Clinical efficacy and safety of a silver ion-releasing foam dressing on hard-to-heal wounds: a meta-analysis.

OBJECTIVE: Delayed or stalled healing in open wounds can result from persisting chronic inflammation related to infection and/or persistent bacterial colonisation and biofilm. Treatment of hard-to-heal wounds focuses on debridement and exudate management, but also on infection prevention and control. Silver dressings have been evaluated in randomised clinical trials (RCTs); this meta-analysis evaluated the efficacy and safety of a silver ion-releasing foam dressing (Biatain Ag; Coloplast A/S, Denmark) to treat hard-to-heal wounds. METHOD: Literature databases (PubMed and Cochrane Library) were searched for studies on silver ion-releasing foam dressings in the treatment of hard-to-heal wounds. Individual patient data from four RCTs were obtained and included in the meta-analysis. RESULTS: Findings showed that treatment with the silver ion-releasing foam dressing was associated with a significantly higher relative reduction in wound area after four (least squares-mean difference (LS-MD): -12.55%, 95% confidence interval (CI): (-15.95, -9.16); p<0.01) and six weeks of treatment (LS-MD: -11.94%, 95%CI: (-17.21, -6.68); p<0.01) compared with controls. Significant benefits were also observed for time to disappearance of odour (hazard ratio: 1.61, 95%CI: (1.31, 1.98); p<0.01), relative reduction of exudate (LS-MD: -5.15, 95%CI: (-7.36, -2.94); p<0.01), proportion of patients with periwound erythema (relative risk (RR): 0.81, 95%CI: (0.69; 0.94); p<0.01), and less pain at dressing removal (LS-MD: -0.35, 95%CI: (-0.63, -0.06); p=0.02). No differences regarding safety outcomes were identified. CONCLUSION: This meta-analysis has demonstrated beneficial outcomes and a good tolerability profile for silver ion-releasing foam dressings in the treatment of moderate-to-highly exuding wounds with delayed healing compared with control dressings.

Magnetic Resonance Perfusion or Fractional Flow Reserve in Coronary Disease.

BACKGROUND: In patients with stable angina, two strategies are often used to guide revascularization: one involves myocardial-perfusion cardiovascular magnetic resonance imaging (MRI), and the other involves invasive angiography and measurement of fractional flow reserve (FFR). Whether a cardiovascular MRI-based strategy is noninferior to an FFR-based strategy with respect to major adverse cardiac events has not been established. METHODS: We performed an unblinded, multicenter, clinical-effectiveness trial by randomly assigning 918 patients with typical angina and either two or more cardiovascular risk factors or a positive exercise treadmill test to a cardiovascular MRI-based strategy or an FFR-based strategy. Revascularization was recommended for patients in the cardiovascular-MRI group with ischemia in at least 6% of the myocardium or in the FFR group with an FFR of 0.8 or less. The composite primary outcome was death, nonfatal myocardial infarction, or target-vessel revascularization within 1 year. The noninferiority margin was a risk difference of 6 percentage points. RESULTS: A total of 184 of 454 patients (40.5%) in the cardiovascular-MRI group and 213 of 464 patients (45.9%) in the FFR group met criteria to recommend revascularization (P = 0.11). Fewer patients in the cardiovascular-MRI group than in the FFR group underwent index revascularization (162 [35.7%] vs. 209 [45.0%], P = 0.005). The primary outcome occurred in 15 of 421 patients (3.6%) in the cardiovascular-MRI group and 16 of 430 patients (3.7%) in the FFR group (risk difference, -0.2 percentage points; 95% confidence interval, -2.7 to 2.4), findings that met the noninferiority threshold. The percentage of patients free from angina at 12 months did not differ significantly between the two groups (49.2% in the cardiovascular-MRI group and 43.8% in the FFR group, P = 0.21). CONCLUSIONS: Among patients with stable angina and risk factors for coronary artery disease, myocardial-perfusion cardiovascular MRI was associated with a lower incidence of coronary revascularization than FFR and was noninferior to FFR with respect to major adverse cardiac events. (Funded by the Guy's and St. Thomas' Biomedical Research Centre of the National Institute for Health Research and others; MR-INFORM ClinicalTrials.gov number, NCT01236807.).

Impact of sequence type and field strength (1.5, 3, and 7T) on 4D flow MRI hemodynamic aortic parameters in healthy volunteers.

