MD Changes Research Articles

Longitudinal history of mammographic breast density and breast cancer risk by familial risk, menopausal status, and initial mammographic density level in a high risk cohort: a nested case–control study

BackgroundElevated mammographic density is associated with increased breast cancer risk. However, the contribution of longitudinal changes in mammographic density to breast cancer risk beyond initial mammographic density levels, considering familial breast cancer risk and menopausal status, remains uncertain but holds important clinical implications.MethodsIn a nested case–control study within the Sister Study (323 cases, 899 controls; 12,095 mammograms), a cohort enriched for family history of breast cancer, we examined case–control status in relation to the largest annual change in percent density and dense area using mammograms available spanning 5.4 years, on average, using multivariable logistic regression and to the rate of mammographic density change using linear mixed-effects models. We considered effect modification by: mammographic density level of the earlier mammogram, the extent of family history, Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation (BOADICEA) risk strata, and menopausal status.ResultsCases (diagnosed < 60 years) had greater initial percent density and dense area levels and a slower rate of decline in dense area than controls. Women with stable mammographic density (≤ 10% annual change) had an increased breast cancer risk as compared with women whose largest mammographic density change was > 10% annual decline (e.g., Odds Ratio (OR) 2.34, 95% Confidence Interval (CI) 1.63–3.37 for dense area). Increasing vs. decreasing dense area was also associated with elevated risk, especially in women with the highest dense area levels at the earlier mammogram (OR: 2.56, 95%CI 1.50–4.36). Although generally similar across menopausal and familial risk categories, the associations of MD change with risk appeared stronger in pre-menopausal and lower-risk women.ConclusionsWomen who maintain higher levels of mammographic density (i.e. do not decrease over time) or have increasing mammographic density over time have a higher risk of subsequent breast cancer than women with high mammographic density that decreases over time. These findings suggest potential for incorporating mammographic density trajectories in clinical risk assessment, and the importance of additional breast cancer monitoring in women not experiencing declines in mammographic density over time.

Rates of Visual Field Progression Before and After the Onset of Atrial Fibrillation.

This case-control study investigated the effect of atrial fibrillation (AF) on the progression of glaucoma. The presence of AF and related microvascular damage were associated with a slightly faster visual field loss in glaucoma patients. To investigate the effect of atrial fibrillation (AF) on glaucoma progression. In this longitudinal case-control study, a total of 144 eyes from 105 patients with primary open angle glaucoma were included. 48 eyes of case developed AF during the follow-up followed for 15.6 years. 96 eyes of control that did not have AF at baseline or during follow-up matched for age, baseline glaucoma severity and follow-up period were followed for an average of 14.7 years. Mixed-effects linear models were used to calculate the difference in the VF MD slopes before and after the AF. CHADS2 and CHA2DS2-VASc scores were used to evaluate the risk of thrombosis event, and related microvascular damage was assessed based on these scores. The rate of VF MD change was -0.20 (-0.42 to 0.02) dB/y before AF and -0.28 (-0.47 to -0.09) dB/y after AF for the patients with AF, and -0.21 (-0.25 to -0.17) dB/y for the control. In the multivariable models, the VF slope difference before and after the onset of AF (-0.10 (-0.14 to -0.05) dB/y, P<0.001), higher CHADS2 score (-0.07 (-0.13 to 0.00) dB/y per 1 unit, P=0.040), and higher CHA2DS2-VASc score (-0.05 (-0.10 to 0.00) dB/y per 1 unit, P=0.039) were associated with faster VF MD loss. The presence of atrial fibrillation and related microvascular damage might accelerate visual field loss. This underscores the need for a comprehensive medical history and management of cardiovascular risk factors to mitigate increase VF loss in glaucoma.

Effects of vitamin D supplementation on a deep learning-based mammographic evaluation in SWOG S0812.

Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20 000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was not statistically significantly different between vitamin D and placebo groups at 12 months (0.005 vs 0.002, P = .875) or at 24 months (0.020 vs 0.001, P = .563). The findings are consistent with the primary analysis of S0812, which did not demonstrate statistically significant changes in mammographic density with vitamin D supplementation compared with placebo. There is an ongoing need to evaluate biomarkers of response to novel breast cancer chemopreventive agents.

White and Gray Matter Abnormality in Burning Mouth Syndrome Evaluated with Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging.

Burning mouth syndrome (BMS) is defined by a burning sensation or pain in the tongue or other oral sites despite the presence of normal mucosa on inspection. Both psychiatric and neuroimaging investigations have examined BMS; however, there have been no analyses using the neurite orientation dispersion and density imaging (NODDI) model, which provides detailed information of intra- and extracellular microstructures. Therefore, we performed voxel-wise analyses using both NODDI and diffusion tensor imaging (DTI) models and compared the results to better comprehend the pathology of BMS. Fourteen patients with BMS and 11 age- and sex-matched healthy control subjects were prospectively scanned using a 3T-MRI machine using 2-shell diffusion imaging. Diffusion tensor metrics (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD], and radial diffusivity [RD]) and neurite orientation and dispersion index metrics (intracellular volume fraction [ICVF], isotropic volume fraction [ISO], and orientation dispersion index [ODI]) were retrieved from diffusion MRI data. These data were analyzed using tract-based spatial statistics (TBSS) and gray matter-based spatial statistics (GBSS). TBSS analysis showed that patients with BMS had significantly higher FA and ICVF and lower MD and RD than the healthy control subjects (family-wise error [FWE] corrected P < 0.05). Changes in ICVF, MD, and RD were observed in widespread white matter areas. Fairly small areas with different FA were included. GBSS analysis showed that patients with BMS had significantly higher ISO and lower MD and RD than the healthy control subjects (FWE-corrected P < 0.05), mainly limited to the amygdala. The increased ICVF in the BMS group may represent myelination and/or astrocytic hypertrophy, and microstructural changes in the amygdala in GBSS analysis indicate the emotional-affective profile of BMS.

Cross-hemicord spinal fiber reorganization associates with cortical sensory and motor network expansion in the rat model of hemicontusion cervical spinal cord injury

Magnetic resonance imaging plays an important role in characterizing microstructural changes and reorganization after traumatic injuries to the nervous system. In this study, we tested the feasibility of ex-vivo spinal cord diffusion tensor imaging (DTI) in combination with in vivo brain functional MRI to characterize spinal reorganization and its supraspinal association after a hemicontusion cervical spinal cord injury (SCI). DTI parameters (fractional anisotropy [FA], mean diffusion [MD]) and fiber orientation changes related to reorganization in the contused cervical spinal cord were compared to sham specimens. Altered fiber density and fiber directions occurred across the ipsilateral and contralateral hemicords but with only ipsilateral FA and MD changes. The hemicontusion SCI resulted in ipsilateral fiber breaks, voids and vivid fiber reorientations along the injury epicenter. Fiber directional changes below the injury level were primarily inter-hemispheric, indicating prominent below-level cross-hemispheric reorganization. In vivo resting state functional connectivity of the brain from the respective rats before obtaining the spinal cord samples indicated spatial expansion and increased connectivity strength across both the sensory and motor networks after SCI. The consistency of the neuroplastic changes along the neuraxis (both brain and spinal cord) at the single-subject level, indicates that distinctive reorganizational relationships exist between the spinal cord and the brain post-SCI.

Intraocular pressure reduction and progression of highly myopic glaucoma: a 12-year follow-up cohort study

AimsTo investigate any association between intraocular pressure (IOP) reduction amount and open-angle glaucoma (OAG) progression in highly myopic eyes and to determine the associated risk factors.MethodsOne hundred and thirty-one (131)...

