IU Indianapolis ScholarWorks :: Browsing by Author "Gutwein, Ashley R."

Browsing by Author "Gutwein, Ashley R."

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Clinical and Laboratory characteristics of patients with COVID-19 Infection and Deep Venous Thrombosis
(Elsevier, 2020-10-22) Motaganahalli, Raghu L.; Kapoor, Rajat; Timsina, Lava R.; Gutwein, Ashley R.; Ingram, Michael D.; Raman, Subha; Roberts, Scott D.; Rahman, Omar; Rollins, David; Dalsing, Michael C.; Surgery, School of Medicine
Objective: Early reports suggest that patients with novel coronavirus disease-2019 (COVID-19) infection carry a significant risk of altered coagulation with an increased risk for venous thromboembolic events. This report investigates the relationship of significant COVID-19 infection and deep venous thrombosis (DVT) as reflected in the patient clinical and laboratory characteristics. Methods: We reviewed the demographics, clinical presentation, laboratory and radiologic evaluations, results of venous duplex imaging and mortality of COVID-19-positive patients (18-89 years) admitted to the Indiana University Academic Health Center. Using oxygen saturation, radiologic findings, and need for advanced respiratory therapies, patients were classified into mild, moderate, or severe categories of COVID-19 infection. A descriptive analysis was performed using univariate and bivariate Fisher's exact and Wilcoxon rank-sum tests to examine the distribution of patient characteristics and compare the DVT outcomes. A multivariable logistic regression model was used to estimate the adjusted odds ratio of experiencing DVT and a receiver operating curve analysis to identify the optimal cutoff for d-dimer to predict DVT in this COVID-19 cohort. Time to the diagnosis of DVT from admission was analyzed using log-rank test and Kaplan-Meier plots. Results: Our study included 71 unique COVID-19-positive patients (mean age, 61 years) categorized as having 3% mild, 14% moderate, and 83% severe infection and evaluated with 107 venous duplex studies. DVT was identified in 47.8% of patients (37% of examinations) at an average of 5.9 days after admission. Patients with DVT were predominantly male (67%; P = .032) with proximal venous involvement (29% upper and 39% in the lower extremities with 55% of the latter demonstrating bilateral involvement). Patients with DVT had a significantly higher mean d-dimer of 5447 ± 7032 ng/mL (P = .0101), and alkaline phosphatase of 110 IU/L (P = .0095) than those without DVT. On multivariable analysis, elevated d-dimer (P = .038) and alkaline phosphatase (P = .021) were associated with risk for DVT, whereas age, sex, elevated C-reactive protein, and ferritin levels were not. A receiver operating curve analysis suggests an optimal d-dimer value of 2450 ng/mL cutoff with 70% sensitivity, 59.5% specificity, and 61% positive predictive value, and 68.8% negative predictive value. Conclusions: This study suggests that males with severe COVID-19 infection requiring hospitalization are at highest risk for developing DVT. Elevated d-dimers and alkaline phosphatase along with our multivariable model can alert the clinician to the increased risk of DVT requiring early evaluation and aggressive treatment
Cryopreserved Homografts in Infected Infrainguinal Fields Are Associated with Frequent Reinterventions and Poor Amputation-Free Survival
(Elsevier, 2018) Wang, S. Keisin; Gutwein, Ashley R.; Drucker, Natalie A.; Murphy, Michael P.; Fajardo, Andres; Dalsing, Michael C.; Motaganahalli, Raghu L.; Lemmon, Gary W.; Surgery, School of Medicine
Background Single-length saphenous vein continues to be the conduit of choice in infected-field critical limb ischemia. However, half of these individuals have inadequate vein secondary to previous use or chronic venous disease. We reviewed our outcomes of infected-field infrainguinal bypasses performed with cryopreserved homografts (CHs), a widely accepted alternative to autogenous vein in this setting. Methods This is a retrospective, institutional descriptive analysis of infected-field infrainguinal revascularizations between 2012 and 2015. Results Twenty-four operations were performed in the same number of patients for limb ischemia with signs of active infection. The mean age of the cohort examined was 62.5 ± 14.4 (standard deviation) years. Mean Society of Vascular Surgery risk score was 3.9 with a baseline Rutherford's chronic ischemia score of 4.3 at presentation. Emergent procedures constituted 29% of cases, and the remainder cases were urgent procedures. The CH bypass captured was a reoperative procedure in all but one of the patients. Culture positivity was present in 75% of cases with Staphylococcus aureus (29%), the most commonly isolated organism. Thirty-day mortality and major adverse cardiovascular events were both 4%. Amputation-free survival (AFS) was 75% at 30 days. Similarly, 30-day reintervention was 38% with debridement (43%) and bleeding (29%), the most common indications. Average duration of follow-up was 27.9 ± 20.4 months (range: 0.5–60.4). Mean length of stay was 14.8 days. Reinfection requiring an additional procedure or antibiotic regimen separate from the index antibiotic course was 13%. Primary patency and AFS at 1 year was 50% and 58%, respectively. Primary patency and AFS at 2 years was 38% and 52%, respectively. Limb salvage at 1 and 2 years was 70% and 65%, respectively. Fifteen patients (63%) required reintervention during the follow-up period with 40% of those subjects undergoing multiple procedures. Conclusions CHs remain a marginal salvage conduit in the setting of infection and no autogenous choices. Therefore, clinicians should individualize usage of this high-cost product in highly selected patients only.
