Publications by authors named "Andrea T Obi"

47 Publications

Inhibition of macrophage histone demethylase JMJD3 protects against abdominal aortic aneurysms.

J Exp Med 2021 Jun;218(6)

Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.

Abdominal aortic aneurysms (AAAs) are a life-threatening disease for which there is a lack of effective therapy preventing aortic rupture. During AAA formation, pathological vascular remodeling is driven by macrophage infiltration, and the mechanisms regulating macrophage-mediated inflammation remain undefined. Recent evidence suggests that an epigenetic enzyme, JMJD3, plays a critical role in establishing macrophage phenotype. Using single-cell RNA sequencing of human AAA tissues, we identified increased JMJD3 in aortic monocyte/macrophages resulting in up-regulation of an inflammatory immune response. Mechanistically, we report that interferon-β regulates Jmjd3 expression via JAK/STAT and that JMJD3 induces NF-κB-mediated inflammatory gene transcription in infiltrating aortic macrophages. In vivo targeted inhibition of JMJD3 with myeloid-specific genetic depletion (JMJD3f/fLyz2Cre+) or pharmacological inhibition in the elastase or angiotensin II-induced AAA model preserved the repressive H3K27me3 on inflammatory gene promoters and markedly reduced AAA expansion and attenuated macrophage-mediated inflammation. Together, our findings suggest that cell-specific pharmacologic therapy targeting JMJD3 may be an effective intervention for AAA expansion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1084/jem.20201839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008365PMC
June 2021

Advances in understanding the interplay between adaptive and innate immunity in experimental venous thrombus resolution.

J Thromb Haemost 2021 Feb 17. Epub 2021 Feb 17.

University of Michigan Health System, Ann Arbor, MI, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jth.15249DOI Listing
February 2021

Low to Moderate Risk Non-Orthopedic Surgical Patients do not Benefit from VTE Chemoprophylaxis.

Ann Surg 2020 Nov 18. Epub 2020 Nov 18.

Section of Vascular Surgery.

Objective: We hypothesized that a high rate of prescription of VTE chemoprophylaxis would be associated with decreased VTE incidence and mortality.

Summary Background Data: Recommendations for VTE prevention in surgical patients include chemoprophylaxis based upon preoperative risk stratification.

Methods: This retrospective cohort study analyzed VTE incidence, morbidity and mortality amongst post-surgical patients with and without VTE chemoprophylaxis between April 2013 - September 2017 from 63 hospitals within the Michigan Surgical Quality Collaborative. A VTE risk assessment survey was distributed to providers. Bivariate and multivariate comparisons were made, as well as using propensity score matched cohorts to determine if VTE chemoprophylaxis was associated with decreased VTE events. Hospitals were compared using risk-reliability adjusted VTE prophylaxis and postoperative VTE event rates.

Results: Within the registry, 80% of practitioners reported performing formal VTE risk assessment. Amongst 32,856 operations, there were 480 (1.46%) postoperative VTE, and an overall mortality of 609 (1.85%) patients. Using a propensity matched cohort, we found that rates of VTE were similar in those receiving UFH or LMWH compared to those not receiving chemoprophylaxis (1.22 vs. 1.13%, p = .57). When stratified further by VTE risk scoring, even the highest risk patients did not have an associated lower VTE rate (3.68 vs 4.22% p = .092). Postoperative transfusion (8.28 vs. 7.50%, p = .057) and mortality (2.00% vs. 1.62%, p = .064) rates were similar amongst those receiving and those not receiving chemoprophylaxis. No correlation was found between postoperative VTE chemoprophylaxis application and hospital specific risk adjusted postoperative VTE rates.

Conclusions: In modern day post-surgical care, VTE remains a significant occurrence, despite wide adoption of VTE risk assessment. While postoperative VTE chemoprophylaxis was broadly applied, after adjusting for confounders, no reduction in VTE was observed in at risk surgical patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000004646DOI Listing
November 2020

Venous thrombosis epidemiology, pathophysiology, and anticoagulant therapies and trials in severe acute respiratory syndrome coronavirus 2 infection.

J Vasc Surg Venous Lymphat Disord 2021 01 8;9(1):23-35. Epub 2020 Sep 8.

Section of Vascular Surgery, Department of Surgery, Samuel and Jean Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Mich. Electronic address:

Objective: Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus confers a risk of significant coagulopathy, with the resulting development of venous thromboembolism (VTE), potentially contributing to the morbidity and mortality. The purpose of the present review was to evaluate the potential mechanisms that contribute to this increased risk of coagulopathy and the role of anticoagulants in treatment.

Methods: A literature review of coronavirus disease 2019 (COVID-19) and/or SARS-CoV-2 and cell-mediated inflammation, clinical coagulation abnormalities, hypercoagulability, pulmonary intravascular coagulopathy, and anticoagulation was performed. The National Clinical Trials database was queried for ongoing studies of anticoagulation and/or antithrombotic treatment or the incidence or prevalence of thrombotic events in patients with SARS-CoV-2 infection.

Results: The reported rate of VTE among critically ill patients infected with SARS-CoV-2 has been 21% to 69%. The phenomenon of breakthrough VTE, or the acute development of VTE despite adequate chemoprophylaxis or treatment dose anticoagulation, has been shown to occur with severe infection. The pathophysiology of overt hypercoagulability and the development of VTE is likely multifactorial, with evidence supporting the role of significant cell-mediated responses, including neutrophils and monocytes/macrophages, endothelialitis, cytokine release syndrome, and dysregulation of fibrinolysis. Collectively, this inflammatory process contributes to the severe pulmonary pathology experienced by patients with COVID-19. As the infection worsens, extreme D-dimer elevations, significant thrombocytopenia, decreasing fibrinogen, and prolongation of prothrombin time and partial thromboplastin time occur, often associated with deep vein thrombosis, in situ pulmonary thrombi, and/or pulmonary embolism. A new phenomenon, termed pulmonary intravascular coagulopathy, has been associated with morbidity in patients with severe infection. Heparin, both unfractionated heparin and low-molecular-weight heparin, have emerged as agents that can address the viral infection, inflammation, and thrombosis in this syndrome.

Conclusions: The overwhelming inflammatory response in patients with SARS-CoV-2 infection can lead to a hypercoagulable state, microthrombosis, large vessel thrombosis, and, ultimately, death. Early VTE prophylaxis should be provided to all admitted patients. Therapeutic anticoagulation therapy might be beneficial for critically ill patients and is the focus of 39 ongoing trials. Close monitoring for thrombotic complications is imperative, and, if confirmed, early transition from prophylactic to therapeutic anticoagulation should be instituted. The interplay between inflammation and thrombosis has been shown to be a hallmark of the SARS-CoV-2 viral infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvsv.2020.08.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834652PMC
January 2021

Recognizing the evolving and beneficial role of regulatory T cells in aneurysm growth.

