Fracture risk prediction in postmenopausal women from GO Study: the comparison between FRAX, Garvan, and POL-RISK algorithms.

In the longitudinal, retrospective study, the ability of the FRAX, Garvan, and POL-RISK algorithms to predict osteoporotic fractures was compared in a group of 457 women. Using the rigid threshold of 10% showed a significant discrepancy in sensitivity and specificity of all tools. New thresholds for high risk of fractures were established for each calculator separately: 6.3% for FRAX major fracture, 20.0% for Garvan any fracture, and 18.0% for POL-RISK any fracture. Such thresholds allow for improving the diagnostic accuracy of all three calculators. INTRODUCTION: The aim of the longitudinal, retrospective study was to compare three tools designed to assess fracture risk: FRAX, Garvan, and POL-RISK in their prediction of fracture incidence. MATERIAL: The study group consisted of 457 postmenopausal women with a mean age of 64.21 ± 5.94 years from the Gliwice Osteoporosis (GO) Study. Comprehensive data on clinical factors related to fractures were collected for all participants. Bone densitometry was performed at the proximal femur using the Prodigy device (GE, USA). Fracture risk was established using the FRAX, Garvan, and POL-RISK algorithms. Data on the incidence of osteoporotic fractures were collected over the last 10 years. RESULTS: During the period of observation 72, osteoporotic fractures occurred in 63 subjects. For a preliminary comparison of the predictive value of analyzed diagnostic tools, the fracture risk threshold of 10% was used. For FRAX, the fracture probability exceeding 10% was observed only in 11 subjects who experienced fractures; thus, the fracture was properly predicted only in 22.9% of women. For Garvan, the respective value was 90.5%, and for POL-RISK, it was 98.4%. That gave a very low true positive value for FRAX and a very high false positive value for Garvan and POL-RISK. Based on ROC curves, new thresholds for high risk of fractures were established for each calculator separately: 6.3% for FRAX major fracture, 20.0% for Garvan any fracture, and 18.0% for POL-RISK any fracture. Such thresholds improve the diagnostic accuracy of all compared fracture prediction tools. CONCLUSION: The current study showed that different fracture risk assessment tools, although having similar clinical purposes, require different cut-off thresholds for making therapeutic decisions. Better identification of patients requiring therapy based on such an approach may help reduce the number of new fractures.

ISCEV standard for clinical pattern electroretinography (2024 update).

The pattern electroretinogram (PERG) is a localized retinal response evoked by a contrast-reversing pattern, usually a black and white checkerboard, which provides information about macular and retinal ganglion cell function. This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV; www.iscev.org ) presents an updated and revised Standard for clinical PERG testing. This replaces the 2013 and all earlier versions. Minimum protocols for basic PERG stimuli, recording methods and reporting are specified, to promote consistency of methods for diagnosis and monitoring purposes, while responding to evolving clinical practices and technology. The main changes in the updated ISCEV Standard for clinical PERG include expanded guidance about large stimulus fields, stimulus parameters for simultaneous PERG and pattern visual evoked potential recording, baseline drift correction, and use of consistent ambient room lighting. These changes aim to provide a clinically relevant document about current practice which will facilitate good quality recordings and inter-laboratory comparisons.

Clinical bleeding diathesis, laboratory haemostatic aberrations and survival in dogs infected with Angiostrongylus vasorum: 180 cases (2005-2019).

