Rationale
We aimed to test the interscan variation of semi-automatic volumetry of subsolid nodules (SSNs), as growth evaluation is important for SSN management.
Methods
From a lung cancer screening ...trial all SSNs that were stable over at least 3 months were included (N = 44). SSNs were quantified on the baseline CT by two observers using semi-automatic volumetry software for effective diameter, volume, and mass. One observer also measured the SSNs on the second CT 3 months later. Interscan variation was evaluated using Bland-Altman plots. Observer agreement was calculated as intraclass correlation coefficient (ICC). Data are presented as mean (± standard deviation) or median and interquartile range (IQR). A Mann-Whitney U test was used for the analysis of the influence of adjustments on the measurements.
Results
Semi-automatic measurements were feasible in all 44 SSNs. The interscan limits of agreement ranged from -12.0 % to 9.7 % for diameter, -35.4 % to 28.6 % for volume and -27.6 % to 30.8 % for mass. Agreement between observers was good with intraclass correlation coefficients of 0.978, 0.957, and 0.968 for diameter, volume, and mass, respectively.
Conclusion
Our data suggest that when using our software an increase in mass of 30 % can be regarded as significant growth.
Key Points
•
Recently, recommendations regarding subsolid nodules have stressed the importance of growth quantification.
•
Volumetric measurement of subsolid nodules is feasible with good interscan agreement.
•
Increase of mass of 30 % can be regarded as significant growth.
Symptomatic vertebral artery stenosis is associated with a high risk of recurrent stroke, with higher risks for intracranial than for extracranial stenosis. Vertebral artery stenosis can be treated ...with stenting with good technical results, but whether it results in improved clinical outcome is uncertain. We aimed to compare vertebral stenting with medical treatment for symptomatic vertebral stenosis.
We did a preplanned pooled individual patient data analysis of three completed randomised controlled trials comparing stenting with medical treatment in patients with symptomatic vertebral stenosis. The primary outcome was any fatal or non-fatal stroke. Analyses were performed for vertebral stenosis at any location and separately for extracranial and intracranial stenoses. Data from the intention-to-treat analysis were used for all studies. We estimated hazard ratios (HRs) with 95% CIs using Cox proportional-hazards regression models stratified by trial.
Data were from 354 individuals from three trials, including 179 patients from VIST (148 with extracranial stenosis and 31 with intracranial stenosis), 115 patients from VAST (96 with extracranial stenosis and 19 with intracranial stenosis), and 60 patients with intracranial stenosis from SAMMPRIS (no patients had extracranial stenosis). Across all trials, 168 participants (46 with intracranial stenosis and 122 with extracranial stenosis) were randomly assigned to medical treatment and 186 to stenting (64 with intracranial stenosis and 122 with extracranial stenosis). In the stenting group, the frequency of periprocedural stroke or death was higher for intracranial stenosis than for extracranial stenosis (ten (16%) of 64 patients vs one (1%) of 121 patients; p<0·0001). During 1036 person-years of follow-up, the hazard ratio (HR) for any stroke in the stenting group compared with the medical treatment group was 0·81% CI 0·45–1·44; p=0·47). For extracranial stenosis alone the HR was 0·63 (95% CI 0·27–1·46) and for intracranial stenosis alone it was 1·06 (0·46–2·42; pinteraction=0·395).
Stenting for vertebral stenosis has a much higher risk for intracranial, compared with extracranial, stenosis. This pooled analysis did not show evidence of a benefit for stroke prevention for either treatment. There was no evidence of benefit of stenting for intracranial stenosis. Stenting for extracranial stenosis might be beneficial, but further larger trials are required to determine the treatment effect in this subgroup.
None.
•Development of a novel antibody (termed as mAb150) developed in our lab which targets annexin A2.•Although there are earlier reports of another monoclonal antibody with the same target, the epitope ...recognized by mAb150 is novel.•mAb150 is specifically recognized to target the achilles heel of cancer viz. cancer stem cells and progenitors that persist after treatments and potentially give rise to minimal residual disease.
