Publications by authors named "Peter Henke"

292 Publications

A statewide quality improvement collaborative significantly improves quality metric adherence and physician engagement in vascular surgery.

J Vasc Surg 2021 Sep 3. Epub 2021 Sep 3.

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

Background: Quality improvement national registries provide structured, clinically relevant outcome and process-of-care data to practitioners-with regional meetings to disseminate best practices. However, whether a quality improvement collaborative affects processes of care is less clear. We examined the effects of a statewide hospital collaborative on the adherence rates to best practice guidelines in vascular surgery.

Methods: A large statewide retrospective quality improvement database was reviewed for 2013 to 2019. Hospitals participating in the quality improvement collaborative were required to submit adherence and outcomes data and meet semiannually. They received an incentive through a pay for participation model. The aggregate adherence rates among all hospitals were calculated and compared.

Results: A total of 39 hospitals participated in the collaborative, with attendance of surgeon champions at face-to-face meetings of >85%. Statewide, the hospital systems improved every year of participation in the collaborative across most "best practice" domains, including adherence to preoperative skin preparation recommendations (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.76-1.79; P < .001), intraoperative antibiotic redosing (OR, 1.09; 95% CI, 1.02-1.17; P = .018), statin use at discharge for appropriate patients (OR, 1.18; 95% CI, 1.16-1.2; P < .001), and reducing transfusions for asymptomatic patients with hemoglobin >8 mg/dL (OR, 0.66; 95% CI, 0.66-0.66; P < .001). The use of antiplatelet therapy at discharge remained high and did not change significantly during the study period. Teaching hospital and urban or rural status did not affect adherence. The adherence rates exceeded the professional society mean rates for guideline adherence.

Conclusions: The use of a statewide hospital collaborative with incentivized semiannual meetings resulted in significant improvements in adherence to "best practice" guidelines across a large, heterogeneous group of hospitals.
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http://dx.doi.org/10.1016/j.jvs.2021.07.234DOI Listing
September 2021

Angioplasty Induced Changes in Dialysis Vascular Access Compliance.

Ann Biomed Eng 2021 Sep 11;49(9):2635-2645. Epub 2021 Aug 11.

VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.

Dialysis vascular access remains vitally important to maintain life and functional capacity with end stage renal disease. Angioplasty is an integral part of maintaining dialysis access function and patency. To understand the effect of angioplasty balloon dilation on vascular wall mechanics, we conducted a clinical study to evaluate the elastic modulus of the anastomosis in five subjects with anastomosis stenoses, before and after six angioplasty procedures, using B-mode ultrasound DICOM data. A novel and open source vascular ultrasound high-resolution speckle tracking software tool was used. The median lumen diameter increased from 3.4 to 5.5 mm after angioplasty. Meanwhile, the median elastic modulus of the 18 measurements at the anastomosis increased by 52.2%, from 2.24 × 10 to 3.41 × 10 mmHg. The results support our hypothesis that the structural changes induced in the vessel wall by balloon dilation lead to reduced vascular compliance and a higher elastic modulus of the vessel wall.
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http://dx.doi.org/10.1007/s10439-021-02844-6DOI Listing
September 2021

Impact of a regional smoking cessation intervention for vascular surgery patients.

J Vasc Surg 2021 Jul 21. Epub 2021 Jul 21.

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

Objective: Tobacco use is common among vascular surgery patients and negatively impacts outcomes and longevity. In the second quarter of 2018, a statewide vascular quality collaborative launched an initiative across its 35 participating hospitals to promote smoking cessation at the time of surgery. This intervention was based on the Vascular Physician Offer and Report (VAPOR) trial and consisted of 3 components: brief physician-delivered advice, referral to telephone-based counseling, and nicotine replacement therapy. The goal of this study is to evaluate the results of this intervention.

Methods: We performed a retrospective analysis of patients undergoing vascular surgery between 2018 and 2020. Procedures included open abdominal aortic aneurysm repair, endovascular aneurysm repair, open vascular bypass, open thrombectomy, carotid endarterectomy, and carotid stenting. The primary explanatory variables were receipt of tobacco cessation interventions as documented in the medical record. The primary outcome was tobacco cessation, captured during 30-day and 1-year chart review and/or patient follow-up. A multivariable logistic regression model was calculated to estimate the association of covariates with smoking cessation while adjusting for patient and clinical characteristics.