OBJECTIVES: Bleeding diathesis is a complication in dogs infected with Angiostrongylus vasorum. This retrospective study investigated clinical and laboratory haemostatic differences in A. vasorum-positive dogs with and without signs of bleeding and impact of bleeding on survival. MATERIALS AND METHODS: Demographics, type of clinical bleeding, haematocrit and a range of haemostatic tests, including thromboelastography and derived velocity curves were retrospectively registered from A. vasorum-positive dogs. All parameters were compared between dogs with and without signs of bleeding using univariable analyses. Binomial and multinomial regression models were applied to examine specific indicators in the bleeding dogs. P-values were false discovery rate adjusted, and adjusted P<0.05 was considered significant. RESULTS: One hundred and eighty dogs entered the study, including 65 dogs (36.1%) presenting with bleeding diathesis. Different types of cutaneous and mucosal bleeding were the most common clinical findings. Twenty dogs presented with neurological signs associated with intracranial and intra-spinal bleeding. One hundred and thirty-seven dogs had haematological and/or haemostatic laboratory analyses performed. Haematocrit, platelet count, thromboelastographic angle, maximum amplitude, global clot strength, maximum rate of thrombin generation and total thrombin generation were decreased, while prothrombin time was prolonged in bleeding dogs. Survival rate of bleeding dogs was lower at hospital discharge (76.9%) and 1 month after diagnosis (66.0%) than in dogs without signs of bleeding (94.8% and 90.1% at discharge and at 1 month, respectively). CLINICAL SIGNIFICANCE: Several haemostatic aberrations were detected in A. vasorum-positive dogs with bleeding diathesis. Bleeding was identified as an important negative prognostic indicator in A. vasorum-positive dogs.

Optimal fracture prediction thresholds for therapy onset, established from FRAX and Garvan algorithms: a longitudinal observation of the population representative female cohort from the RAC-OST-POL Study.

The study shows that the use of unified cutoff thresholds to identify high fracture risks by two popular calculators-FRAX and Garvan-leads to a significant discrepancy between the prediction of fractures and their actual prevalence over the period of 10 years. On the basis of the ROC analyses, a proposal of differentiated thresholds is presented. They were established at 6% for FRAX major fracture risk, 1.4% for FRAX hip fracture risk, 14.4% for Garvan any fracture risk, and 8.8% for Garvan hip fracture risk. PURPOSE/INTRODUCTION: The aim of the study was to verify how much were the tools, designed to predict fracture risks, precise vs. the actual fracture incidence values over a prospective observation. METHODS: The study group consisted of a population-based postmenopausal sample from the RAC-OST-POL Study. At baseline, there were 978 subjects at the mean age of 66.4 ± 7.8 years and, after a 10-year follow-up, 640 women remained at the mean age of 75.0 ± 6.95 years. At baseline, the fracture risk was established by the FRAX and Garvan tools. RESULTS: During the observation period, 190 osteoporotic fractures were identified in 129 subjects. When high-risk fracture cutoff thresholds (of 10% for major/any and 3% for hip fractures) were employed, only 19.59% of major fractures and 50% of hip fractures were identified in the high-risk group. For the Garvan tool, the percentage of correctly predicted fractures for any and hip fractures was 86.05% and 71.43%, respectively. Nevertheless, the fracture prediction by the Garvan tool was associated with the qualification of numerous subjects to the high-risk group, who subsequently did not experience a fracture in the 10-year follow-up period (false-positive prediction). Based on the ROC analyses, new high-risk thresholds were proposed individually for each calculator, improving the sensitivity, specificity, and diagnostic accuracy of these tools. They were established at 6% for FRAX major fracture risk, 1.4% for FRAX hip fracture risk, 14.4% for Garvan any fracture risk, and 8.8% for Garvan hip fracture risk. CONCLUSIONS: The current prospective study enabled to establish new, optimal thresholds for therapy initiation. Such a modified approach may enable a more accurate identification of treatment requiring patients and, in consequence, reduce the number of new fractures.

Non-invasive assessment of left ventricular relaxation property using color M-mode-derived intraventricular pressure gradients in cats.

