Safety and collection efficiency with a lower transfusion threshold for extracorporeal photopheresis in adult patients with graft-versus-host disease.

BACKGROUND: Extracorporeal photopheresis (ECP) is an established treatment for graft-versus-host disease (GVHD). Various haematocrit thresholds have been used to trigger red blood cells transfusion prior to ECP. Moderate-to-severe GVHD is frequently complicated by anaemia; the safety and collection efficiency with a lower haematocrit for ECP is unknown. METHODS: We prospectively enrolled 26 consecutive adult GVHD patients with haematocrits between 25% and 28·9% who received ECP on the CELLEX system. Preprocedural transfusion was withheld. We monitored the adverse events and transfusions avoided. A complete blood cell count with differential was performed on preprocedural peripheral blood and buffy coat collected. Lymphocyte fold enrichment (LFE) was compared between this cohort and two historical control groups with haematocrits of 29% or higher. RESULTS: Red Blood Cells transfusion was avoided in the lower-haematocrit cohort without adverse events. The median LFE was 4·5 (95%CI, 3·1-5·7) in the lower-haematocrit cohort and 5·2 (95%CI, 4·1-6·5) in the higher-haematocrit CELLEX-treated control group. The median difference was 0·7 (95%CI, -0·3 to 2·0, P = 0·14). It could not be established that the lower-haematocrit cohort was non-inferior to the higher-haematocrit control group with a prespecified non-inferiority margin of 1·3. However, LFE was significantly higher in the lower-haematocrit cohort than the higher-haematocrit UVAR XTS-treated control group (P < 0·01). CONCLUSION: Buffy coat can be collected for ECP using CELLEX in GVHD patients with a haematocrit of 25% or higher, with a collection efficiency superior to that in patients with higher haematocrits but treated using UVAR XTS. No increase in adverse events was observed at these lower haematocrits.

Follow-up on Small Abdominal Aortic Aneurysms Using Three Dimensional Ultrasound: Volume Versus Diameter.

OBJECTIVES: Rupture risk in abdominal aortic aneurysms (AAAs) is assessed using AAA diameter; yet 10% of ruptures occur in a small aneurysm. This underlines the inadequacy of diameter as a standalone parameter. In this prospective follow-up study, ultrasound determined aneurysm diameter was compared with aneurysm volume determined by three dimensional ultrasound (3D-US) in a group of 179 AAAs. DESIGN: This was a prospective cohort study with repeated diameter and volume measurements by 3D-US. MATERIAL AND METHODS: In total, 179 patients with small infrarenal AAAs (diameter 30-55 mm) were enrolled consecutively. At enrolment and at 12 month follow-up, maximum diameter, using dual plane technique, and three dimensional volume were measured. Based on a previous accuracy study, significant change in diameter and volume were defined as an increase exceeding the known range of variability (ROV) of each US technique; ±3.7 mm and ±8.8 mL, respectively. Post-hoc Kaplan-Meier analysis was performed to estimate time to conversion to treatment after the conclusion of the follow-up period between two groups. RESULTS: In total, 125 patients (70%) had an unchanged diameter during follow-up. In this group, 50 patients (40%) had an increasing aortic volume. Forty-five (83%) of the 54 patients with an increasing aortic diameter showed a corresponding volume increase. During a median follow-up of 367 days (364-380 days), a mean increase in diameter of 2.7 mm (±2.6 mm) and a mean increase in volume of 11.6 mL (±9.9 mL) were recorded. In post-hoc analysis, it was found that more AAAs with a stable diameter and a growing volume than AAAs with a stable diameter and volume were undergoing aortic repair during follow-up, based on the maximum diameter. CONCLUSION: In this cohort of small AAAs, 40% of patients with a stable diameter had an increasing volume at 12 month follow-up. From this perspective, 3D-US could have a future supplemental role in AAA surveillance programmes.

Contrast Enhanced Ultrasound can Replace Computed Tomography Angiography for Surveillance After Endovascular Aortic Aneurysm Repair.