Description of human AAA by cytokine and immune cell aberrations compared to risk-factor matched controls
(Elsevier, 2018-08) Wang, S. Keisin; Green, Linden A.; Gutwein, Ashley R.; Drucker, Natalie A.; Motaganahalli, Raghu L.; Gupta, Alok K.; Fajardo, Andres; Murphy, Michael P.; Surgery, School of Medicine
BACKGROUND: The pathogenesis driving the formation of abdominal aortic aneurysms continues to be poorly understood. Therefore, we systemically define the cytokine and circulating immune cell environment observed in human abdominal aortic aneurysm compared with risk-factor matched controls. METHODS: From 2015 to 2017, a total of 274 patients donated blood to the Indiana University Center for Aortic Disease. Absolute concentrations of circulating cytokines were determined, using enzyme-linked immunosorbent assays while the expression of circulating immune cell phenotypes were assayed via flow cytometric analysis. RESULTS: Human abdominal aortic aneurysm is characterized by a significant depletion of the antigen-specific, CD4+ Tr1 regulatory lymphocyte that corresponds to an upregulation of the antigen-specific, inflammatory Th17 cell. We found no differences in the incidence of Treg, B10, and myeloid-derived suppressor regulatory cells. Similarly, no disparities were noted in the following inflammatory cytokines: IL-1β, C-reactive protein, tumor necrosis factor α, interferon γ, and IL-23. However, significant upregulation of the inflammatory cytokines osteopontin, IL-6, and IL-17 were noted. Additionally, no changes were observed in the regulatory cytokines IL-2, IL-4, IL-13, TNF-stimulated gene 6 protein, and prostaglandin E2, but we did observe a significant decrease in the essential regulatory cytokine IL-10. CONCLUSION: In this investigation, we systematically characterize the abdominal aortic aneurysm-immune environment and present preliminary evidence that faulty immune regulation may also contribute to aneurysm formation and growth.
Metformin does not reduce inflammation in diabetics with abdominal aortic aneurysm or at high risk of abdominal aortic aneurysm formation
(Sage, 2018-12) Wang, S. Keisin; Green, Linden A.; Gutwein, Ashley R.; Kenyon, Bianca; Motaganahalli, Raghu L.; Fajardo, Andres; Gupta, Alok K.; Murphy, Michael P.; Surgery, School of Medicine
Introduction The protective effect of diabetes mellitus on abdominal aortic aneurysm formation and growth has been repeatedly observed in population studies but continues to be poorly understood. However, recent investigations have suggested that metformin, a staple antihyperglycemic medication, may be independently protective against abdominal aortic aneurysm formation and growth. Therefore, we describe the effect of metformin in abdominal aortic aneurysm and at-risk patients on markers of inflammation, the driver of early abdominal aortic aneurysm formation and growth. Methods Peripheral blood was collected from patients previously diagnosed with abdominal aortic aneurysm or presenting for their U.S. Preventive Task Force-recommended abdominal aortic aneurysm screening. Plasma and circulating peripheral blood mononuclear cells were isolated using Ficoll density centrifugation. Circulating plasma inflammatory and regulatory cytokines were assessed with enzyme-linked immunosorbent assays. CD4+ cell phenotyping was performed using flow cytometric analysis and expressed as a proportion of total CD4+ cells. To determine the circulating antibody to self-antigen response, a modified enzyme-linked immunosorbent assay was performed against antibodies to collagen type V and elastin fragments. Results Peripheral blood was isolated from 266 patients without diabetes mellitus (n=182), with diabetes mellitus not treated with metformin (n=34), and with diabetes mellitus actively taking metformin (n=50) from 2015 to 2017. We found no differences in the expression of Tr1, Th17, and Treg CD4+ fractions within diabetics ± metformin. When comparing inflammatory cytokines, we detected no differences in IL-1β, IL-6, IL-17, IL-23, IFN-γ, and TNF-α. Conversely, no differences were observed pertaining to the expression to regulatory cytokines IL-4, IL-10, IL-13, TSG-6, or TGF-β. Lastly, no differences in expression of collagen type V and elastin fragment antigen and/or antibodies were detected with metformin use in diabetics. Conclusion Metformin in diabetics at-risk for abdominal aortic aneurysm or diagnosed with abdominal aortic aneurysm does not seem to alter the peripheral inflammatory environment.