INTRODUCTION: Diastolic dysfunction is an early clinical feature of feline hypertrophic cardiomyopathy (HCM). The left ventricular filling in early diastole is facilitated by the diastolic intraventricular pressure gradient (IVPG). The study objectives were to evaluate color Doppler M-mode-derived IVPG calculation in cats as a non-invasive assessment of the left ventricular relaxation property to determine the normal ranges of peak IVPG in cats and investigate the influence of left ventricular function and heart rate (HR). ANIMALS: One hundred and six client-owned apparently healthy cats. METHODS: Prospective cross-sectional study. Quantitative analysis of color Doppler M-mode images was used to estimate total and segmental IVPGs non-invasively. RESULTS: The total IVPG was 0.76 mmHg (95% reference interval (RI): 0.28-1.29 mmHg), the basal IVPG 0.34 mmHg (95% RI: 0.07-0.63 mmHg), and the mid-apical IVPG 0.42 mmHg (95% RI: 0.15-0.71 mmHg). Total and segmental IVPG increased with HR (P < 0.003), while segmental percent IVPG was HR independent. A short isovolumic relaxation time (IVRT) and a high mitral annular velocity in early diastole were associated with an increase in total IVPG (P = 0.008 and P = 0.009, respectively) adjusted for HR. An increase in IVPG was associated with an increase in mitral inflow velocity (P < 0.001). CONCLUSIONS: Feline IVPGs increase with HR and a short IVRT, which was believed to be a normal physiologic adrenergic response associated with an increased sympathetic tone. Future studies of segmental IVPG changes in feline HCM are needed to evaluate the clinical applicability of color Doppler M-mode estimated IVPGs in feline cardiology.

Epidemiology of heart disease in English Bull Terriers and echocardiographic characteristics of mitral valve abnormalities.

OBJECTIVES: To present the prevalence and distribution of heart disease as well as echocardiographic findings in English Bull Terriers. MATERIALS AND METHODS: One hundred and one English Bull Terriers were retrospectively included to evaluate the prevalence and distribution of heart disease. Secondly, a retrospective study on mitral valve abnormalities was performed on three groups: a control group (n=120, 19 breeds) used to establish reference intervals for mean transmitral gradient; a healthy English Bull Terriers group (n=25) and an English Bull Terriers group with mitral valve abnormalities (n= 18). Healthy English Bull Terriers for which mitral inflow parameters were not obtainable and English Bull Terriers with other types of heart disease were excluded. RESULTS: The prevalence of heart disease in English Bull Terriers was 65% (66/101), with mitral valve abnormalities (47%, 47/101) and aortic stenosis (29%, 29/101) being most common. The cut-off value for normal mean transmitral gradient was 3.5 mmHg in the control group. The mean transmitral gradient for healthy English Bull Terriers was higher than for other dog breeds. Healthy English Bull Terriers had a smaller mitral valve area and mitral annulus diameter compared with dogs with a similar body surface area. A high heart rate, smaller mitral valve area, mitral regurgitation, and volume overload are associated with increased mean transmitral gradient in English Bull Terriers with mitral valve abnormalities. CLINICAL SIGNIFICANCE: We suggest that mitral valve area, mitral annulus diameter and mean transmitral gradient measurements should be included in the echocardiographic protocol for English Bull Terriers.

Detection of congestive heart failure by mitral annular displacement in cats with hypertrophic cardiomyopathy - concordance between tissue Doppler imaging-derived tissue tracking and M-mode.

INTRODUCTION: The left ventricular systolic longitudinal function, traditionally measured by M-mode-derived mitral annular plane systolic excursion (MAPSE), is reduced in feline hypertrophic cardiomyopathy (HCM) and further reduced in cats with left-sided congestive heart failure (CHF). The objectives of this study were to compare longitudinal displacement measured by tissue tracking (TT-LD) and MAPSE in feline HCM and assess these methods' ability to differentiate CHF from preclinical HCM. A further objective was to provide preliminary reference intervals for TT-LD. ANIMALS: Eighty-five client-owned cats. METHODS: A retrospective case-control study. Anatomical M-mode was used to record MAPSE, and TT-LD was recorded by tissue tracking. RESULTS: Reduced longitudinal displacement measured by either MAPSE or TT-LD was significantly associated with CHF in cats with HCM (p < 0.036). Receiver-operating characteristic analysis indicated that TT-LD (AUC: 92.9%-97.9%) was more sensitive and specific than MAPSE (AUC: 85.8%-89.1%) for the detection of CHF. A diagnostic cut-off of 2.89 mm for maximal TT-LD in the left ventricular septum resulted in a sensitivity and specificity of 100% and 83.3%, while a diagnostic cut-off of 2.41 mm in the left ventricular posterior wall resulted in a sensitivity of 100% and a specificity of 90%. CONCLUSIONS: M-mode-derived mitral annular plane systolic excursion and TT-LD were strongly correlated, but not interchangeable. Longitudinal displacement measured by tissue tracking decreased more with disease severity than traditional MAPSE. Longitudinal displacement may help detect CHF in cats with HCM - with the maximal TT-LD of the left ventricular posterior wall achieving the highest AUC value.