Results: A total of 13,890 patients underwent surgery during the study period. The mean age was 69.4 ± 10 years; 4687 patients (34%) were female, and 5158 patients (37%) were current smokers. At least one smoking cessation component was delivered to 2245 patients (44% of smokers). The quit rate was 35% among 4671 patients with 30-day follow-up and 43% among 2936 patients with 1-year follow up. On multivariable regression, at 30 days, receiving two intervention components was associated with 1.29 (95% confidence interval [CI], 1.07-1.55) higher odds of quitting. At both time points, smoking cessation was also associated with undergoing an emergent procedure (30-day odds ratio [OR], 1.52; 95% CI, 1.16-1.99; 1-year OR, 1.41; 95% CI, 1.01-1.97) and undergoing open abdominal aortic aneurysm repair (30-day OR, 1.71; 95% CI, 1.20-2.43; 1-year OR, 1.75; 95% CI, 1.11-2.78).

Conclusions: In a cohort of vascular surgical patients where tobacco use was common, nearly one-half of patients quit smoking 1 year after surgery. Receiving two smoking cessation intervention components was associated with quitting at 30 days. Overall, these results demonstrate encouraging quit rates and identify an opportunity for longer-term intervention to maintain even greater 1-year tobacco cessation.
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http://dx.doi.org/10.1016/j.jvs.2021.07.103DOI Listing
July 2021

Prevalence of coronary risk factors in contemporary practice among patients undergoing their first percutaneous coronary intervention: Implications for primary prevention.

PLoS One 2021 9;16(6):e0250801. Epub 2021 Jun 9.

University of Michigan Health System, Ann Arbor, MI, United States of America.

Background: Cigarette smoking, hypertension, dyslipidemia, diabetes, and obesity are conventional risk factors (RFs) for coronary artery disease (CAD). Population trends for these RFs have varied in recent decades. Consequently, the risk factor profile for patients presenting with a new diagnosis of CAD in contemporary practice remains unknown.

Objectives: To examine the prevalence of RFs and their temporal trends among patients without a history of myocardial infarction or revascularization who underwent their first percutaneous coronary intervention (PCI).

Methods: We examined the prevalence and temporal trends of RFs among patients without a history of prior myocardial infarction, PCI, or coronary artery bypass graft surgery who underwent PCI at 47 non-federal hospitals in Michigan between 1/1/2010 and 3/31/2018.

Results: Of 69,571 men and 38,930 women in the study cohort, 95.5% of patients had 1 or more RFs and nearly half (55.2% of women and 48.7% of men) had ≥3 RFs. The gap in the mean age at the time of presentation between men and women narrowed as the number of RFs increased with a gap of 6 years among those with 2 RFs to <1 year among those with 5 RFs. Compared with patients without a current/recent history of smoking, those with a current/recent history of smoking presented a decade earlier (age 56.8 versus 66.9 years; p <0.0001). Compared with patients without obesity, patients with obesity presented 4.0 years earlier (age 61.4 years versus 65.4 years; p <0.0001).

Conclusions: Modifiable RFs are widely prevalent among patients undergoing their first PCI. Smoking and obesity are associated with an earlier age of presentation. Population-level interventions aimed at preventing obesity and smoking could significantly delay the onset of CAD and the need for PCI.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250801PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189482PMC
June 2021

Detecting High-Resolution Intramural Vascular Wall Strain Signals Using DICOM Data.

ASAIO J 2021 May 28. Epub 2021 May 28.

From the Research Service, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USA Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan Department of Statistics, University of Michigan, Ann Arbor, Michigan Michigan Tech Research Institute, Michigan Technological University, Ann Arbor, Michigan Department of Psychiatry, University of Michigan, Ann Arbor, Michigan Radiology, Weill Cornell Medicine, New York City, New York Radiology, Rocky Vista University, Ivins, Utah Emerge Now Inc., Los Angeles, California Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan Department of Mechanical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts Departments of Radiology and Surgery, University of Michigan, Ann Arbor, Michigan.

