Effects of preset sequential administrations of sunitinib and everolimus on tumour differentiation in Caki-1 renal cell carcinoma.

BACKGROUND: Sunitinib (VEGFR/PDGFR inhibitor) and everolimus (mTOR inhibitor) are both approved for advanced renal cell carcinoma (RCC) as first-line and second-line therapy, respectively. In the clinics, sunitinib treatment is limited by the emergence of acquired resistance, leading to a switch to second-line treatment at progression, often based on everolimus. No data have been yet generated on programmed alternating sequential strategies combining alternative use of sunitinib and everolimus before progression. Such strategy is expected to delay the emergence of acquired resistance and improve tumour control. The aim of our study was to assess the changes in tumours induced by three different sequences administration of sunitinib and everolimus. METHODS: In human Caki-1 RCC xenograft model, sunitinib was alternated with everolimus every week, every 2 weeks, or every 3 weeks. Effects on necrosis, hypoxia, angiogenesis, and EMT status were assessed by immunohisochemistry and immunofluorescence. RESULTS: Sunitinib and everolimus programmed sequential regimens before progression yielded longer median time to tumour progression than sunitinib and everolimus monotherapies. In each group of treatment, tumour growth control was associated with inhibition of mTOR pathway and changes from a mesenchymal towards an epithelial phenotype, with a decrease in vimentin and an increase in E-cadherin expression. The sequential combinations of these two agents in a RCC mouse clinical trial induced antiangiogenic effects, leading to tumour necrosis. CONCLUSIONS: In summary, our study showed that alternate sequence of sunitinib and everolimus mitigated the development of mesenchymal phenotype compared with sunitinib as single agent

Seroprevalence of 34 Human Papillomavirus Types in the German General Population

The natural history of infections with many human papillomavirus (HPV) types is poorly understood. Here, we describe for the first time the age- and sex-dependent antibody prevalence for 29 cutaneous and five mucosal HPV types from 15 species within five phylogenetic genera (alpha, beta, gamma, mu, nu) in a general population. Sera from 1,797 German adults and children (758 males and 1,039 females) between 1 and 82 years (median 37 years) were analysed for antibodies to the major capsid protein L1 by Luminex-based multiplex serology. The first substantial HPV antibody reactions observed already in children and young adults are those to cutaneous types of the genera nu (HPV 41) and mu (HPV 1, 63). The antibody prevalence to mucosal high-risk types, most prominently HPV 16, was elevated after puberty in women but not in men and peaked between 25 and 34 years. Antibodies to beta and gamma papillomaviruses (PV) were rare in children and increased homogeneously with age, with prevalence peaks at 40 and 60 years in women and 50 and 70 years in men. Antibodies to cutaneous alpha PV showed a heterogeneous age distribution. In summary, these data suggest three major seroprevalence patterns for HPV of phylogenetically distinct genera: antibodies to mu and nu skin PV appear early in life, those to mucosal alpha PV in women after puberty, and antibodies to beta as well as to gamma skin PV accumulate later in life

Partial Segmental Thrombosis of the Corpus Cavernosum (PSTCC) diagnosed by contrast-enhanced ultrasound: a case report

Background Partial segmental thrombosis of the corpus cavernosum (PSTCC) is a rare disease predominantly occurring in young men. Cardinal symptoms are pain and perineal swelling. Although several risk factors are described in the literature, the exact etiology of penile thrombosis remains unclear in most cases. MRI or ultrasound (US) is usually used for diagnosing this condition. Case presentation We report a case of penile thrombosis after left-sided varicocele ligature in a young patient. The diagnosis was established using contrast-enhanced ultrasound (CEUS) and was confirmed by contrast-enhanced magnetic resonance imaging (ceMRI). Successful conservative treatment consisted of systemic anticoagulation using low molecular weight heparin and acetylsalicylic acid. Conclusion PSTCC is a rare condition in young men and appears with massive pain and perineal swelling. In case of suspected PSTCC utilization of CEUS may be of diagnostic benefit

Quantification of liver and muscular fat using contrast-enhanced Dual Source Dual Energy Computed Tomography compared to an established multi-echo Dixon MRI sequence.