Transthoracic two-dimensional and three-dimensional echocardiography for the measurement of mitral valve area planimetry in English Bull Terriers with and without heart disease.

INTRODUCTION: Mitral valve area (MVA) planimetry is used to diagnose and classify mitral stenosis (MS) in humans using two-dimensional and three-dimensional echocardiography (MVA2D and MVA3D). This study aimed to evaluate agreement, feasibility, and observer variability between MVA2D and MVA3D in English Bull Terriers (BT). Our hypotheses were (1) that the MVA of BT is generally smaller than that of breeds with similar body weight and (2) that these techniques could be used to diagnose MS in BTs. ANIMALS: Twenty healthy BTs, 15 healthy Boxers, and 49 BTs with heart disease. MATERIALS AND METHODS: A prospective diagnostic agreement study was conducted. All dogs underwent a thorough clinical examination, conventional transthoracic echocardiography, and three-dimensional echocardiography. RESULTS: Bland-Altman plots (limits of agreement: 0.12-1.5) showed consistent bias and poor agreement between MVA2D and MVA3D. For the 69 BTs, MVA3D (2.1 ± 0.50 cm2) measurements were significantly lower than MVA2D measurements (2.9 ± 0.60 cm2), and healthy BTs had significantly lower MVA parameters than healthy Boxers (p < 0.001). Intraobserver and interobserver variability were excellent for both MVA2D and MVA3D (intraclass correlation coefficient >0.9). Six BTs were diagnosed with MS, with MVA3D less than 1.8 cm2 and a mean transmitral gradient (MTG) of more than 5 mmHg. CONCLUSIONS: Both MVA2D and MVA3D are feasible, have low observer variability and can be used to diagnose MS in BTs. For assessing the narrowest orifice area, the preferred method is MVA3D. The smaller MVA in BTs compared to Boxers may indicate some degree of MS.

Insulin-degrading enzyme higher in subjects with metabolic syndrome.

Metabolic syndrome (MS) is comprised of a cluster of abnormalities in glucose, lipid, and vascular homeostasis, which is most commonly linked to abdominal obesity. MS heralds increased risk for development of diabetes and is linked to impairment in insulin signaling. Insulin-degrading enzyme (IDE) is one of the mechanisms through which insulin blood levels are maintained. It has been previously suggested that controlling IDE levels could provide yet another potential therapeutic approach in diabetes. Here we aim to investigate whether changes in serum IDE levels correlate with the severity of MS. Using a highly sensitive ELISA assay of active IDE in human serum, we found a strong correlation between circulating IDE levels and circulating levels of triglycerides, insulin, and c-peptide and an inverse correlation with HDL cholesterol (HDLc). Serum IDE levels were higher in MS subjects than in control subjects. Hence, circulating IDE may serve as a tool to identify subjects with abnormal insulin metabolism, possibly those with MS that are at risk to develop diabetes.

[Neurological symptoms in a patient on anti-TNF therapy, methotrexate and prednisolone for rheumatoid arthritis]. / Neurologische Symptome bei einer Patientin unter TNF-α-Inhibitor, Methotrexat und Prednisolon bei rheumatoider Arthritis.

A 78-year-old woman with rheumatoid arthritis on TNF-α inhibitor, methotrexate and prednisolone presented with severe but unspecific symptoms such as leg weakness, shivering, bifrontal headache, nausea and staggering. The broad range of differential diagnoses lead to intricate and time-consuming diagnostic procedures. Serology, magnetic resonance imaging and microbiological investigations represent important steps to make the final diagnosis of cerebral toxoplasmosis. Both diagnostic approach and therapy require close cooperation of different disciplines. Therapies of rheumatoid arthritis as well as of toxoplasmosis are based on a long-term treatment and could be associated with numerous harmful side effects. Continuous monitoring and permanent adjustment of therapy regimes are therefore mandatory.