Diffusion MRI track cortical microstructural changes over time during the early stages of the Alzheimer’s disease continuum

AbstractBackgroundMarkers of downstream events are a key component of clinical trials of disease‐modifying therapies for Alzheimer’s disease (AD). Previous cross‐sectional investigations suggested that diffusion MRI (dMRI) can provide metrics sensitive to cortical microstructural alteration linked to multiple aspects of the AD pathological cascade including Aß‐accumulation and astrocytic activity. However, currently little evidence is available regarding the ability of dMRI in tracking changes over time.MethodMean diffusivity (MD) was computed from dMRI data acquired from 363 cognitively unimpaired elderly and patients with mild cognitive impairment from the Swedish BioFINDER‐1 study. Each participant underwent multiple dMRI scan (range 2‐4 scans) and was classified as Aß‐negative/tau‐negative, Aß‐positive/tau‐negative, and Aß‐positive/tau‐positive based on CSF levels of Aß42/40 and ptau‐181. Rates of changes in MD, cortical thickness and plasma level of GFAP were computed in a linear mixed effect framework. Cortical regional values of MD were compared across biomarkers‐defined groups as well as to rates of change of GFAP.ResultAnalyses of MD revealed widespread differences in rates of change already between Aß‐negative/tau‐negative and Aß‐positive/tau‐negative participants with a spatial distribution that closely resembled the pattern of Aß accumulation (fig.1). Further, analyses focusing on two composite ROIs, one encompassing regions that accumulate Aß early in the disease process and a temporal meta‐ROI, confirmed that rates of change in MD significantly differed between groups even when cortical thickness was included in the model (Ps&lt;0.05,fig.2). Regional MD rates of change in both neocortical temporal areas and key regions for Aß‐accumulation, were also positively correlated with rates of change in GFAP (fig.3). Such result was supported by the analysis based on the two meta‐ROIs which confirmed the positive association between rates of change GFAP and MD.ConclusionMean diffusivity from dMRI is able to track cortical microstructural changes over time and to differentiate trajectories even during the early stages of the AD pathological cascade. The association between rates of change of MD and rates of change of GFAP suggested dMRI might reflect microstructural changes related to the astrocytic response to AD pathology. dMRI might help monitoring the effects of disease‐modifying therapies (e.g. Ab immunotherapies) in clinical trials.

Diffusion MRI track cortical microstructural changes over time during the early stages of the Alzheimer’s disease continuum

AbstractBackgroundMarkers of downstream events are a key component of clinical trials of disease‐modifying therapies for Alzheimer’s disease (AD). Previous cross‐sectional investigations suggested that diffusion MRI (dMRI) can provide metrics sensitive to cortical microstructural alteration linked to multiple aspects of the AD pathological cascade including Aβ‐accumulation and astrocytic activity. However, currently little evidence is available regarding the ability of dMRI in tracking changes over time.MethodsMean diffusivity (MD) was computed from dMRI data acquired from 363 cognitively unimpaired elderly and patients with mild cognitive impairment from the Swedish BioFINDER‐1 study. Each participant underwent multiple dMRI scan (range 2‐4 scans) and was classified as Aβ‐negative/tau‐negative, Aβ‐positive/tau‐negative, and Aβ‐positive/tau‐positive based on CSF levels of Aβ42/40 and ptau‐181. Rates of changes in MD, cortical thickness and plasma level of GFAP were computed in a linear mixed effect framework. Cortical regional values of MD were compared across biomarkers‐defined groups as well as to rates of change of GFAP.ResultsAnalyses of MD revealed widespread differences in rates of change already between Aβ‐negative/tau‐negative and Aβ‐positive/tau‐negative participants with a spatial distribution that closely resembled the pattern of Aβ accumulation (fig.1). Further, analyses focusing on two composite ROIs, one encompassing regions that accumulate Aβ early in the disease process and a temporal meta‐ROI, confirmed that rates of change in MD significantly differed between groups even when cortical thickness was included in the model (Ps&lt;0.05,fig.2). Regional MD rates of change in both neocortical temporal areas and key regions for Aβ‐accumulation, were also positively correlated with rates of change in GFAP (fig.3). Such result was supported by the analysis based on the two meta‐ROIs which confirmed the positive association between rates of change GFAP and MD.ConclusionMean diffusivity from dMRI is able to track cortical microstructural changes over time and to differentiate trajectories even during the early stages of the AD pathological cascade. The association between rates of change of MD and rates of change of GFAP suggested dMRI might reflect microstructural changes related to the astrocytic response to AD pathology. dMRI might help monitoring the effects of disease‐modifying therapies (e.g. Ab immunotherapies) in clinical trials.