Maintaining dialysis vascular access is a source of considerable morbidity in patients with end-stage renal disease (ESRD). High-resolution radiofrequency (RF) ultrasound vascular strain imaging has been applied experimentally in the vascular access setting to assist in diagnosis and management. Unfortunately, high-resolution RF data are not routinely accessible to clinicians. In contrast, the standard DICOM formatted B-mode ultrasound data are widely accessible. However, B-mode, representing the envelope of the RF signal, is of much lower resolution. If strain imaging could use open-source B-mode data, these imaging techniques could be more broadly investigated. We conducted experiments to detect wall strain signals with submillimeter tracking resolutions ranging from 0.2 mm (3 pixels) to 0.65 mm (10 pixels) using DICOM B-mode data. We compared this submillimeter tracking to the overall vascular distensibility as the reference measurements to see if high-strain resolution strain could be detected using open-source B-Mode data. We measured the best-fit coefficient of determination between signals, expressed as the percentage of strain waveforms that exhibited a correlation with a p value of 0.05 or less. The lowest percentage was 86.7%, and most were 90% and higher. This indicates high-resolution strain signals can be detected within the vessel wall using B-mode DICOM data.
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http://dx.doi.org/10.1097/MAT.0000000000001490DOI Listing
May 2021

A narrative review on the epidemiology, prevention, and treatment of venous thromboembolic events in the context of chronic venous disease.

J Vasc Surg Venous Lymphat Disord 2021 Apr 16. Epub 2021 Apr 16.

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

Objective: Chronic venous disease (CVD) describes a spectrum of conditions associated with venous hypertension. The association between various CVD etiologies and the subsequent risk of venous thromboembolism (VTE), such as deep vein thrombosis or pulmonary embolism, is a topic of considerable clinical interest. The aims of the present review were to characterize the risk of VTE according to the CVD etiology and to determine the optimal anticoagulation strategy for the treatment or prevention of VTE in patients with CVD.

Methods: An extensive search of the available surgical and medical data was conducted in PubMed and Google Scholar. We searched for the following terms and other related terms to identify relevant studies: CVD, chronic venous insufficiency, varicose veins, post-thrombotic syndrome (PTS), anticoagulation, venous thromboembolism, and venous disease scoring systems (eg, CEAP [clinical, etiology, anatomic, pathophysiology], Villalta, Ginsberg, venous clinical severity score). The identified studies included randomized control trials, retrospective and prospective observational studies, narrative and systematic reviews, case reports, and case series that contributed to the proposed aims. The ClinicalTrials.gov database was also queried to identify any relevant ongoing clinical trials.

Results: Congenital CVD carries a heightened risk of VTE, although few higher level studies are available to inform on this topic or on the appropriate anticoagulation strategies for these patients. Noncongenital CVD seems to carry a heightened risk of VTE, although few studies have adequately differentiated between primary and secondary etiologies. Varicose veins are a risk factor for primary VTE but might not be associated with an increased risk of recurrent VTE. In the hospital setting, patients with varicosities should be provided thromboprophylaxis. In the setting of varicose vein intervention, high-risk patients should be identified using risk assessment models and receive thromboprophylaxis. The risk of recurrent VTE in the setting of PTS is unclear but indefinite anticoagulation is not currently indicated. For patients with PTS, residual vein thrombosis might be an indicator of when anticoagulation can be safely stopped, although practical limitations to its application exist.

Conclusions: CVD is associated with an increased risk of VTE. Few studies have differentiated between classes of CVD using a standardized method and have assessed the efficacy of anticoagulation prophylaxis against or treatment of VTE. Additional studies are needed to determine the optimal therapy for preventing and treating VTE in patients with active concurrent CVD.
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http://dx.doi.org/10.1016/j.jvsv.2021.03.018DOI Listing
April 2021

Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging Predicts Vein Wall Scarring and Statin Benefit in Murine Venous Thrombosis.

Circ Cardiovasc Imaging 2021 03 16;14(3):e011898. Epub 2021 Mar 16.

Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA (C.W.K., G.Q., F.A.J.).

Background: The postthrombotic syndrome is a common, often morbid sequela of venous thrombosis (VT) that arises from thrombus persistence and inflammatory scarring of juxtaposed vein walls and valves. Noninvasive F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging can measure neutrophil inflammation in VT. Here, we hypothesized (1) early fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) VT inflammation can predict subsequent vein wall scarring (VWS) and (2) statin therapy can reduce FDG-PET VT inflammation and subsequent VWS.