[New DIN and ISO norms for determination of visual acuity]. / Neue DIN- und ISO-Normen zur Sehschärfebestimmung.

Recently, three international norms (ISO) for visual acuity assessment were revised. The DIN EN ISO 8596:2018 stipulates the Landolt C eye chart as the standard optotype and specifies display characteristics. An informative annex lists clinical optotypes for the first time. These include the ETDRS chart, Snellen chart and pediatric optotypes; however, these clinical optotypes do not have the same status as the Landolt C chart, since even with identical font size and stroke width they may differ in recognizability. The technical report ISO/TR 19498:2015 complements DIN EN ISO 8596. A scientifically appropriate procedure is described, which enables a quantitative correlation of clinical optotypes with the Landolt C chart. The DIN EN ISO 10938:2016 describes the required optical quality of optotypes. For the first time, electronic devices are explicitly approved for standardized visual acuity tests. Consequently, according to this amendment electronic devices may be used for acuity assessment for ophthalmological expert opinions according to DIN 58220, part 3.

Determination of scotopic and photopic conventional visual acuity and hyperacuity.

PURPOSE: Visual acuity (VA) is an important determinant of visual function. Here we establish procedures and recommendations for VA testing extending beyond the classical VA and thus make them available for future studies of visual function in health and disease. Specifically, we provide reference values for photopic and scotopic conventional uncrowded visual acuity (cVA) and Vernier-hyperacuity (hVA) and assess their reproducibility and dependence on contrast polarity. METHODS: For ten observers with normal vision, we determined photopic ("p"; maximal luminance 220 cd/m2) and scotopic ("s"; maximal luminance 0.004 cd/m2; 40 min of dark adaptation) cVA and hVA, for two contrast polarities i.e. black optotypes on white background and vice versa. To assess intersession effects, two sets of measurements were obtained on different days. RESULTS: Compared to pcVA (1.32 decimal VA; - 0.12 ± 0.02 LogMAR), the phVA (14.45 decimal VA; - 1.16 ± 0.04 LogMAR) scaled (in terms of decimal visual acuity) on average with a factor 11.0, the scVA (0.12 decimal VA; 0.91 ± 0.03 LogMAR) with a factor of 0.1, and the shVA (1.47 decimal VA; - 0.17 ± 0.02 LogMAR) with a factor of 1.1. There were neither significant effects of contrast polarity (p > 0.12), nor of session (p > 0.28). CONCLUSIONS: Our approach optimises integrated photopic and scotopic cVA and hVA measurements for general use and thus encourages the integration of these important measures of scotopic visual function in future studies. The absence of strong intersession effects demonstrates that no dedicated training session is needed to obtain scotopic and hVA measurements. The combined measures of scotopic and photopic VAs open a field of applications to study interplay and plasticity of the retinal photoreceptor systems and cortical processing in health and visual disease. As a rule of thumb, hyperacuity is 10× higher both in the photopic and scotopic range than conventional acuity. Thus, scotopic hyperacuity is close to photopic conventional acuity.

The ADAM-pelvis phantom-an anthropomorphic, deformable and multimodal phantom for MRgRT.

Applicability and accuracy of the rapidly developing tools and workflows for image-guided radiotherapy need to be validated under realistic treatment-like conditions. We present the construction of the ADAM-pelvis phantom, an anthropomorphic, deformable and multimodal (CT and MRI) phantom of the male pelvis. The phantom covers patient-like uncertainties in image-guided radiotherapy workflows including imaging artifacts for the special case of the human anatomy as well as organ motion. Principles and methods were further improved from previous work. The phantom includes surrogates for muscle tissue, adipose, inner and outer bone, as well as deformable silicone organs. Anthropomorphic shapes are realized with 3D-printing techniques for the bone and the construction of the hollow silicone organ shells. Organs are constructed from patient image segmentation and further guided by reported deformation models. Imaging markers and pockets for dosimeters are included in the organ shells. The improved phantom surrogates match imaging characteristics in MRI (T1 and T2 relaxation time) and CT (Hounsfield units) of human tissues. The surrogates are suited for long term use (several months) of the phantom. Previously reported artifacts of the muscle surrogate were avoided by improved composition of the used agarose gel. Interfractional organ motion is successfully realized for the water filled bladder and the air filled rectum and showed to be reproducible with deviation below 1 mm. Volume variations of both induce displacement, rotation and deformation of the prostate. We present solutions for the construction of an anthropomorphic phantom suitable for MRI and CT imaging including deformable organs. The developed concepts of phantom surrogates and construction techniques were successfully applied in building the ADAM-pelvis phantom and can as well be adopted for other anthropomorphic phantoms. The presented phantom allows for the systematic and controlled investigation of image-guided radiotherapy workflows in presence of organ motion.

