Characterizing Trends in Chronic Superficial Venous Disease Treatment among Medicare Beneficiaries from 2010 to 2018.

This study describes trends in surgical versus endovascular interventions for treatment of chronic superficial venous disease (SVD) in the Medicare population. Medicare Part B data from 2010 to 2018 were obtained. Claims for SVD treatment were identified using Healthcare Common Procedure Coding System codes. Total percentage change in utilization rates and market share was determined for each provider group. Utilization of SVD treatments increased by 58%, mostly owing to growing utilization of endovascular treatments. There was a 66% decrease in surgical treatments. The utilization of ablation and sclerotherapy plateaued in 2016 and decreased in 2017-2018 with the advent of mechanochemical ablation, endovenous microfoam, and cyanoacrylate adhesive, respectively. Analysis showed that endovascular utilization increased across most specialties, with the largest growth seen in cardiology by 427%. Radiologists showed utilization growth of 125%, encompassing 11% of the market share. Endovascular treatment for SVD remains predominant, with increased utilization and concomitant decrease in surgical methods.

Evaluation of Uterine Fibroid Vascularity Using Contrast-Enhanced Ultrasound in Comparison with Contrast-Enhanced Magnetic Resonance Imaging.

OBJECTIVE: The aim of the work described here was to assess uterine fibroid vascularity using contrast-enhanced ultrasound (CEUS) as compared with magnetic resonance imaging (MRI). METHODS: Forty women diagnosed with symptomatic uterine fibroids scheduled for uterine artery embolization (UAE) were enrolled in this institutional review board-approved study. Before UAE, participants underwent CEUS examination with an Aplio i800 scanner (Canon Medical Systems, Tustin, CA, USA) with curvilinear array (8C1). CEUS was performed using 2.0 mL of the ultrasound contrast agent Lumason (Bracco, Milan, Italy) administered intravenously. Digital CEUS clips were acquired and randomized offline, and fibroids were characterized as hyper- or hypovascular. MRI was used as reference standard for fibroid vascularity and compared with CEUS. Results were analyzed using McNemar's test. RESULTS: Forty participants were enrolled in the trial. One patient did not proceed with the UAE procedure and one patient refused pre-procedure MRI because of claustrophobia. Therefore, 38 participants underwent CEUS and MRI examinations before UAE. Hypervascular fibroids were seen on MRI and CEUS in 24 and 26 participants, respectively. Hypovascular fibroids were seen with MRI and CEUS in 14 and 12 participants, respectively. Fibroids characterized as hypovascular in two participants by MRI were characterized as hypervascular by CEUS. CEUS and MRI findings were similar in 36 of 38 participants, corresponding to an accuracy of 95% (p = 0.62). CONCLUSION: Contrast-enhanced ultrasound can accurately assess uterine fibroid vascularity, serving as a potential alternative to MRI in determination of the vascularity of uterine fibroids.

Contrast-enhanced US Evaluation of Hepatocellular Carcinoma Response to Chemoembolization: A Prospective Multicenter Trial.

Background Contrast-enhanced (CE) US has been studied for use in the detection of residual viable hepatocellular carcinoma (HCC) after locoregional therapy, but multicenter data are lacking. Purpose To compare two-dimensional (2D) and three-dimensional (3D) CE US diagnostic performance with that of CE MRI or CT, the current clinical standard, in the detection of residual viable HCC after transarterial chemoembolization (TACE) in a prospective multicenter trial. Materials and Methods Participants aged at least 21 years with US-visible HCC scheduled for TACE were consecutively enrolled at one of three participating academic medical centers from May 2016 to March 2022. Each underwent baseline 2D and 3D CE US before TACE, 2D and 3D CE US 1-2 weeks and/or 4-6 weeks after TACE, and CE MRI or CT 4-6 weeks after TACE. CE US and CE MRI or CT were evaluated by three fellowship-trained radiologists for the presence or absence of viable tumors and were compared with reference standards of pathology (18%), angiography on re-treatment after identification of residual disease at 1-2-month follow-up imaging (31%), 4-8-month CE MRI or CT (42%), or short-term (approximately 1-2 months) CE MRI or CT if clinically decompensated and estimated viability was greater than 50% at imaging (9%). Diagnostic performance criteria, including sensitivity and specificity, were obtained for each modality and time point with generalized estimating equation analysis. Results A total of 132 participants were included (mean age, 64 years ± 7 [SD], 87 male). Sensitivity of 2D CE US 4-6 weeks after TACE was 91% (95% CI: 84, 95), which was higher than that of CE MRI or CT (68%; 95% CI: 58, 76; P < .001). Sensitivity of 3D CE US 4-6 weeks after TACE was 89% (95% CI: 81, 94), which was higher than that of CE MRI or CT (P < .001), with no evidence of a difference from 2D CE US (P = .22). CE MRI or CT had 85% (95% CI: 76, 91) specificity, higher than that of 4-6-week 2D and 3D CE US (70% [95% CI: 56, 80] and 67% [95% CI: 53, 78], respectively; P = .046 and P = .023, respectively). No evidence of differences in any diagnostic criteria were observed between 1-2-week and 4-6-week 2D CE US (P > .21). Conclusion The 2D and 3D CE US examinations 4-6 weeks after TACE revealed higher sensitivity in the detection of residual HCC than CE MRI or CT, albeit with lower specificity. Importantly, CE US performance was independent of follow-up time. Clinical trial registration no. NCT02764801 © RSNA, 2023 Supplemental material is available for this article.