Effects of grazing and precipitation addition induced by functional groups on the relationship between aboveground biomass and species richness of a typical steppe

Several studies have explored the influence of grazing or precipitation addition (PA), two important components of human activities and global climate change on the structure and function of communities. However, the response of communities to a combination of grazing and PA remains largely unexplored. We investigated the impact of grazing and PA on the relationship between aboveground biomass (AGB) and species richness (SR) of communities in three-year field experiments conducted in a typical steppe in the Loess Plateau, using a split-plot design with grazing as the main-plot factor and PA as the split-plot factor. AGB and SR have response threshold value to PA, which was decreased by grazing for AGB, but increased for SR. This indicates that implementing grazing management strategies is conducive to strengthening the protection of biodiversity in arid and semi-arid grasslands. Grazing promoted the AGB-SR coupling of the community by increasing the SR of medium drought tolerance (MD), low drought tolerance, and grazing tolerant functional groups. Grazing also accelerated the AGB-SR decoupling of the community by changing the AGB of high drought tolerance, MD, high grazing tolerance, and medium grazing tolerance functional groups. PA mediated changes in MD and SR of both drought and grazing tolerant functional groups and AGB of low grazing tolerance promoted the coupling of AGB-SR of the community. The Two-dimension functional groups classification method reflects the changes of AGB and SR in communities more reasonable than the division of single-factor functional groups.

Is cortical grey matter diffusivity an early biomarker for neuronal damage?

AbstractBackgroundThere is growing evidence that pathological changes in Alzheimer’s disease (AD) begin several years before the symptom onset. Neuroimaging approaches can be used to detect microstructural alterations in the early stages of neurodegeneration using diffusion‐weighted MRI. Cortical grey matter mean diffusivity (cMD) is thought to be increased in AD following pathological alterations resulting in disrupted neuronal function, neuronal death and cellular atrophy. We hypothesised that changes in MD could be detected early in the disease progression and that they would be correlated with structural imaging biomarkers.Method72 patients (mean age=69.1, SD=9.2) cognitively normal (CN, n=21) and with mild cognitive impairment (MCI, n=51) were included in this study. All participants underwent T1‐weighted MPRAGE MRI, diffusion tensor imaging (DTI) and PET amyloid ([18F]flutemetamol). Regional cortical thickness was measured on T1‐MPRAGE using FreeSurfer v.6.0. DTI data were processed with FSL v.6.0 to compute MD maps. Standard uptake ratio (SUVR) values were calculated in SPM12 to identify the amyloid deposition within cortical regions. Amyloid status (Aβ‐positive/Aβ‐negative) was determined from processed data using a cerebellar gray matter reference to create target‐to‐cerebellar ratio. Subjects were considered positive with an uptake value of greater than mean+2SD of the control subjects. Student's t‐test were used to compare imaging modalities between CN and MCI participants. Pearson’s correlation coefficients were calculated to assess the relationship between imaging modalities.ResultThere was a significantly increased MD in MCI compared to CN participants in hippocampus (p=0.0213) and in medial temporal lobe (p=0.033). There were no significant group differences neither in whole brain mean cortical thickness (p=0.6984) nor in temporal cortical thickness (p=0.0923). Interestingly, when splitting subjects based on their amyloid status, we found that whole brain MD was significantly negatively correlated with whole brain cortical thickness in amyloid negative (CN+MCI amyloid negative, p&lt;0.001) but not in amyloid positive (CN+MCI amyloid positive, p=0.99).ConclusionWe found that changes in gray matter diffusivity could be detected in the early stages of AD pathology. We also found that there is a direct relationship between MD and structural changes (i.e. cortical thickness) only before amyloid deposition suggesting that MD provides information about early microstructural changes before macrostructural changes.

