Radiological features of screening-detected and interval breast cancers and subsequent survival in Eastern Finnish women.

Interval breast cancers are diagnosed between scheduled screenings and differ in many respects from screening-detected cancers. Studies comparing the survival of patients with interval and screening-detected cancers have reported differing results. The aim of this study was to investigate the radiological and histopathological features and growth rates of screening-detected and interval breast cancers and subsequent survival. This retrospective study included 942 female patients aged 50-69 years with breast cancers treated and followed-up at Kuopio University Hospital between January 2010 and December 2016. The screening-detected and interval cancers were classified as true, minimal-signs, missed, or occult. The radiological features were assessed on mammograms by one of two specialist breast radiologists with over 15 years of experience. A χ2 test was used to examine the association between radiological and pathological variables; an unpaired t test was used to compare the growth rates of missed and minimal-signs cancers; and the Kaplan-Meier estimator was used to examine survival after screening-detected and interval cancers. Sixty occult cancers were excluded, so a total of 882 women (mean age 60.4 ± 5.5 years) were included, in whom 581 had screening-detected cancers and 301 interval cancers. Disease-specific survival, overall survival and disease-free survival were all worse after interval cancer than after screening-detected cancer (p < 0.001), with a mean follow-up period of 8.2 years. There were no statistically significant differences in survival between the subgroups of screening-detected or interval cancers. Missed interval cancers had faster growth rates (0.47% ± 0.77%/day) than missed screening-detected cancers (0.21% ± 0.11%/day). Most cancers (77.2%) occurred in low-density breasts (< 25%). The most common lesion types were masses (73.9%) and calcifications (13.4%), whereas distortions (1.8%) and asymmetries (1.7%) were the least common. Survival was worse after interval cancers than after screening-detected cancers, attributed to their more-aggressive histopathological characteristics, more nodal and distant metastases, and faster growth rates.

European intersocietal recommendations for the biomarker-based diagnosis of neurocognitive disorders.

The recent commercialisation of the first disease-modifying drugs for Alzheimer's disease emphasises the need for consensus recommendations on the rational use of biomarkers to diagnose people with suspected neurocognitive disorders in memory clinics. Most available recommendations and guidelines are either disease-centred or biomarker-centred. A European multidisciplinary taskforce consisting of 22 experts from 11 European scientific societies set out to define the first patient-centred diagnostic workflow that aims to prioritise testing for available biomarkers in individuals attending memory clinics. After an extensive literature review, we used a Delphi consensus procedure to identify 11 clinical syndromes, based on clinical history and examination, neuropsychology, blood tests, structural imaging, and, in some cases, EEG. We recommend first-line and, if needed, second-line testing for biomarkers according to the patient's clinical profile and the results of previous biomarker findings. This diagnostic workflow will promote consistency in the diagnosis of neurocognitive disorders across European countries.

Specimen tomosynthesis provides no additional value to specimen ultrasound in ultrasound-visible malignant breast lesions.

BACKGROUND: The aim of this study was to evaluate the accuracy and added value of specimen tomosynthesis (ST) to specimen ultrasound (SUS) in margin assessment of excised breast specimens in breast-conserving therapy for non-palpable US-visible breast lesions. MATERIALS: Between January 2018 and August 2019, all consecutive patients diagnosed with non-palpable breast cancer visible by ultrasound (US), treated with breast-conserving surgery (BCS) and requiring radiological intraoperative breast specimen assessment, were included in this study. Excised breast specimens were examined with SUS by radiologists blinded to the ST results, and margins smaller than 10 mm were recorded. STs were evaluated retrospectively by experienced radiologists. RESULTS: A total of 120 specimens were included. SUS showed a statistically significant correlation with pathological margin measurements, while ST did not and provided no additional information. The odds ratios (ORs) for SUS to predict a positive margin was 3.429 (confidence interval (CI) = 0.548-21.432) using a 10-mm cut-off point and 14.182 (CI = 2.134-94.254) using a 5-mm cut-off point, while the OR for ST were 2.528 (CI = 0.400-15.994) and 3.188 (CI = 0.318-31.998), respectively. CONCLUSIONS: SUS was superior in evaluating intraoperative resection margins of US-visible breast resection specimens when compared to ST. Therefore, ST could be considered redundant in applicable situations.