The involvement of cancer stem cells (CSCs) in driving tumor dormancy and drug resistance is well established. Most therapeutic regimens however are ineffective in targeting these regenerative populations. We report the development and evaluation of a monoclonal antibody, mAb150, which targets the metastasis associated antigen, Annexin A2 (AnxA2) through recognition of a N-terminal epitope. Treatment with mAb150 potentiated re-entry of CSCs into the cell cycle that perturbed tumor dormancy and facilitated targeting of CSCs as was validated by in vitro and in vivo assays. Epigenetic potentiation further improved mAb150 efficacy in achieving total tumor regression by targeting regenerative populations to achieve tumor regression, specifically in high-grade serous ovarian adenocarcinoma.
To prospectively determine the effect of anatomic variations in the circle of Willis on volume flow in the internal carotid arteries (ICAs) and basilar artery (BA).
Institutional review board ...approval and informed consent were obtained. Phase-contrast magnetic resonance (MR) angiography was used to measure the volume flow in the BA and ICAs in 208 patients (182 men, 26 women; mean age, 60 years) with symptomatic atherosclerosis or risk factors for atherosclerosis. Patients with steno-occlusive disease were excluded, and flow values were normalized for age. Three-dimensional time-of-flight MR angiograms were used to assess the anatomy of the circle of Willis. Differences in volume flow between a complete circle of Willis, a circle with a missing A1 segment, and a circle with a fetal-type posterior cerebral artery were analyzed (analysis of variance and Scheffe post hoc tests).
The ICA volume flow in subjects with a complete configuration of the circle of Willis was 245 mL/min +/- 65 (standard deviation). Flow in the contralateral ICA was significantly increased (P < .01) in subjects with a missing A1 segment (303 mL/min +/- 56) compared with control subjects and compared with flow on the ipsilateral side (214 mL/min +/- 94; P < .01). In subjects with a unilateral or bilateral fetal-type posterior cerebral artery, the ICA volume flow was increased (P < .01) and the BA volume flow was decreased (P < .01) in comparison with the flow in subjects with no fetal-type circle of Willis.
Large asymmetries in volume flow between the right and left ICAs or decreased volume flow in the BA is not necessarily caused by vascular disease but may be caused by variations in the anatomy of the circle of Willis.
Introduction
Recurrent joint bleeding is the hallmark of haemophilia. Synovial hypertrophy observed with Magnetic Resonance Imaging (MRI) is associated with an increased risk of future joint ...bleeding.
Aim
The aim of this study was to investigate whether point‐of‐care ultrasound (POC‐US) is an accurate alternative for MRI for the detection of early joint changes.
Methods
In this single centre diagnostic accuracy study, bilateral knees and ankles of haemophilia patients with no or minimal arthropathy on X‐rays were scanned using POC‐US and 3 Tesla MRI. POC‐US was performed by 1 medical doctor, blinded for MRI, according to the “Haemophilia Early Arthropathy Detection with Ultrasound” (HEAD‐US) protocol. MRIs were independently scored by 2 radiologists, blinded for clinical data and ultrasound results. Diagnostic accuracy parameters were calculated with 95% confidence intervals (CI).
Results
Knees and ankles of 24 haemophilia patients (96 joints), aged 18‐34, were studied. Synovial hypertrophy on MRI was observed in 20% of joints. POC‐US for synovial tissue was correct (overall accuracy) in 97% (CI: 91‐99) with a positive predictive value of 94% (CI: 73‐100) and a negative predictive value of 97% (CI: 91‐100). The overall accuracy of POC‐US for cartilage abnormalities was 91% (CI: 83‐96) and for bone surface irregularities 97% (CI: 91‐99).