PURPOSE: 4D flow magnetic resonance imaging (4D-MRI) allows time-resolved visualization of blood flow patterns, quantification of volumes, velocities, and advanced parameters, such as wall shear stress (WSS). As 4D-MRI enters the clinical arena, standardization and awareness of confounders are important. Our aim was to evaluate the equivalence of 4D flow-derived aortic hemodynamics in healthy volunteers using different sequences and field strengths. METHODS: 4D-MRI was acquired in 10 healthy volunteers at 1.5T using three different prototype sequences, at 3T and at 7T (Siemens Healthineers). After evaluation of diagnostic quality in three segments (ascending-, descending aorta, aortic arch), peak velocity, flow volumes, and WSS were investigated. Equivalence limits for comparison of field strengths/sequences were based on the limits of Bland-Altman analyses of the intraobserver variability. RESULTS: Non-diagnostic quality was found in 10/144 segments, 9/10 were obtained at 7T. Apart for the comparison of forward flow between sequence 1 and 3, the differences in measurements between field strengths/sequences exceeded the range of agreement. Significant differences were found between field strengths/sequences for forward flow (1.5T vs. 3T, 3T vs. 7T, sequence 1 vs. 3, 2 vs. 3 [P < .001]), WSS (1.5T vs. 3T [P < .05], sequence 1 vs. 2, 1 vs. 3, 2 vs. 3 [P < .001]), and peak velocity (1.5T vs. 7T, sequence 1 vs. 3 [P > .001]). All parameters at all field strengths/with all sequences correlated moderately to strongly (r ≥ 0.5). CONCLUSION: Data from all sequences could be acquired and resulting images showed sufficient quality for further analysis. However, the variability of the measurements of peak velocity, flow volumes, and WSS was higher when comparing field strengths/sequences as the equivalence limits defined by the intraobserver assessments.

A phase I study assessing the safety, tolerability, immunogenicity, and low-density lipoprotein cholesterol-lowering activity of immunotherapeutics targeting PCSK9.

PURPOSE: AT04A and AT06A are two AFFITOPE® peptide vaccine candidates being developed for the treatment of hypercholesterolemia by inducing proprotein convertase subtilisin/kexin type 9 (PCSK9)-specific antibodies. This study aimed to investigate safety, tolerability, antibody development, and reduction of low-density lipoprotein cholesterol (LDLc) following four subcutaneous immunizations. METHODS: This phase I, single-blind, randomized, placebo-controlled study was conducted in a total of 72 healthy subjects with a mean fasting LDLc level at baseline of 117.1 mg/dL (range 77-196 mg/dL). Each cohort enrolled 24 subjects to receive three priming immunizations at weeks 0, 4, and 8 and to receive a single booster immunization at week 60 of either AT04A, AT06A, or placebo. In addition to safety (primary objective), the antigenic peptide- and PCSK9-specific antibody response and the impact on LDLc were evaluated over a period of 90 weeks. RESULTS: The most common systemic treatment-related adverse events (AEs) reported were fatigue, headache, and myalgia in 75% of subjects in the AT06A group and 58% and 46% of subjects in the placebo and AT04A groups, respectively. Injection site reactions (ISR) representing 63% of all treatment-emergent adverse events (TEAEs), were transient and mostly of mild or moderate intensity and rarely severe (3%). Both active treatments triggered a robust, long-lasting antibody response towards the antigenic peptides used for immunization that optimally cross-reacted with the target epitope on PCSK9. In the AT04A group, a reduction in serum LDLc was observed with a mean peak reduction of 11.2% and 13.3% from baseline compared to placebo at week 20 and 70 respectively, and over the whole study period, the mean LDLc reduction for the AT04A group vs. placebo was -7.2% (95% CI [-10.4 to -3.9], P < 0.0001). In this group, PCSK9 target epitope titers above 50 were associated with clinically relevant LDLc reductions with an individual maximal decrease of 39%. CONCLUSIONS: Although both AT04A and AT06 were safe and immunogenic, only AT04A demonstrated significant LDLc-lowering activity, justifying further development. TRIAL REGISTRATION: EudraCT: 2015-001719-11. ClinicalTrials.gov Identifier: NCT02508896.

DCE-MR imaging of orbital lesions: diagnostic performance of the tumor flow residence time τ calculated by a multi-compartmental pharmacokinetic tumor model based on individual factors.

