Rapid Access to Contrast-Enhanced spectral mammogRaphy in women recalled from breast cancer screening: the RACER trial study design.

BACKGROUND: In the Dutch breast cancer screening program, women recalled with a BI-RADS 0 score are referred for additional imaging, while those with BI-RADS 4/5 scores are also directed to an outpatient breast clinic. Approximately six out of ten women are recalled without being diagnosed with a malignancy. However, these recalls require additional imaging and doctor visits, which result in patient anxiety and increased health care costs. Conventional types of imaging used for additional imaging are full-field digital mammography and tomosynthesis. Contrast-enhanced spectral mammography has proved to have higher sensitivity and specificity than conventional imaging in women recalled from screening. Therefore, the aim is to study if CESM instead of conventional imaging is a more accurate, patient-friendly, and cost-effective strategy in the work-up of women recalled from breast cancer screening. METHODS: This prospective, multicenter, randomized controlled trial will be conducted at four centers and will include 528 patients recalled for suspicious breast lesions from the Dutch breast cancer screening program. Participants are randomized in two groups: (1) standard care using conventional breast imaging techniques as initial imaging after recall versus (2) work-up primarily based on CESM. Written informed consent will be collected prior to study inclusion. The primary outcome is the diagnostic accuracy for detection of breast cancer. Secondary outcomes are numbers of additional diagnostic exams, days until final diagnosis, health care costs, and experienced patient anxiety. DISCUSSION: Based on previously published retrospective studies, we expect to demonstrate in this prospective multicenter randomized controlled trial, that using CESM as a primary work-up tool in women recalled from breast cancer screening is a more accurate, cost-effective, and patient-friendly strategy. TRIAL REGISTRATION: Netherlands Trial Register, NL6413/NTR6589. Registered on 6 July, 2017.

Evaluation of single-view contrast-enhanced mammography as novel reading strategy: a non-inferiority feasibility study.

BACKGROUND: Guidelines recommend screening of high-risk women using breast magnetic resonance imaging (MRI). Contrast-enhanced mammography (CEM) has matured, providing excellent diagnostic accuracy. To lower total radiation dose, evaluation of single-view (1 V) CEM exams might be considered instead of double-view (2 V) readings as an alternative reading strategy in women who cannot undergo MRI. METHODS: This retrospective non-inferiority feasibility study evaluates whether the use of 1 V results in an acceptable sensitivity for detecting breast cancer (non-inferiority margin, - 10%). CEM images from May 2013 to December 2017 were included. 1 V readings were performed by consensus opinion of three radiologists, followed by 2 V readings being performed after 6 weeks. Cases were considered "malignant" if the final BI-RADS score was ≥ 4, enabling calculation of sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Histopathological results or follow-up served as a gold standard. RESULTS: A total of 368 cases were evaluated. Mean follow-up for benign or negative cases was 20.9 months. Sensitivity decreased by 9.6% from 92.9 to 83.3% when only 1 V was used for evaluation (p < 0.001). The lower limit of the 90% confidence interval around the difference in sensitivity between 1 V and 2 V readings was - 15% and lies below the predefined non-inferiority margin of - 10%. Hence, non-inferiority of 1 V to 2 V reading cannot be concluded. AUC for 1 V was significantly lower, 0.861 versus 0.899 for 2 V (p = 0.0174). CONCLUSION: Non-inferiority of 1 V evaluations as an alternative reading strategy to standard 2 V evaluations could not be concluded. 1 V evaluations had lower diagnostic performance compared with 2 V evaluations. KEY POINTS: • To lower radiation exposure used in contrast-enhanced mammography, we studied a hypothetical alternative strategy: single-view readings (1 V) versus (standard) double-view readings (2 V). • Based on our predefined margin of - 10%, non-inferiority of 1 V could not be concluded. • 1 V evaluation is not recommended as an alternative reading strategy to lower CEM-related radiation exposure.