Motor difficulties from childhood to midlife: A 40-year cohort study.

BACKGROUND: There are few studies of the persistence of childhood motor difficulties (MD) into adulthood. AIMS: To investigate the association of childhood MD with motor skills and body mass index (BMI) in midlife. METHODS AND PROCEDURES: We studied 324 adults aged 40 from a cohort born in 1971-1974. At age 9, they had undergone the Test of Motor Impairment, used to classify them into groups: childhood MD (cMD), borderline cMD (bcMD), or no cMD. At age 40, participants comprised 23 with cMD, 47 with bcMD, and 254 with no cMD. Participants completed motor tests of balance, manual dexterity, and visuomotor speed, followed by recording of their BMI. OUTCOMES AND RESULTS: At age 40, the cMD group performed worse than the no-cMD group on all motor tests (p < .001-.008). The bcMD group had slower visuomotor speed than the no-cMD group (p = .025). The groups differed in BMI (p = .002). Having cMD was associated with obesity in midlife (p < .001). After adjusting for sex, childhood socioeconomic status, and BMI at age 9, both cMD and bcMD were associated with obesity in midlife (p = .015). CONCLUSIONS AND IMPLICATIONS: Childhood MD are associated with poor motor skills, overweight, and obesity in midlife. This emphasises the importance of early intervention and follow-up when a child exhibits MD. WHAT THIS PAPER ADDS: This prospective longitudinal study presents novel evidence that individuals with a history of comprehensively and objectively assessed childhood motor difficulties (MD) have worse motor skills and a higher risk of obesity in midlife than do those with no childhood MD. There is a growing literature on adults with developmental coordination disorder or a history of MD. There is, however, a scarcity of longitudinal studies of childhood MD that continue beyond early adulthood, into midlife. In a systematic search, we could identify only one longitudinal study of objectively measured childhood MD with a reassessment of motor skills in those same participants in adulthood, and no study with a reassessment after age 20. Furthermore, longitudinal studies of the association of comprehensively and objectively assessed childhood MD with BMI in midlife have been lacking.

Progressive myoclonic epilepsy type 1 (EPM1) patients present with abnormal 1H MRS brain metabolic profiles associated with cognitive function.

PURPOSE: Progressive myoclonic epilepsy, type 1A (EPM1, Unverricht-Lundborg disease), is a rare neurodegenerative autosomal recessive disorder characterized by stimulus-sensitive and action myoclonus and tonic-clonic epileptic seizures. Patients develop neurological symptoms, including ataxia, intention tremor, and dysarthria, over time, with relatively limited and nonspecific MRI atrophy findings. The effects of the disease on brain metabolism are largely unknown. METHOD: Eighteen EPM1 patients (9 M, 9F) underwent clinical evaluation and neuropsychological testing, which included the assessment of intellectual ability, verbal memory, and psychomotor and executive functions. Magnetic resonance spectroscopy (MRS) and imaging (MRI) were performed on a 1.5 T MRI system. 2D MRS chemical shift imaging (CSI) maps (TE = 270) were obtained from the following regions of the brain: basal ganglia, thalamus, insula, splenium, and occipital white and gray matter, and N-acetyl-aspartate (NAA)-, choline (Cho)-, and lactate (Lac)-to-creatine (Cr) ratios were analyzed. Ten healthy age-and sex-matched subjects (5M, 5F) were used as controls for MRS. RESULTS: We found significant brain metabolic changes involving lactate, NAA, and choline, which are widespread in the basal ganglia, thalamic nuclei, insula, and occipital areas of EPM1 patients. Changes, especially in the right insula, basal ganglia, and thalamus, were associated with intellectual abilities and impairment of the psychomotor and executive functions of EPM1 patients. CONCLUSION: Multiple brain metabolic alterations suggest the presence of neurodegeneration associated with EPM1 progression. The changes in metabolite ratios are associated with the neurocognitive dysfunction caused by the disease. However, the role of MRS findings in understanding pathophysiology of EPM1 warrants further studies.

