Breast cancer screening in women with extremely dense breasts recommendations of the European Society of Breast Imaging (EUSOBI)

Breast density is an independent risk factor for the development of breast cancer and also decreases the sensitivity of mammography for screening. Consequently, women with extremely dense breasts face an increased risk of late diagnosis of breast cancer. These women are, therefore, underserved with current mammographic screening programs. The results of recent studies reporting on contrast-enhanced breast MRI as a screening method in women with extremely dense breasts provide compelling evidence that this approach can enable an important reduction in breast cancer mortality for these women and is cost-effective. Because there is now a valid option to improve breast cancer screening, the European Society of Breast Imaging (EUSOBI) recommends that women should be informed about their breast density. EUSOBI thus calls on all providers of mammography screening to share density information with the women being screened. In light of the available evidence, in women aged 50 to 70 years with extremely dense breasts, the EUSOBI now recommends offering screening breast MRI every 2 to 4 years. The EUSOBI acknowledges that it may currently not be possible to offer breast MRI immediately and everywhere and underscores that quality assurance procedures need to be established, but urges radiological societies and policymakers to act on this now. Since the wishes and values of individual women differ, in screening the principles of shared decision-making should be embraced. In particular, women should be counselled on the benefits and risks of mammography and MRI-based screening, so that they are capable of making an informed choice about their preferred screening method

Impact of the COVID-19 pandemic on breast cancer incidence and tumor stage in the Netherlands and Norway:A population-based study

BACKGROUND: Comparing the impact of the COVID-19 pandemic on the incidence of newly diagnosed breast tumors and their tumor stage between the Netherlands and Norway will help us understand the effect of differences in governmental and social reactions towards the pandemic.METHODS: Women newly diagnosed with breast cancer in 2017-2021 were selected from the Netherlands Cancer Registry and the Cancer Registry of Norway. The crude breast cancer incidence rate (tumors per 100,000 women) during the first (March-September 2020), second (October 2020-April 2021), and Delta COVID-19 wave (May-December 2021) was compared with the incidence rate in the corresponding periods in 2017, 2018, and 2019. Incidence rates were stratified by age group, method of detection, and clinical tumor stage.RESULTS: During the first wave breast cancer incidence declined to a larger extent in the Netherlands than in Norway (27.7% vs. 17.2% decrease, respectively). In both countries, incidence decreased in women eligible for screening. In the Netherlands, incidence also decreased in women not eligible for screening. During the second wave an increase in the incidence of stage IV tumors in women aged 50-69 years was seen in the Netherlands. During the Delta wave an increase in overall incidence and incidence of stage I tumors was seen in Norway.CONCLUSION: Alterations in breast cancer incidence and tumor stage seem related to a combined effect of the suspension of the screening program, health care avoidance due to the severity of the pandemic, and other unknown factors.</p

Lentiviral Gene Therapy for Mucopolysaccharidosis II with Tagged Iduronate 2-Sulfatase Prevents Life-Threatening Pathology in Peripheral Tissues But Fails to Correct Cartilage

Deficiency of iduronate 2-sulfatase (IDS) causes Mucopolysaccharidosis type II (MPS II), a lysosomal storage disorder characterized by systemic accumulation of glycosaminoglycans (GAGs), leading to a devastating cognitive decline and life-threatening respiratory and cardiac complications. We previously found that hematopoietic stem and progenitor cell-mediated lentiviral gene therapy (HSPC-LVGT) employing tagged IDS with insulin-like growth factor 2 (IGF2) or ApoE2, but not receptor-associated protein minimal peptide (RAP12x2), efficiently prevented brain pathology in a murine model of MPS II. In this study, we report on the effects of HSPC-LVGT on peripheral pathology and we analyzed IDS biodistribution. We found that HSPC-LVGT with all vectors completely corrected GAG accumulation and lysosomal pathology in liver, spleen, kidney, tracheal mucosa, and heart valves. Full correction of tunica media of the great heart vessels was achieved only with IDS.IGF2co gene therapy, while the other vectors provided near complete (IDS.ApoE2co) or no (IDSco and IDS.RAP12x2co) correction. In contrast, tracheal, epiphyseal, and articular cartilage remained largely uncorrected by all vectors tested. These efficacies were closely matched by IDS protein levels following HSPC-LVGT. Our results demonstrate the capability of HSPC-LVGT to correct pathology in tissues of high clinical relevance, including those of the heart and respiratory system, while challenges remain for the correction of cartilage pathology