Conclusion
POC‐US could accurately assess synovial hypertrophy, bone surface irregularities and cartilage abnormalities in haemophilia patients with limited joint disease. As POC‐US is an accurate and available alternative for MRI, it can be used for routine evaluation of early joint changes.
Optimizing the treatment of breast cancer remains a major topic of interest. In current clinical practice, breast-conserving therapy is the standard of care for patients with localized breast cancer. ...Technological developments have fueled interest in less invasive breast cancer treatment. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a completely noninvasive ablation technique. Focused beams of ultrasound are used for ablation of the target lesion without disrupting the skin and subcutaneous tissues in the beam path. MRI is an excellent imaging method for tumor targeting, treatment monitoring, and evaluation of treatment results. The combination of HIFU and MR imaging offers an opportunity for image-guided ablation of breast cancer. Previous studies of MR-HIFU in breast cancer patients reported a limited efficacy, which hampered the clinical translation of this technique. These prior studies were performed without an MR-HIFU system specifically developed for breast cancer treatment. In this article, a novel and dedicated MR-HIFU breast platform is presented. This system has been designed for safe and effective MR-HIFU ablation of breast cancer. Furthermore, both clinical and technical challenges are discussed, which have to be solved before MR-HIFU ablation of breast cancer can be implemented in routine clinical practice.
Objectives
To investigate whether iterative reconstruction (IR) in cerebral CT perfusion (CTP) allows for 50 % dose reduction while maintaining image quality (IQ).
Methods
A total of 48 CTP ...examinations were reconstructed into a standard dose (150 mAs) with filtered back projection (FBP) and half-dose (75 mAs) with two strengths of IR (middle and high). Objective IQ (quantitative perfusion values, contrast-to-noise ratio (CNR), penumbra, infarct area and penumbra/infarct (P/I) index) and subjective IQ (diagnostic IQ on a four-point Likert scale and overall IQ binomial) were compared among the reconstructions.
Results
Half-dose CTP with high IR level had, compared with standard dose with FBP, similar objective (grey matter cerebral blood volume (CBV) 4.4 versus 4.3 mL/100 g, CNR 1.59 versus 1.64 and P/I index 0.74 versus 0.73, respectively) and subjective diagnostic IQ (mean Likert scale 1.42 versus 1.49, respectively). The overall IQ in half-dose with high IR level was scored lower in 26–31 %. Half-dose with FBP and with the middle IR level were inferior to standard dose with FBP.
Conclusion
With the use of IR in CTP imaging it is possible to examine patients with a half dose without significantly altering the objective and diagnostic IQ. The standard dose with FBP is still preferable in terms of subjective overall IQ in about one quarter of patients.
Key points
• Computed tomography perfusion (CTP) is increasingly important in ischaemia imaging.
• Radiation exposure of CTP is a drawback.
• Iterative reconstruction (IR) allows reduction of radiation dose in unenhanced head CT.
• CTP IR enables 50 % dose reduction without altering objective and diagnostic quality.
The reported incidence of PCE during PV varies, depending on the sensitivity of diagnostic tests used. To assess the true incidence of PCE, we performed native chest CT during follow-up in a large ...proportion of patients from the VERTOS II trial.
VERTOS II is a prospective multicenter randomized controlled trial comparing PV with conservative therapy in 202 patients. After a mean follow-up of 22 months (median, 21 months; range, 6-42 months), 54 of 78 patients (69%) with 80 vertebrae treated with PV underwent native chest CT to detect possible PCE. The presence, location, number, and size of PCE were recorded. In addition, the presence of pulmonary parenchymal changes adjacent to PCE was noted. Possible risk factors for PCE, such as age, sex, number of treated vertebrae, cement volume per vertebra, and presence and location of perivertebral cement leakage, were evaluated.
PCE was detected in 14 of 54 patients (26% 95% CI, 16%-39%). All patients were asymptomatic. Cement emboli were small and randomly distributed in peripheral small vessels. There were no reactive pulmonary changes. Cement leakage in the azygos vein was the only risk factor for the occurrence of PCE (OR, 43; 95% CI, 5-396).