Can high school students help to improve breast radiologists in detecting missed breast cancer lesions on full-field digital mammography?

Aim: To investigate whether full-field digital mammography (FFDM) and contrast-enhanced mammography (CEM), evaluated by non-experienced high school students, improves detection of missed breast cancer lesions on FFDM, in the same cohort of patients. Methods: Non-experienced first- and second year high school students examined fourteen cases of patients diagnosed with breast cancer. These cases consisted of missed breast cancer lesions on FFDM by a breast radiologist. Sensitivity of assessment of the students on FFDM and CEM was analysed and compared with the initial results of the breast radiologists. Results: A total of 134 high school students participated in this study. Mean age was 12.8 years (range 10-14). Based on FFDM, mean overall sensitivity of the students was 29.2% (18.9 - 39.6%). When recombined CEM images were used, mean overall sensitivity of students improved to 82.6% (74.0 - 91.2%) (p=0.001). Mean overall sensitivity of FFDM exams evaluated by radiologists was 75.7% (64.2 - 87.3%), which was lower when compared to student's evaluations on recombined CEM exams, yet not statistically significant (p=0.098). Conclusions: Contrast-enhanced mammography evaluated by non-experienced high school students might improve detection rate of breast cancer when compared to evaluations of only full-field digital mammography by radiologists.

The Non-Union Scoring System: an interobserver reliability study.

PURPOSE: The Non-Union Scoring System (NUSS) aims to classify non-unions according to their severity and relate them to four treatment categories. The main purpose of this study was to evaluate the reliability of the NUSS. In addition we assessed its clinical validity. METHODS: Forty-four Patients with a tibia non-union between 2005 and 2015 were included in this study. Data from all included patients were scored independently by three observers according to the NUSS criteria. The interobserver agreement was evaluated using the intraclass correlation coefficient (ICC). The interobserver agreement of the Weber-Cech system was assessed using Fleiss' kappa. Finally, the clinical validity of the NUSS was analysed by comparing outcomes of the actual treatment groups to the proposed treatment groups following from the NUSS scores. RESULTS: Forty-four patients were included. The comparison of NUSS scores between observers showed substantial agreement [ICC; 0.78 (0.67-0.86)]. The comparison of the Weber-Cech classification between observers showed only fair agreement [Fleiss κ; 0.30 (0.17-0.42)]. The χ2 test for the treatment groups according to the NUSS and the treatments at index procedure showed an independent relation (χ2 = 5.794, 6 degrees of freedom, p: 0.447). In contrast, the proposed treatment strategy corresponds well to the definitive treatment (χ2 = 29.963, 9 degrees of freedom, p < 0.001). CONCLUSION: We conclude that the NUSS is both a reliable and valid system to classify non-unions.

Delay in weight bearing in surgically treated tibial shaft fractures is associated with impaired healing: a cohort analysis of 166 tibial fractures.

BACKGROUND: The relation between timing of weight bearing after a fracture and the healing outcome is yet to be established, thereby limiting the implementation of a possibly beneficial effect for our patients. The current study was undertaken to determine the effect of timing of weight bearing after a surgically treated tibial shaft fracture. MATERIALS AND METHODS: Surgically treated diaphyseal tibial fractures were retrospectively studied between 2007 and 2015. The timing of initial weight bearing (IWB) was analysed as a predictor for impaired healing in a multivariate regression. RESULTS: Totally, 166 diaphyseal tibial fractures were included, 86 cases with impaired healing and 80 with normal healing. The mean age was 38.7 years (range 16-89). The mean time until IWB was significantly shorter in the normal fracture healing group (2.6 vs 7.4 weeks, p < 0.001). Correlation analysis yielded four possible confounders: infection requiring surgical intervention, fracture type, fasciotomy and open fractures. Logistic regression identified IWB as an independent predictor for impaired healing with an odds ratio of 1.13 per week delay (95% CI 1.03-1.25). CONCLUSIONS: Delay in initial weight bearing is independently associated with impaired fracture healing in surgically treated tibial shaft fractures. Unlike other factors such as fracture type or soft tissue condition, early resumption of weight bearing can be influenced by the treating physician and this factor therefore has a direct clinical relevance. This study indicates that early resumption of weight bearing should be the treatment goal in fracture fixation. LEVEL OF EVIDENCE: 3b.