BACKGROUND: Differentiating benign from malignant orbital lesions by imaging and clinical presentation can be challenging. PURPOSE: To differentiate benign from malignant orbital masses using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on tumor flow residence time τ calculated with the aid of a pharmacokinetic tumor model. MATERIAL AND METHODS: Sixty patients with orbital masses were investigated by 3-T MRI including dynamic sequences. The signal intensity-time curve after i.v. contrast medium administration within lesions was approximated by Gd-concentration profiles on the basis of model calculations where the tumor is embedded in a whole-body kinetic model. One output of the model was tumor flow residence time τ, defined as the ratio of the tumor volume and the tumor blood flow rate. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic performance of τ. The results were compared with those of Ktrans, kep, ve, iAUC, and ADC. RESULTS: Thirty-one benign and 29 malignant orbital masses were identified (reference standard: histopathology, clinical characteristics). Mean τ was significantly longer for benign masses (94 ± 48 s) than for malignant masses (21 ± 19 s, P < 0.001). ROC analysis revealed the highest area under the curve (AUC = 0.94) for τ in orbital masses compared to standard methods. CONCLUSION: Tumor flow residence times τ of benign and malignant orbital masses are valuable in the diagnostic work-up of orbital tumors. Measures of diagnostic accuracy were superior for τ compared to ADC, Ktrans, ve, and iAUC.

On estimands and the analysis of adverse events in the presence of varying follow-up times within the benefit assessment of therapies.

The analysis of adverse events (AEs) is a key component in the assessment of a drug's safety profile. Inappropriate analysis methods may result in misleading conclusions about a therapy's safety and consequently its benefit-risk ratio. The statistical analysis of AEs is complicated by the fact that the follow-up times can vary between the patients included in a clinical trial. This paper takes as its focus the analysis of AE data in the presence of varying follow-up times within the benefit assessment of therapeutic interventions. Instead of approaching this issue directly and solely from an analysis point of view, we first discuss what should be estimated in the context of safety data, leading to the concept of estimands. Although the current discussion on estimands is mainly related to efficacy evaluation, the concept is applicable to safety endpoints as well. Within the framework of estimands, we present statistical methods for analysing AEs with the focus being on the time to the occurrence of the first AE of a specific type. We give recommendations which estimators should be used for the estimands described. Furthermore, we state practical implications of the analysis of AEs in clinical trials and give an overview of examples across different indications. We also provide a review of current practices of health technology assessment (HTA) agencies with respect to the evaluation of safety data. Finally, we describe problems with meta-analyses of AE data and sketch possible solutions.

Quantification of the left atrium applying cardiovascular magnetic resonance in clinical routine.

OBJECTIVES: In recent years the impact of the left atrium (LA) has become more evident in different cardiovascular pathologies. We aim to provide LA parameters in healthy volunteers for cardiovascular magnetic resonance (CMR) using a fast approach. DESIGN: We analyzed 203 healthy volunteers (mean age 44.6 years (y), range 19y-76y) at 1.5 and 3.0 Tesla (T) using steady-state free precession (SSFP) cine in routine long axis view. Left atrial enddiastolic volume (LA-EDV), endsystolic volume (LA-ESV), stroke volume (LA-SV) and ejection fraction (LA-EF) were quantified and indexed to body-surface-area (BSA). Dependency on age and sex was analyzed. RESULTS: 21 subjects had to be excluded. In the remaining, there was no significant difference between 1.5 T and 3.0 T. Absolut LA-EDV and LA-ESV were larger in men than in women (LA-EDV: male 70 ± 19 ml vs. female 61 ± 16 ml (p = .001); LA-ESV: male 24 ± 9 ml vs. female 21 ± 8 ml (p = .01)). These differences disappeared after indexing to BSA (LA-EDV/BSA: male 34 ± 10 ml/m2 vs. female 33 ± 9 ml/m2 (p = .65) and LA-ESV/BSA: male 12 ± 4 ml/m2 vs. female 11 ± 4 ml/m2 (p = .71)). LA-EDV/BSA decreased with older age. CONCLUSIONS: Reference values for LA size and function based on a fast approach are provided. LA size decreases with older age. Normalization to body size overcomes sex-dependency. Reports should be related to body size.

Safety profile of gadoxetate disodium in elderly patients (≥65 years).