Cortical thickness is inversely associated with transcranial magnetic stimulation-evoked N45 potential among young adults whose heavy drinking began in adolescence.

BACKGROUND: Adolescence is a particularly vulnerable stage of development in terms of the deleterious effects of alcohol. Both lower gray matter (GM) volume and greater GABAergic activity have been associated with chronic alcohol consumption during adolescence. However, the association between these measures has not been investigated. METHODS: In this exploratory study, we compared 26 young adults with a 10year history of heavy alcohol consumption with 21 controls who used little or no alcohol. Simultaneous transcranial magnetic stimulation and electroencephalography were used to assess transcranial magnetic stimulation-evoked N45 potentials, reflecting a balance between GABAergic inhibition and N-methyl-D-aspartate (NMDA) receptor-mediated glutaminergic excitation in the brain. GM thickness was measured from magnetic resonance images and GM and N45 potentials were then correlated. RESULTS: Cortical thickness was significantly lower in several brain regions in the heavy-drinking group than the light-drinking group. The N45 amplitude was significantly larger frontally in the heavy-drinking group. Among heavy drinkers, there were several statistically significant correlations between thinner GM and larger frontal N45 amplitudes that were not detectable in the light-drinking group. The strongest correlations were detected in the frontal and parietal lobes, especially in the left superior frontal gyrus and the left supramarginal gyrus, and in both hemispheres in the superior parietal lobes. CONCLUSIONS: These findings show that a thinner cortex and greater inhibitory neurotransmission are correlated in certain brain regions among young, long-term heavy alcohol users. Studies are needed to explore the possible causal mechanisms underlying these effects.

Dynamic contrast-enhanced MRI to characterize angiogenesis in primary epithelial ovarian cancer: An exploratory study.

PURPOSE: Angiogenesis is essential for tumor growth. Currently, there are no established imaging biomarkers to show angiogenesis in tumor tissue. The aim of this prospective study was to evaluate whether semiquantitative and pharmacokinetic DCE-MRI perfusion parameters could be used to assess angiogenesis in epithelial ovarian cancer (EOC). METHOD: We enrolled 38 patients with primary EOC treated in 2011-2014. DCE-MRI was performed with a 3.0 T imaging system before the surgical treatment. Two different sizes of ROI were used to evaluate semiquantitative and pharmacokinetic DCE perfusion parameters: a large ROI (L-ROI) covering the whole primary lesion on one plane and a small ROI (S-ROI) covering a small solid, highly enhancing focus. Tissue samples from tumors were collected during the surgery. Immunohistochemistry was used to measure the expression of vascular endothelial growth factor (VEGF), its receptors (VEGFRs) and to analyse microvascular density (MVD) and the number of microvessels. RESULTS: VEGF expression correlated inversely with Ktrans (L-ROI, r = -0.395 (p = 0.009), S-ROI, r = -0.390, (p = 0.010)), Ve (L-ROI, r = -0.395 (p = 0.009), S-ROI, r = -0.412 (p = 0.006)) and Vp (L-ROI, r = -0.388 (p = 0.011), S-ROI, r = -0.339 (p = 0.028)) values in EOC. Higher VEGFR-2 correlated with lower DCE parameters Ktrans (L-ROI, r = -0.311 (p = 0.040), S-ROI, r = -0.337 (p = 0.025)) and Ve (L-ROI, r = -0.305 (p = 0.044), S-ROI, r = -0.355 (p = 0.018)). We also found that MVD and the number of microvessels correlated positively with AUC, Peak and WashIn values. CONCLUSIONS: We observed that several DCE-MRI parameters correlated with VEGF and VEGFR-2 expression and MVD. Thus, both semiquantitative and pharmacokinetic perfusion parameters of DCE-MRI represent promising tools for the assessment of angiogenesis in EOC.

Greater increases in intratumoral apparent diffusion coefficients after chemoradiotherapy predict better overall survival of patients with cervical cancer.