Calculation and plotting of retinal nerve fiber paths based on Jansonius et al. 2009/2012 with an R program.

The data presented in this article are related to the research article entitled "Retinal conduction speed analysis reveals different origins of the P50 and N95 components of the (multifocal) pattern electroretinogram" (Bach et al., 2018) [1]. That analysis required the individual length data of the retinal nerve fibers (from ganglion cell body to optic nerve head, depending on the position of the ganglion cell body). Jansonius et al. (2009, 2012) [2,3] mathematically modeled the path morphology of the human retinal nerve fibers. We here present a working implementation with source code (for the free and open-source programming environment "R") of the Jansonius' formulas, including all errata. One file defines Jansonius et al.'s "phi" function. This function allows quantitative modelling of paths (and any measures derived from them) of the retinal nerve fibers. As a working demonstration, a second file contains a graph which plots samples of nerve fibers. The included R code runs in base R without the need of any additional packages.

[Cut-off filter : Physical and physiological basics]. / Kantenfilter : Physikalische und physiologische Grundlagen.

Light filters with wavelength-dependent transmission and in particular cut-off or step filters (steep dependence of transmission on wavelength) have a broad optical application and are relevant in ophthalmology. This article describes some physical and physiological principles of cut-off filters, discusses the physiological aspects of applications, specifically the not always relevant necessity of blue-reducing filters and the lack of efficacy of color filters with color vision deficiencies.

[Edge filters : Medical indications and clinical application]. / Kantenfilter : Medizinische Indikation und klinischer Einsatz.

Edge filters are used in aphakic eyes as a substitute of the natural cut-off filter of the intact eye or in other causes of a lack of light absorption in the eye itself. Furthermore, they can remedy light adaptation disturbances, especially in hereditary retinal diseases and retinal dystrophy. They enhance contrast and reduce glare. In order to choose an adequate cut-off filter it is necessary to let the participants test various filters before prescription. Because of the (absolute) absorption of blue light, cut-off filters normally lead to a loss of ability to drive.

Risk Factors for Fractures Identified in the Algorithm Developed in 5-Year Follow-Up of Postmenopausal Women From RAC-OST-POL Study.

The aim of the study was to establish factors with an impact on fracture risk and to develop an algorithm to predict osteoporotic fracture. A total of 978 postmenopausal women from the epidemiological, population-based RAC-OST-POL study with a mean age of 65.7 ± 7.3 years were enrolled. At baseline, bone mineral density at hip and clinical risk factors for fracture were collected. Afterward, each person was asked annually on fracture incidence in the 5-year follow-up. Finally, data for complete 5-year observation were gathered for the group of 802 patients. During the follow-up, 92 osteoporotic fractures occurred in 78 women. The most common fracture site was the forearm (n = 45). The following baseline factors were found as significant for fracture incidence: femoral neck bone mineral density, prior fractures, steroid use, falls within previous 12 months, and height. Fracture risk was predicted by the following formula: Riskoffractureincidence=11+e-(-9.899+1.077∗STEROIDS+0.681∗PRIORFALLS+0.611∗PRIORFRACTURES-0.483∗FNTscore+0.042∗HEIGHT). In our current longitudinal study, an algorithm predicting fracture occurrence over a period of 5 years was developed. It may find application in daily medical practice.

Maximum intensity breast diffusion MRI for BI-RADS 4 lesions detected on X-ray mammography.