Background Safety data on routine clinical use of gadoxetate disodium in elderly patients is not reported yet. Purpose To assess the safety of liver specific gadoxetate disodium in contrast enhanced magnetic resonance imaging in elderly patients (≥65 years) in comparison to adults (18-64 years). Material and Methods Safety data on gadoxetate disodium were analyzed from 12 clinical phase II-III studies and from our pharmacovigilance database. A comparison between elderly (≥65 years) versus adults (18-64 years) was performed with respect to the frequency of drug-related adverse events (AEs) in clinical phase II-III studies and adverse drug reactions (ADRs) in the pharmacovigilance database. Results In clinical studies, 1989 patients were enrolled: 675 elderly and 1314 adults. Twenty-three elderly patients (3.4%) suffered at least one drug-related AE in contrast to 58 patients (4.4%) in the group of adults (odds ratio = 0.76; 95% confidence interval = 0.45-1.27). Since marketing authorization in 2004, more than 3.5 million patients have been exposed to gadoxetate disodium worldwide: 1.7 million (48.6%) in elderly and 1.8 million (51.4%) in adults. The number of patients with post-marketing ADRs (total n = 793) was 354 (0.021%) in the elderly group and 439 (0.024%) in the adult group. Thus, there were significantly fewer patients with ADRs reported in the group of elderly versus adults ( P = 0.028). Hypersensitivity/immune system disorders, gastrointestinal disorders, and respiratory disorders were the most frequent ADRs in both groups, elderly and adults. Conclusion The incidence of drug-related AEs in clinical studies was similar and that of patients with ADRs in the post-marketing setting was lower in elderly (≥65 years) compared with younger adults aged 18-64 years. Overall, gadoxetate disodium shows a favorable safety profile in both age groups.

Image quality of low-radiation dose left atrial CT using filtered back projection and an iterative reconstruction algorithm: intra-individual comparison in unselected patients undergoing pulmonary vein isolation.

Background Computed tomography (CT) of the left atrium (LA) is performed prior to pulmonary vein isolation (PVI) to improve success of circumferential ablation for atrial fibrillation. The ablation procedure itself exposes patients to substantial radiation doses, therefore radiation dose reduction in pre-ablational imaging is of concern. Purpose To assess and compare diagnostic performance of low-radiation dose preprocedural CT in patients scheduled for PVI using two types of reconstruction algorithms. Material and Methods Forty-six patients (61 ± 10 years) scheduled for PVI were enrolled in this study irrespective of body-mass-index or cardiac rhythm at examination. An electrocardiographically triggered dual-source CT scan was performed. Filtered back projection (FBP) and iterative reconstruction (IR) algorithms were applied. Images were integrated into an electroanatomic mapping (EAM) system. Subjective image quality was scored independently by two readers on a five-point scale for both reconstruction algorithms (1 = excellent to 5 = non-diagnostic). Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and effective radiation dose were calculated. Results Data acquisition and EAM integration were successful in all patients. Median image quality score was 1 for both FBP (quartiles = 1, 1.62; range = 1-3) and IR (quartiles = 1, 1.5; range = 1-3). Mean SNR was 7.61 ± 2.14 for FBP and 9.02 ± 2.69 for IR. Mean CNR was 5.92 ± 1.80 for FBP and 6.95 ± 2.29 for IR. Mean effective radiation dose was 0.3 ± 0.1 mSv. Conclusion At a radiation dose of 0.3 ± 0.1 mSv, high-pitch dual-source CT yields LA images of consistently high quality using both FBP and IR. IR raises SNR and CNR without significantly improving subjective image quality.

Comparison of MRI with radiography for detecting structural lesions of the sacroiliac joint using CT as standard of reference: results from the SIMACT study.

OBJECTIVE: Radiographs of sacroiliac (SI) joints are used for the detection of structural damage in patients with axial spondyloarthritis (axSpA), but are often difficult to interpret. Here, we address the question how the T1-weighted MRI (T1w MRI) sequence compares with radiography for SI joints' structural lesions using low-dose CT as the standard of reference. METHODS: Radiographs, T1w MRI and low-dose CT of the SI joints from 110 patients (mean age 36.1 (19-57) years, 52% males and 48% females; 53% with axSpA, 21 non-radiographic axSpA and 32% radiographic axSpA, 47% with non-SpA) referred to the rheumatologist because of unclear chronic back pain, but possible axSpA, were scored for structural lesions (erosions, sclerosis, joint space changes and an overall impression of positivity). RESULTS: Using low-dose CT as the standard of reference, T1w MRI showed markedly better sensitivity with significantly more correct imaging findings compared with radiography for erosions (79% vs 42%; p=0.002), joint space changes (75% vs 41%; p=0.002) and overall positivity (85% vs 48%; p=0.001), respectively, while there were no differences between X-rays and MRI-T1 sequence regarding specificity (>80% for all scores). Only for sclerosis, MRI-T1 was inferior to radiography (sensitivity 30% vs 70%, respectively), however, not statistically significant (p=0.663). CONCLUSIONS: T1w MRI was superior to radiography in the detection of structural lesion of the SI joints in patients with axSpA. Future studies should focus on finding an agreement on the definition of MRI-T1 positivity.