OBJECTIVE/BACKGROUND: Surveillance after endovascular aortic aneurysm repair (EVAR) is mandatory and computed tomography angiography (CTA) is considered the standard imaging modality, although patients are exposed to ionizing radiation and nephrotoxic contrast medium. The primary aim of this study was to determine the diagnostic efficacy of duplex ultrasound (DUS) and contrast enhanced ultrasound (CEUS) using CTA as the gold standard. The secondary aim was to determine the clinical consequences of endoleaks missed by DUS and CEUS, or CTA. METHODS: All patients with EVAR for an aorto-iliac aneurysm between 1 August 2011 and 31 October 2014 were prospectively and consecutively enrolled. CEUS was added to the existing surveillance protocol, which included DUS, plain abdominal X-ray, and CTA at 3 and 12 months after stent implantation. RESULTS: In 278 patients, endoleaks were detected in 68, 69, and 46 cases by CTA, CEUS, and DUS, respectively. The sensitivity and specificity of DUS and CEUS were 46% and 93%, and 85% and 95%, respectively. CEUS and CTA were diagnostically equivalent, as opposed to DUS and CTA (p = .002). Endoleaks detected by CTA led to re-intervention in 11 (4%) patients. These endoleaks were also detected by CEUS; however, three out of 11 patients were missed by DUS and underwent re-intervention: limb extension, re-cuff, and attempt to coil lumbar leaks. Endoleaks missed by CEUS or CTA were type II endoleaks without sac expansion. CONCLUSION: In surveillance programs after EVAR a diagnostic CEUS examination may replace CTA.

Three-dimensional Ultrasound in the Management of Abdominal Aortic Aneurysms: A Topical Review.

Three-dimensional (3D) ultrasound is an evolving modality that may have numerous applications in the management of abdominal aortic aneurysms. Many vascular specialists will not be familiar with the different ways in which 3D vascular ultrasound data can be acquired nor how potential applications are being explored by researchers. Most of the current literature consists of small series and single-centre experience, although clinical themes such as measurement of abdominal aortic aneurysm volume and surveillance following endovascular repair are emerging. The aim of this topical review is to introduce clinicians to the current concepts of 3D ultrasound, review the current literature, and highlight avenues for further research in this new and exciting field of vascular imaging.

Randomized clinical trial of mast cell inhibition in patients with a medium-sized abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is thought to develop as a result of inflammatory processes in the aortic wall. In particular, mast cells are believed to play a central role. The AORTA trial was undertaken to investigate whether the mast cell inhibitor, pemirolast, could retard the growth of medium-sized AAAs. In preclinical and clinical trials, pemirolast has been shown to inhibit antigen-induced allergic reactions. METHODS: Inclusion criteria for the trial were patients with an AAA of 39-49 mm in diameter on ultrasound imaging. Among exclusion criteria were previous aortic surgery, diabetes mellitus, and severe concomitant disease with a life expectancy of less than 2 years. Included patients were treated with 10, 25 or 40 mg pemirolast, or matching placebo for 52 weeks. The primary endpoint was change in aortic diameter as measured from leading edge adventitia at the anterior wall to leading edge adventitia at the posterior wall in systole. All ultrasound scans were read in a central imaging laboratory. RESULTS: Some 326 patients (mean age 70·8 years; 88·0 per cent men) were included in the trial. The overall mean growth rate was 2·42 mm during the 12-month study. There was no statistically significant difference in growth between patients receiving placebo and those in the three dose groups of pemirolast. Similarly, there were no differences in adverse events. CONCLUSION: Treatment with pemirolast did not retard the growth of medium-sized AAAs. REGISTRATION NUMBER: NCT01354184 (https://www.clinicaltrials.gov).

Three-dimensional ultrasound evaluation of small asymptomatic abdominal aortic aneurysms.