Small and clinically silent PCE occurred in a quarter of patients treated with PV. Cement leakage into the azygos vein was the only risk factor. With time, these small cement emboli remained inert, without inflammatory pulmonary response. Standard postprocedural CT or chest radiographs are not necessary.
Pseudoxanthoma elasticum (PXE), a monogenic disorder resulting in calcification affecting the skin, eyes and peripheral arteries, is caused by mutations in the ABCC6 gene, and is associated with low ...plasma inorganic pyrophosphate (PP
). It is unknown how ABCC6 genotype affects plasma PP
.
We studied the association of ABCC6 genotype (192 patients with biallelic pathogenic ABCC6 mutations) and PP
levels, and its association with the severity of arterial and ophthalmological phenotypes. ABCC6 variants were classified as truncating or non-truncating, and three groups of the 192 patients were formed: those with truncating mutations on both chromosomes (
= 121), those with two non-truncating mutations (
= 10), and a group who had one truncating and one non-truncating ABCC6 mutation (
= 61). The hypothesis formulated before this study was that there was a negative association between PP
level and disease severity.
Our findings confirm low PP
in PXE compared with healthy controls (0.53 ± 0.15 vs. 1.13 ± 0.29 µM,
< 0.01). The PP
of patients correlated with increasing age (β: 0.05 µM, 95% CI: 0.03-0.06 per 10 years) and was higher in females (0.55 ± 0.17 vs. 0.51 ± 0.13 µM in males,
= 0.03). However, no association between PP
and PXE phenotypes was found. When adjusted for age and sex, no association between PP
and ABCC6 genotype was found.
Our data suggest that the relationship between ABCC6 mutations and reduced plasma PP
may not be as direct as previously thought. PP
levels varied widely, even in patients with the same ABCC6 mutations, further suggesting a lack of direct correlation between them, even though the ABCC6 protein-mediated pathway is responsible for ~60% of this metabolite in the circulation. We discuss potential factors that may perturb the expected associations between ABCC6 genotype and PP
and between PP
and disease severity. Our findings support the argument that predictions of pathogenicity made on the basis of mutations (or on the structure of the mutated protein) could be misleading.
Objectives
Multimodal non-invasive imaging plays a key role in establishing a diagnosis of PHV endocarditis. The objective of this study was to provide a systematic review of the literature and ...meta-analysis of the diagnostic accuracy of TTE, TEE, and MDCT in patients with (suspected) PHV endocarditis.
Methods
Studies published between 1985 and 2013 were identified via search and cross-reference of PubMed/Embase databases. Studies were included if (1) they reported on the non-invasive index tests TTE, TEE, or MDCT; (2) data was provided on PHV endocarditis as the condition of interest; and (3) imaging results were verified against either surgical inspection/autopsy or clinical follow-up reference standards, thereby enabling the extraction of 2-by-2 tables.
Results
Twenty articles (including 496 patients) met the inclusion criteria for PHV endocarditis. TTE, TEE, and MDCT + TEE had a pooled sensitivity/specificity for vegetations of 29/100 %; 82/95 %, and 88/94 %, respectively. The pooled sensitivity/specificity of TTE, TEE, and MDCT + TEE for periannular complications was 36/93 %, 86/98 %, and 100/94 %, respectively.
Conclusions
TEE showed good sensitivity and specificity for establishing a diagnosis of PHV endocarditis. Although MDCT data are limited, this review showed that MDCT in addition to TEE may improve sensitivity in detecting life-threatening periannular complications.
Key Points
•
Multimodal imaging is an important ingredient of diagnostic workup for PHV endocarditis
.
•
Transthoracic and transesophageal echography may miss life-threatening periannular complications
.
•
MDCT can improve sensitivity for the detection of life-threatening periannular complications
.
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