PURPOSE: To evaluate whether 1) the intratumoral apparent diffusion coefficients (ADCs) change during cervical cancer treatment and 2) the pretreatment ADC values or their change after treatment predict the treatment outcome or overall survival of patients with cervical cancer. METHODS: We retrospectively enrolled 52 patients with inoperable cervical cancer treated with chemoradiotherapy, who had undergone diffusion weighted MRI before treatment and post external beam radiotherapy (EBRT) and concurrent chemotherapy. A subgroup of patients (n = 28) underwent altogether six consecutive diffusion weighted MRIs; 1) pretreatment, 2) post-EBRT and concurrent chemotherapy; 3-5) during image-guided brachytherapy (IGBT) and 6) after completing the whole treatment course. To assess interobserver and intertechnique reproducibility two observers independently measured the ADCs by drawing freehand a large region of interest (L-ROI) covering the whole tumor and three small ROIs (S-ROIs) in areas with most restricted diffusion. RESULTS: Reproducibility was equally good for L-ROIs and S-ROIs. The pretreatment ADCs were higher in L-ROIs (883 mm2/s) than in S-ROIs (687 mm2/s, P < 0.001). The ADCs increased significantly between the pretreatment and post-EBRT scans (L-ROI: P < 0.001; S-ROI: P = 0.001). The ADCs remained significantly higher than pretreatment values during the whole IGBT. Using S-ROIs, greater increases in ADCs between pretreatment and post-EBRT MRI predicted better overall survival (P = 0.018). CONCLUSION: ADC values significantly increase during cervical cancer treatment. Greater increases in ADC values between pretreatment and post-EBRT predicted better overall survival using S-ROIs. Standardized methods for timing and delineation of ADC measurements are advocated in future studies.

Neoadjuvant chemotherapy induces an elevation of tumour apparent diffusion coefficient values in patients with ovarian cancer.

OBJECTIVES: Multiparametric magnetic resonance imaging (mMRI) is the modality of choice in the imaging of ovarian cancer (OC). We aimed to investigate the feasibility of different types of regions of interest (ROIs) in the measurement of apparent diffusion coefficient (ADC) values of diffusion-weighted imaging in OC patients treated with neoadjuvant chemotherapy (NACT). METHODS: We retrospectively enrolled 23 consecutive patients with advanced OC who had undergone NACT and mMRI. Seventeen of them had been imaged before and after NACT. Two observers independently measured the ADC values in both ovaries and in the metastatic mass by drawing on a single slice of (1) freehand large ROIs (L-ROIs) covering the solid parts of the whole tumour and (2) three small round ROIs (S-ROIs). The side of the primary ovarian tumour was defined. We evaluated the interobserver reproducibility and statistical significance of the change in tumoural pre- and post-NACT ADC values. Each patient's disease was defined as platinum-sensitive, semi-sensitive, or resistant. The patients were deemed either responders or non-responders. RESULTS: The interobserver reproducibility of the L-ROI and S-ROI measurements ranged from good to excellent (ICC range: 0.71-0.99). The mean ADC values were significantly higher after NACT in the primary tumour (L-ROI p < 0.001, S-ROIs p < 0.01), and the increase after NACT was associated with sensitivity to platinum-based chemotherapy. The changes in the ADC values of the omental mass were associated with a response to NACT. CONCLUSION: The mean ADC values of the primary tumour increased significantly after NACT in the OC patients, and the amount of increase in omental mass was associated with the response to platinum-based NACT. Our study indicates that quantitative analysis of ADC values with a single slice and a whole tumour ROI placement is a reproducible method that has a potential role in the evaluation of NACT response in patients with OC. TRIAL REGISTRATION: Retrospectively registered (institutional permission code: 5302501; date of the permission: 31.7.2020).

The Role of Brain Integrity in the Association between Occupational Complexity and Cognitive Performance in Subjects with Increased Risk of Dementia.