Perioperative Outcomes are Adversely Affected by Poor Pretransfer Adherence to Acute Limb Ischemia Practice Guidelines
(Elsevier, 2018) Wang, S. Keisin; Murphy, Michael P.; Gutwein, Ashley R.; Drucker, Natalie A.; Dalsing, Michael C.; Motaganahalli, Raghu L.; Lemmon, Gary W.; Akingba, A. George; Surgery, School of Medicine
Objectives The accepted treatment for acute limb ischemia (ALI) is immediate systemic anticoagulation and timely reperfusion to restore blood flow. In this study, we describe the retrospective assessment of pretransfer management decisions by referring hospitals to an academic tertiary care facility and its impact on perioperative adverse events. Methods A retrospective analysis of ALI patients transferred to us via our Level I Vascular Emergency program from 2010 to 2013 was performed. Patient demographics, comorbidities, Rutherford ischemia classification, time to anticoagulation, and time to reperfusion were tabulated and analyzed for correlation to incidence of major adverse limb events (MALE), mortality, and bypass patency in the perioperative period (30-day postoperative). All time intervals were calculated from the onset of symptoms and categorized into three subcohorts (<6 hrs, 6-48 hrs, and >48 hrs). Results Eighty-seven patients with an average age of 64.0 (± 16.2) years presented to outlying hospitals and was transferred to us with lower extremity ALI. The mean delay from symptom onset to initial referring physician evaluation was 18.3 hrs. At that time of evaluation, 53.8% had Rutherford class IIA ischemia and 36.3% had class IIB ischemia. Seventy-six (87.4%) patients were started on heparin previous to transfer. However, only 44 (57.9%) patients reached therapeutic levels as measured by activated partial thromboplastin time (aPTT) prior to definitive revascularization. A delay of anticoagulation initiation >48 hrs from symptom onset was associated with increased 30-day reintervention rates compared with the <6 hrs group (66.7% vs. 23.5%; p<0.05). However, time to reperfusion had no statistically significant impact on MALE, 30-day mortality, or 30-day interventional patency in our small cohorts. Additionally, patients with a previous revascularization had a higher 30-day reintervention rate (46.5%; p<0.05). Conclusions The practice of timely therapeutic anticoagulation of patients referred for ALI from community facilities occurs less frequently than expected and is associated with an increased perioperative reintervention rate.
Rationale and Design of the ARREST Trial Investigating Mesenchymal Stem Cells in the Treatment of Small Abdominal Aortic Aneurysm
(Elsevier, 2017) Wang, S. Keisin; Green, Linden A.; Gutwein, Ashley R.; Drucker, Natalie A.; Motaganahalli, Raghu L.; Fajardo, Andres; Babbey, Clifford C.; Murphy, Michael P.; Surgery, School of Medicine
Background Abdominal aortic aneurysms (AAAs) are a major source of morbidity and mortality despite continuing advances in surgical technique and care. Although the inciting factors for AAA development continue to be elusive, accumulating evidence suggests a significant periaortic inflammatory response leading to degradation and dilation of the aortic wall. Previous human trials have demonstrated safety and efficacy of mesenchymal stem cells (MSCs) in the treatment of inflammation-related pathologies such as rheumatoid arthritis, graft versus host disease, and transplant rejection. Therefore, herein, we describe the Aortic Aneurysm Repression with Mesenchymal Stem Cells (ARREST) trial, a phase I investigation into the safety of MSC infusion for patients with small AAA and the cells' effects on modulation of AAA-related inflammation. Methods ARREST is a phase I, single-center, double-blind, randomized controlled trial (RCT) investigating infusion both dilute and concentrated MSCs compared to placebo in 36 small AAA (35–45 mm) patients. Subjects will be followed by study personnel for 12 months to ascertain incidence of adverse events, immune cell phenotype expression, peripheral cytokine profile, and periaortic inflammation. Maximum transverse aortic diameter will be assessed regularly for 5 years by a combination of computed tomography and duplex sonography. Results Four patients have thus far been enrolled, randomized, and treated per protocol. We anticipate the conclusion of the treatment phase within the next 24 months with ongoing long-term follow-up. Conclusions ARREST will be pivotal in assessing the safety of MSC infusion and provide preliminary data on the ability of MSCs to favorably modulate the pathogenic AAA host immune response. The data gleaned from this phase I trial will provide the groundwork for a larger, phase III RCT which may provide the first pharmaceutical intervention for AAA.
Staged endovascular repair of an abdominal aortic aneurysm adjacent to a chronic high-flow iliocaval traumatic arteriovenous fistula
(Elsevier, 2017-12-18) Wang, S. Keisin; Gutwein, Ashley R.; Casciani, Tom; Murphy, Michael P.; Lemmon, Gary W.; Surgery, School of Medicine
Large-vessel chronic traumatic arteriovenous fistulas are a rare complication after trauma. Delayed presentation can consist of one or more features of high-output cardiac failure, pulsatile abdominal mass, bruit, limb ischemia, and venous congestion. We describe a patient with a complex iliocaval fistula secondary to a remote gunshot wound associated with a large 8.5-cm aortic aneurysm. Informed consent of the patient was obtained for publication of the case.

Browsing by Author "Gutwein, Ashley R."

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