Publications by authors named "Sydney L Olson"

10 Publications

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Anatomic eligibility for endovascular aneurysm repair preserved over 2 years of surveillance.

J Vasc Surg 2021 May 4. Epub 2021 May 4.

School of Medicine and Public Health, Division of Vascular Surgery, University of Wisconsin, Madison, Wisc.

Objective: Endovascular aneurysm repair (EVAR) is a widely used option for patients with suitable vascular anatomy who have a large infrarenal abdominal aortic aneurysm (AAA). Patients with small AAAs are managed with careful surveillance and it is a common concern that their anatomy may change with AAA growth, and their option for EVAR may become limited. Device innovation has resulted in expanded ranges of anatomy that may be eligible for EVAR. This study sought to identify changes in anatomic eligibility for repair with contemporary endovascular devices in AAA patients, monitored by computed tomography scan over the course of 2 years.

Methods: Patients from the Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TACT, NCT01756833) were included in this analysis. Females had baseline AAA maximum transverse diameter between 3.5 and 4.5 cm, and males had baseline maximum transverse diameter between 3.5 and 5.0 cm. Patients were included in this analysis if they completed pre-enrollment and 2-year follow-up computed tomography imaging. Pertinent anatomic measurements were performed on a postprocessing workstation in a centralized imaging core laboratory. EVAR candidacy was determined by measuring proximal aortic neck diameter, AAA length, and infrarenal neck angulation. Patients were considered to be eligible for EVAR if they qualified for at least one of the seven studied devices' instructions for use at baseline and at 2 years. A paired t test analysis was used to detect differences in aortic measurements over 2 years, and the McNemar test was used to compare eligibility over 2 years.

Results: We included 192 patients in this analysis-168 male and 24 female. Of these patients, 85% were eligible for EVAR at baseline and 85% after 2 years of follow-up (P = 1.00; 95% confidence interval -0.034 to 0.034). Of the 164 EVAR candidates at baseline, 160 (98%) remained eligible over 2 years of surveillance. Insufficient neck length was the most common reason for both ineligibility at baseline (18 of 28 patients) as well as loss of candidacy over 2 years (3 of 4 patients).

Conclusions: The majority of patients eligible for EVAR when entering a surveillance program for small AAA remain eligible after 2 years. Substantial changes in AAA neck anatomy resulting in loss of EVAR treatment options are infrequent. Patients with anatomic AAA progression beyond EVAR eligibility remain candidates for complex EVAR and open repair.
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http://dx.doi.org/10.1016/j.jvs.2021.04.044DOI Listing
May 2021

CXCR4 allows T cell acute lymphoblastic leukemia to escape from JAK1/2 and BCL2 inhibition through CNS infiltration.

Leuk Lymphoma 2021 05 11;62(5):1167-1177. Epub 2021 Apr 11.

Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Targeting the JAK/STAT and BCL2 pathways in patients with relapsed/refractory T cell acute lymphoblastic leukemia (T-ALL) may provide an alternative approach to achieve clinical remissions. Ruxolitinib and venetoclax show a dose-dependent effect on T-ALL individually, but combination treatment reduces survival and proliferation of T-ALL . Using a xenograft model, the combination treatment fails to improve survival, with death from hind limb paralysis. Despite on-target inhibition by the drugs, histopathology demonstrates increased leukemic infiltration into the central nervous system (CNS) as compared to liver or bone marrow. Liquid chromatography-tandem mass spectroscopy shows that ruxolitinib and venetoclax insufficiently cross into the CNS. The addition of the CXCR4 inhibitor plerixafor with ruxolitinib and venetoclax reduces clinical scores and enhances survival. While combination therapy with ruxolitinib and venetoclax shows promise for treating T-ALL, additional inhibition of the CXCR4-CXCL12 axis may be needed to maximize the possibility of complete remission.
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http://dx.doi.org/10.1080/10428194.2021.1910684DOI Listing
May 2021

Evaluating Growth Patterns of Abdominal Aortic Aneurysm Diameter With Serial Computed Tomography Surveillance.

JAMA Surg 2021 Apr;156(4):363-370

Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison.

Importance: Small abdominal aortic aneurysms (AAAs) are common in the elderly population. Their growth rates and patterns, which drive clinical surveillance, are widely disputed.

Objective: To assess the growth patterns and rates of AAAs as documented on serial computed tomography (CT) scans.