J Vasc Surg 2020 09;72(3):1097

Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, Mich.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvs.2019.09.045DOI Listing
September 2020

Management and treatment outcomes of patients undergoing endovenous ablation are significantly different between Intersocietal Accreditation Commission-accredited and nonaccredited vein centers.

J Vasc Surg Venous Lymphat Disord 2021 03 25;9(2):346-351. Epub 2020 Jul 25.

Section of Vascular Surgery, Department of Surgery, University of Michigan Health System, Ann Arbor, Mich; Department of Vascular Surgery, Jobst Vascular Institute, Promedica, Toledo, OH. Electronic address:

Objective: The Intersocietal Accreditation Commission of vein centers was instituted in 2014, yet data regarding impact of accreditation on patients undergoing superficial vein interventions are lacking. This study was undertaken to identify differences in patient outcomes and utilization index as a measure of appropriate use in accredited compared with nonaccredited centers.

Methods: This study was performed with a matched control design using prospectively collected data from two major U.S.-based venous registries: the Society for Vascular Surgery Vascular Quality Initiative Varicose Vein Registry and the American Vein & Lymphatic Society PRO Venous Registry.

Results: A total of 39,001 patients treated between 2015 and 2018 in 192 centers were included in the study. The Vascular Quality Initiative Varicose Vein Registry provided information on 19,810 (50.8%) patients, and the American Vein & Lymphatic Society PRO Venous Registry provided information on 19,191 (49.2%) patients. Accredited centers were significantly more likely to treat patients with advanced venous disease as characterized by trophic skin changes (C4-C6, 38.1% vs 25.2%; P < .001). Percentage of patients treated 2 standard deviations above the Medicare-reported mean (3.4 utilization index) was significantly higher among patients treated at nonaccredited centers (3.3% vs 0.1%; P < .001). Venous Clinical Severity Score of those who were assessed between 1 month and 1 year after ablation decreased by 4.98 ± 4.01 in nonaccredited centers compared with 5.61 ± 3.64 in accredited centers (P < .001). Complications were low in both cohorts (nonaccredited centers, 71 [0.4%]; accredited centers, 17 [0.1%]; P < .001). One-year clinical follow-up was higher in nonaccredited centers (76.4% vs 31.5%; P < .001).

Conclusions: Venous registries are a powerful tool for capturing and identifying significant variations in procedure utilization and complications in low-risk procedures. Intersocietal Accreditation Commission accreditation was associated with reduced use of endovenous therapies, slightly lower complication rates, lower 1-year follow up, and greater improvement in Venous Clinical Severity Score.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvsv.2020.07.007DOI Listing
March 2021

Effect of concomitant deep venous reflux on truncal endovenous ablation outcomes in the Vascular Quality Initiative.

J Vasc Surg Venous Lymphat Disord 2021 03 24;9(2):361-368.e3. Epub 2020 Jun 24.

Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, Mich.

Objective: Few studies have investigated outcomes after truncal endovenous ablation in patients with combined deep and superficial reflux and no studies have evaluated patient-reported outcomes.

Methods: We investigated the short- and long-term clinical and patient-reported outcomes among patients with and without deep venous reflux undergoing truncal endovenous ablation from 2015 to 2019 in the Vascular Quality Initiative. Preprocedural and postprocedural comparisons were performed using the t-test, χ, or their nonparametric counterpart when appropriate. Multivariable logistic regression models were used to assess for confounding.

Results: A total of 4881 patients were included, of which 2254 (46.2%) had combined deep and superficial reflux. The median follow-up was 336.5 days. Patients with deep reflux were less likely to be female (65.9% vs 69.9%; P = .003), more likely to be Caucasian (90.2% vs 86.5%; P = .003) and had no difference in BMI (30.6 ± 7.5 vs 30.6 ± 7.2; P = .904). Additionally, no difference was seen in rates of prior varicose vein treatments, number of pregnancies, or history of deep venous thrombosis; however, patients without deep reflux were more likely to be on anticoagulation at the time of the procedure (10.9% vs 8.1%; P < .001). Patients without deep reflux had slightly higher median preprocedural Venous Clinical Severity Score (VCSS) scores (8 [interquartile range (IQR), 6-10]) vs 7 [IQR, 6-10]; P = .005) as well as postprocedural VCSS scores (5 [IQR, 3-7] vs 4 [IQR, 2-6]; P < .001). The median change in VCSS from before to after the procedure was lower for patients without deep reflux (3 [IQR, 1.0-5.5] vs 3.5 [IQR, 1-6]; P = .006). Total symptom score was higher for patients without deep reflux both before (median, 14 [IQR, 10-19] vs median, 13.5 [IQR, 9.5-18]; P = .005) and postprocedurally (median, 4 [IQR, 1-9] vs median, 3.25 [IQR, 1-7]; P < .001), but no difference was seen in change in symptom score (median, 8 [IQR, 4-13] vs median, 9 [IQR, 4-13]; P = .172). Patients with deep reflux had substantially higher rates of complications (10.4% vs 3.0%; P < .001), with a particular increase in proximal thrombus extension (3.1% vs 1.1%; P < .001). After controlling for confounding, this estimate of effect size for any complication increased (odds ratio, 5.72; 95% confidence interval, 2.21-14.81; P < .001).

Conclusions: No significant difference is seen in total symptom improvement when patients undergo truncal endovenous ablation with concomitant deep venous reflux, although a greater improvement was seen in VCSS score in these patients. Patients with deep venous reflux had a significantly increased rate of complications, independent of confounding variables, and should be counseled appropriately before the decision for treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvsv.2020.04.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768610PMC
March 2021

Outcomes after truncal ablation with or without concomitant phlebectomy for isolated symptomatic varicose veins (C2 disease).

J Vasc Surg Venous Lymphat Disord 2021 03 2;9(2):369-376. Epub 2020 Jun 2.

Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, Mich.

Objective: Many insurance payers are hesitating to cover interventional treatments in patients with isolated symptomatic varicose veins. In this study, we sought to determine the outcomes of patients with varicose veins who were treated with venous ablation alone or ablation plus phlebectomy using the Vascular Quality Initiative Varicose Vein Registry.

Methods: Using data from the Varicose Vein Registry between January 2015 and March 2019, we investigated immediate postoperative as well as long-term clinical and patient-reported outcomes among patients with documented symptomatic C2 disease undergoing truncal endovenous ablations alone and combined ablation and phlebectomy. Preprocedural and postprocedural comparisons were performed using t-test, χ test, or nonparametric tests when appropriate. Multivariable ordinal logistic regression was performed on ordinal outcome variables.