Effects of heart valve prostheses on phase contrast flow measurements in Cardiovascular Magnetic Resonance - a phantom study.

BACKGROUND: Cardiovascular Magnetic Resonance is often used to evaluate patients after heart valve replacement. This study systematically analyses the influence of heart valve prostheses on phase contrast measurements in a phantom trial. METHODS: Two biological and one mechanical aortic valve prostheses were integrated in a flow phantom. B0 maps and phase contrast measurements were acquired at a 1.5 T MR scanner using conventional gradient-echo sequences in predefined distances to the prostheses. Results were compared to measurements with a synthetic metal-free aortic valve. RESULTS: The flow results at the level of the prosthesis differed significantly from the reference flow acquired before the level of the prosthesis. The maximum flow miscalculation was 154 ml/s for one of the biological prostheses and 140 ml/s for the mechanical prosthesis. Measurements with the synthetic aortic valve did not show significant deviations. Flow values measured approximately 20 mm distal to the level of the prosthesis agreed with the reference flow for all tested all prostheses. CONCLUSIONS: The tested heart valve prostheses lead to a significant deviation of the measured flow rates compared to a reference. A distance of 20 mm was effective in our setting to avoid this influence.

Nonenhanced magnetic resonance angiography (MRA) of the calf arteries at 3 Tesla: intraindividual comparison of 3D flow-dependent subtractive MRA and 2D flow-independent non-subtractive MRA.

PURPOSE: To prospectively compare 3D flow-dependent subtractive MRA vs. 2D flow-independent non-subtractive MRA for assessment of the calf arteries at 3 Tesla. METHODS: Forty-two patients with peripheral arterial occlusive disease underwent nonenhanced MRA of calf arteries at 3 Tesla with 3D flow-dependent subtractive MRA (fast spin echo sequence; 3D-FSE-MRA) and 2D flow-independent non-subtractive MRA (balanced steady-state-free-precession sequence; 2D-bSSFP-MRA). Moreover, all patients underwent contrast-enhanced MRA (CE-MRA) as standard-of-reference. Two readers performed a per-segment evaluation for image quality (4 = excellent to 0 = non-diagnostic) and severity of stenosis. RESULTS: Image quality scores of 2D-bSSFP-MRA were significantly higher compared to 3D-FSE-MRA (medians across readers: 4 vs. 3; p < 0.0001) with lower rates of non-diagnostic vessel segments on 2D-bSSFP-MRA (reader 1: <1 % vs. 15 %; reader 2: 1 % vs. 29 %; p < 0.05). Diagnostic performance of 2D-bSSFP-MRA and 3D-FSE-MRA across readers showed sensitivities of 89 % (214/240) vs. 70 % (168/240), p = 0.0153; specificities: 91 % (840/926) vs. 63 % (585/926), p < 0.0001; and diagnostic accuracies of 90 % (1054/1166) vs. 65 % (753/1166), p < 0.0001. CONCLUSION: 2D flow-independent non-subtractive MRA (2D-bSSFP-MRA) is a robust nonenhanced MRA technique for assessment of the calf arteries at 3 Tesla with significantly higher image quality and diagnostic accuracy compared to 3D flow-dependent subtractive MRA (3D-FSE-MRA). KEY POINTS: • 2D flow-independent non-subtractive MRA (2D-bSSFP-MRA) is a robust NE-MRA technique at 3T • 2D-bSSFP-MRA outperforms 3D flow-dependent subtractive MRA (3D-FSE-MRA) as NE-MRA of calf arteries • 2D-bSSFP-MRA is a promising alternative to CE-MRA for calf PAOD evaluation.

MRI in multiple sclerosis: an intra-individual, randomized and multicentric comparison of gadobutrol with gadoterate meglumine at 3 T.