Design, Setting, And Participants: Cohort study and secondary analysis of the Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA3CT), a randomized, double-blind placebo-controlled clinical trial conducted from 2013 to 2018, with CT imaging every 6 months for 2 years. The trial was a multicenter, observational secondary analysis, not related to treatment hypotheses of data collected in the N-TA3CT. Participants included 254 patients with baseline AAA diameter between 3.5 and 5.0 cm.

Exposures: Patients received serial CT scan measurements, analyzed for maximum transverse diameter, at 6-month intervals.

Main Outcomes And Measures: The primary study outcome was AAA annual growth rate. Secondary analyses included characterizing AAA growth patterns, assessing likelihood of AAA diameter to exceed sex-specific intervention thresholds over 2 years.

Results: A total of 254 patients, 35 women with baseline AAA diameter 3.5 to 4.5 cm and 219 men with baseline diameter 3.5 to 5.0 cm, were included. Yearly growth rates of AAA diameters were a median of 0.17 cm/y (interquartile range [IQR], 0.16) and a mean (SD), 0.19 (0.14) cm/y. Ten percent of AAAs displayed minimal to no growth (<0.05 cm/y), 62% displayed low growth (0.05-0.25 cm/y), and 28% displayed high growth (>0.25 cm/y). Baseline AAA diameter accounted for 5.4% of variance of growth rate (P < .001; R2, 0.054). Most AAAs displayed linear growth (70%); large variations in interval growth rates occurred infrequently (3% staccato growth and 4% exponential growth); and some patients' growth patterns were not clearly classifiable (23% indeterminate). No patients with a maximum transverse diameter less than 4.25 cm exceeded sex-specific repair thresholds at 2 years (men, 0 of 92; 95% CI, 0.00-0.055; women, 0 of 25 ; 95% CI, 0.00-0.247). Twenty-six percent of patients with a maximum transverse diameter of at least 4.25 cm exceeded sex-specific repair thresholds at 2 years (n = 12 of 83 men with diameter ranging from 4.25 to <4.75 cm; 95% CI, 0.091-0.264; n = 21 of 44 men with diameter ranging from 4.75-5.0 cm; 95% CI, 0.362-0.669; n = 3 of 10 women with diameter ≥4.25 cm; 95% CI, 0.093-0.726).

Conclusions And Relevance: Most small AAAs showed linear growth; large intrapatient variations in interval growth rates were infrequently observed over 2 years. Linear growth modeling of AAAs in individual patients suggests smaller AAAs (<4.25 cm) can be followed up with a CT scan in at least 2 years with little chance of exceeding interventional thresholds.

Trial Registration: ClinicalTrials.gov Identifier: NCT01756833.
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http://dx.doi.org/10.1001/jamasurg.2020.7190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890454PMC
April 2021

Interferon regulatory factor 4 as a therapeutic target in adult T-cell leukemia lymphoma.

Retrovirology 2020 08 28;17(1):27. Epub 2020 Aug 28.

Division of Oncology, Department of Medicine, Washington University in St. Louis, 660 S Euclid Ave, Box 8069, St Louis, MO, 63110, USA.

Background: Adult T-cell leukemia lymphoma (ATLL) is a chemotherapy-resistant malignancy with a median survival of less than one year that will afflict between one hundred thousand and one million individuals worldwide who are currently infected with human T-cell leukemia virus type 1. Recurrent somatic mutations in host genes have exposed the T-cell receptor pathway through nuclear factor κB to interferon regulatory factor 4 (IRF4) as an essential driver for this malignancy. We sought to determine if IRF4 represents a therapeutic target for ATLL and to identify downstream effectors and biomarkers of IRF4 signaling in vivo.

Results: ATLL cell lines, particularly Tax viral oncoprotein-negative cell lines, that most closely resemble ATLL in humans, were sensitive to dose- and time-dependent inhibition by a next-generation class of IRF4 antisense oligonucleotides (ASOs) that employ constrained ethyl residues that mediate RNase H-dependent RNA degradation. ATLL cell lines were also sensitive to lenalidomide, which repressed IRF4 expression. Both ASOs and lenalidomide inhibited ATLL proliferation in vitro and in vivo. To identify biomarkers of IRF4-mediated CD4 + T-cell expansion in vivo, transcriptomic analysis identified several genes that encode key regulators of ATLL, including interleukin 2 receptor subunits α and β, KIT ligand, cytotoxic T-lymphocyte-associated protein 4, and thymocyte selection-associated high mobility group protein TOX 2.