INTRODUCTION: Mechanisms underlying the positive association between occupational mental demands and late-life cognition are poorly understood. The objective of this study was to assess whether the association between occupational complexity and cognition is related to and moderated by brain integrity in individuals at risk for dementia. Brain integrity was appraised throughout structural measures (magnetic resonance imaging, MRI) and amyloid accumulation (Pittsburgh compound B (PiB)-positron emission tomography, PiB-PET). METHODS: Participants from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) neuroimaging sample - MRI (N = 126), PiB-PET (N = 41) - were included in a post hoc cross-sectional analysis. Neuroimaging parameters comprised the Alzheimer's disease signature (ADS) cortical thickness (FreeSurfer 5.3), medial temporal atrophy (MTA), and amyloid accumulation (PiB-PET). Cognition was assessed using the neuropsychological test battery. Occupational complexity with data, people, and substantive complexity were classified through the Dictionary of Occupational Titles. Linear regression models included cognition as dependent variable, and occupational complexity, measures of brain integrity, and their interaction terms as predictors. RESULTS: Occupational complexity with data and substantive complexity were associated with better cognition (overall cognition, executive function) when adjusting for ADS and MTA (independent association). Significant interaction effects between occupational complexity and brain integrity were also found, indicating that, for some indicators of brain integrity and cognition (e.g., overall cognition, processing speed), the positive association between occupational complexity and cognition occurred only among persons with higher brain integrity (moderated association). CONCLUSIONS: Among individuals at risk for dementia, occupational complexity does not seem to contribute toward resilience against neuropathology. These exploratory findings require validation in larger populations.

Self-reported skills and self-confidence in point-of-care ultrasound: a cross-sectional nationwide survey amongst Finnish emergency physicians.

BACKGROUND: The use of point-of-care ultrasound (POCUS) is increasing. Numerous investigators have evaluated the learning curves in POCUS, but there are no published studies on how emergency physicians perceive their own competence level with this skill. METHODS: A nationwide survey amongst Finnish emergency physicians was conducted. The respondents reported their use of POCUS and how it has affected their clinical decision-making. The number of POCUS examinations performed was compared to the self-assessed skill level with different applications. Cut-off values were determined for the number of examinations required to acquire a good self-assessed skill level in each POCUS application. The correlation between self-confidence and the self-estimated skill level was analyzed. Several different statistical methods were used, such as Student's t-test, Pearson's correlation test, Loess method and ROC curve analysis. RESULTS: A total of 134 out of 253 Finnish emergency medicine specialists and residents (52%) responded to the survey. The most commonly used POCUS applications were POCUS-assisted procedures, pleural effusion and pneumothorax, inferior vena cava and lower extremity deep venous thrombosis. The initial rate of perceived skill acquisition was very steep with the curve flattening with greater skill and more experience. The number of examinations performed to reach a self-assessed good competence varied from seven to 75 with different applications. The lowest cut-off point for self-assessed good competence was obtained for rapid ultrasound for the shock and hypotension-protocol and the highest for focused cardiac examinations. There was an excellent correlation between self-confidence and the self-assessed skill level. CONCLUSIONS: The Finnish emergency practitioners' self-assessed development of POCUS skills parallels the previously published learning curves of POCUS. The correlation of self-confidence and the self-assessed skill level was found to be excellent. These findings add information on the development of perceived POCUS skills amongst emergency physicians and could complement a formal performance assessment.

European consensus for the diagnosis of MCI and mild dementia: Preparatory phase.

INTRODUCTION: Etiological diagnosis of neurocognitive disorders of middle-old age relies on biomarkers, although evidence for their rational use is incomplete. A European task force is defining a diagnostic workflow where expert experience fills evidence gaps for biomarker validity and prioritization. We report methodology and preliminary results. METHODS: Using a Delphi consensus method supported by a systematic literature review, 22 delegates from 11 relevant scientific societies defined workflow assumptions. RESULTS: We extracted diagnostic accuracy figures from literature on the use of biomarkers in the diagnosis of main forms of neurocognitive disorders. Supported by this evidence, panelists defined clinical setting (specialist outpatient service), application stage (MCI-mild dementia), and detailed pre-assessment screening (clinical-neuropsychological evaluations, brain imaging, and blood tests). DISCUSSION: The Delphi consensus on these assumptions set the stage for the development of the first pan-European workflow for biomarkers' use in the etiological diagnosis of middle-old age neurocognitive disorders at MCI-mild dementia stages. HIGHLIGHTS: Rational use of biomarkers in neurocognitive disorders lacks consensus in Europe. A consensus of experts will define a workflow for the rational use of biomarkers. The diagnostic workflow will be patient-centered and based on clinical presentation. The workflow will be updated as new evidence accrues.