Results: Among 3375 patients with symptomatic C2 disease, 40.1% of patients (1376) underwent isolated truncal ablation and 59.9% (1999) underwent ablation and phlebectomy. Complications overall were low (8.6%) and varied between 8.4% and 8.7% in patients undergoing ablation alone and ablation plus phlebectomy, respectively (P = .820). The most common complication noted was paresthesia, 3.4% overall, which occurred more commonly after ablation and phlebectomy (4.5%) than after ablation alone (1.3%; P < .001). An improvement in Venous Clinical Severity Score (VCSS) was experienced by 87.4% of patients; median change in VCSS was 4 points (interquartile range [IQR], 2-5 points), with an improvement of 3 points among patients undergoing ablation alone (IQR, 1-5 points) and 5 points among patients undergoing ablation and phlebectomy (IQR, 3-5 points; P < .001). An improvement in overall symptoms was experienced by 94.4% of patients (median improvement, 11 points; (maximum, 30 points), with more significant decreases among patients undergoing ablation and phlebectomy (median, 12 points; IQR, 8-17 points) compared with ablation alone (median, 9 points; IQR, 5-13 points; P < .001).

Conclusions: Among patients with isolated symptomatic varicose veins (C2 disease), ablation and ablation with phlebectomy are safe and effective in improving both patient-reported outcomes and clinical severity (VCSS). Given these data, payers should continue to cover these treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvsv.2020.05.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788516PMC
March 2021

Comparison of unilateral vs bilateral and staged bilateral vs concurrent bilateral truncal endovenous ablation in the Vascular Quality Initiative.

J Vasc Surg Venous Lymphat Disord 2021 01 26;9(1):113-121.e3. Epub 2020 May 26.

Division of Vascular Surgery, Montefiore Medical Center, Bronx, NY.

Objective: Venous insufficiency is commonly bilateral, and patients often prefer single-episode care compared with staged procedures. Few studies have investigated clinical outcomes after unilateral vs bilateral venous ablation procedures or between staged and concurrent bilateral procedures. Here, we report data from the Vascular Quality Initiative regarding truncal venous ablation for chronic venous insufficiency.

Methods: Using data from the Vascular Quality Initiative, we investigated immediate postoperative as well as long-term clinical and patient-reported outcomes of patients undergoing unilateral vs bilateral truncal endovenous ablation from 2015 to 2019. We further investigated outcomes between staged bilateral and concurrent bilateral ablations. Preprocedural and postprocedural comparisons were performed using t-test, χ test, or their nonparametric counterpart when appropriate. Multivariable ordinal logistic regression was performed on ordinal outcome variables.

Results: A total of 5029 patients were included, of whom 3782 (75.2%) underwent unilateral procedures. Median follow-up was 227 days (interquartile range [IQR], 55-788 days). Unilateral patients were less likely to be female (67.0% vs 70.3%; P = .031) and white (86.3% vs 91.2%; P < .001) and had lower body mass index (30.3 ± 7.3 kg/m vs 31.8 ± 7.6 kg/m; P < .001) compared with patients undergoing bilateral procedures. In addition, unilateral patients had fewer prior varicose vein treatments (23.0% vs 15.7%; P < .001) and had higher median preprocedural Venous Clinical Severity Score (VCSS; 8 [IQR, 6-10] vs 7 [IQR, 5.5-9]; P < .001). No difference was seen in complications (6.9% vs 8.2%; P = .292), and systemic complications were rare in both groups. No difference was seen in VCSS improvement after treatment (median, 3 [IQR, 1-6] for unilateral; median, 3 [IQR 1-5] for bilateral; P = .055). In comparing staged with concurrent bilateral procedures, there was no difference in overall complications (7.5% vs 12.2%; P = .144). Staged bilateral patients were older (56.9 ± 13.3 years vs 54.2 ± 12.9 years; P = .002), less likely to have had prior varicose vein treatment (14.3% vs 19.8%; P = .020), and more likely to be therapeutically anticoagulated (10.8% vs 6.5%; P = .028) compared with concurrent bilateral patients. Staged patients also have higher preprocedural VCSS compared with concurrent patients (median, 8 [IQR, 6-10] vs 7 [IQR, 5.5-9]; P < .001). In multivariable analysis, there was no difference in the likelihood of VCSS improvement for concurrent compared with staged procedures (odds ratio, 0.70; 95% confidence interval, 0.40-1.24; P = .226).

Conclusions: Concurrent bilateral truncal endovenous ablation can be performed safely without increased morbidity compared with staged bilateral or unilateral ablations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvsv.2020.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768602PMC
January 2021

Flow dynamics, false lumens and implications for endografting.

J Vasc Surg 2020 06;71(6):2119-2120

Section of Vascular Surgery, Department of Surgery, University of Michigan Health System, Ann Arbor, Mich; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Mich.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvs.2019.06.223DOI Listing
June 2020

Closed plication is a safe and effective method for treating popliteal vein aneurysm.

J Vasc Surg Venous Lymphat Disord 2021 01 20;9(1):187-192. Epub 2020 May 20.

Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, Mich. Electronic address:

Background: Popliteal vein aneurysms are a rare vascular anomaly first reported in the 1980s. Degeneration of elastic fibers and smooth muscle cell reduction, possibly secondary to inflammation, are implicated as integral steps in the development of these aneurysms. Given the rarity of this clinical entity, significant controversy exists regarding ideal treatment strategies, including the role of observation, medical management with anticoagulation, and surgical intervention. Retrospective reviews have demonstrated a failure rate of >40% with anticoagulation alone, with patients often presenting with pulmonary embolism. This has prompted our institutional preference for surgical management once the aneurysm is identified. Surgical management involves tangential repair with lateral venorrhaphy most commonly, followed in prevalence by aneurysm resection and end-to-end anastomosis either primarily or with vein interposition. Herein, we report our results with venous plications, through both closed and open techniques.

Methods: We performed a retrospective review of prospectively collected data for 10 patients undergoing popliteal vein plication for treatment of popliteal vein aneurysms. Patient-level characteristics and operative details were examined from periprocedural and follow-up records.

Results: We identified 10 patients undergoing popliteal vein plication, including 9 closed plications and 1 open plication. The average aneurysm size at presentation was 2.35 ± 0.69 cm for closed plication and 4.74 cm for the one open plication. After treatment, the average popliteal vein size was significantly reduced to 1.12 ± 0.45 cm for the closed plications (P < .001 from preprocedural size) and 1.13 cm for the open plication with 100% primary patency. Average follow-up for patients treated with closed plication was 35.0 ± 25.2 months, during which seven (78%) patients had a stable, normal popliteal vein size. One patient with recurrence was diagnosed with Klippel-Trénaunay syndrome. The other had degeneration of the popliteal vein cranial to the previous repair at 39 months after the original operation that required additional plication. The open plication patient experienced a hematoma requiring washout and resulting in a transient peroneal mononeuropathy. There was one case of cellulitis after closed plication but no hematomas within this group.

Conclusions: Closed plication demonstrated favorable primary patency rates and low recurrence rates, avoiding technical issues or need for early institution of systemic anticoagulation associated with tangential repair and venorrhaphy or resection methods. Closed plication represents an attractive option in patients without luminal thrombus to limit the risk of these postoperative complications and obviates the need for bypass conduit and postoperative anticoagulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvsv.2020.04.026DOI Listing
January 2021

Practical diagnosis and treatment of suspected venous thromboembolism during COVID-19 pandemic.