Contrast-Enhanced Ultrasound and High Sensitive Doppler for Monitoring Outcomes of Uterine Artery Embolization.

RATIONALE AND OBJECTIVES: To monitor fibroid microvascularity using contrast-enhanced ultrasound (CEUS) and a new high-sensitive Doppler mode (SMI) for assessment of uterine artery embolization (UAE) outcomes. MATERIALS AND METHODS: Forty women with symptomatic uterine fibroids scheduled for UAE were enrolled in this Institutional Review Board-approved study. Subjects underwent three examinations (day 0, 15, and 90 post-UAE) with Color Doppler (CDI), power Doppler (PDI), color and monochrome SMI (cSMI and mSMI), and CEUS imaging of the fibroids. Clips were assessed by two radiologists classifying fibroids based on their vascularity. Fibroid fractional vascularity (FV; % of enhanced pixels within the fibroid) and flow intensity (as mean brightness level of the enhanced pixels) were quantified. Results were analyzed using repeated measures ANOVA and nonparametric Wilcoxon sign rank tests. Inter-reader agreement was assessed with κ-values. RESULTS: There was overall agreement between readers for all imaging modalities and examination times (P = .25; κ = 0.70). The FV analysis showed statistically significant differences between CEUS and the Doppler imaging modes (CDI, PDI, cSMI, and mSMI) for the three examination times were compared (P < .0001). The comparison using CDI, PDI, and cSMI showed no statistically significant difference (P = .53). The flow intensity analysis comparison between the Doppler imaging modes (CDI, PDI, cSMI and mSMI) and examination times showed statistically significant differences between all the Doppler imaging modalities (P = .02), except for the 90days post-UAE (P = .34). When the comparison was made for CDI, PDI, and cSMI there was no statistically significant differences (P < .47). CONCLUSION: CEUS and SMI can accurately evaluate fibroid microvascularity, and therefore, can be a noninvasive and accurate method for monitoring outcomes following UAE treatment.

Hematuria Leads to a New Diagnosis of Cirrhosis.

A known consequence of portal hypertension is the development of varices, which are described as "ectopic" when located at unusual sites in the abdomen. Ectopic varices carry a mortality rate as high as 40% after initial hemorrhagic episode. We report a patient who presented with hematuria secondary to bladder varices as the presenting symptom for a new diagnosis of cirrhosis. Cross-sectional imaging, early recognition of this rare event, combined with multidisciplinary management was essential for this patient to have a successful outcome.

Predicting Long-Term Hepatocellular Carcinoma Response to Transarterial Radioembolization Using Contrast-Enhanced Ultrasound: Initial Experiences.

Conventional cross-sectional imaging done shortly after radioembolization of hepatocellular carcinoma (HCC) does not reliably predict long-term response to treatment. This study evaluated whether quantitative contrast-enhanced ultrasound (CEUS) can predict the long-term response of HCC to yttrium-90 (Y-90) treatment. Fifteen patients underwent CEUS at three time points: immediately following treatment and 1 and 2 wk post-treatment. Response 3-6 mo after treatment was categorized on contrast-enhanced magnetic resonance imaging by two experienced radiologists using the Modified Response Evaluation Criteria in Solid Tumors. CEUS data were analyzed by quantifying tumor perfusion and residual fractional vascularity using time-intensity curves. Patients with stable disease on magnetic resonance imaging had significantly greater fractional vascularity 2 wk post-treatment (65.15%) than those with partial or complete response (13.8 ± 9.9%, p = 0.007, and 14.9 ± 15.4%, p = 0.009, respectively). Complete responders had lower tumor vascularity at 2 wk than at post-operative examination (-38.3 ± 15.4%, p = 0.045). Thus, this pilot study suggests CEUS may provide an earlier indication of Y-90 treatment response than cross-sectional imaging.