Glaucoma progression in patients receiving intravitreal anti-VEGF treatment for neovascular age-related macular degeneration.

The purpose of this study was to investigate how often glaucoma and neovascular age-related macular degeneration (nAMD) occur in the same patient and to evaluate whether glaucoma progression is faster in eyes treated with intravitreal anti-VEGF medications for nAMD. This single-centre retrospective real-world data (RWD) consists of medical records of 6314 glaucoma and 2166 nAMD patients treated in 2008-2017 in Tays Eye Centre, Finland. To study glaucoma progression, changes in visual fields (mean deviation [MD], dB/year), IOP (mmHg/year) and fundus photographs (progression, yes/no) were compared in glaucoma eyes with and without anti-VEGF treatment for nAMD and ≥1year follow-up. During the 10-year period, 147 patients with glaucoma received intravitreal anti-VEGF treatment for nAMD corresponding to 2% of glaucoma and 7% of nAMD patients. The mean change in MD was -0.70 dB/year (SD 1.8) vs. -0.27 dB/year (SD 1.7) (p= 0.027) in glaucoma eyes with (n= 37) and without (n= 4304) anti-VEGF injections, respectively. In patients with bilateral glaucoma and unilateral nAMD treated with anti-VEGF injections (n= 20), MD declined at -0.62 dB/year (SD 1.9) vs 0.33 dB/year (SD 1.5) (p= 0.654), and glaucoma progression was detected in 14/20 vs 10/20 (p= 0.219) fundus photographs in eyes with anti-VEGF treatment compared with their untreated fellow eyes. nAMD and glaucoma were found co-existing in the same eye at rates that were similar to the age-corrected prevalence of the two diseases in the general population. Our results suggest that intravitreal anti-VEGF treatment for nAMD may accelerate glaucoma progression.

Pengaruh Pelatihan dengan Metode PBL Terhadap Keterampilan Kader dalam SDIDTK

ABSTRACTBackground: Detection and Intervention Program (SDIDTK) is a revision of the Early Detection of Growth and Development (DDTK) program which has been carried out since 1988 and is one of the main programs of the Puskesmas. Based on a report from the Ministry of Health of the Republic of Indonesia, the coverage of Toddler health services in early detection of toddler growth and development is 78.11% 10. Monitoring and detection of early childhood growth and development is part of the duties of posyandu cadres in their respective working areas. The task of cadres is very important and complex because the problem of child growth and development is not only directed at physical growth and development, but also the psychological development of children under five. Harisman, stated that the lack of training and coaching to improve adequate skills for cadres caused a lack of understanding of cadres' duties. Early detection education efforts must be increased and one way is through training. Method: With pre-experimental design with non-standardized control group pretest design on 80 trainees. Results: skill changes in the treatment group MD = -13.07, and control group MD = -9.71. The effect of training on skills F = 12,867 sig 0.001 means there is influence. Conclusion: Training with problem-based learning methods is significantly more effective than conventional groups to improve the skills of posyandu cadres in SDIDTK. Keywords: Skills, SDIDTK, PBL

Longitudinal Structure–Function Relationship between Macular Vessel Density and Thickness and Central Visual Field in Early Glaucoma