J Vasc Surg Venous Lymphat Disord 2020 07 17;8(4):526-534. Epub 2020 Apr 17.

Department of Surgery, Section of Vascular Surgery, University of Michigan Health System, Ann Arbor, Mich. Electronic address:

A markedly increased demand for vascular ultrasound laboratory and other imaging studies in COVID-19-positive patients has occurred, due to most of these patients having a markedly elevated D-dimer and a presumed prothrombotic state in many of the very ill patients. In the present report, we have summarized a broad institutional consensus focusing on evaluation and recommended empirical therapy for COVID-19-positive patients. We recommend following the algorithms with the idea that as more data becomes available these algorithms may well change.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvsv.2020.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162794PMC
July 2020

Bleeding and thrombotic outcomes associated with postoperative use of direct oral anticoagulants after open peripheral artery bypass procedures.

J Vasc Surg 2020 12 8;72(6):1996-2005.e4. Epub 2020 Apr 8.

Section of Vascular Surgery, Department of Surgery, University of Michigan Health System, Ann Arbor, Mich. Electronic address:

Objective: Widespread adoption of direct oral anticoagulants (DOACs) for atrial fibrillation and venous thromboembolism treatment has resulted in peripheral bypass patients receiving therapeutic anticoagulation with DOACs postoperatively. This study was undertaken to evaluate patient outcomes after open peripheral bypass based on anticoagulation treatment.

Methods: Postoperative treatment and outcomes of patients undergoing peripheral bypass operations between January 2012 and December 2017 from a statewide multicenter quality improvement registry were examined. Surgeons participating in the registry were surveyed on practice patterns regarding DOACs in bypass patients. Multivariate logistic regression was performed for 30-day transfusion outcomes, and multiple linear regression was performed for length of stay.

Results: Among 9682 patients, 7685 patients received no anticoagulation, whereas 1379 received a vitamin K antagonist (VKA) and 618 received a DOAC postoperatively. Patients receiving anticoagulation compared with no anticoagulation had a higher body mass index and were more likely to have preoperative anemia, congestive heart failure, and atrial fibrillation (all P < .001). Compared with patients receiving VKAs, patients receiving DOACs were less likely to have chronic kidney disease (P = .002) and more likely to have atrial fibrillation (P < .001). The shortest length of stay was among patients receiving no anticoagulation (median, 5 days; interquartile range, 3-9 days; P < .001), followed by DOACs (median, 6 days; interquartile range 3-11 days; P < .001) and VKAs (median, 8 days; interquartile range, 5-13 days; P < .001). Compared with patients receiving VKAs postoperatively, there was no difference in readmission for anticoagulation complications, bypass thrombectomy or thrombolysis, major amputation, or graft patency at 1 year among patients receiving DOACs. On multivariate logistic regression, patients receiving a DOAC (odds ratio, 0.743; confidence interval, 0.59-0.94; P = .011) or no anticoagulation (odds ratio, 0.792; confidence interval, 0.69-0.91; P = .001) were less likely to require transfusion within 30 days than patients taking VKAs. Approximately 70% of the surveyed surgeons reported that they "sometimes" or "always" use DOACs instead of VKAs for protection of a high-risk bypass.

Conclusions: Among patients undergoing lower extremity surgical bypass, those receiving a DOAC postoperatively had a shorter length of stay and were less likely to receive a transfusion in 30 days without compromising graft patency and readmission for anticoagulation complications, thrombectomy, or thrombolysis or affecting amputation rate compared with those receiving a VKA. A majority of surgeons within the quality collaborative have adopted the use of DOACs after peripheral bypass, suggesting the need for a prospective trial evaluating DOAC safety and efficacy in patients requiring anticoagulation for high-risk bypass grafts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvs.2020.02.021DOI Listing
December 2020

Epigenetic Regulation of TLR4 in Diabetic Macrophages Modulates Immunometabolism and Wound Repair.

J Immunol 2020 05 23;204(9):2503-2513. Epub 2020 Mar 23.

Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI 48109;

Macrophages are critical for the initiation and resolution of the inflammatory phase of wound healing. In diabetes, macrophages display a prolonged inflammatory phenotype preventing tissue repair. TLRs, particularly TLR4, have been shown to regulate myeloid-mediated inflammation in wounds. We examined macrophages isolated from wounds of patients afflicted with diabetes and healthy controls as well as a murine diabetic model demonstrating dynamic expression of TLR4 results in altered metabolic pathways in diabetic macrophages. Further, using a myeloid-specific mixed-lineage leukemia 1 (MLL1) knockout ( ), we determined that MLL1 drives expression in diabetic macrophages by regulating levels of histone H3 lysine 4 trimethylation on the promoter. Mechanistically, MLL1-mediated epigenetic alterations influence diabetic macrophage responsiveness to TLR4 stimulation and inhibit tissue repair. Pharmacological inhibition of the TLR4 pathway using a small molecule inhibitor (TAK-242) as well as genetic depletion of either ( ) or myeloid-specific resulted in improved diabetic wound healing. These results define an important role for MLL1-mediated epigenetic regulation of TLR4 in pathologic diabetic wound repair and suggest a target for therapeutic manipulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.1901263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443363PMC
May 2020

Inflammatory biomarkers in deep venous thrombosis organization, resolution, and post-thrombotic syndrome.

J Vasc Surg Venous Lymphat Disord 2020 03;8(2):299-305

Section of Vascular Surgery, Department of Surgery, Michigan Medicine, University of Michigan, Ann Arbor, Mich. Electronic address:

Objective: Venous thromboembolism (VTE) is a common disease with potentially devastating and long-term sequelae, such as pulmonary embolism and post-thrombotic syndrome (PTS). Given the mortality risk, prevalence of VTE, and limited access to diagnostic imaging, clinically relevant biomarkers for diagnosis and prognostication are needed. Therefore, this review aimed to summarize the data on clinically applicable biomarkers that best indicate acute VTE and chronic PTS.

Methods: We reviewed the medical and scientific literature from 2001 to 2019 for VTE biomarkers. Randomized controlled trials, meta-analyses, and review articles were included. Primary basic research papers with no clinical applicability, opinion papers, institutional guidelines, and case reports were excluded.

Results: We highlight the diagnostic value of D-dimer alongside other promising biomarkers, including cellular adhesion molecules, P-selectin, cytokines (interleukins 6 and 10), fibrin monomer complexes, and coagulation factors (factor VIII).

Conclusions: High-sensitivity D-dimer remains the most clinically established VTE biomarker. Current research endeavors are under way to identify more precise biomarkers of VTE and PTS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvsv.2019.09.008DOI Listing
March 2020

Accessing the academic influence of vascular surgeons within the National Institutes of Health iCite database.

J Vasc Surg 2020 05 9;71(5):1741-1748.e2. Epub 2019 Dec 9.

Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, Mich. Electronic address:

Objective: A diverse array of measures are used to evaluate academic physicians. One critical factor is the scholarly influence an author has on the research discourse within a field. The National Institutes of Health recently developed the Relative Citation Ratio (RCR) as a method to quantify the influence of published research. The aim of this study was to examine the academic influence of vascular surgeons using RCR within common vascular disease research fields.

Methods: Using the PubMed and National Institutes of Health iCite databases, scientific fields of abdominal and thoracic aortic aneurysm, peripheral artery disease (PAD), cerebral vascular occlusive disease, deep venous thrombosis (DVT), and venous insufficiency were queried for the highest rated RCR articles in each category (2007-2012). To calculate the RCR, article citation rates are divided by an expected citation rate derived from performance of articles in the same field, with the resulting RCR being level and field independent. Article categories were divided into basic science, health services, and clinical research on the basis of two independent reviews. For articles, academic backgrounds of the first, second, and last authors ("influential authors") were collected analyzing procedural specialty: surgery, medicine subspecialty (cardiology, neurology, nephrology), radiology/engineering, and other (anesthesia and pediatrics). Statistical significance between scientific fields and academic background was determined using Student t-test or analysis of variance followed by Newman-Keuls post hoc test.

Results: The academic influence of vascular surgeons varied substantially by the scientific field. Vascular surgeons compared with medical specialists were found to have the highest academic influence in abdominal aortic aneurysm research, composing 51% of the influential authors on the highest rated RCR studies (5.9 ± 0.8 vs 5.6 ± 0.8; P = .6). In contrast, vascular surgeons composed only 13% of influential authors compared with medical specialists in DVT (RCR, 2.6 ± 0.3 vs 15.7 ± 1.7; P < .003) and 18% in PAD (RCR, 1.9 ± 0.5 vs 2.1 ± 0.2; P = .78) research fields. Grouping all vascular fields of study together, no difference in RCR was found between vascular surgery and radiology/engineering. However, the mean RCR was significantly lower for vascular surgeons compared with medical subspecialties (4.5 ± 0.4 vs 6.8 ± 0.5; P < .05).

Conclusions: Vascular surgeons exhibit a moderate academic influence in the field of aneurysmal disease but lag behind medical subspecialists in high-impact scientific contributions to the fields of PAD and DVT. Innovative strategies and collaborations are likely needed to increase the influence of vascular surgeons on the academic discourse of several vascular disease research fields.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvs.2019.09.036DOI Listing
May 2020

Sepsis Induces Prolonged Epigenetic Modifications in Bone Marrow and Peripheral Macrophages Impairing Inflammation and Wound Healing.

Arterioscler Thromb Vasc Biol 2019 11 5;39(11):2353-2366. Epub 2019 Sep 5.

From the Section of Vascular Surgery, Department of Surgery (F.M.D., A.D., A.D.J., A.S.K., A.T.O., W.J.M., K.A.G.), University of Michigan, Ann Arbor.

Objective: Sepsis represents an acute life-threatening disorder resulting from a dysregulated host response. For patients who survive sepsis, there remains long-term consequences, including impaired inflammation, as a result of profound immunosuppression. The mechanisms involved in this long-lasting deficient immune response are poorly defined. Approach and Results: Sepsis was induced using the murine model of cecal ligation and puncture. Following a full recovery period from sepsis physiology, mice were subjected to our wound healing model and wound macrophages (CD11b+, CD3-, CD19-, Ly6G-) were sorted. Post-sepsis mice demonstrated impaired wound healing and decreased reepithelization in comparison to controls. Further, post-sepsis bone marrow-derived macrophages and wound macrophages exhibited decreased expression of inflammatory cytokines vital for wound repair (IL [interleukin]-1β, IL-12, and IL-23). To evaluate if decreased inflammatory gene expression was secondary to epigenetic modification, we conducted chromatin immunoprecipitation on post-sepsis bone marrow-derived macrophages and wound macrophages. This demonstrated decreased expression of , an epigenetic enzyme, and impaired histone 3 lysine 4 trimethylation (activation mark) at NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells)-binding sites on inflammatory gene promoters in bone marrow-derived macrophages and wound macrophages from postcecal ligation and puncture mice. Bone marrow transplantation studies demonstrated epigenetic modifications initiate in bone marrow progenitor/stem cells following sepsis resulting in lasting impairment in peripheral macrophage function. Importantly, human peripheral blood leukocytes from post-septic patients demonstrate a significant reduction in compared with nonseptic controls.

Conclusions: These data demonstrate that severe sepsis induces stable mixed-lineage leukemia 1-mediated epigenetic modifications in the bone marrow, which are passed to peripheral macrophages resulting in impaired macrophage function and deficient wound healing persisting long after sepsis recovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/ATVBAHA.119.312754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818743PMC
November 2019

The Histone Methyltransferase Setdb2 Modulates Macrophage Phenotype and Uric Acid Production in Diabetic Wound Repair.

Immunity 2019 08 23;51(2):258-271.e5. Epub 2019 Jul 23.

Department of Surgery, University of Michigan, Ann Arbor, MI, USA; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA. Electronic address:

Macrophage plasticity is critical for normal tissue repair to ensure transition from the inflammatory to the proliferative phase of healing. We examined macrophages isolated from wounds of patients afflicted with diabetes and of healthy controls and found differential expression of the methyltransferase Setdb2. Myeloid-specific deletion of Setdb2 impaired the transition of macrophages from an inflammatory phenotype to a reparative one in normal wound healing. Mechanistically, Setdb2 trimethylated histone 3 at NF-κB binding sites on inflammatory cytokine gene promoters to suppress transcription. Setdb2 expression in wound macrophages was regulated by interferon (IFN) β, and under diabetic conditions, this IFNβ-Setdb2 axis was impaired, leading to a persistent inflammatory macrophage phenotype in diabetic wounds. Setdb2 regulated the expression of xanthine oxidase and thereby the uric acid (UA) pathway of purine catabolism in macrophages, and pharmacologic targeting of Setdb2 or the UA pathway improved healing. Thus, Setdb2 regulates macrophage plasticity during normal and pathologic wound repair and is a target for therapeutic manipulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.immuni.2019.06.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6703945PMC
August 2019

SIRT3 Regulates Macrophage-Mediated Inflammation in Diabetic Wound Repair.

J Invest Dermatol 2019 12 15;139(12):2528-2537.e2. Epub 2019 Jun 15.

Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA. Electronic address:

Control of inflammation is critical for the treatment of nonhealing wounds, but a delicate balance exists between early inflammation that is essential for normal tissue repair and the pathologic inflammation that can occur later in the repair process. This necessitates the development of novel therapies that can target inflammation at the appropriate time during repair. Here, we found that SIRT3 is essential for normal healing and regulates inflammation in wound macrophages after injury. Under prediabetic conditions, SIRT3 was decreased in wound macrophages and resulted in dysregulated inflammation. In addition, we found that FABP4 regulates SIRT3 in human blood monocytes, and inhibition of FABP4 in wound macrophages decreases inflammatory cytokine expression, making FABP4 a viable target for the regulation of excess inflammation and wound repair in diabetes. Using a series of ex vivo and in vivo studies with genetically engineered mouse models and diabetic human monocytes, we showed that FABP4 expression is epigenetically upregulated in diabetic wound macrophages and, in turn, diminishes SIRT3 expression, thereby promoting inflammation. These findings have significant implications for controlling inflammation and promoting tissue repair in diabetic wounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2019.05.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185380PMC
December 2019

Empirical systemic anticoagulation is associated with decreased venous thromboembolism in critically ill influenza A H1N1 acute respiratory distress syndrome patients.

J Vasc Surg Venous Lymphat Disord 2019 05 23;7(3):317-324. Epub 2018 Nov 23.

Acute Care Surgery, Department of Surgery, University of Michigan, Ann Arbor, Mich. Electronic address:

Background: An association between increased venous thromboembolism (VTE) events and influenza A H1N1 (H1N1) was noted in the first 10 patients with severe acute respiratory distress syndrome (ARDS). An empirical systemic anticoagulation protocol (heparin intravenous infusion) was initiated when autopsy of patients with severe hypoxemia confirmed multiple primary pulmonary thrombi and emboli. The purpose of this study was to examine the relationship between H1N1 and VTE events and to assess the efficacy of empirical systemic heparin anticoagulation in preventing VTE and death in H1N1 severe ARDS patients.

Methods: An observational cohort study of critically ill severe ARDS patients with possible H1N1 viral pneumonia was performed in a surgical intensive care unit in a single 990-bed academic tertiary care center. Early empirical systemic heparin anticoagulation for all severe ARDS patients with possible H1N1 viral pneumonia was initiated as a VTE preventive strategy.

Results: Univariate comparisons and multivariate logistic regression were used to identify risk factors for VTE. Independent risk factors for VTE included H1N1, culture-positive bacterial pneumonia, and vasopressor requirement. Independent risk factors for pulmonary embolism included H1N1, culture-positive bacterial pneumonia, and male sex. H1N1 ARDS patients had 23.3-fold higher risk for pulmonary embolism and 17.9-fold increased risk for VTE. Kaplan-Meier analysis and log-rank test confirmed that empirical systemic heparin anticoagulation provided significant protection from thrombotic events in the H1N1-positive but not in the H1N1-negative critically ill ARDs patients. In multivariate analysis, adjusting for H1N1 status, patients without empirical systemic anticoagulation were 33 times more likely to have any VTE compared with those treated with empirical systemic heparin anticoagulation (P = .01).

Conclusions: Critically ill patients with H1N1 ARDS have increased risk of venous thrombotic complications, particularly pulmonary thromboembolism. Empirical systemic heparin anticoagulation in this cohort of patients significantly reduced VTE incidence without increased hemorrhagic complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvsv.2018.08.010DOI Listing
May 2019

Venous Thrombosis and Post-Thrombotic Syndrome: From Novel Biomarkers to Biology.

Methodist Debakey Cardiovasc J 2018 Jul-Sep;14(3):173-181

UNIVERSITY OF MICHIGAN, ANN ARBOR, MICHIGAN.

Deep vein thrombosis (DVT) is a common disease that carries serious ramifications for patients, including pulmonary embolism and post-thrombotic syndrome (PTS). Although standard treatment for DVT is anticoagulation, this carries an added risk of bleeding and increased medication monitoring. Identifying those at risk for DVT and PTS can be difficult, and current research with murine models is helping to illuminate the biologic changes associated with these two disorders. Potential novel biomarkers for improving the diagnosis of DVT and PTS include ICAM-1, P-selectin, and cell-free DNA. Inhibition of factor XI, P- and E-selectin, and neutrophil extracellular traps holds promise for novel clinical treatment of DVT. Experimental research on PTS suggests potential cellular and mediator therapy targets of TLR9, MMP-2 and-9, PAI-1, and IL-6. Although many important concepts and mechanisms have been elucidated through research on DVT and PTS, more work must be done to translate experimental findings to the clinical arena. This review examines the currently used murine models of DVT, biomarkers involved in the pathophysiology and diagnosis of DVT and PTS, and potential pharmacologic targets for PTS treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14797/mdcj-14-3-173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217569PMC
January 2019

Aggressive Phenotype of Intravascular Lymphoma Relative to Other Malignant Intraabdominal Tumors Requiring Vascular Reconstruction.

Ann Vasc Surg 2019 Jan 27;54:72-83. Epub 2018 Sep 27.

Department of Surgery, Section of Vascular Surgery, University of Michigan Health System, Frankel Cardiovascular Center, Ann Arbor, MI.

Background: Safe resection of intraabdominal and retroperitoneal malignancies with a goal of negative margins may require vascular surgical assistance with grafting of the aorta and/or vena cava. The current report reviews malignancies associated with major vascular reconstructions at a single tertiary referral center.

Methods: Adults with abdominal or retroperitoneal tumors involving the aorta, vena cava, or iliac arteries that underwent reconstruction with vascular grafts at the University of Michigan from 2010 to 2016 were reviewed retrospectively. The initial presentation, surgical management, and outcomes were analyzed.

Results: Twelve patients with tumors involving the abdominal aorta, vena cava, or iliac arteries underwent major vascular reconstruction in this seven-year study period. Tumor pathology included solid tumors (leiomyosarcoma [n = 7], germ cell tumor [n = 3], and intravascular lymphoma [n = 2]). Surgical treatment included grafting of the vena cava (n = 6), aorta (n = 3), iliac artery (n = 4), or both the aorta and vena cava (n = 1). Patients with intravascular lymphoma were identified incidentally during treatment of abdominal aortic aneurysm or on pathological analysis of thromboembolism from an aortic source. Other patients had planned resection. Follow-up ranged from 9 to 86 months (median: 28.9). There were no graft occlusions. Tumor metastasized or recurred in patients with sarcoma (n = 2; 28.6%), germ cell tumor (n = 1; 33.3%), and intravascular lymphoma (n = 2; 100%). Both patients with lymphoma had multiple anastomotic or tumor-embolic pseudoaneurysms for <14 months after vascular reconstruction. Both lymphoma patients died during follow-up.

Conclusions: This single-center review suggests that sarcoma and germ cell tumors may be safely resected in conjunction with major vascular reconstruction in carefully selected patients. In comparison, intravascular lymphoma identified incidentally at the time of aortic reconstruction resulted in a more malignant course with pseudoaneurysm formation of anastomoses or native vessels, cancer recurrence, and 100% mortality. Aneurysm contents and emboli should be carefully reviewed perioperatively by pathologists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.avsg.2018.09.003DOI Listing
January 2019

Invited commentary.