Cost-effectiveness and Cost-utility of the Adherence Improving Self-management Strategy in Human Immunodeficiency Virus Care : A Trial-based Economic Evaluation

This study was funded by ZonMw (the Netherlands), program Doelmatigheidsonderzoek (grant number 171002208). This funding source had no role in study design, data collection, analysis, interpretation, or writing of the report. All authors declare that they have no competing interests. We thank the HIV-nurses and physicians from the seven HIV-clinics who were involved in the AIMSstudy (Academic Medical Center, Amsterdam; Slotervaart Hospital, Amsterdam; St. Lucas-Andreas Hospital, Amsterdam; the Leiden University Medical Center, Leiden; Haga Teaching Hospital, Den Haag; Erasmus Medical Center, Rotterdam; Isala Clinics, Zwolle) for their input and collaboration. We also would like to express our gratitude to the study participants. Written informed consent was obtained from each patient. The study has been approved by the ethics committee of each participating center.Peer reviewedPostprin

Природный и антропогенный факторы формирования и развития культурного ландшафта Форосского парка

Цель данной статьи: на примере небольшой территории Южного берега Крыма – парка в пгт. Форос и прилегающей к нему местности – показать роль и место культурного ландшафта в формировании человеком исторического геокультурного пространства

Diagnostic accuracy for different strategies of image-guided breast intervention in cases of nonpalpable breast lesions

To find out whether ultrasound-guided fine-needle aspiration (FNA) and ultrasound and stereotactic-guided large core needle biopsy (LCNB) are reliable alternatives to needle-localised open breast biopsy (NLBB) in daily practice, we performed a retrospective study and evaluated the validity of these methods. In all, 718 women with 749 nonpalpable breast lesions from three Dutch Hospitals were included, and the validity of the various methods for diagnosis was assessed. This was carried out according to a method described by Burbank and Parker for evaluating the quality of an image-guided breast intervention. We compared our results with the outcome of the COBRA study. Overall, all diagnostic strategies (NLBB, FNA, LCNB ultrasound and stereotactic guided) show comparable agreement rates. However, the miss rates differ: 2% for NLBB, 3% for COBRA (LCNB in study setting), 5% for FNA and 8-12% for LCNB in practice. Fine-needle aspiration was nonconclusive in 29%, and shows an overestimation for DCIS in 9%. The DCIS underestimate rate in NLBB was 8%. For the assessment of lesions consisting of microcalcifications only and to exclude malignancy in all other lesions, a 14-gauge needle should be used. Ultrasound-guided intervention can be performed in a large percentage of nonpalpable lesions. Lesions consisting only of microcalcifications on mammography need special attention

Supine MRI for regional breast radiotherapy: Imaging axillary lymph nodes before and after sentinel-node biopsy

Regional radiotherapy (RT) is increasingly used in breast cancer treatment. Conventionally, computed tomography (CT) is performed for RT planning. Lymph node (LN) target levels are delineated according to anatomical boundaries. Magnetic resonance imaging (MRI) could enable individual LN delineation. The purpose was to evaluate the applicability of MRI for LN detection in supine treatment position, before and after sentinel-node biopsy (SNB). Twenty-three female breast cancer patients (cTis-3N0M0) underwent 1.5 T MRI, before and after SNB, in addition to CT. Endurance for MRI was monitored. Axillary levels were delineated. LNs were identified and delineated on MRI from before and after SNB, and on CT, and compared by Wilcoxon signed-rank tests. LN locations and LN-based volumes were related to axillary delineations and associated volumes. Although postoperative effects were visible, LN numbers on postoperative MRI (median 26 LNs) were highly reproducible compared to preoperative MRI when adding excised sentinel nodes, and higher than on CT (median 11, p < 0.001). LN-based volumes were considerably smaller than respective axillary levels. Supine MRI of LNs is feasible and reproducible before and after SNB. This may lead to more accurate RT target definition compared to CT, with potentially lower toxicity. With the MRI techniques described here, initiation of novel MRI-guided RT strategies aiming at individual LNs could be possible