OBJECTIVE: Non-invasive and reproducible size measurements that correlate well with computed tomography (CT) are desirable in the management of small abdominal aortic aneurysms (AAA). Three dimensional ultrasound (3D-US) technology may reduce inaccuracy because of variations in orientation of the image planes and axis. This study aimed to determine any differences in paired size estimation associated with three 3D-US derived methods using 3D-CT as the gold standard. When CTA was not available, the patients were enrolled anyway to assess 3D-US reproducibility in terms of agreement between two physicians. METHODS: In the period from 1 March 2013 to 27 February 2014, consecutive patients with a small AAA, <5.5 cm for men and <5.2 cm for women, underwent 3D-US examination and three AAA size measures were obtained: dual plane diameter, diameter perpendicular to the residual sac's centreline and a partial volume. RESULT: In all, 122 consecutive US examinations were performed. Patients were excluded because of inadequate AAA size (n = 11) and for technical reasons (n = 11). Thus, 100 patients (F/M; 20/80) with a median maximum AAA diameter of 46 (range 31-55) mm were analysed. The mean US dual plane diameter and the 3D-US centreline diameter were 2.6 mm and 1.8 mm smaller than the mean 3D-CT centreline diameter, respectively (p = .003). The inter-observer reproducibility coefficient was 3.7 mm for the US dual plane diameter and 3.2 mm for the 3D-US centreline diameter (p = 0.222). For the partial volume, the reproducibility was 8-12%, corresponding to a diameter variability of ±3 mm. The median time used for post-processing of the 3D-US acquisition was 72 (range 46-108) seconds per examination. CONCLUSION: 3D-US demonstrated an acceptable reproducibility and a good agreement with 3D-CT, and has the potential to improve future AAA management through more reliable ultrasound guided size estimates.

Reproducibility of ECG-gated ultrasound diameter assessment of small abdominal aortic aneurysms.

OBJECTIVE: No standardised ultrasound procedure to obtain reliable growth estimates for abdominal aortic aneurysms (AAA) is currently available. We investigated the feasibility and reproducibility of a novel approach controlling for a combination of vessel wall delineation and cardiac cycle variation. DESIGN: Prospective comparative study. METHODS: Consecutive patients (N = 27) with an AAA, attending their 6-month control as part of a medical treatment trial, were scanned twice by two ultrasound operators. Then, all ultrasound recordings were transferred to a core facility and analysed by a third person. The AAA diameter was determined in four different ways: from the leading edge of adventitia on the anterior wall to either the leading edge of the adventitia (method A) or leading edge of the intima (method B) on the posterior wall, with both measurements performed in systole and diastole. RESULT: Inter-operator reproducibility was ± 3 mm for all methods applied. There was no difference in outcome between methods A and B; likewise, end-diastolic measurement did not improve reproducibility in preference to peak-systolic measurement. CONCLUSION: The use of a standardised ultrasound protocol including ECG-gating and subsequent off-line reading with minute calliper placement reduces variability. This may be of use in developing protocols to better detect even small AAA growth rates during clinical trials.

Volume estimation of the aortic sac after EVAR using 3-D ultrasound - a novel, accurate and promising technique.

OBJECTIVES: Volume estimation is more sensitive than diameter measurement for detection of aneurysm growth after endovascular aneurysm repair (EVAR), but this has only been confirmed on three-dimensional, reconstructed computer tomography (3-D CT). The potential of 3-D ultrasound (3-D US) for volume estimation in EVAR surveillance is unknown. DESIGN: Prospective validation study comparing 3-D US with 3-D CT, using 3-D CT as the gold standard. MATERIALS AND METHODS: From August 2011 to March 2012, 93 consecutive EVAR patients were enrolled and examined with both 3-D US and CT angiography (CTA). Image data were analysed in a mutual blinded setup using a 3-D interactive segmentation technique. RESULTS: The technical success rate of 3D-US was 98% (91/93). In 91 EVAR patients (F/M; 10/81) eligible for further analysis, the mean maximum volume (SD) was 126 (58) ml using 3-D US and 128 (58) ml using 3-D CT. The mean difference was 1 ml (0.4%) and the limits of agreement were -14 to 16 ml (-11; 12%). CONCLUSION: Volume estimation of the aortic sac after EVAR using 3-D US is a feasible and accurate method using 3-D CT as the gold standard.