OBJECTIVES: To compare contrast effects of gadobutrol with gadoterate meglumine for brain MRI in multiple sclerosis (MS) in a multicentre, randomized, prospective, intraindividual study at 3 T. METHODS: Institutional review board approval was obtained. Patients with known or suspected active MS lesions were included. Two identical MRIs were performed using randomized contrast agent order. Four post-contrast T1 sequences were acquired (start time points 0, 3, 6 and 9 min). If no enhancing lesion was present in first MRI, second MRI was cancelled. Quantitative (number and signal intensity of enhancing lesions) and qualitative parameters (time points of first and all lesions enhancing; subjective preference regarding contrast enhancement and lesion delineation; global preference) were evaluated blinded. RESULTS: Seventy-four patients (male, 26; mean age, 35 years) were enrolled in three centres. In 45 patients enhancing lesions were found. Number of enhancing lesions increased over time for both contrast agents without significant difference (median 2 for both). Lesions signal intensity was significantly higher for gadobutrol (p < 0.05 at time points 3, 6 and 9 min). Subjective preference rating showed non-significant tendency in favour of gadobutrol. CONCLUSION: Both gadobutrol and gadoterate meglumine can be used for imaging of acute inflammatory MS lesions. However, gadobutrol generates higher lesion SI. KEY POINTS: Contrast-enhanced MRI plays a key role in the management of multiple sclerosis. Different gadolinium-based contrast agents are available. Number of visibly enhancing lesions increases over time after contrast injection. Gadobutrol and gadoterate meglumine do not differ in number of visible lesions. Gadobutrol generates higher signal intensity than gadoterate meglumine.

Maximizing Information From Routine Staging Computed Tomography in Functional Neuroendocrine Neoplasms: Are There Findings Indicating the Presence of Carcinoid Heart Disease?

PURPOSE: The aim of this study was to evaluate signs of right-sided heart dysfunction on staging computed tomography (CT) as indirect indicators of carcinoid heart disease. PATIENTS AND METHODS: Patients with functionally active neuroendocrine neoplasm and different grades of tricuspid valve regurgitation (TR) were identified. Two readers independently reviewed contrast-enhanced staging CT performed within 90 days before or after echocardiography. Logistic regression and receiver operating analyses were used to asses the predictive value of right ventricle-left ventricle ratio (RV-LV ratio), ventricular septal bowing, retrograde contrast filling of the hepatic veins during contrast injection, and time to aortal enhancement greater than 100 Hounsfield units during bolus tracking for TR. RESULTS: Forty-four examinations were evaluated (11 with TR = 0, 16 with TR = 1, 9 with TR = 2, and 8 with TR = 3). Right ventricle-LV ratio was found to predict TR less than or equal to 1 versus TR greater than 1 (P = 0.0188) and TR less than or equal to 1 versus TR equals 2 (P = 0.0082). A prolonged time to aortal enhancement greater than 100 Hounsfield units during bolus tracking predicted TR less than or equal to 1 versus TR greater than 1 (P = 0.0077). Area under the curve for RV-LV ratio was 0.86 when differentiating TR less than or equal to 1 versus TR equals 2. With a cutoff of 1.07, sensitivity was 0.89, and specificity was 0.72. CONCLUSIONS: In patients with functionally active neuroendocrine neoplasm, an RV-LV ratio of more than 1.07 predicted TR with a relatively high sensitivity and moderate specificity and thus could serve as an indicator of subclinical carcinoid heart disease on routine staging CT.

Intraindividual, randomized comparison of the macrocyclic contrast agents gadobutrol and gadoterate meglumine in breast magnetic resonance imaging.

OBJECTIVES: To compare intraindividually two macrocyclic contrast agents - gadobutrol and gadoterate meglumine (Gd-DOTA) - for dynamic and quantitative assessment of relative enhancement (RE) in benign and malignant breast lesions. METHODS: This was an ethically approved, prospective, single-centre, randomized, crossover study in 52 women with suspected breast lesions referred for magnetic resonance imaging (MRI). Each patient underwent one examination with gadobutrol and one with Gd-DOTA (0.1 mmol/kg BW) on a 1.5 T system 1 - 7 days apart. Dynamic, T1-weighted, 3D gradient echo sequences were acquired under identical conditions. Quantitative evaluation with at least three regions of interest (ROI) per lesion was performed. Primary endpoint was RE during the initial postcontrast phase after the first and second dynamic acquisition, and peak RE. All lesions were histologically proven; differences between the examinations were evaluated. RESULTS: Forty-five patients with a total of 11 benign and 34 malignant lesions were assessed. Mean RE was significantly higher for gadobutrol than Gd-DOTA (p < 0.0001). Gadobutrol showed significantly less washout (64.4 %) than Gd-DOTA (75.4 %) in malignant lesions (p = 0.048) CONCLUSIONS: Gadobutrol has higher RE values compared with Gd-DOTA, whereas Gd-DOTA shows more marked washout in malignant lesions. This might improve the detection of breast lesions and influence the specificity of breast MRI-imaging.