Diagnostic performance of tomosynthesis, digital mammography and a dedicated digital specimen radiography system versus pathological assessment of excised breast lesions.

BACKGROUND: The aim of the study was to compare the performance of full-field digital mammography (FFDM), digital breast tomosynthesis and a dedicated digital specimen radiography system (SRS) in consecutive patients, and to compare the margin status of resected lesions versus pathological assessment. PATIENTS AND METHODS: Resected tissue specimens from consecutive patients who underwent intraoperative breast specimen assessment following wide local excision or oncoplastic breast conservative surgery were examined by FFDM, tomosynthesis and SRS. Two independent observers retrospectively evaluated the visibility of lesions, size, margins, spiculations, calcifications and diagnostic certainty, and chose the best performing method in a blinded manner. RESULTS: We evaluated 216 specimens from 204 patients. All target malignant lesions were removed with no tumouron-ink. One papilloma had positive microscopic margins and one patient underwent reoperation owing to extensive in situ components. There were no significant differences in measured lesion size among the three methods. However, tomosynthesis was the most accurate modality when compared with the final pathological report. Both observers reported that tomosynthesis had significantly better lesion visibility than SRS and FFDM, which translated into a significantly greater diagnostic certainty. Tomosynthesis was superior to the other two methods in identifying spiculations and calcifications. Both observers reported that tomosynthesis was the best performing method in 76.9% of cases. The interobserver reproducibilities of lesion visibility and diagnostic certainty were high for all three methods. CONCLUSIONS: Tomosynthesis was superior to SRS and FFDM for detecting and evaluating the target lesions, spiculations and calcifications, and was therefore more reliable for assessing complete excision of breast lesions.

Wall Shear Stress Predicts Media Degeneration and Biomechanical Changes in Thoracic Aorta.

Objectives: In thoracic aortic aneurysm (TAA) of the ascending aorta (AA), AA is progressively dilating due to the weakening of the aortic wall. Predicting and preventing aortic dissections and ruptures in TAA continues to be challenging, and more accurate assessment of the AA dilatation, identification of high-risk patients, and timing of repair surgery are required. We investigated whether wall shear stress (WSS) predicts pathological and biomechanical changes in the aortic wall in TAA. Methods: The study included 12 patients with bicuspid (BAV) and 20 patients with the tricuspid aortic valve (TAV). 4D flow magnetic resonance imaging (MRI) was performed a day before aortic replacement surgery. Biomechanical and histological parameters, including assessing of wall strength, media degeneration, elastin, and cell content were analyzed from the resected AA samples. Results: WSSs were greater in the outer curves of the AA compared to the inner curves in all TAA patients. WSSs correlated with media degeneration of the aortic wall (ρ = -0.48, p < 0.01), elastin content (ρ = 0.47, p < 0.01), and aortic wall strength (ρ = -0.49, p = 0.029). Subsequently, the media of the outer curves was thinner, more rigid, and tolerated lower failure strains. Failure values were shown to correlate with smooth muscle cell (SMC) density (ρ = -0.45, p < 0.02), and indicated the more MYH10+ SMCs the lower the strength of the aortic wall structure. More macrophages were detected in patients with severe media degeneration and the areas with lower WSSs. Conclusion: The findings indicate that MRI-derived WSS predicts pathological and biomechanical changes in the aortic wall in patients with TAA and could be used for identification of high-risk patients.

No Clinically Relevant Memory Effects in Perinatal Hyperglycemia and Hypoglycemia: A 40-Year Follow-Up of a Small Cohort.