Assessing the Risk of Contrast-Induced Nephropathy Using a Finger Stick Analysis in Recalls from Breast Screening: The CINFIBS Explorative Study.

Purpose: To evaluate whether a handheld point-of-care (POC) device is able to predict and discriminate patients at potential risk of contrast-induced nephropathy (CIN) prior to iodine-based contrast media delivery. Methods and Materials: Between December 2014 and June 2016, women undergoing contrast-enhanced spectral mammography (CESM) with an iodine-based contrast agent were asked to have their risk of CIN assessed by a dedicated POC device (StatSensor CREAT) and a risk factor questionnaire based on national guidelines. Prior to contrast injection, a venous blood sample was drawn to compare the results of POC with regular laboratory testing. Results: A total of 351 patients were included; 344 were finally categorized as low risk patients by blood creatinine evaluation. Seven patients had a eGFR below 60 ml/min/1.73 m2, necessitating additional preparation prior to contrast delivery. The POC device failed to categorize six out of seven patients (86%), leading to (at that stage) unwanted contrast administration. Two patients subsequently developed CIN after 2-5 days, which was self-limiting after 30 days. Conclusion: The POC device tested was not able to reliably assess impairment of renal function in our patient cohort undergoing CESM. Consequently, we still consider classic clinical laboratory testing preferable in patients at potential risk for developing CIN.

Contrast-enhanced spectral mammography as work-up tool in patients recalled from breast cancer screening has low risks and might hold clinical benefits.

OBJECTIVE: Contrast-enhanced spectral mammography (CESM) is a reliable problem solving tool in the work-up of women recalled from breast cancer screening. We evaluated additional findings caused by CESM alone and outweighed them against the disadvantages of this technique. METHODS: From December 2012 to December 2015, all women recalled from screening who underwent CESM were considered for this study. Radiation exposure and number of adverse contrast reactions were analysed. An experienced breast radiologist reviewed all exams and identified cases with lesions detected by CESM alone and scored their conspicuity. From these cases, data on breast density and final diagnosis were collected. For malignant cases, tumour grade and receptor characteristics were also collected. RESULTS: During this study, 839 women underwent CESM after a screening recall, in which five minor adverse contrast reactions were observed. Median radiation dose per exam was 6.0mGy (0.9-23.4mGy). Seventy CESM-only lesions were detected in 65 patients. Of these 70 lesions, 54.3% proved to be malignant, most commonly invasive ductal carcinomas. The remaining CESM-only lesions were benign, predominantly fibroadenomas. No complications were observed during biopsy of these lesions. Retrospectively, the majority of the lesions were either occult or a 'minimal sign' on low-energy CESM images or the screening mammogram. CONCLUSION: Using CESM as a work-up tool for women recalled from screening carries low risk for the patient, while additionally detected tumour foci might hold important clinical implications which need to be further studied in large, randomized controlled trials.

Contrast-enhanced spectral mammography in recalls from the Dutch breast cancer screening program: validation of results in a large multireader, multicase study.