J Vasc Surg Venous Lymphat Disord 2018 07;6(4):448-449

Ann Arbor, Mich.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvsv.2018.01.009DOI Listing
July 2018

Murine macrophage chemokine receptor CCR2 plays a crucial role in macrophage recruitment and regulated inflammation in wound healing.

Eur J Immunol 2018 09 26;48(9):1445-1455. Epub 2018 Jun 26.

Department of Surgery, University of Michigan, Ann Arbor, MI, USA.

Macrophages play a critical role in the establishment of a regulated inflammatory response following tissue injury. Following injury, CCR2 monocytes are recruited from peripheral blood to wound tissue, and direct the initiation and resolution of inflammation that is essential for tissue repair. In pathologic states where chronic inflammation prevents healing, macrophages fail to transition to a reparative phenotype. Using a murine model of cutaneous wound healing, we found that CCR2-deficient mice (CCR2 ) demonstrate significantly impaired wound healing at all time points postinjury. Flow cytometry analysis of wounds from CCR2 and WT mice revealed a significant decrease in inflammatory, Ly6C recruited monocyte/macrophages in CCR2 wounds. We further show that wound macrophage inflammatory cytokine production is decreased in CCR2 wounds. Adoptive transfer of mT/mG monocyte/macrophages into CCR2 and CCR2 mice demonstrated that labeled cells on days 2 and 4 traveled to wounds in both CCR2 and CCR2 mice. Further, adoptive transfer of monocyte/macrophages from WT mice restored normal healing, likely through a restored inflammatory response in the CCR2-deficient mice. Taken together, these data suggest that CCR2 plays a critical role in the recruitment and inflammatory response following injury, and that wound repair may be therapeutically manipulated through modulation of CCR2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/eji.201747400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371802PMC
September 2018

Clinical outcomes after varicose vein procedures in octogenarians within the Vascular Quality Initiative Varicose Vein Registry.

J Vasc Surg Venous Lymphat Disord 2018 07 8;6(4):464-470. Epub 2018 May 8.

Section of Vascular Surgery, University of Michigan Medical School, Ann Arbor, Mich.

Background: Whereas chronic venous insufficiency and varicose veins (VVs) are a universally recognized problem, they are frequently underappreciated as major contributors to long-term morbidity in the elderly despite the increasing prevalence with age. Previous studies have demonstrated that chronic venous insufficiency and VV treatments in patients ≥65 years old yield an overall benefit; however, there have been few data as to whether octogenarians are undergoing these procedures and with what success. As such, our objectives were to investigate the procedures selected, to examine clinical outcomes after VV procedures in elderly patients ≥80 years old, and to explore complication rates (both systemic and leg specific) after VV procedures in patients ≥80 years old.

Methods: We performed a retrospective review using the Vascular Quality Initiative Varicose Vein Registry of all VV procedures performed for ≥C2 disease from January 2015 to February 2017. We divided all procedures into three age groups: patients <65 years, patients ≥65 to 79 years, and patients ≥80 years. Statistical testing included χ test for categorical variables and Student t-test for continuous variables. Two comparisons were performed: first, comparing patients <65 years old with patients ≥65 to 79 years old; and second, comparing patients ≥65 to 79 years old with patients ≥80 years old.

Results: There were a total of 12,262 procedures performed, with 8608 procedures in the patients <65 years, 3226 in patients 65 to 79 years, and 428 procedures in patients ≥80 years. A total of 22,050 veins were treated during the 12,262 procedures. Almost half of procedures (46.51%; n = 5703) had only one vein treated during a single procedure. Between age groups, the percentage of one vein treated increased as the patient's age increased, ranging from 45.39% (n = 3875) for patients <65 years to 48.55% (n = 1555) for patients between 65 and 79 years and 64.08% (n = 273) for patients ≥80 years. Patients in the group ≥80 years had an overall lower average body mass index and were more likely to be receiving anticoagulation and to undergo truncal procedures alone compared with the other groups. The group ≥80 years had a significant improvement in both Venous Clinical Severity Score (4.37 ± 4.16; P < .001) and patient-reported outcomes (8.79 ± 7.27; P < .001) from before to after the procedure. Overall complications were low in all age groups. The octogenarians had no higher risk of systemic complications.

Conclusions: Vascular specialists are performing VV procedures in octogenarians and are more likely to perform truncal only therapy. In addition, octogenarians have statistically significant improvement of Venous Clinical Severity Score and patient-reported outcomes with a low risk of complications despite more advanced venous disease at presentation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvsv.2018.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005729PMC
July 2018

Invited commentary.

J Vasc Surg 2018 01;67(1):299

Ann Arbor, Mich.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvs.2016.12.089DOI Listing
January 2018

Risk Factors Associated with Perioperative Myocardial Infarction in Major Open Vascular Surgery.

Ann Vasc Surg 2018 Feb 8;47:24-30. Epub 2017 Sep 8.

Department of Surgery, Section of Vascular Surgery, University of Michigan, Ann Arbor, MI.

Background: Among patients undergoing noncardiac surgery, major vascular surgery is associated with a high risk of perioperative myocardial infarction (MI). Currently, there are no perioperative MI risk calculators accounting for intraoperative and postoperative risk factors in vascular surgery patients. We aimed to investigate specific risk factors for perioperative MI after major open vascular surgery to determine which patients are at highest risk of MI and the association of perioperative MI with perioperative transfusion.

Methods: This statewide, retrospective cohort study analyzed risk factors for perioperative MI in major open vascular surgery between July 2012 and December 2015 using the Michigan Surgical Quality Collaborative, a multicenter quality collaborative. Patients were identified using current procedure terminology codes including open abdominal aortic aneurysm repairs (oAAA), aortobifemoral bypasses (AFB), and lower extremity bypasses (LEB). Rates of myocardial infarction were described for each procedure. A priori, preoperative, intraoperative, and postoperative variables were evaluated using univariate and multivariable statistics after adjusting for intraoperative factors including anesthesia type, intraoperative blood loss, intraoperative transfusion, and intraoperative vasopressor medications.

Results: A total of 3,689 patients underwent major open vascular surgery, including 375 oAAA, 392 AFB, and 2,922 LEB procedures. The overall incidence of MI was 2.4%, varying from 1.8% for aortobifemoral bypass, 2.4% for lower extremity bypass, and 3.7% for open abdominal aortic aneurysm repair. Although preoperative risk factors for myocardial infarction included age, American Society of Anesthesiologists score, diabetes, coronary artery disease, congestive heart failure, use of beta blocker, lower preoperative hematocrit, and surgical priority (urgent/emergent cases), after adjusting for intraoperative risk factors, all preoperative risk factors were not significant with the exception of surgical priority. After adjusting for intraoperative factors, only surgical priority (odds ratio [OR] = 1.70, 95% confidence interval [CI] [1.01-2.85], P < 0.001) and postoperative transfusion (OR = 2.65, 95% CI [1.59-4.44], P < 0.001) was associated with myocardial infarction, and higher nadir hematocrit was inversely associated with myocardial infarction (OR = 0.89, 95% CI [0.85-0.94], P < 0.001).