Conclusions: These data support the pursuit of IRF4 as a therapeutic target in ATLL with the use of either ASOs or lenalidomide.
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http://dx.doi.org/10.1186/s12977-020-00535-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456374PMC
August 2020

Segmental arterial mediolysis (SAM): Systematic review and analysis of 143 cases.

Vasc Med 2019 12;24(6):549-563

Vascular Medicine Section, Minneapolis Heart Institute, Minneapolis, MN, USA.

Segmental arterial mediolysis (SAM) is a rare but serious nonatherosclerotic, noninflammatory vasculopathy of unknown etiology that often results in dissection, aneurysm, occlusion, or stenosis of, primarily, the abdominal arteries. Current literature lacks consensus on diagnostic criteria and management options for SAM. This review summarizes 143 cases and aims to advance appropriate recognition and management of SAM. Literature review of all relevant SAM case studies from 2005 to 2018 yielded 126 individual SAM cases from 66 reports. We identified 17 additional SAM cases from our center, bringing our analysis to 143 patients. Patients with SAM were most commonly men (68%) in their 60s. Hypertension (43%), tobacco use (12%), and hyperlipidemia (12%) were common comorbidities. Abdominal pain (80%) and intraabdominal bleeding (50%) were the most common presenting symptoms. Computed tomography was the most frequently used imaging method (78%), and histology was available in 44% of cases. The most commonly affected vessels were the superior mesenteric (53%), hepatic (45%), celiac (36%), renal (26%), and splenic (25%) arteries with aneurysm (76%), dissection (61%), and arterial rupture (46%). Treatments included coil embolization (28%), abdominal organ surgery (24%), open arterial repair (21%), and medical management (20%). Case-specific treatment modalities yielded symptom relief in the vast majority (91%) of patients, with a mortality rate of 7%.
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http://dx.doi.org/10.1177/1358863X19873410DOI Listing
December 2019

CT-Derived Pretreatment Thoracic Sarcopenia Is Associated with Late Mortality after Thoracic Endovascular Aortic Repair.

Ann Vasc Surg 2020 Jul 6;66:171-178. Epub 2019 Nov 6.

Division of Vascular Surgery, University of Wisconsin School of Medicine & Public Health, Madison, WI.

Background: Frailty, characterized by physiologic depletion, predicts postoperative morbidity and mortality in vascular surgery patients. CT-derived sarcopenia is a valuable method for objectively staging frailty preoperatively.

Purpose: With prior analyses primarily measuring psoas cross-sectional area on CT, we compared a method of measuring thoracic sarcopenia to existing techniques of lumbar sarcopenia and assessed the association with long-term survival and outcomes post-Thoracic Endovascular Aortic Repair (TEVAR).

Methods: Prospectively collected data of 217 patients undergoing TEVAR from 2009 to 2012 were reviewed. Thoracic sarcopenia was quantified by measuring total area of the rectus abdominis, latissimus dorsi, intercostal, erector spinae, and external and internal oblique muscles at the T12 vertebral level. Total psoas area at the L3 was used to measure lumbar sarcopenia.

Results: 200 patients had preoperative imaging enabling measurements of thoracic sarcopenia, 186 of these patients were also assessed for lumbar sarcopenia. Thoracic sarcopenic patients were older, had lower body mass indices, were more commonly female, and most commonly being treated for aneurysms. Thoracic sarcopenic patients had significantly higher rates of congestive heart failure, hypertension, prior vascular intervention, and TEVAR-related adverse events. Thoracic sarcopenia was associated with significantly higher mortality at 2 and 5 years post-TEVAR (2-year mortality: 19% vs 8%, P = 0.02; 5-year mortality: 31% vs 18%, P = 0.03). Lumbar sarcopenia was not associated with increased mortality at any time point. Patients whose muscle mass degraded over 48-month follow-up did not experience significantly higher rates of adverse events.

Conclusions: CT-derived thoracic sarcopenia, but not lumbar sarcopenia, is significantly associated with 5-year mortality post-TEVAR.
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http://dx.doi.org/10.1016/j.avsg.2019.10.089DOI Listing
July 2020

A Frailty-Based Risk Score Predicts Morbidity and Mortality After Elective Endovascular Repair of Descending Thoracic Aortic Aneurysms.

Ann Vasc Surg 2020 Aug 6;67:90-99. Epub 2019 Nov 6.

Division of Vascular Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI.