AIM: To investigate an abbreviated, contrast-agent free diffusion-weighted (DW) breast magnetic resonance imaging (MRI) protocol that provides a single image for the radiologist to read in order to non-invasively examine Breast Imaging-Reporting and Data System (BI-RADS) 4 lesions detected using breast cancer screening X-ray mammography. MATERIALS AND METHODS: This retrospective evaluation within a institutional review board-approved, prospective study included 115 women (mean 57 years, range 50-69 years) with BI-RADS 4 findings on X-ray mammography and indication for biopsy over a period of 15 months. Full diagnostic breast MRI (FDP) was performed prior to biopsy (1.5 T). Maximum intensity breast diffusion (MIBD) images were generated from DW images (b = 1,500 mm/s2, 3 mm section thickness) of the breast. MIBD and T2-weighted (T2W) images were read by two radiologists and compared to the diagnostic accuracy of an expert reading of the FDP with histopathology as the reference standard. The acquisition time of MIBD and T2W MRI was about 7 minutes. RESULTS: MIBD MRI provided a diagnostic accuracy of 87.93% (95% confidence interval [CI]: 80.58-93.24%) for R1 and 89.66% (95% CI: 82.63-94.54%) for R2. Expert reading of the FDP revealed a similar accuracy of 86.2% (95% CI: 78.67-91.43%). The positive predictive value (PPV) could be increased from 36.2% (95% CI: 28.02-45.28; X-ray mammography alone) to a mean PPV of 80.89% (R1 79.17%, R2 82.16%) using MIBD MRI. Mean reading time was 30 seconds (25%/75 percentile 24.5-41.25). CONCLUSIONS: MIBD MRI might be of supplemental value if added to the work-up of BI-RADS 4 X-ray mammography screening findings. MIBD MRI might help reduce the false-positive rate prior to biopsy for reference lesions at only limited expense of measurement and reading time.

clickECM: Development of a cell-derived extracellular matrix with azide functionalities.

In vitro cultured cells produce a complex extracellular matrix (ECM) that remains intact after decellularization. The biological complexity derived from the variety of distinct ECM molecules makes these matrices ideal candidates for biomaterials. Biomaterials with the ability to guide cell function are a topic of high interest in biomaterial development. However, these matrices lack specific addressable functional groups, which are often required for their use as a biomaterial. Due to the biological complexity of the cell-derived ECM, it is a challenge to incorporate such functional groups without affecting the integrity of the biomolecules within the ECM. The azide-alkyne cycloaddition (click reaction, Huisgen-reaction) is an efficient and specific ligation reaction that is known to be biocompatible when strained alkynes are used to avoid the use of copper (I) as a catalyst. In our work, the ubiquitous modification of a fibroblast cell-derived ECM with azides was achieved through metabolic oligosaccharide engineering by adding the azide-modified monosaccharide Ac4GalNAz (1,3,4,6-tetra-O-acetyl-N-azidoacetylgalactosamine) to the cell culture medium. The resulting azide-modified network remained intact after removing the cells by lysis and the molecular structure of the ECM proteins was unimpaired after a gentle homogenization process. The biological composition was characterized in order to show that the functionalization does not impair the complexity and integrity of the ECM. The azides within this "clickECM" could be accessed by small molecules (such as an alkyne-modified fluorophore) or by surface-bound cyclooctynes to achieve a covalent coating with clickECM. STATEMENT OF SIGNIFICANCE: The clickECM was produced by the incorporation of azide-functionalized sugar analogues into the extracellular glycans of fibroblast cell cultures by metabolic oligosaccharide engineering. By introducing these azide groups into the glycan structures, we enabled this cell-derived ECM for bioorthogonal click reactions. Click chemistry provides extremely specific reactions with high efficiency, high selectivity, and high reaction yields. We could show that the azide functionalities within the clickECM are chemically accessible. Based on our here described clickECM technique it will be possible to create and investigate new clickECM materials with tunable bioactive properties and additional functionalities, which offers a promising approach for basic and applied research in the field of biomaterial science, biomedical applications, and tissue engineering.