm patients. CONCLUSIONS: Dissection and aneurysm patients undergoing TEVAR are comprised of different patient populations, with dissection patients more often enduring prolonged hospitalizations. In contrast, TEVAR performed for nonemergent aneurysm repair had the shortest LOS. These data support the development of separate pathways defined by indication and acuity for patients undergoing TEVAR.

MicroRNA-181b Improves Glucose Homeostasis and Insulin Sensitivity by Regulating Endothelial Function in White Adipose Tissue.

RATIONALE: The pathogenesis of insulin resistance involves dysregulated gene expression and function in multiple cell types, including endothelial cells (ECs). Post-transcriptional mechanisms such as microRNA-mediated regulation of gene expression could affect insulin action by modulating EC function. OBJECTIVE: To determine whether microRNA-181b (miR-181b) affects the pathogenesis of insulin resistance by regulating EC function in white adipose tissue during obesity. METHODS AND RESULTS: MiR-181b expression was reduced in adipose tissue ECs of obese mice, and rescue of miR-181b expression improved glucose homeostasis and insulin sensitivity. Systemic intravenous delivery of miR-181b robustly accumulated in adipose tissue ECs, enhanced insulin-mediated Akt phosphorylation at Ser473, and reduced endothelial dysfunction, an effect that shifted macrophage polarization toward an M2 anti-inflammatory phenotype in epididymal white adipose tissue. These effects were associated with increased endothelial nitric oxide synthase and FoxO1 phosphorylation as well as nitric oxide activity in epididymal white adipose tissue. In contrast, miR-181b did not affect insulin-stimulated Akt phosphorylation in liver and skeletal muscle. Bioinformatics and gene profiling approaches revealed that Pleckstrin homology domain leucine-rich repeat protein phosphatase, a phosphatase that dephosphorylates Akt at Ser473, is a novel target of miR-181b. Knockdown of Pleckstrin homology domain leucine-rich repeat protein phosphatase increased Akt phosphorylation at Ser473 in ECs, and phenocopied miR-181b's effects on glucose homeostasis, insulin sensitivity, and inflammation of epididymal white adipose tissue in vivo. Finally, ECs from diabetic subjects exhibited increased Pleckstrin homology domain leucine-rich repeat protein phosphatase expression. CONCLUSIONS: Our data underscore the importance of adipose tissue EC function in controlling the development of insulin resistance. Delivery of miR-181b or Pleckstrin homology domain leucine-rich repeat protein phosphatase inhibitors may represent a new therapeutic approach to ameliorate insulin resistance by improving adipose tissue endothelial Akt-endothelial nitric oxide synthase-nitric oxide signaling.

Peripheral Arterial Disease Genetics: Progress to Date and Challenges Ahead.

PURPOSE OF REVIEW: In this paper, we review the progress made thus far in research related to the genetics of peripheral arterial disease (PAD) by detailing efforts to date in heritability, linkage analyses, and candidate gene studies. We further summarize more contemporary genome-wide association studies (GWAS) and epigenetic studies of PAD. Finally, we review current challenges and future avenues of advanced research in PAD genetics including whole genome sequencing studies. RECENT FINDINGS: Studies have estimated the heritability of PAD to be moderate, though the contribution to this heritability that is independent of traditional cardiovascular risk factors remains unclear. Recent efforts have identified SNPs associated with PAD in GWAS analyses, but these have yet to be replicated in independent studies. Much remains to be discovered in the field of PAD genetics. An improved understanding of the genetic foundation for PAD will allow for earlier diagnosis of disease and a more complete pathophysiological understanding of the mechanisms of the disease leading to novel therapeutic interventions. Future avenues for success will likely arise from very large-scale GWAS, whole genome sequencing, and epigenetic studies involving very well-characterized cohorts.

Systemic delivery of microRNA-181b inhibits nuclear factor-κB activation, vascular inflammation, and atherosclerosis in apolipoprotein E-deficient mice.