Low Dose Computed Tomography for 3D Planning of Total Hip Arthroplasty: Evaluation of Radiation Exposure and Image Quality.

OBJECTIVE: The aim of the study was to compare radiation exposure and image quality between dedicated computed tomography (CT) protocols for preoperative total hip arthroplasty (THA) planning. METHODS: Three protocols with automated tube current modulation using 64-slice (n = 177) and 128-slice CT scanners without (n = 129) and with automated tube voltage preselection (n = 84) were compared. RESULTS: All 390 CTs were of sufficient quality for THA planning. Mean DLP was 235.0 mGy*cm (effective dose 2.8 mSv). Lowest radiation exposure (2.5 mSv) was seen with automated voltage preselection and the algorithm's selection was 100 kV (90.5% of patients) and 120 kV. Lowest image noise was seen in the highest dose group (3.1 mSv, 128-slice CT fixed tube voltage). A significant difference in cortical bone radiodensity was seen between 100 kV and 120 kV (P < 0.0001). CONCLUSIONS: Preoperative pelvic CT for THA planning is possible with very low radiation dose and reliable quality. Automated voltage preselection further decreases the effective dose by 18.2%.

High-pitch dual-source CT coronary angiography with low volumes of contrast medium.

OBJECTIVES: To assess the effect of lower volumes of contrast medium (CM) on image quality in high-pitch dual-source computed tomography coronary angiography (CTCA). METHODS: One-hundred consecutive patients (body weight 65-85 kg, stable heart rate ≤65 bpm, cardiac index ≥2.5 L/min/m(2)) referred for CTCA were prospectively enrolled. Patients were randomly assigned to one of five groups of different CM volumes (G30, 30 mL; G40, 40 mL; G50, 50 mL; G60, 60 mL; G70, 70 mL; flow rate 5 mL/s each, iodine content 370 mg/mL). Attenuation within the proximal and distal coronary artery segments was analysed. RESULTS: Mean attenuation for men and women ranged from 345.0 and 399.1 HU in G30 to 478.2 and 571.8 HU in G70. Mean attenuation values were higher in groups with higher CM volumes (P < 0.0001) and higher in women than in men (P < 0.0001). The proportions of segments with attenuation of at least 300 HU in G30, G40, G50, G60 and G70 were 89 %, 95 %, 98 %, 98 % and 99 %. CM volume of 30 mL in women and 40 mL in men proved to be sufficient to guarantee attenuation of at least 300 HU. CONCLUSIONS: In selected patients high-pitch dual-source CTCA can be performed with CM volumes of 40 mL in men or 30 mL in women. KEY POINTS: • High-pitch dual-source coronary angiography is feasible with low contrast media volumes. • Traditional injection rules still apply: higher volumes result in higher enhancement. • The patient's gender is a co-factor determining the level of contrast enhancement. • Volumes can be reduced down to 30-40 mL in selected patients.

Indocyanine green-enhanced fluorescence optical imaging in patients with early and very early arthritis: a comparative study with magnetic resonance imaging.

OBJECTIVE: Indocyanine green-enhanced fluorescence optical imaging (FOI) is a novel diagnostic tool for the assessment of inflammation in arthritis. We undertook this study to compare FOI with magnetic resonance imaging (MRI) in 32 patients with early and very early untreated arthritis (mean disease duration 7.1 months). METHODS: FOI images were acquired with the commercially available Xiralite system. Image interpretation was done for an early phase (phase 1), an intermediate phase (phase 2), and a late phase (phase 3), and for an electronically generated composite image. The results were compared with those of clinical examination (960 joints) and contrast (gadolinium)-enhanced 1.5T MRI (382 joints) of the clinically more affected hand. Additionally, we evaluated FOI in a control group of 46 subjects without any signs of inflammatory joint disease (1,380 joints). RESULTS: With MRI as the reference method, the sensitivity of FOI was 86% and the specificity was 63%, while the composite image, phase 1, and phase 3 reached high specificities (87%, 90%, and 88%, respectively). The results differed considerably between the composite image and the phases. FOI did not detect inflammation in 11 joint regions that showed palmar tenosynovitis on MRI. Intrareader and interreader agreements were moderate to substantial (κ = 0.55-0.73). In the control group, FOI showed positive findings in 5% of normal joints in phase 2. CONCLUSION: Further multicenter studies will address the question of whether FOI allows sensitive and reliable detection of inflammatory changes in early arthritis, as suggested by our initial findings. If this is confirmed, FOI has the potential to be a sensitive and valuable tool for monitoring disease activity on site in clinical settings and for serving as an outcome parameter in clinical trials.