US-triggered Microbubble Destruction for Augmenting Hepatocellular Carcinoma Response to Transarterial Radioembolization: A Randomized Pilot Clinical Trial.

Background US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. Purpose To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). Materials and Methods In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1-4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. Results Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P > .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02). Conclusion The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response. © RSNA, 2020.

Contrast-enhanced Ultrasound Identifies Patent Feeding Vessels in Transarterial Chemoembolization Patients With Residual Tumor Vascularity.

Transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) often requires retreatment and identification of feeding vessels supplying the residual/recurrent tumor is an important step in treatment planning. The objective of this study was to determine if contrast-enhanced ultrasound (CEUS) could correctly identify the vessel supplying the residual tumor. To date, 69 patients have undergone CEUS follow-up of HCC TACE therapy at our institution as part of an ongoing institutional review board approved trial (NCT02764801). The CEUS examinations were performed before HCC TACE as well as 1 to 2 weeks and 1 month after treatment using a Logiq E9 scanner with a C1-6 curved array transducer (GE Healthcare, Waukesha, WI). The CEUS images obtained 2 weeks after initial TACE treatment were reviewed, and any feeding vessels supplying the residual HCC were identified. Digital subtraction angiograms during the retreatment TACE were used as reference standard for feeding vessel identification. Thirteen patients with viable HCC post-TACE were included in this study. In these cases, the sonographer correctly identified 85% (11 of 13) of the feeding vessels later confirmed by angiography. Importantly, one of the false-negative cases involved a segment 8 tumor with parasitic blood supply from the medial left hepatic artery. In this case, CEUS identified a largely treated tumor with some residual internal flow, but was unable to visualize any major hepatic vascularity supplying the tumor. In conclusion, CEUS appears to be a valuable tool for planning retreatment of residual HCC post-TACE.

Catheter-directed thrombolysis versus percutaneous mechanical thrombectomy in the management of acute limb ischemia: a single center review.

BACKGROUND: Acute limb ischemia is associated with significant mortality and amputation rate. Early restoration of flow can be obtained by various treatment methods that include catheter-directed thrombolysis (CDT) and percutaneous mechanical thrombectomy (PMT). These treatments have been shown to be effective but associated with various complications. There is lack of data comparing these two treatments. We aim to review our experience in the treatment of acute limb ischemia (ALI) and compare CDT with PMT. RESULTS: A total of 94 patients [mean age 65 years, 67% male (n = 63)] presented with ALI between 2006 and 2015 and were treated with either CDT or PMT. Outcomes were retrospectively reviewed. Primary outcomes were technical and clinical success; secondary outcomes were amputation rate at 30 days, duration of hospitalization and 30-day mortality. A total of 117 procedures were performed in 94 patients: 27 surgical bypass grafts, 31 previously stented arteries and 59 native vessels. Twenty eight procedures (24%) were performed with PMT, and 89 (76%) procedures were performed with CDT. Higher technical success was achieved in the PMT group (68%, 19/28) compared to the CDT group (47%, 42/89), p = 0.056. Clinical success was similar in both groups (75%, 21/28 in the PMT group and 73%, 65/89) in the CDT group (p = 0.837). There was no statistically significant difference in 30-day mortality between the PMT vs CDT groups (4% vs 8%, p = 0.425). The length of post-procedural hospital stay was shorter in patients with PMT (6.0 vs 12.6 days, p = 0.001). The absence of end-stage renal failure appears to be a predictor for clinical succes (HR 3.3, 95% CI 0.809-13.592). CONCLUSION: PMT is associated with higher technical success and significantly shorter length of stay compared to CDT; however, clinical success is similar across both treatment entities. The safety profile is comparable.

Repetitive Blunt Trauma and Arterial Injury in the Hand.