PURPOSE: To investigate the feasibility of liver fat quantification in contrast-enhanced dual source dual energy computed tomography (DECT) using multi-echo Dixon magnetic resonance imaging (MRI) as reference standard. METHOD: Patients who underwent MRI of the liver including a multi-echo Dixon sequence for estimation of proton density fat fraction in 2017 as well as contrast-enhanced DECT imaging of the abdomen were included in this retrospective, monocentric IRB approved study. Furthermore, patients with a hepatic fat amount >5% who were examined in 2018 with MRI and DECT were included. The final study group consisted of 81 patients with 90 pairs of examinations. Analysis of parameter maps was performed manually using congruent regions of interest which were placed in the liver parenchyma, in the erector spinae muscles, and psoas major muscles. RESULTS: Mean patient age was 61 ± 13 years. Median time between MRI and DECT was 48 days. MRI liver fat quantification resulted in a median of 3.8% (IQR: 2.2-8.2%) compared to 1.8% (IQR: 0-6.3%) in DECT (p < 0.001), with a Spearman correlation of 0.73. Bland-Altman analysis resulted in a systematic underestimation of liver fat in DECT, with a mean difference of -1.7%. Fat quantification in the erector spinae muscles (p = 0.257) and the psoas major muscles (p = 0.208) was not significantly different in DECT compared to MRI. CONCLUSIONS: Liver and muscular fat quantification in portal-venous phase DECT is feasible with good to excellent correlation compared to a multi-echo Dixon MRI sequence analysis. While there is an underestimation of the liver fat content in DECT, there are no significant differences between DECT and MRI fat quantification of the erector spinae and psoas major muscles

Differentiation of Hamartomas and Malignant Lung Tumors in Single-Phased Dual-Energy Computed Tomography

This study investigated the efficacy of single-phase dual-energy CT (DECT) in differentiating pulmonary hamartomas from malignant lung lesions using virtual non-contrast (VNC), iodine, and fat quantification. Forty-six patients with 47 pulmonary lesions (mean age: 65.2 ± 12.1 years; hamartomas-to-malignant lesions = 22:25; male: 67%) underwent portal venous DECT using histology, PET-CT and follow-up CTs as a reference. Quantitative parameters such as VNC, fat fraction, iodine density and CT mixed values were statistically analyzed. Significant differences were found in fat fractions (hamartomas: 48.9%; malignancies: 22.9%; p ≤ 0.0001) and VNC HU values (hamartomas: −20.5 HU; malignancies: 17.8 HU; p ≤ 0.0001), with hamartomas having higher fat content and lower VNC HU values than malignancies. CT mixed values also differed significantly (p ≤ 0.0001), but iodine density showed no significant differences. ROC analysis favored the fat fraction (AUC = 96.4%; sensitivity: 100%) over the VNC, CT mixed value and iodine density for differentiation. The study concludes that the DECT-based fat fraction is superior to the single-energy CT in differentiating between incidental pulmonary hamartomas and malignant lesions, while post-contrast iodine density is ineffective for differentiation

An investigation into potential gender-specific differences in myocardial triglyceride content assessed by 1^{1}H-Magnetic Resonance Spectroscopy at 3Tesla

Objective: Over the past decade, myocardial triglyceride content has become an accepted biomarker for chronic metabolic and cardiac disease. The purpose of this study was to use proton (hydrogen 1)-magnetic resonance spectroscopy ($^{1}$H-MRS) at 3Tesla (3 T) field strength to assess potential gender-related differences in myocardial triglyceride content in healthy individuals. Methods: Cardiac MR imaging was performed to enable accurate voxel placement and obtain functional and morphological information. Double triggered (i.e., ECG and respiratory motion gating) $^{1}$H-MRS was used to quantify myocardial triglyceride levels for each gender. Two-sample t-test and Mann-Whitney U-test were used for statistical analyses. Results: In total, 40 healthy volunteers (22 male, 18 female; aged >18 years and age matched) were included in the study. Median myocardial triglyceride content was 0.28% (interquartile range [IQR] 0.17–0.42%) in male and 0.24% (IQR 0.14–0.45%) in female participants, and no statistically significant difference was observed between the genders. Furthermore, no gender-specific difference in ejection fraction was observed, although on average, male participants presented with a higher mean ± SD left ventricular mass (136.3 ± 25.2 g) than female participants (103.9 ± 16.1 g). Conclusions: The study showed that $^{1}$H-MRS is a capable, noninvasive tool for acquisition of myocardial triglyceride metabolites. Myocardial triglyceride concentration was shown to be unrelated to gender in this group of healthy volunteers