To investigate the relationship of longitudinal changes in macular vessel density (VD) from OCT angiography and in ganglion cell complex (GCC) from OCT with central visual field (VF) in eyes with early glaucoma. Observational cohort. A total of 95 eyes, 37 preperimetric and 58 with early glaucoma (24-2 VF mean deviation [MD] ≥-6 decibels), with an average follow-up of 3.8 years and 5.3 visits, were included. Whole-image VD (wiVD) and whole-image GCC (wiGCC) and parafoveal scans, as well as localized regions of interest (LROIs), hemiretinae of whole images, and superior, inferior, temporal, and nasal sectors of parafoveal maps, were matched with central VF locations. Age-adjusted rates of change of VD, GCC, mean sensitivity of VF locations, and 10-2 VF MD were calculated using linear mixed-effect models. Normalized rates of change were calculated for comparison of change rates in wiVD and wiGCC. Structure-function (SF) correlations of VD and GCC with central VF measurement change rates and comparison of different correlations of SF relationships after bootstrapping the difference of the correlation coefficients. Vessel density loss and GCC thinning demonstrated significant correlations with central VF damage, globally and with most LROIs. The SF correlation (r, 95% confidence interval [CI]) between wiVD and 10-2 VF MD change rates was 0.42 [0.24, 0.58], whereas it was 0.27 [0.08, 0.45] between wiGCC and 10-2 VF MD changes rates (all P < 0.05). In contrast to GCC thinning, VD loss in the parafoveal sectors demonstrated significant correlations with central VF damage in inferior and temporal sectors. Differences in the relationship of SF with central VF damage were not significant between VD loss and GCC thinning. The mean (95% CI) normalized change rates of wiVD (-7.40 [-7.71 to 7.09] %/year) was faster than that of wiGCC (-2.39 [-2.94 to 1.84] %/year) (P < 0.05). Rates of VD loss and GCC thinning are associated with central VF loss over time. Assessment of both macular VD and GCC thickness should be considered for evaluation of glaucoma progression.

Diffusion tensor imaging (DTI) and plasma p-tau 181 in Alzheimer’s disease

Alzheimer’s Disease (AD) is characterized by cognitive impairments and memory difficulties, which cause daily activities, and personal and behavioral problems. In recent years blood-based biomarkers like plasma phosphorylated tau protein at threonine 181 (p tau 181) emerged as new tools and showed a sufficient power in detecting AD patients from healthy people. Here we investigate the correlation between p tau 181 and white matter microstructural changes in AD patients. We add 21 Alzheimer diagnosed patients with baseline plasma p tau level, CSF Amyloidβ, CSF Tau, CSF p Tau, and DTI metrics from the ADNI database. The analysis revealed that the plasma level of p tau 181 could predict changes in MD, RD, AD, and FA parameters in several regions Also, there is a significant association between white matter pathways alteration in different regions with each of the CSF biomarkers. In conclusion, our study results show that plasma p tau 181 levels are associated with microstructural changes in pathogenesis areas of Alzheimer's disease, which enhance this biomarker's diagnostic status. Longitudinal studies are also necessary to prove the efficacy of these biomarkers and predicting role in structural changes.

Gaze tracker parameters have little association with visual field metrics of intrasession frontloaded SITA-Faster 24-2 visual field results.

PurposeTo determine the usefulness of Humphrey Field Analyser (HFA) SITA‐Faster 24–2 gaze tracker outputs on interpreting intra‐visit visual field (VF) result pairs.MethodsAnalysis of 1380 right–left eye pairs and 1432 pairs of test 1‐test 2 intrasession VF results of patients seen within a university‐based glaucoma service was undertaken to understand gaze deviation distributions. Output gaze tracker results were aggregated into total ticks, sum of amplitudes and average amplitudes. Correlations between visual field indices (mean deviation [MD], “events” and overall hill of vision) and independent variables (age and test order) were performed using one eye from each subject.ResultsThere was no association of test order (right–left, test 1‐test 2) with eye movements. There was a significant, but weak correlation between eye movements and age (r = 0.16). Correlations of eye movements with MD were driven by more severe MD values. There were no significant correlations between intrasession difference in eye movements and the change in MD, number of “events” and hill of vision, or in the root mean square of sensitivity and total deviation values. There was also no significant correlation between gaze tracker outputs and another commonly used “reliability” metric, false positive rate.ConclusionsEye movement parameters as currently reported by the HFA do not appear to be correlated with key sensitivity parameters when considering the repeatability of intrasession SITA‐Faster 24–2 VF results. Thus, current gaze tracker outputs do not appear to provide clinically meaningful information for interpretation of intra‐visit visual field results that cannot already be garnered using other strategies.