Estimation of metabolite T1 relaxation times using tissue specific analysis, signal averaging and bootstrapping from magnetic resonance spectroscopic imaging data

Object A novel method of estimating metabolite T1 relaxation times using MR spectroscopic imaging (MRSI) is proposed. As opposed to conventional single-voxel metabolite T1 estimation methods, this method investigates regional and gray matter (GM)/white matter (WM) differences in metabolite T1 by taking advantage of the spatial distribution information provided by MRSI

Computer-aided detection in breast MRI: a systematic review and meta-analysis

To evaluate the additional value of computer-aided detection (CAD) in breast MRI by assessing radiologists' accuracy in discriminating benign from malignant breast lesions. A literature search was performed with inclusion of relevant studies using a commercially available CAD system with automatic colour mapping. Two independent researchers assessed the quality of the studies. The accuracy of the radiologists' performance with and without CAD was presented as pooled sensitivity and specificity. Of 587 articles, 10 met the inclusion criteria, all of good methodological quality. Experienced radiologists reached comparable pooled sensitivity and specificity before and after using CAD (sensitivity: without CAD: 89%; 95% CI: 78-94%, with CAD: 89%; 95%CI: 81-94%) (specificity: without CAD: 86%; 95% CI: 79-91%, with CAD: 82%; 95% CI: 76-87%). For residents the pooled sensitivity increased from 72% (95% CI: 62-81%) without CAD to 89% (95% CI: 80-94%) with CAD, however, not significantly. Concerning specificity, the results were similar (without CAD: 79%; 95% CI: 69-86%, with CAD: 78%; 95% CI: 69-84%). CAD in breast MRI has little influence on the sensitivity and specificity of experienced radiologists and therefore their interpretation remains essential. However, residents or inexperienced radiologists seem to benefit from CAD concerning breast MRI evaluation

H3 Lysine 4 Is Acetylated at Active Gene Promoters and Is Regulated by H3 Lysine 4 Methylation

Methylation of histone H3 lysine 4 (H3K4me) is an evolutionarily conserved modification whose role in the regulation of gene expression has been extensively studied. In contrast, the function of H3K4 acetylation (H3K4ac) has received little attention because of a lack of tools to separate its function from that of H3K4me. Here we show that, in addition to being methylated, H3K4 is also acetylated in budding yeast. Genetic studies reveal that the histone acetyltransferases (HATs) Gcn5 and Rtt109 contribute to H3K4 acetylation in vivo. Whilst removal of H3K4ac from euchromatin mainly requires the histone deacetylase (HDAC) Hst1, Sir2 is needed for H3K4 deacetylation in heterochomatin. Using genome-wide chromatin immunoprecipitation (ChIP), we show that H3K4ac is enriched at promoters of actively transcribed genes and located just upstream of H3K4 tri-methylation (H3K4me3), a pattern that has been conserved in human cells. We find that the Set1-containing complex (COMPASS), which promotes H3K4me2 and -me3, also serves to limit the abundance of H3K4ac at gene promoters. In addition, we identify a group of genes that have high levels of H3K4ac in their promoters and are inadequately expressed in H3-K4R, but not in set1Δ mutant strains, suggesting that H3K4ac plays a positive role in transcription. Our results reveal a novel regulatory feature of promoter-proximal chromatin, involving mutually exclusive histone modifications of the same histone residue (H3K4ac and H3K4me)