Three-dimensional ultrasound improves the accuracy of diameter measurement of the residual sac in EVAR patients.

OBJECTIVES: Discrepancy between maximum diameters obtained with two-dimensional ultrasound and computed tomography (CT) after endovascular aneurysm repair (EVAR) is well known. The maximal diameter is ideally measured perpendicular to the centerline, a methodology so far only feasible with three-dimensional (3D) CT and magnetic resonance angiography (MRA). We aimed to investigate the agreement between 3D ultrasound and 3D CT and to determine reproducibility measures. METHODS: Prospective study comparing 3D ultrasound with 3D CT in 124 consecutive patients seen 3 or 12 month after EVAR. RESULTS: Replacing 2D with 3D ultrasound, the mean difference was improved from 6.0 mm to -1.3 mm (p < .001), and the range of variability was reduced from 9.4 mm to 6.6 mm (p = .009) using 3D CT as the gold standard. The mean difference between 3D ultrasound and 3D CT maximum diameter of the residual sac was -1.3 mm with upper and lower limits of agreement of 5.2 mm and -7.9 mm, respectively. Reproducibility measures of 3D ultrasound were ± 4 mm. CONCLUSION: 3D ultrasound correlate significantly better to 3D CT than the currently used 2D ultrasound method when assessing maximum diameter of the residual sac after EVAR, and reproducibility measures were within clinical acceptable values.

CT and 3D-ultrasound registration for spatial comparison of post-EVAR abdominal aortic aneurysm measurements: A cross-sectional study.

OBJECTIVE: The aim of the present study is to provide a methodology to register volumes of stented abdominal aortic aneurysm, imaged by 3D-US and CT modalities. After registration, the method enables to compare the spatial location of measurements and AAA size in a common coordinate system. METHODS: The study is cross-sectional and compares volumes acquired within a few days, in order to eliminate changes due to the evolution of AAA shape after treatment. The key element is to rely on stent alignment to register the CT and 3D-US volumes, providing access to a patient-specific common spatial coordinate system. In parallel, 3D segmentations are performed and used to extract multi-planar reconstructions at the locations of maximum diameter in each modality. The positions of the planes extracted in each modality, and the AAA diameters are finally compared in the common coordinate system. RESULTS: Results are validated on a database of 52 patients. After registrations, results show a mean inter-planar distance of 6.4 ±â€¯4.5 mm and a mean inter-planar angle of 10.2°±6.7 between CT and 3D-US multi-planar reconstructions. Bland-Altman comparisons of diameter measurements in the CT, US and non-registered volumes are respectively 5.1 ±â€¯2.8, 3.9 ±â€¯2.8, 4.6 ±â€¯3.0 mm. CONCLUSION: The proposed approach provides both visual and quantitative validations of measurements extracted from multi-modality images of the same pathology, in terms of spatial relationship and diameters. SIGNIFICANCE: The present work provides additional confidence in the use of 3D-US without CT for the follow-up of patients with abdominal aortic aneurysms after endovascular treatment.

A minimally interactive and reproducible method for abdominal aortic aneurysm quantification in 3D ultrasound and computed tomography with implicit template deformations.

The maximum diameter of abdominal aortic aneurysm (AAA) is a key quantification parameter for disease assessment. Although it is routinely measured on 2D-ultrasound images, using a volumetric approach is expected to improve measurement reproducibility. In this work, 3D-ultrasound or computed tomography imaging of patients with AAA was combined with a minimally interactive 3D segmentation based on implicit template deformation. Segmentation usability and reproducibility were evaluated on 81 patients, showing a mean measurement time of [2;8]min per case, and Dice coefficients of 0.87±0.12 for 3D-US and 0.81±0.08 for CT. Quantification parameters included a diameter measurement from 3D-US and CT volumes with respective confidence intervals of 0.51 [-2.5;3.52]mm and 1.00 [-1.68;3.67]mm. Additional volume measurements showed confidence intervals of 0.91 [-4.17;5.99]ml for 3D-US and 4.10 [-4.11;12.30]ml for CT.