Methods: C57BL/6J mice (n=75) underwent induction of stasis-induced VT of the inferior vena cava or jugular vein. Inferior vena cava VT mice (n=44) were randomized to daily oral rosuvastatin 5 mg/kg or saline starting at day -1. Subgroups of mice then underwent FDG-PET/CT 2 days after VT induction. On day 14, a subset of mice was euthanized, and VWS was assessed via histology. In vitro studies were further performed on bone marrow-derived neutrophils.

Results: Statin therapy reduced early day 2 FDG-PET VT inflammation, thrombus neutrophil influx, and plasma IL (interleukin)-6 levels. At day 14, statin therapy reduced VWS but did not affect day 2 thrombus mass, cholesterol, or white blood counts, nor reduce day 2 glucose transporter 1 or myeloperoxidase expression in thrombus or in isolated neutrophils. In survival studies, the day 2 FDG-PET VT inflammation signal as measured by mean and maximum standardized uptake values predicted the extent of day 14 VWS (area under the receiver operating characteristic curve =0.82) with a strong correlation coefficient () of =0.73 and =0.74, respectively. Mediation analyses revealed that 40% of the statin-induced VWS reduction was mediated by reductions in VT inflammation as quantified by FDG-PET.

Conclusions: Early noninvasive FDG-PET/CT imaging of VT inflammation predicts the magnitude of subsequent VWS and may provide a new translatable approach to identify individuals at risk for postthrombotic syndrome and to assess anti-inflammatory postthrombotic syndrome therapies, such as statins.
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http://dx.doi.org/10.1161/CIRCIMAGING.120.011898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202732PMC
March 2021

Exploring the rapid expansion of office-based laboratories and peripheral vascular interventions across the United States.

J Vasc Surg 2021 09 19;74(3):997-1005.e1. Epub 2021 Feb 19.

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

Objective: To characterize the relationship between office-based laboratory (OBL) use and Medicare payments for peripheral vascular interventions (PVI).

Methods: Using the Centers for Medicare and Medicaid Services Provider Utilization and Payment Data Public Use Files from 2014 to 2017, we identified providers who performed percutaneous transluminal angioplasty, stent placement, and atherectomy. Procedures were aggregated at the provider and hospital referral region (HRR) level.

Results: Between 2014 and 2017, 2641 providers performed 308,247 procedures. The mean payment for OBL stent placement in 2017 was $4383.39, and mean payment for OBL atherectomy was $13,079.63. The change in the mean payment amount varied significantly, from a decrease of $16.97 in HRR 146 to an increase of $43.77 per beneficiary over the study period in HRR 11. The change in the rate of PVI also varied substantially, and moderately correlated with change in payment across HRRs (R = 0.40; P < .001). The majority of HRRs experienced an increase in rate of PVI within OBLs, which strongly correlated with changes in payments (R = 0.85; P < .001). Furthermore, 85% of the variance in change in payment was explained by increases in OBL atherectomy (P < .001).

Conclusions: A rapid shift into the office setting for PVIs occurred within some HRRs, which was highly geographically variable and was strongly correlated with payments. Policymakers should revisit the current payment structure for OBL use and, in particular atherectomy, to better align the policy with its intended goals.
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http://dx.doi.org/10.1016/j.jvs.2021.01.061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373995PMC
September 2021

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

J Thromb Haemost 2021 06 17;19(6):1387-1389. Epub 2021 Feb 17.

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

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

Using Payment Incentives to Decrease Atherectomy Overutilization.

Ann Vasc Surg 2021 05 21;73:144-146. Epub 2021 Jan 21.

Department of Surgery, University of Michigan, Ann Arbor, MI; Center for Healthcare Outcomes and Policy, University of Michigan, Ann Arbor, MI.

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http://dx.doi.org/10.1016/j.avsg.2021.01.061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187266PMC
May 2021

Time-Restricted Salutary Effects of Blood Flow Restoration on Venous Thrombosis and Vein Wall Injury in Mouse and Human Subjects.

Circulation 2021 Mar 15;143(12):1224-1238. Epub 2021 Jan 15.

Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (W.L., C.W.K., M.O., L.W., A.T., F.A.J.).

Background: Up to 50% of patients with proximal deep vein thrombosis (DVT) will develop the postthrombotic syndrome characterized by limb swelling and discomfort, hyperpigmentation, skin ulcers, and impaired quality of life. Although catheter-based interventions enabling the restoration of blood flow (RBF) have demonstrated little benefit on postthrombotic syndrome, the impact on the acuity of the thrombus and mechanisms underlying this finding remain obscure. In experimental and clinical studies, we examined whether RBF has a restricted time window for improving DVT resolution.