RATIONALE: Activated nuclear factor (NF)-κB signaling in the vascular endothelium promotes the initiation and progression of atherosclerosis. Targeting endothelial NF-κB may provide a novel strategy to limit chronic inflammation. OBJECTIVE: To examine the role of microRNA-181b (miR-181b) in endothelial NF-κB signaling and effects on atherosclerosis. METHODS AND RESULTS: MiR-181b expression was reduced in the aortic intima and plasma in apolipoprotein E-deficient mice fed a high-fat diet. Correspondingly, circulating miR-181b in the plasma was markedly reduced in human subjects with coronary artery disease. Systemic delivery of miR-181b resulted in a 2.3-fold overexpression of miR-181b in the aortic intima of apolipoprotein E-deficient mice and suppressed NF-κB signaling revealed by bioluminescence imaging and reduced target gene expression in the aortic arch in apolipoprotein E-deficient/NF-κB-luciferase transgenic mice. MiR-181b significantly inhibited atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4+ T cells in the vessel wall. Mechanistically, miR-181b inhibited the expression of the target gene importin-α3, an effect that reduced NF-κB nuclear translocation specifically in the vascular endothelium of lesions, whereas surprisingly leukocyte NF-κB signaling was unaffected despite a 7-fold overexpression of miR-181b. Our findings uncover that NF-κB nuclear translocation in leukocytes does not involve importin-α3, but rather importin-α5, which miR-181b does not target, highlighting that inhibition of NF-κB signaling in the endothelium is sufficient to mediate miR-181b's protective effects. CONCLUSIONS: Systemic delivery of miR-181b inhibits the activation of NF-κB and atherosclerosis through cell-specific mechanisms in the vascular endothelium. These findings support the rationale that delivery of miR-181b may provide a novel therapeutic approach to treat chronic inflammatory diseases such as atherosclerosis.

Biochemical characterization of P4-ATPase mutations identified in patients with progressive familial intrahepatic cholestasis.

Mutations in the P4-ATPase ATP8B1 cause the inherited liver disease progressive familial intrahepatic cholestasis. Several of these mutations are located in conserved regions of the transmembrane domain associated with substrate binding and transport. Assays for P4-ATPase-mediated transport in living yeast cells were developed and used to characterize the specificity and kinetic parameters of this transport. Progressive familial intrahepatic cholestasis mutations were introduced into the yeast plasma membrane P4-ATPase Dnf2p, and the effect of these mutations on its catalysis of phospholipid transport were determined. The results of these measurements have implications for the basis of the disease and for the mechanism of phospholipid transit through the enzyme during the reaction cycle.

Endothelial microRNAs and atherosclerosis.

The vascular endothelium, a thin layer of endothelial cells (ECs) that line the inner surface of blood vessels, is a critical interface between blood and all tissues. EC activation, dysfunction, and vascular inflammation occur when the endothelium is exposed to various insults such as proinflammatory cytokines, oxidative stress, hypertension, hyperglycemia, aging, and shear stress. These insults lead to the pathogenesis of a range of disease states, including atherosclerosis. Several signaling pathways, especially nuclear factor κB mediated signaling, play crucial roles in these pathophysiological processes. Recently, microRNAs (miRNAs) have emerged as important regulators of EC function by fine-tuning gene expression. In this review, we discuss how miRNAs regulate EC function and vascular inflammation in response to a variety of pathophysiologic stimuli. An understanding of the role of miRNAs in EC activation and dysfunction may provide novel targets and therapeutic opportunities for controlling atherosclerosis and other chronic inflammatory disease states.

The surgical mask: are new tests relevant for OR practice?

Since the turn of the 20th century, when researchers were discovering the presence of bacteria in droplets from the nose and mouth and the role these bacteria played in disease transmission, masks have been used as a method to protect both health care providers and patients from respiratory diseases. In 1926, the first study was published that indicated masks might also play a role in reducing the incidence of surgical site infections. That report spearheaded the development of new mask materials and designs and devices to demonstrate their filtering efficiency. This article provides a historical review of the work done by researchers over the years and examines whether tests to determine the filtering efficiency of surgical masks, including those recently adopted by the US Food and Drug Administration (FDA), are relevant to actual OR conditions.

Trends in inferior vena cava filter placement and retrieval at a tertiary care institution.