INTRODUCTION/PURPOSE: Arterial injury in the hand is most often due to repetitive blunt trauma. Although not always associated with significant impairment, it may cause serious ischemic damage or considerable disability. As a cause of digital ischemia, the frequency of this disorder is widely under appreciated. This study reviews the clinical and angiographic features of this condition. MATERIALS/METHODS: An extensive literature review combined with the authors experience with arterial injury in the hand due to repetitive blunt hand trauma is summarized with emphasis on mechanisms of injury and pathologic changes to explain the angiographic findings and clinical presentations. RESULTS: Angiographic findings are related to severity of injury and underlying changes in the arterial wall. The clinical presentation varies from asymptomatic to digital necrosis and gangrene, related to severity of arterial injury, collateral circulation, and the highly variable arterial anatomy in the hand. CONCLUSION: Early recognition is important because compared to many other causes of digital ischemia in the upper extremities, traumatic arterial injury is frequently readily treatable. Angiographic findings and clinical presentation are often characteristic. The diagnosis should not be based on a clear history of repetitive hand trauma since the patient may be unaware of this occurrence.

Unbiased modifier screen reveals that signal strength determines the regulatory role murine TLR9 plays in autoantibody production.

The autoimmune disease systemic lupus erythematosus has a complex environmental and multifactorial genetic basis. Genome-wide association studies have recently identified numerous disease-associated polymorphisms, but it remains unclear in which cells and during which step of pathogenesis specific polymorphisms interact to cause disease. Using a mouse model in which the same activating mutation (CD45E613R) causes distinct genetic background-dependent disease phenotypes, we performed a screen for genetic modifiers of autoreactivity between anti-nuclear Ab (ANA)-resistant CD45E613R.B6 and ANA-permissive CD45E613R.BALB/c mice. Within a novel autoreactivity-associated locus on chromosome 9, we identify a putative modifier, TLR9. Validating a role for TLR9 in modifying autoreactivity in the context of the CD45E613R mutation, manipulation of TLR9 gene dosage eliminates ANA in CD45E613R.BALB/c mice, but confoundingly permits ANA in CD45E613R.B6 mice. We demonstrate that sensitivity to ANA is modulated by strength of TLR9 signal, because stronger TLR9(B6) signals, but not weaker TLR9(BALB/c) signals, negatively regulate CD45E613R B cell development during competitive reconstitution at the central tolerance checkpoint. Our results identify a novel autoreactivity-associated locus and validate Tlr9 as a candidate gene within the locus. We further demonstrate a novel role for TLR9 signal strength in central tolerance, providing insight into the interplay of disease-associated polymorphisms at a discrete step of systemic lupus erythematosus pathogenesis.

Differential impact of the CD45 juxtamembrane wedge on central and peripheral T cell receptor responses.

The cooperative activity of protein tyrosine kinases and phosphatases plays a central role in regulation of T cell receptor (TCR) signal strength. Perturbing this balance, and thus the threshold for TCR signals, has profound impacts on T cell development and function. We previously generated mice containing a point mutation in the juxtamembrane wedge of the receptor-like protein tyrosine phosphatase CD45. Demonstrating the critical negative regulatory function of the wedge, the CD45 E613R (WEDGE) mutation led to a lymphoproliferative disorder (LPD) and a lupus-like autoimmune syndrome. Using genetic, cellular, and biochemical approaches, we now demonstrate that the CD45 wedge influences T cell development and function. Consistent with increased TCR signal strength, WEDGE mice have augmented positive selection and enhanced sensitivity to the CD4-mediated disease experimental autoimmune encephalitis (EAE). These correspond with hyperresponsive calcium and pERK responses to TCR stimulation in thymocytes, but surprisingly, not in peripheral T cells, where these responses are actually depressed. Together, the data support a role for the CD45 wedge in regulation of T cell responses in vivo and suggest that its effects depend on cellular context.

The juxtamembrane wedge negatively regulates CD45 function in B cells.

CD45 is a receptor-like protein tyrosine phosphatase highly expressed on all nucleated hematopoietic cells. We previously generated mice containing a point mutation in the juxtamembrane wedge of CD45. Demonstrating the critical negative regulatory function of the wedge, the CD45 E613R mutation led to a lymphoproliferative disorder (LPD) and a lupus-like autoimmune syndrome. Here we show the central role of B cells in this phenotype. Genetic elimination of B cells, but not T cells, ablates the LPD. In contrast to CD45-deficient B cells, the E613R mutation generates hyperresponsive B cells. Comparison of CD45-deficient and CD45 E613R mice reveals dichotomous effects of these mutations on B cell development. Together, the results support a role for CD45 as a rheostat, with both positive and negative regulatory functions, that fine-tunes the signal transduction threshold at multiple checkpoints in B cell development.