Methods: First, experimental stasis DVT was generated in C57/BL6 mice (n=291) by inferior vena cava ligation. To promote RBF, mice underwent mechanical deligation with or without intravenous recombinant tissue plasminogen activator administered 2 days after deligation. RBF was assessed over time by ultrasonography and intravital microscopy. Resected thrombosed inferior vena cava specimens underwent thrombus and vein wall histological and gene expression assays. Next, in a clinical study, we conducted a post hoc analysis of the ATTRACT (Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis) pharmacomechanical catheter-directed thrombolysis (PCDT) trial (NCT00790335) to assess the effects of PCDT on Venous Insufficiency Epidemiological and Economic Study quality-of-life and Villalta scores for specific symptom-onset-to-randomization timeframes.

Results: Mice that developed RBF by day 4, but not later, exhibited reduced day 8 thrombus burden parameters and reduced day 8 vein wall fibrosis and inflammation, compared with controls. In mice without RBF, recombinant tissue plasminogen activator administered at day 4, but not later, reduced day 8 thrombus burden and vein wall fibrosis. It is notable that, in mice already exhibiting RBF by day 4, recombinant tissue plasminogen activator administration did not further reduce thrombus burden or vein wall fibrosis. In the ATTRACT trial, patients receiving PCDT in an intermediate symptom-onset-to-randomization timeframe of 4 to 8 days demonstrated maximal benefits in Venous Insufficiency Epidemiological and Economic Study quality-of-life and Villalta scores (between-group difference=8.41 and 1.68, respectively, <0.001 versus patients not receiving PCDT). PCDT did not improve postthrombotic syndrome scores for patients having a symptom-onset-to-randomization time of <4 days or >8 days.

Conclusions: Taken together, these data illustrate that, within a restricted therapeutic window, RBF improves DVT resolution, and PCDT may improve clinical outcomes. Further studies are warranted to examine the value of time-restricted RBF strategies to reduce postthrombotic syndrome in patients with DVT.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.049096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988304PMC
March 2021

Modeling the elective vascular surgery recovery after coronavirus disease 2019: Implications for moving forward.

J Vasc Surg 2021 06 25;73(6):1876-1880.e1. Epub 2020 Nov 25.

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

Objective: The delays in elective surgery caused by the coronavirus disease 2019 (COVID-19) pandemic have resulted in a substantial backlog of cases. In the present study, we sought to determine the estimated time to recovery for vascular surgery procedures delayed by the COVID-19 pandemic in a regional health system.

Methods: Using data from a 35-hospital regional vascular surgical collaborative consisting of all hospitals performing vascular surgery in the state of Michigan, we estimated the number of delayed surgical cases for adults undergoing carotid endarterectomy, carotid stenting, endovascular and open abdominal aortic aneurysm repair, and lower extremity bypass. We used seasonal autoregressive integrated moving average models to predict the surgical volume in the absence of the COVID-19 pandemic and historical data to predict the elective surgical recovery time.

Results: The median statewide monthly vascular surgical volume for the study period was 439 procedures, with a maximum statewide monthly case volume of 519 procedures. For the month of April 2020, the elective vascular surgery procedural volume decreased by ∼90%. Significant variability was seen in the estimated hospital capacity and estimated number of backlogged cases, with the recovery of elective cases estimated to require ∼8 months. If hospitals across the collaborative were to share the burden of backlogged cases, the recovery could be shortened to ∼3 months.

Conclusions: In the present study of vascular surgical volume in a regional health collaborative, elective surgical procedures decreased by 90%, resulting in a backlog of >700 cases. The recovery time if all hospitals in the collaborative were to share the burden of backlogged cases would be reduced from 8 months to 3 months, underscoring the necessity of regional and statewide policies to minimize patient harm by delays in recovery for elective surgery.
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http://dx.doi.org/10.1016/j.jvs.2020.11.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687586PMC
June 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.
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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.
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http://dx.doi.org/10.1016/j.jvsv.2020.08.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834652PMC
January 2021

Managing suspected venous thromboembolism when a pandemic limits diagnostic testing.

Thromb Res 2020 12 19;196:213-214. Epub 2020 Aug 19.

Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, United States of America; Department of Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, United States of America.