OBJECTIVE: The aim of this study was to examine practice patterns of inferior vena cava (IVC) filter insertion and retrieval at a tertiary care institution. METHODS: A retrospective review of all IVC filter procedures performed at the University of Pennsylvania and entered into the Penn cohort of the Vascular Quality Initiative registry between January 2013 and September 2017 was performed. Data collected included demographics, venous thromboembolism risk factors, indications for filter placement, and presence and timing of retrieval. Trend analysis and multivariable logistic regression were performed to evaluate factors associated with failure to retrieve the filter. RESULTS: During the study period, 627 IVC filters were inserted. The mean age was 52.8 ± 16.9 years, and 49.3% were male; 39.2% were placed for a major indication, whereas 58.1% were placed for prophylaxis. There was a significant decline in overall frequency of filter placement during the period observed, with a 33% decrease from 2015 to 2016 and a 26% decrease from 2016 to 2017 (P < .001), with an overall retrieval rate of 44.9%. In contrast, there was a corresponding increase in filter retrieval, with a 20% increase in 2015 and a 68% increase in 2016 (P = .02). In evaluating trends separated by indication, there was a significant decline in prophylactic filter placement (P < .001) and a trend toward an increase in retrieval of prophylactic filters (P = .09). Whereas there was not a significant change in number of filter insertions for major indication (P = .06), filter retrievals for major indication filters increased (P = .01). Multivariable regression analysis revealed that longer time to follow-up (odds ratio [OR], 1.08; P < .001) and discharge to rehabilitation facility (OR, 6.14; P < .001) were predictive of failure to retrieve the filter. In contrast, filter placement at a later date within our study period (OR, 0.90; P < .001) and prophylactic indication for filter placement (OR, 0.36; P < .001) were protective from filter nonretrieval. CONCLUSIONS: These results show both a decline in overall IVC filter placement and an increase in overall IVC filter retrieval at our institution. These trends are predominantly due to a decrease in prophylactic filter placement as well as an overall increase in filter retrieval. Further study should be dedicated to increasing the retrieval rate in this population of patients.

Morbidity Associated with Diverting Loop Ileostomies: Weighing Diversion in Rectosigmoid Resection.

Anterior resection with primary anastomosis is the procedure of choice for patients with rectosigmoid cancers with good sphincter function. Surgeons may perform an associated diverting loop ileostomy (DLI) to minimize the likelihood and/or the severity of an anastomotic leak. To examine the morbidity of DLIs, we performed a review of a prospectively maintained database. Participants included all patients at the Massachusetts General Hospital who underwent anterior resection from January 2013 to July 2015 for rectosigmoid cancers and who subsequently underwent adjuvant chemotherapy. The primary outcome was time to start of adjuvant chemotherapy. Secondary outcomes included length of hospitalization, perioperative complications, and 60-day postoperative complications. Inclusion criteria were met in 57 patients and DLI was performed in 21 (37%). The DLI group had higher estimated blood loss (431.7 vs 192.1 mL, P = 0.03) and a longer operation time (3.7 vs 2.3 hours, P = 0.0007). The DLI group took over a week longer to start adjuvant chemotherapy than the non-DLI group (median time to chemo: 43 vs 34 days, P = 0.002). Postoperatively, DLI was associated with a longer hospitalization (6.7 vs 3.1 days, P = 0.0003), more perioperative complications (57.1% vs 13.9%, P = 0.0006), and more 60-day readmissions or emergency department visits (38.1% vs 5.6%, P = 0.002). Ostomies are associated with appreciable morbidity. In turn, they do not eliminate postoperative complications. Surgeons should closely consider ostomy morbidity in rectosigmoid resection and institute a proactive approach toward identification and prevention of complications.

Creutzfeldt-Jakob disease--identifying prions and carriers.

Two major obstacles to be overcome in minimizing the possibility of transmitting Creutzfeldt-Jakob disease or variant Creutzfeldt-Jakob disease are associated with identifying the prion on disinfected surgical instruments and identifying carriers of the protease-resistant form of the prion. New developments indicate that the means for doing both soon may be available.

A historical review of barrier materials.

When surgical gowns first were used, their primary purpose was to protect patients from members of the surgical team. In 1952, it was revealed that although the muslin the garments were made from may have been an effective barrier when dry, it lost barrier capability after it became wet. This disclosure triggered research to develop more satisfactory materials for this unique application. In the interim, the emergence of HIV was accompanied by the need to protect surgical team members from patients, and barrier effectiveness attained even greater importance. During the past 50 years, several attempts have been made to develop a universally acceptable and meaningful test method to demonstrate a material's barrier capability under conditions that simulate usual conditions of use. None has been successful. Today, with the trend toward minimally invasive surgery and pressure to reduce costs, perioperative nurses are confronted with selecting a product that is appropriate for the task and degree of exposure anticipated.