Maternal diabetes mellitus in pregnancy is associated with impairments in memory functions of the offspring in childhood and adolescence but has not been studied in adulthood. The association of perinatal hypoglycemia with memory has not been studied in adulthood either. The combined sequelae of these two risk factors have not been directly compared. We studied general cognitive ability and memory functions in a prospective follow-up of a cohort born in 1971 to 1974. The sample included participants exposed to prenatal hyperglycemia (n = 24), perinatal hypoglycemia (n = 19), or both (n = 7). It also included controls with no early risks (n = 82). We assessed the participants' Intelligence quotient (IQ), working memory, and immediate and delayed recall of both verbal and visual material at the age of 40. We did not find significant differences in IQ or the memory tests between the groups. We did identify an interaction (p = 0.03) of the early risk with the type of digit span task: compared to the controls, the participants exposed to perinatal hypoglycemia had a larger difference between the forward digit span, a measure of attention, and the backward digit span, a measure of working memory processing (p = 0.022). The interaction remained significant when birth weight was controlled for (p = 0.026). Thus, in this small cohort, prenatal hyperglycemia, perinatal hypoglycemia, and their combination appeared relatively benign disorders. The association of these conditions with neurocognitive impairments in adulthood remains unconfirmed. The significance of the working memory difference needs to be verified with a larger sample.

Area-based breast percentage density estimation in mammograms using weight-adaptive multitask learning.

Breast density, which is a measure of the relative amount of fibroglandular tissue within the breast area, is one of the most important breast cancer risk factors. Accurate segmentation of fibroglandular tissues and breast area is crucial for computing the breast density. Semiautomatic and fully automatic computer-aided design tools have been developed to estimate the percentage of breast density in mammograms. However, the available approaches are usually limited to specific mammogram views and are inadequate for complete delineation of the pectoral muscle. These tools also perform poorly in cases of data variability and often require an experienced radiologist to adjust the segmentation threshold for fibroglandular tissue within the breast area. This study proposes a new deep learning architecture that automatically estimates the area-based breast percentage density from mammograms using a weight-adaptive multitask learning approach. The proposed approach simultaneously segments the breast and dense tissues and further estimates the breast percentage density. We evaluate the performance of the proposed model in both segmentation and density estimation on an independent evaluation set of 7500 craniocaudal and mediolateral oblique-view mammograms from Kuopio University Hospital, Finland. The proposed multitask segmentation approach outperforms and achieves average relative improvements of 2.88% and 9.78% in terms of F-score compared to the multitask U-net and a fully convolutional neural network, respectively. The estimated breast density values using our approach strongly correlate with radiologists' assessments with a Pearson's correlation of [Formula: see text] (95% confidence interval [0.89, 0.91]). We conclude that our approach greatly improves the segmentation accuracy of the breast area and dense tissues; thus, it can play a vital role in accurately computing the breast density. Our density estimation model considerably reduces the time and effort needed to estimate density values from mammograms by radiologists and therefore, decreases inter- and intra-reader variability.

Dual-Layer Rotation: A Versatile Therapeutic Mammoplasty Technique.

BACKGROUND: Multifocal or complex breast lesions are a challenge for breast-conserving surgery, particularly surgery in small breasts or those located in the upper inner quadrant. The dual-layer rotation technique exploits the idea of manipulating the skin and glandular tissue in separate layers to fill the resection cavity via vertical mammoplasty if skin excision is not required, except in the central area. METHODS: The authors performed a retrospective review of consecutive breast cancer patients who underwent DLR mammoplasty between 2017 and 2019 at a single institution. Clinical data, reoperations, surgical complications, delays in adjuvant treatments, and the need for late revisional surgery were evaluated. Aesthetic outcomes were evaluated objectively and subjectively from photographs. RESULTS: The study included 46 breasts of 40 patients. Tumors were located in the UIQ (30%, 14/46) or in multiple quadrants (22%, 10/46). One third (33%, 13/40) of the patients had a small breast cup size (A-B). Negative margins were primarily achieved in 45 of the 46 breasts. Major complications occurred in three patients, who needed reoperation, and adjuvant therapy was delayed for one of these patients. Late refinement surgery was needed for two patients. The objective and subjective aesthetic outcomes were good or excellent regardless of the tumor position. CONCLUSION: As a novel oncoplastic approach, DLR mammoplasty offers a one-step procedure to treat selected breast cancer patients with challenging resection defects due to different breast sizes or lesion locations. The technique preserves the breast's natural appearance.