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http://dx.doi.org/10.1016/j.thromres.2020.08.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437535PMC
December 2020

Venous Thromboembolism Research Priorities: A Scientific Statement From the American Heart Association and the International Society on Thrombosis and Haemostasis.

Circulation 2020 08 8;142(6):e85-e94. Epub 2020 Jul 8.

Venous thromboembolism is a major cause of morbidity and mortality. The impact of the US Surgeon General's in 2008 has been lower than expected given the public health impact of this disease. This scientific statement highlights future research priorities in venous thromboembolism, developed by experts and a crowdsourcing survey across 16 scientific organizations. At the fundamental research level (T0), researchers need to identify pathobiological causative mechanisms for the 50% of patients with unprovoked venous thromboembolism and to better understand mechanisms that differentiate hemostasis from thrombosis. At the human level (T1), new methods for diagnosing, treating, and preventing venous thromboembolism will allow tailoring of diagnostic and therapeutic approaches to individuals. At the patient level (T2), research efforts are required to understand how foundational evidence impacts care of patients (eg, biomarkers). New treatments, such as catheter-based therapies, require further testing to identify which patients are most likely to experience benefit. At the practice level (T3), translating evidence into practice remains challenging. Areas of overuse and underuse will require evidence-based tools to improve care delivery. At the community and population level (T4), public awareness campaigns need thorough impact assessment. Large population-based cohort studies can elucidate the biological and environmental underpinnings of venous thromboembolism and its complications. To achieve these goals, funding agencies and training programs must support a new generation of scientists and clinicians who work in multidisciplinary teams to solve the pressing public health problem of venous thromboembolism.
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http://dx.doi.org/10.1161/CIR.0000000000000818DOI Listing
August 2020

Venous thromboembolism research priorities: A scientific statement from the American Heart Association and the International Society on Thrombosis and Haemostasis.

Res Pract Thromb Haemost 2020 Jul 8;4(5):714-721. Epub 2020 Jul 8.

Department of Pathology and Laboratory Medicine UNC Blood Research Center University of North Carolina at Chapel Hill Chapel Hill NC USA.

Venous thromboembolism (VTE) is a major cause of morbidity and mortality. The impact of the Surgeon General's Call to Action in 2008 has been lower than expected given the public health impact of this disease. This scientific statement highlights future research priorities in VTE, developed by experts and a crowdsourcing survey across 16 scientific organizations. At the fundamental research level (T0), researchers need to identify pathobiologic causative mechanisms for the 50% of patients with unprovoked VTE and better understand mechanisms that differentiate hemostasis from thrombosis. At the human level (T1), new methods for diagnosing, treating, and preventing VTE will allow tailoring of diagnostic and therapeutic approaches to individuals. At the patient level (T2), research efforts are required to understand how foundational evidence impacts care of patients (eg, biomarkers). New treatments, such as catheter-based therapies, require further testing to identify which patients are most likely to experience benefit. At the practice level (T3), translating evidence into practice remains challenging. Areas of overuse and underuse will require evidence-based tools to improve care delivery. At the community and population level (T4), public awareness campaigns need thorough impact assessment. Large population-based cohort studies can elucidate the biologic and environmental underpinings of VTE and its complications. To achieve these goals, funding agencies and training programs must support a new generation of scientists and clinicians who work in multidisciplinary teams to solve the pressing public health problem of VTE.
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http://dx.doi.org/10.1002/rth2.12373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354403PMC
July 2020

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

Reply.

J Vasc Surg Venous Lymphat Disord 2020 09 1;8(5):899-900. Epub 2020 Jun 1.

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

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http://dx.doi.org/10.1016/j.jvsv.2020.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263224PMC
September 2020

Fenestrated repair improves perioperative outcomes but lacks a hospital volume association for complex abdominal aortic aneurysms.

J Vasc Surg 2021 02 27;73(2):417-425.e1. Epub 2020 May 27.

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

Background: Complex abdominal aortic aneurysms (AAAs) have traditionally been treated with an open surgical repair (OSR). During the past decade, fenestrated endovascular aneurysm repair (FEVAR) has emerged as a viable option. Hospital procedural volume to outcome relationship for OSR of complex AAAs has been well established, but the impact of procedural volume on FEVAR outcomes remains undefined. This study investigated the outcomes of OSR and FEVAR for the treatment of complex AAAs and examined the hospital volume-outcome relationship for these procedures.