Background: Thoracic endovascular aortic repair (TEVAR) has expanded access to descending thoracic aortic aneurysm (DTAA) repair particularly for elderly and frail patients. This high-risk population has limited long-term overall survival, such that appropriate patient selection is required to optimize patient benefit and resource utilization. Our objective is to develop and validate a frailty-based, procedure-specific risk score for patients undergoing elective TEVAR for DTAA.

Methods: Patients undergoing nonemergent TEVAR for DTAA during 2005-2016 were identified in the National Surgical Quality Improvement Program database. Those with concurrent cardiac or open aortic surgery, abdominal visceral intervention, or Zone 0 deployment were excluded. Patients were randomly divided between derivation and validation samples. The primary outcome was 30-day major adverse events (MAE), including mortality and major systemic complications. Using the derivation cohort, variables associated with MAE were identified by univariable analyses. Those with P < 0.05 were included in multivariable logistic regression analysis. Independent procedure-specific and frailty-related risk factors for MAE were used to develop a pragmatic score to assess risk for TEVAR.

Results: Overall, 1,784 patients were included. 14% of the derivation patients had MAE (14% major complications, 4% mortality). Independent risk factors for MAE were primarily associated with markers of frailty and TEVAR extent and complexity and included functional dependence (OR 2.9, 95% CI 1.6-5.4), pulmonary disease (1.6, 1.1-2.4), thoracoabdominal extent (2.2 (1.4-3.4), need for iliac access (2.1, 1.1-3.8), and Zone I or II deployment (OR 1.7, 1.1-2.5). According to their respective beta coefficients, each variable was assigned a single point. Based on total points, patients were stratified as low- (0 points), intermediate- (1 point), or high-risk (≥2 points), with stepwise increases in mortality (0%, 4%, and 9%) and major complications (7%, 11%, and 23%) between strata. Validation patients had similar characteristics, risk strata distribution, and outcomes as the derivation patients, and the risk model had similar performance in both groups.

Conclusions: Markers of frailty and procedure complexity strongly predict MAE after TEVAR for DTAA and can improve patient selection by enabling patient and procedure-specific risk stratification. While TEVAR is safe in low-risk patients, intermediate-risk patients warrant careful discussion of the risks and benefits of aortic intervention; under certain circumstances, high-risk patients may not benefit. Further study is required to define the association between frailty and long-term outcomes.
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http://dx.doi.org/10.1016/j.avsg.2019.10.090DOI Listing
August 2020

A Novel Frameshift COL3A1 Variant in Vascular Ehlers-Danlos Syndrome.

Ann Vasc Surg 2019 Nov 5;61:472.e9-472.e13. Epub 2019 Aug 5.

Minneapolis Heart Institute, Minneapolis, MN. Electronic address:

Ehlers-Danlos syndromes (EDSs) are a group of heritable connective tissue disorders with distinct genetic etiologies. Of the 13 currently recognized types of EDS, the vascular type EDS (vEDS) is generally considered the most severe and is associated with a decreased life expectancy due to spontaneous arterial, intestinal, and or uterine rupture. Diagnosis of vEDS is supported by genetic testing confirming the presence of pathogenic variations in COL3A1, a type III procollagen gene. Management of vEDS is usually conservative with control of hemodynamic stress, frequent cardiovascular imaging, and, if indicated, a thoughtful endovascular intervention or surgical repair. We present a novel frameshift variant in COL3A1 leading to vEDS with multiple vascular involvements. Based on our literature review, this variant has not been reported and may result in a less severe form of vEDS. Our case report provides insight into genetic variants and clinical expression of vEDS.
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http://dx.doi.org/10.1016/j.avsg.2019.05.057DOI Listing
November 2019

Nonatherosclerotic Abdominal Vasculopathies.

Ann Vasc Surg 2019 Oct 12;60:128-146. Epub 2019 Jun 12.

Minneapolis Heart Institute, Minneapolis, MN, USA.

Background: Nonatherosclerotic abdominal arterial vasculopathies (NAVs), including mesenteric or renal artery dissection, aneurysm, stenosis, and vasculitis, are rare but have great clinical significance. Patients may present emergently with life-threatening complications such as arterial rupture and hemorrhagic shock. Herein, we present our center's experience with NAVs and provide extensive literature review to close the gap in the scarce, related literature.

Methods: From a single-center retrospective data analysis, we identified and characterized subjects (aged 18-60 years) who presented with NAV between January 2000 and December 2015. Of the 1416 charts reviewed, 118 met inclusion criteria.