Preference-Based Implementation of Video Consultations in Urban and Rural Regions in Outpatient Care in Germany: Protocol for a Mixed Methods Study.

BACKGROUND: Particularly in rural regions, factors such as lower physician density and long travel distances complicate adequate outpatient care. However, urban regions can also be affected by deficits in care, for example, long waiting times. One model of care intending to improve the situation is the implementation of video consultations. The study protocol presents the methodology of the research project titled "Preference-based implementation of the video consultation in urban and rural regions" funded by the German Federal Joint Committee (funding number 01VSF20011). OBJECTIVE: This study aims to identify existing barriers to the use of video consultation and the preferences of insured individuals and physicians as well as psychotherapists in order to optimize its design and thus increase acceptance and use of video consultations in urban and rural regions. METHODS: Built on a mixed methods approach, this study first assesses the status quo of video consultation use through claims data analysis and carries out a systematic literature review on barriers and promoting factors for the use of video consultations. Based on this preliminary work, focus groups are conducted in order to prepare surveys with insureds as well as physicians and psychotherapists in the second study phase. The central element of the survey is the implementation of discrete choice experiments to elicit relevant preferences of (potential) user groups and service providers. The summarized findings are discussed in a stakeholder workshop and translated into health policy recommendations. RESULTS: The methodological approach used in this study is the focus of this paper. The study is still ongoing and will continue until March 2024. The first study phase has already been completed, in which preliminary work has been done on potential applications and hurdles for the use of video consultations. Currently, the survey is being conducted and analyses are being prepared. CONCLUSIONS: This study is intended to develop a targeted strategy for health policy makers based on actual preferences and perceived obstacles to the use of video consultations. The results of this study will contribute to further user-oriented development of the implementation of video consultations in German statutory health insurance. Furthermore, the iterative and mixed methods approach used in this study protocol is also suitable for a variety of other research projects. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50932.

Macrocyclic contrast agents for magnetic resonance imaging of chronic myocardial infarction: intraindividual comparison of gadobutrol and gadoterate meglumine.

OBJECTIVES: To compare 0.15 mmol/kg gadobutrol for late gadolinium enhancement (LGE) imaging of chronic myocardial infarction with a relaxivity-adjusted dose of gadoterate meglumine (Gd-DOTA). METHODS: Seventeen patients with suspected chronic myocardial infarction underwent LGE imaging at 1.5 T, acquiring an inversion-recovery-prepared gradient echo sequence 15 min after contrast agent administration. Each patient underwent LGE imaging twice, once after administration of 0.15 mmol/kg gadobutrol (r1 = 5.2 l mmol(-1) s(-1)) and after 0.22 mmol/kg Gd-DOTA (r1 = 3.6 l mmol(-1) s(-1)). Two readers independently determined infarct size and contrast-to-noise ratios of infarcted myocardium to remote myocardium (CNR(remote)) and to the left ventricular lumen (CNR(lumen)). RESULTS: LGE was present in 14 patients. Infarct sizes determined after administration of gadobutrol [23.4 ml; 95 % CI (14.4; 32.5)] and Gd-DOTA [22.1 ml; 95 % CI (13.0; 31.1)] were not statistically different (P = 0.22). The CNR(remote) of LGE in infarcted myocardium on gadobutrol- and Gd-DOTA-enhanced images was 44.1 [95 % CI (31.0; 57.1)] and 45.2 [95 % CI (32.2; 58.3)], respectively (P = 0.73). CNR(lumen) was significantly higher on gadobutrol-enhanced LGE images [12.7; 95 % CI (2.5; 23.0) versus 6.8; 95 % CI (-3.5; 17.0); P = 0.02]. CONCLUSION: At relaxivity-adjusted doses, gadobutrol and Gd-DOTA yielded similar infarct sizes with superior contrast between infarcted myocardium and left ventricular lumen on gadobutrol-enhanced images.