Methods: A retrospective review of a statewide vascular surgery registry was queried for all patients between 2012 and 2018 who underwent elective repair of a juxtarenal/pararenal AAA with FEVAR or OSR. The primary outcomes were 30-day mortality, myocardial infarction, and new dialysis. Secondary end points included postoperative pneumonia, renal dysfunction (creatine concentration increase of >2 mg/dL from preoperative baseline), major bleeding, early procedural complications, length of stay, and need for reintervention. To evaluate procedural volume-outcomes relationship, hospitals were stratified into low- and high-volume aortic centers based on a FEVAR annual procedural volume. To account for baseline differences, we calculated propensity scores and employed inverse probability of treatment weighting in comparing outcomes between treatment groups.

Results: A total of 589 patients underwent FEVAR (n = 186) or OSR (n = 403) for a complex AAA. After adjustment, OSR was associated with higher rates of 30-day mortality (10.7% vs 2.9%; P < .001) and need for dialysis (11.3% vs 1.8; P < .001). Postoperative pneumonia (6.8% vs 0.3%; P < .001) and need for transfusion (39.4% vs 10.4%; P < .001) were also significantly higher in the OSR cohort. The median length of stay for OSR and FEVAR was 9 days and 3 days, respectively. For those who underwent FEVAR, endoleaks were present in 12.1% of patients at 30 days and 6.1% of patients at 1 year, with the majority being type II. With a median follow-up period of 331 days (229-378 days), 1% of FEVAR patients required a secondary procedure, and there were no FEVAR conversions to an open aortic repair. Hospitals were divided into low- and high-volume aortic centers based on their annual FEVAR volume of complex AAAs. After adjustment, hospital FEVAR procedural volume was not associated with 30-day mortality or myocardial infarction.

Conclusions: FEVAR was associated with lower perioperative morbidity and mortality compared with OSR for the management of complex AAAs. Procedural FEVAR volume outcome analysis suggests limited differences in 30-day morbidity, although long-term durability warrants further research.
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http://dx.doi.org/10.1016/j.jvs.2020.05.039DOI Listing
February 2021

Insights from experimental post-thrombotic syndrome and potential for novel therapies.

Transl Res 2020 11 19;225:95-104. Epub 2020 May 19.

From the University of Michigan Health System, Frankel Cardiovascular Center, Ann Arbor, MI.

Post-thrombotic syndrome (PTS) is an end stage manifestation of deep vein thrombosis. This is an inherently inflammatory process, with consequent fibrosis. Multiple cellular types are involved, and are likely driven by leukocytes. Herein, we review the current gaps in therapy, and insights from rodent models of venous thrombosis that suggest possible targets to treat and prevent PTS.
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http://dx.doi.org/10.1016/j.trsl.2020.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487018PMC
November 2020

Stress Gastric Ulcers and Cytoprotective Strategies: Perspectives and Trends.

Curr Pharm Des 2020 ;26(25):2982-2990

St. Francis Xavier University, Antigonish, Nova Scotia, B2G 2W5, Canada.

Stress gastric ulceration is a clinical condition leading to morbidity/mortality and complex etiopathological factors are involved. Pharmacotherapy of such gastric mucosal lesions is not consistent and novel strategies are being explored. Targeting gastrointestinal factors have showed equivocal results and there is a possibility of involvement of extra-gastrointestinal factors. Stress is a highly interactive biological response in which the brain plays a key role. The involvement of brain substrates like the limbic system (amygdala, cortex, hippocampus) and behavioral traits has been investigated and research data has shown that the limbic brain-gut axis may be involved in the regulation of gastric mucosal integrity during stressful situations. The amygdaloid complex, its connections with other limbic structures and their neural networks act in tandem to contribute to both stress ulceration and gastroprotection. Complex neurotransmitter interactions in these areas involving biogenic amines and neuropeptides have been shown to modulate stress ulcerogenesis in experimental models. The immune system and brain-immune interactions also appear to play a decisive role in the genesis of such stress gastric lesions and the possibility of a brain-gut-immune axis has been proposed during stress gastric lesions. More recent studies have shown the involvement of oxidative stress and nitric oxide as well as their interactions during such stress gastric pathology, indicating the possible role of antioxidants and NO modulators as gastroprotective agents for stress ulceration. In view of the complex pathophysiology, multiple targets and lack of consistent therapeutic modalities, newer/alternative hypotheses are constantly emerging, which could be explored for effective treatment strategies aimed at gastric cytoprotection. Herbal agents with adaptogenic properties could be worth exploring in this regard as some of these phytopharmaceutical agents used in traditional medicine have been shown to exhibit gastric cytoprotection as part of their anti-stress profile. Further, their interactions with brain neurotransmitters and immune mechanisms and their relative safety could make them prospective leads for stress ulcer prophylaxis and treatment.
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http://dx.doi.org/10.2174/1381612826666200521143203DOI Listing
January 2021