AI Lung Segmentation and Perfusion Analysis of Dual-Energy CT Can Help to Distinguish COVID-19 Infiltrates from Visually Similar Immunotherapy-Related Pneumonitis Findings and Can Optimize Radiological Workflows

(1) To explore the potential impact of an AI dual-energy CT (DECT) prototype on decision making and workflows by investigating its capabilities to differentiate COVID-19 from immunotherapy-related pneumonitis. (2) Methods: From 3 April 2020 to 12 February 2021, DECT from biometrically matching patients with COVID-19, pneumonitis, and inconspicuous findings were selected from our clinical routine. Three blinded readers independently scored each pulmonary lobe analogous to CO-RADS. Inter-rater agreement was determined with an intraclass correlation coefficient (ICC). Averaged perfusion metrics per lobe (iodine uptake in mg, volume without vessels in ml, iodine concentration in mg/mL) were extracted using manual segmentation and an AI DECT prototype. A generalized linear mixed model was used to investigate metric validity and potential distinctions at equal CO-RADS scores. Multinomial regression measured the contribution “Reader”, “CO-RADS score”, and “perfusion metrics” to diagnosis. The time to diagnosis was measured for manual vs. AI segmentation. (3) Results: We included 105 patients (62 ± 13 years, mean BMI 27 ± 2). There were no significant differences between manually and AI-extracted perfusion metrics (p = 0.999). Regardless of the CO-RADS score, iodine uptake and concentration per lobe were significantly higher in COVID-19 than in pneumonitis (p p < 0.001). (4) Conclusions: The investigated AI prototype positively impacts decision making and workflows by extracting perfusion metrics that differentiate COVID-19 from visually similar pneumonitis significantly faster than radiologists

Long term evolution of MRI characteristics in a case of atypical left lateral wall hypertrophic cardiomyopathy

We are reporting a long-time magnetic resonance imaging (MRI) follow-up in a rare case of cardiac left lateral wall hypertrophy. Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disorder and a significant cause of sudden cardiac death. Cardiac magnetic resonance (CMR) imaging can be a valuable tool for assessment of detailed information on size, localization, and tissue characteristics of hypertrophied myocardium. However, there is still little knowledge of long-term evolution of HCM as visualized by magnetic resonance imaging. Recently, our group reported a case of left lateral wall HCM as a rare variant of the more common forms, such as septal HCM, or apical HCM. As we now retrieved an old cardiac MRI acquired in this patient more than 20 years ago, we are able to provide the thrilling experience of an ultra-long MRI follow-up presentation in this rare case of left lateral wall hypertrophy. Furthermore, this case outlines the tremendous improvements in imaging quality within the last two decades of CMR imaging

Application of a Deep Learning Algorithm for Combined Super-Resolution and Partial Fourier Reconstruction Including Time Reduction in T1-Weighted Precontrast and Postcontrast Gradient Echo Imaging of Abdominopelvic MR Imaging

Purpose: The purpose of this study was to test the technical feasibility and the impact on the image quality of a deep learning-based super-resolution reconstruction algorithm in 1.5 T abdominopelvic MR imaging. Methods: 44 patients who underwent abdominopelvic MRI were retrospectively included, of which 4 had to be subsequently excluded. After the acquisition of the conventional volume interpolated breath-hold examination (VIBEStd), images underwent postprocessing, using a deep learning-based iterative denoising super-resolution reconstruction algorithm for partial Fourier acquisitions (VIBESR). Image analysis of 40 patients with a mean age of 56 years (range 18&ndash;84 years) was performed qualitatively by two radiologists independently using a Likert scale ranging from 1 to 5, where 5 was considered the best rating. Results: Image analysis showed an improvement of image quality, noise, sharpness of the organs and lymph nodes, and sharpness of the intestine for pre- and postcontrast images in VIBESR compared to VIBEStd (each p &lt; 0.001). Lesion detectability was better for VIBESR (p &lt; 0.001), while there were no differences concerning the number of lesions. Average acquisition time was 16 s (&plusmn;1) for the upper abdomen and 15 s (&plusmn;1) for the pelvis for VIBEStd, and 15 s (&plusmn;1) for the upper abdomen and 14 s (&plusmn;1) for the pelvis for VIBESR. Conclusion: This study demonstrated the technical feasibility of a deep learning-based super-resolution algorithm including partial Fourier technique in abdominopelvic MR images and illustrated a significant improvement of image quality, noise, and sharpness while reducing TA