OBJECTIVES: Contrast-enhanced spectral mammography (CESM) is a promising problem-solving tool in women referred from a breast cancer screening program. We aimed to study the validity of preliminary results of CESM using a larger panel of radiologists with different levels of CESM experience. METHODS: All women referred from the Dutch breast cancer screening program were eligible for CESM. 199 consecutive cases were viewed by ten radiologists. Four had extensive CESM experience, three had no CESM experience but were experienced breast radiologists, and three were residents. All readers provided a BI-RADS score for the low-energy CESM images first, after which the score could be adjusted when viewing the entire CESM exam. BI-RADS 1-3 were considered benign and BI-RADS 4-5 malignant. With this cutoff, we calculated sensitivity, specificity and area under the ROC curve. RESULTS: CESM increased diagnostic accuracy in all readers. The performance for all readers using CESM was: sensitivity 96.9 % (+3.9 %), specificity 69.7 % (+33.8 %) and area under the ROC curve 0.833 (+0.188). CONCLUSION: CESM is superior to conventional mammography, with excellent problem-solving capabilities in women referred from the breast cancer screening program. Previous results were confirmed even in a larger panel of readers with varying CESM experience. KEY POINTS: • CESM is consistently superior to conventional mammography • CESM increases diagnostic accuracy regardless of a reader's experience • CESM is an excellent problem-solving tool in recalls from screening programs.

Evaluation of low-energy contrast-enhanced spectral mammography images by comparing them to full-field digital mammography using EUREF image quality criteria.

OBJECTIVE: Contrast-enhanced spectral mammography (CESM) examination results in a low-energy (LE) and contrast-enhanced image. The LE appears similar to a full-field digital mammogram (FFDM). Our aim was to evaluate LE CESM image quality by comparing it to FFDM using criteria defined by the European Reference Organization for Quality Assured Breast Screening and Diagnostic Services (EUREF). METHODS: A total of 147 cases with both FFDM and LE images were independently scored by two experienced radiologists using these (20) EUREF criteria. Contrast detail measurements were performed using a dedicated phantom. Differences in image quality scores, average glandular dose, and contrast detail measurements between LE and FFDM were tested for statistical significance. RESULTS: No significant differences in image quality scores were observed between LE and FFDM images for 17 out of 20 criteria. LE scored significantly lower on one criterion regarding the sharpness of the pectoral muscle (p < 0.001), and significantly better on two criteria on the visualization of micro-calcifications (p = 0.02 and p = 0.034). Dose and contrast detail measurements did not reveal any physical explanation for these observed differences. CONCLUSIONS: Low-energy CESM images are non-inferior to FFDM images. From this perspective FFDM can be omitted in patients with an indication for CESM. KEY POINTS: • Low-energy CESM images are non-inferior to FFDM images. • Micro-calcifications are significantly more visible on LE CESM than on FFDM. • There is no physical explanation for this improved visibility of micro-calcifications. • There is no need for an extra FFDM when CESM is indicated.

[Hypnogogic hallucinations of macrosomatognosia and microsomatognosia]. / Hypnagoge Halluzinationen der Köpervergrösserung und der Körperverkleinerung.

Macrosomatognosia and microsomatognosia, in which the entire body or parts of the body are perceived as abnormally large or small, can occur as hypnagogic hallucinations in sane and healthy subjects. A review of the literature and five original observations are presented. The mouth and the hands are anatomic regions which are frequently affected, paralleling the dominance of their representation in the sensory maps of the human brain. The clinical differential diagnosis of the said phenomena includes narcolepsy, epileptic and migraine aura, drug-induced body schema disturbances and basic symptoms of functional psychoses.

Personality disorders: conceptual issues and responsibility.

The historical roots of the concepts of abnormal personality, social deviance, delinquency and penal responsibility are described, demonstrating that former concepts of psychopathic personality often included negative social evaluations. Modern classification systems such as DSM-III-R and ICD-10 prefer a behavior-oriented definition of personality disorders, which increases reliability but may lead to a reductionistic and purely criteriological assessment of personality. A checklist for the assessment of personality disorders (AMPS) according to ICD-10 and DSM-III-R is presented, including four subaffective forms derived from the typology of personality disorders described by Kurt Schneider and Kretschmer. To justify statements of diminished legal responsibility or irresponsibility under the German Penal Code, a differentiation between psychopathological phenomena in personality disorders and pure social deviance is needed. The three notions of psychopathy, sociopathy and dissocial behavior are suggested to guide necessary decisions concerning prognosis and therapy chances.