Conclusions: Among vascular surgery patients undergoing major open vascular surgery, surgical priority was the only preoperative risk factors independently associated with MI, and only postoperative variables such as nadir hematocrit and postoperative transfusion were associated with MI. This suggests minimizing intraoperative blood loss and prioritizing early intraoperative transfusion may be the potential targets for process improvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.avsg.2017.08.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805566PMC
February 2018

The association of venous thromboembolism chemoprophylaxis timing on venous thromboembolism after major vascular surgery.

J Vasc Surg 2018 01 1;67(1):262-271.e1. Epub 2017 Sep 1.

Section of Vascular Surgery, University of Michigan Health System, Ann Arbor, Mich.

Objective: Venous thromboembolism (VTE) is reported to occur in up to 33% of patients undergoing major vascular surgery. Despite this high incidence, patients inconsistently receive timely VTE chemoprophylaxis. The true incidence of VTE among patients receiving delayed VTE chemoprophylaxis is unknown. We sought to identify the association of VTE chemoprophylaxis timing on VTE risk, postoperative transfusion rates, and 30-day mortality and morbidity in patients undergoing major open vascular surgery.

Methods: Patients undergoing major open vascular surgery (open abdominal aortic aneurysm [oAAA] repair, aortofemoral bypass, and lower extremity infrainguinal bypass [LEB]) were identified using the Michigan Surgical Quality Collaborative (MSQC) between July 2012 and June 2015. The VTE rate was compared between patients receiving early versus delayed VTE chemoprophylaxis. VTE chemoprophylaxis delay was defined as therapy initiation more than 24 hours after surgery. The risk-adjusted association of the chemoprophylaxis timing and VTE development was determined using multivariable logistic regression. Blood transfusion rates, 30-day mortality, and postoperative complications were compared across groups.

Results: A total of 2421 patients underwent major open vascular surgery, including 196 oAAA repair, 259 aortofemoral bypass, and 1966 LEB. The overall incidence of 30-day VTE was 1.40%, ranging from 1.12% for LEB to 3.57% for oAAA repair. Among patients receiving early VTE chemoprophylaxis, the rate of VTE was 0.78% versus 2.26% among those with a delay in VTE chemoprophylaxis (P = .002). When accounting for the preoperative risk of VTE, delayed chemoprophylaxis was associated with a significantly higher risk of VTE (odds ratio, 2.38; 95% confidence interval, 1.12-5.06; P = .024). The early VTE chemoprophylaxis group was associated with a significantly decreased risk of bleeding compared with those with a delay (14.31% vs 18.90%; P = .002). Overall 30-day mortality and postoperative complications were similar with the exception of an associated higher rate of infectious complications in the delayed VTE chemoprophylaxis group, including superficial surgical site infection (6.00% vs 4.06%; P = .028), pneumonia (3.25% vs 1.85%; P = .028), urinary tract infection (2.95% vs 1.57%; P = .020), and severe sepsis (3.05% vs 1.71%; P = .029).

Conclusions: Although patients undergoing major open vascular surgery have a low risk of VTE at baseline, there is a significantly greater risk of developing VTE among patients who have a delay in the administration of VTE chemoprophylaxis. Postoperative transfusion rates were significantly lower among patients receiving early chemoprophylaxis. There were no differences in the 30-day mortality and postoperative complications, except for infectious complications. Given these findings, surgeons should consider early chemoprophylaxis in the postoperative setting after major open vascular surgery without contraindication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvs.2017.06.087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741504PMC
January 2018

Age is not a barrier to good outcomes after varicose vein procedures.

J Vasc Surg Venous Lymphat Disord 2017 09;5(5):647-657.e1

Section of Vascular Surgery, University of Michigan Medical School, Ann Arbor, Mich.

Background: The Vascular Quality Initiative (VQI) Varicose Vein Registry (VVR) represents a patient-centered database launched in January 2015. Previous work describing overall trends and outcomes of varicose vein procedures across the United States demonstrates a benefit from these procedures. The existing gaps in evidence to support current and future Medicare coverage of varicose vein procedures necessitate further description of clinical outcomes in patients ≥65 years old compared with the population <65 years old.

Methods: This study analyzed prospectively captured anatomic, procedural, and outcome data for all patients in a national cohort of all VQI VVR-participating centers. The VQI VVR database was queried for all patients undergoing varicose vein procedures between January 2015 and July 2016. Preprocedural and postprocedural Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) classification, Venous Clinical Severity Score (VCSS), and patient-reported outcomes (PROs) were compared between patients <65 years and ≥65 years old. Univariate descriptive statistics of demographic and procedural data were performed. Student t-tests were then performed on change in CEAP classification, VCSS score, and PROs (heaviness, achiness, throbbing, swelling, itching, appearance, and impact on work) for each group.

Results: There were 4841 varicose vein procedures performed from January 2015 to May 2016. There were 3441 procedures performed in 2691 patients (3631 limbs) in the group <65 years old and 1400 procedures performed in 1068 patients (1467 limbs) in the group ≥65 years old. Truncal veins alone were the most common veins treated in both groups. The majority of patients were white and female in both groups. Most of the demographic characteristics were clinically similar (although statistically different) in both groups with the exception of a higher body mass index in the group <65 years old and a history of bilateral varicose vein treatment, and anticoagulation was more common among patients ≥65 years old. Patients in both groups experienced statistically significant improvement in VCSS, PROs, and CEAP class. There was no difference in overall complications between age groups.

Conclusions: All patients demonstrated an associated improvement in both clinical outcomes (CEAP class, VCSS) and PROs. There was no significant difference in the improvement in CEAP class and VCSS between patients younger and older than 65 years, although the younger population reported greater improvement in PROs. Given these findings, patients older than 65 years appear to benefit from varicose vein procedures and should not be denied interventions on their varicose veins and venous insufficiency on the basis of their age only.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvsv.2017.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584572PMC
September 2017

Venous Thromboembolism in Patients with Thermal Injury: A Review of Risk Assessment Tools and Current Knowledge on the Effectiveness and Risks of Mechanical and Chemical Prophylaxis.

Clin Plast Surg 2017 Jul;44(3):573-581

Department of Surgery, University of Utah Burn Center, University of Utah, 30 North 1900 East 3B400, Salt Lake City, UT 84132, USA.

Venous thromboembolism (VTE) can be a life-threatening or limb-threatening complication of thermal injury. The severity of burn injury can be used to predict VTE risk among patients with thermal injury, and a weighted risk-stratification tool has been developed. This article reviews the incidence, diagnosis, and management of thromboembolic events in patients with burns. The article particularly focuses on identifying those patients who are at highest risk for VTE and provides recommendations on mechanical and chemical prophylaxis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cps.2017.02.002DOI Listing
July 2017