Results: The average age of patients with NAV was 47.0 ± 9.9 years, mostly affecting women (64%). Primary diagnoses included fibromuscular dysplasia (FMD) (25.4%), isolated aneurysms (24.6%), and median arcuate ligament syndrome (MALS) (15.3%). Less common diagnoses were localized vasculitis of the gastrointestinal tract (LVGT) (7.6%), isolated dissection (5.1%), microscopic polyangiitis and granulomatosis with polyangiitis (5.1%), trauma (4.2%), segmental arterial mediolysis (4.2%), Ehlers-Danlos syndrome (2.5%), Takayasu's arteritis (2.5%), polyarteritis nodosa (1.7%), idiopathic abdominal aortitis (0.8%), and Loeys-Dietz syndrome (0.8%). Females constituted 90% of patients with FMD, 77.8% with MALS, 77.8% with isolated aneurysms, 66.7% with Takayasu arteritis, and 55.6% with LVGT. Prevalent comorbidities included tobacco use (43.6%) and hypertension (52.1%). Coil embolization was used in 14.4%, anticoagulation in 11.9%, angioplasty/stenting in 11.9%, open resection/surgical revascularization in 10.2%, and prednisone in 10.2% of the cases. Conservative management was pursued in 33.1% of the patients. A high degree of symptom relief was shown in 91.7%.

Conclusions: NAV are rare and can be caused by different etiologies that primarily affect females. Hypertension and tobacco use were prevalent. Various imaging strategies revealed aneurysms, stenosis, dissection, and/or thrombosis affecting renal and celiac arteries. Most patients improved with conservative, medical, endovascular, or surgical approach. More research is needed to standardize management approach to patients with NAV.
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http://dx.doi.org/10.1016/j.avsg.2019.04.004DOI Listing
October 2019

Derivation and validation of thoracic sarcopenia assessment in patients undergoing thoracic endovascular aortic repair.

J Vasc Surg 2019 05 28;69(5):1379-1386. Epub 2018 Dec 28.

Division of Vascular Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisc.

Objective: Sarcopenia, as assessed by computed tomography (CT)-based measurements of muscle mass, is an objective and patient-specific indicator of frailty, which is an important predictor of operative morbidity and mortality. Studies to date have primarily focused on psoas-defined sarcopenia, which may not be valid among patients with thoracic aortic disease. Using psoas sarcopenia as the reference for sarcopenia, the purpose of this study was to create and to validate a new thoracic-level method of measuring sarcopenia as a novel method to assess frailty among patients undergoing thoracic endovascular aortic repair.

Methods: Prospectively collected data of patients undergoing thoracic endovascular aortic repair for thoracic aortic dissection, aneurysm, or injury using a conformable thoracic graft were reviewed. Patients with preoperative abdominal and thoracic CT imaging were included. Thoracic muscle mass was measured on axial images at the T12 level using our newly established standardized computer-assisted protocol. Psoas sarcopenia was measured at the L3 level using standard methods. Optimal sex-specific diagnostic T12 measurements were determined by receiver operating characteristic (ROC) curve analysis. A subset of scans were reviewed in duplicate by two trained observers and intraobserver and interobserver reliability tested by intraclass correlation coefficient. Agreement between T12 and L3 sarcopenia was tested by Cohen κ (scale, 0-1).

Results: There were 147 patients included for analysis, including 34 dissection, 80 trauma, and 33 aneurysm patients. ROC curve analysis yielded sarcopenic cutoff values of 106.00 cm/m for women and 110.00 cm/m for men at the T12 level. Based on ROC curve analysis, overall accuracy of T12 measurements was high (area under ROC curve, 0.91 for men and 0.90 for women). Quantitative interobserver and intraobserver reliability yielded excellent intraclass correlation coefficient values (>0.95). Qualitative interobserver reliability yielded nearly perfect Cohen κ values (>0.85). Qualitative intraobserver reliability of calculating sarcopenia at both the T12 and L3 levels was fair for both readers (0.361 and 0.288). There was additionally a general correlation between changes in muscle area at L3 with changes at T12 during 48 months.

Conclusions: Thoracic sarcopenia can be readily and reliably reproduced from CT-derived measurement of T12-level muscle area. This approach may be used as an alternative method to objectively define sarcopenia in patients without abdominal CT imaging. Future studies to assess the predictability of thoracic vs abdominal sarcopenia on postoperative outcomes will enhance the utility of these tools.
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http://dx.doi.org/10.1016/j.jvs.2018.08.180DOI Listing
May 2019