Call to Action to Prevent Venous Thromboembolism in Hospitalized Patients: A Policy Statement From the American Heart Association.

Circulation 2020 06 7;141(24):e914-e931. Epub 2020 May 7.

Venous thromboembolism (VTE) is a major preventable disease that affects hospitalized inpatients. Risk stratification and prophylactic measures have good evidence supporting their use, but multiple reasons exist that prevent full adoption, compliance, and efficacy that may underlie the persistence of VTE over the past several decades. This policy statement provides a focused review of VTE, risk scoring systems, prophylaxis, and tracking methods. From this summary, 5 major areas of policy guidance are presented that the American Heart Association believes will lead to better implementation, tracking, and prevention of VTE events. They include performing VTE risk assessment and reporting the level of VTE risk in all hospitalized patients, integrating preventable VTE as a benchmark for hospital comparison and pay-for-performance programs, supporting appropriations to improve public awareness of VTE, tracking VTE nationwide with the use of standardized definitions, and developing a centralized data steward for data tracking on VTE risk assessment, prophylaxis, and rates.
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http://dx.doi.org/10.1161/CIR.0000000000000769DOI Listing
June 2020

Assessment for dementia in vascular surgical patients should be routine.

Authors:
Peter Henke

J Vasc Surg 2020 05;71(5):1691

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

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http://dx.doi.org/10.1016/j.jvs.2019.08.226DOI Listing
May 2020

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

Thrombo-Inflammation in Cardiovascular Disease: An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis.

Thromb Haemost 2020 Apr 14;120(4):538-564. Epub 2020 Apr 14.

Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Haemostasis Research Unit, University College London, London, United Kingdom.

Thrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating cells and thrombo-inflammation, focused on platelets, neutrophils, and neutrophil extracellular traps; (3) procoagulant mechanisms; (4) arterial vascular changes in atherogenesis; attenuating atherosclerosis and ischemia/reperfusion injury; (5) management of patients with arterial vascular disease; and (6) pathogenesis of venous thrombosis and late consequences of venous thromboembolism.
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http://dx.doi.org/10.1055/s-0040-1708035DOI Listing
April 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.
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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.
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http://dx.doi.org/10.4049/jimmunol.1901263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443363PMC
May 2020

Resolution of Deep Venous Thrombosis: Proposed Immune Paradigms.

Int J Mol Sci 2020 Mar 18;21(6). Epub 2020 Mar 18.

School of Medicine, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.

Venous thromboembolism (VTE) is a pathology encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE) associated with high morbidity and mortality. Because patients often present after a thrombus has already formed, the mechanisms that drive DVT resolution are being investigated in search of treatment. Herein, we review the current literature, including the molecular mechanisms of fibrinolysis and collagenolysis, as well as the critical cellular roles of macrophages, neutrophils, and endothelial cells. We propose two general models for the operation of the immune system in the context of venous thrombosis. In early thrombus resolution, neutrophil influx stabilizes the tissue through NETosis. Meanwhile, macrophages and intact neutrophils recognize the extracellular DNA by the TLR9 receptor and induce fibrosis, a complimentary stabilization method. At later stages of resolution, pro-inflammatory macrophages police the thrombus for pathogens, a role supported by both T-cells and mast cells. Once they verify sterility, these macrophages transform into their pro-resolving phenotype. Endothelial cells both coat the stabilized thrombus, a necessary early step, and can undergo an endothelial-mesenchymal transition, which impedes DVT resolution. Several of these interactions hold promise for future therapy.
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http://dx.doi.org/10.3390/ijms21062080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139924PMC
March 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.
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http://dx.doi.org/10.1016/j.jvsv.2019.09.008DOI Listing
March 2020
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