Grey matter atrophy in patients with benign multiple sclerosis.

BACKGROUND: Brain atrophy appears during the progression of multiple sclerosis (MS) and is associated with the disability caused by the disease. METHODS: We investigated global and regional grey matter (GM) and white matter (WM) volumes, WM lesion load, and corpus callosum index (CCI), in benign relapsing-remitting MS (BRRMS, n = 35) with and without any treatment and compared those to aggressive relapsing-remitting MS (ARRMS, n = 46). Structures were analyzed by using an automated MRI quantification tool (cNeuro®). RESULTS: The total brain and cerebral WM volumes were larger in BRRMS than in ARRMS (p = .014, p = .017 respectively). In BRRMS, total brain volumes, regional GM volumes, and CCI were found similar whether or not disease-modifying treatment (DMT) was used. The total (p = .033), as well as subcortical (p = .046) and deep WM (p = .041) lesion load volumes were larger in BRRMS patients without DMT. Cortical GM volumes did not differ between BRRMS and ARRMS, but the volumes of total brain tissue (p = .014) and thalami (p = .003) were larger in patients with BRRMS compared to ARRMS. A positive correlation was found between CCI and whole-brain volume in both BRRMS (r = .73, p < .001) and ARRMS (r = .80, p < .01). CONCLUSIONS: Thalamic volume is the most prominent measure to differentiate BRRMS and ARRMS. Validation of automated quantification of CCI provides an additional applicable MRI biomarker to detect brain atrophy in MS.

Mortality in individuals with childhood ADHD or subthreshold symptoms - a prospective perinatal risk cohort study over 40 years.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with negative life outcomes and recent studies have linked it to increased mortality. These studies have examined nationwide registers or clinic-referred samples and mostly included participants up until the age of 30. No studies have investigated mortality associated with subthreshold levels of ADHD symptoms. Our aim was to analyze mortality in a perinatal risk cohort of 46-year-old adults with childhood ADHD (cADHD) and milder childhood attention problems (including hyperactivity and inattention; cAP) compared with a group with similar birth risks but no or low levels of childhood ADHD symptoms (Non-cAP). Causes of death obtained from a national register were examined. METHODS: Mortality was analyzed with Cox proportional hazard models for all-cause mortality, cause-specific mortality (natural and unnatural causes), and age-specific mortality (under and over age 30). All models were adjusted with gender. The total n in the study was 839 (cADHD n = 115; cAP n = 216; Non-cAP n = 508). RESULTS: By the age of 46, 11 (9.6%) deaths occurred in the cADHD group, 7 (3.2%) in the cAP group, and 20 (3.9%) in the Non-cAP group. The cADHD group had the highest mortality risk (adjusted hazard ratio = 2.15; 95% CI 1.02, 4.54). Mortality was not elevated in the cAP group (adjusted hazard ratio = 0.72; 95% CI .30, 1.72). Mortality in the cADHD group was mainly attributed to unnatural causes of death (adjusted hazard ratio = 2.82; 95% CI 1.12, 7.12). The mortality risk in the cADHD group was sixfold before age 30 (adjusted hazard ratio = 6.20; 95% CI 1.78, 21.57). CONCLUSIONS: Childhood ADHD was associated with a twofold risk of premature death by the age of 46 in this prospective longitudinal cohort study. Our results corroborate previous findings and the morbidity of ADHD. Subthreshold levels of childhood ADHD symptoms were not linked to increased mortality. Our results suggest that mortality risk is higher in young than middle adulthood. Future studies should examine mortality associated with ADHD in different ages in adulthood to identify those in greatest risk of premature death.