Impact of systemic adjuvant therapy and CYP2D6 activity on mammographic density in a cohort of tamoxifen-treated breast cancer patients

PurposeChange in mammographic density has been suggested to be a proxy of tamoxifen response. We investigated the effect of additional adjuvant systemic therapy and CYP2D6 activity on MD change in a cohort of tamoxifen-treated pre- and postmenopausal breast cancer patients.MethodsSwedish breast cancer patients (n = 699) operated 2006–2014, genotyped for CYP2D6, having at least three months postoperative tamoxifen treatment, a baseline, and at least one follow-up digital mammogram were included in the study. Other systemic adjuvant treatment included chemotherapy, goserelin, and aromatase inhibitors. Change in MD, dense area, was assessed using the automated STRATUS method. Patients were stratified on baseline characteristics, treatments, and CYP2D6 activity (poor, intermediate, extensive, and ultrarapid). Relative density change was calculated at year 1, 2, and 5 during follow-up in relation to treatments and CYP2D6 activity.ResultsMean relative DA decreased under the follow-up period, with a more pronounced MD reduction in premenopausal patients. No significant effect of chemotherapy, aromatase inhibitors, goserelin, or CYP2D6 activity on DA change was found. DA did not revert to baseline levels after tamoxifen discontinuation.ConclusionOur results indicate that other systemic adjuvant therapy does not further reduce MD in tamoxifen-treated breast cancer patients. We could not confirm the previously suggested association between CYP2D6 activity and MD reduction in a clinical setting with multimodality adjuvant treatment. No rebound effect on MD decline after tamoxifen discontinuation was evident.

Burden of Ventricular Arrhythmias in Cardiac Resynchronization Therapy Defibrillation and Implantable Cardioverter-Defibrillator Recipients with Recovered Left Ventricular Ejection Fraction: The Additive Role of Speckle-Tracking Echocardiography

Patients with heart failure undergoing cardiac resynchronization therapy with or without defibrillator function may exhibit recovery of left ventricular ejection fraction (LVEF) during follow-up. Mechanical dispersion (MD; the SD of time to peak longitudinal strain by two-dimensional speckle-tracking echocardiography) is a known predictor of life-threatening ventricular arrhythmias (VAs). Relationships among LVEF recovery, changes in MD, and incidence of VA are still not extensively investigated. In this retrospective study, recipients of cardiac resynchronization therapy defibrillation (n=183) or implantable cardioverter-defibrillators only (n=87) underwent conventional and speckle-tracking echocardiography, both at baseline and after 10 to 12months, and were followed clinically. Both a ≥10% increase in LVEF and a final LVEF > 35% defined echocardiographic response (EchoResp). Reduction in MD ≥10 msec defined MD response (MDResp). Risk for appropriate implantable cardioverter-defibrillator therapy for VAs was assessed using a multivariable Cox hazard model. The prevalence of EchoResp+ and MDResp+ was 39% and 46%, respectively. During follow-up (49.8±33.5months), 74 VA events occurred. The incidence rate (per 100 patient-years) of VAs was lowest in the EchoResp+/MDResp+group (1.66%; 95% CI, 0.69%-3.99%), highest in the EchoResp-/MDResp- group (12.8%; 95% CI, 9.53%-17.2%; P<.0001), and intermediate in the EchoResp-/MDResp+ (5.5%; 95% CI, 3.3%-9.4%) or EchoResp+/MDResp- (5.3%; 95% CI, 3.0%-9.4%) group. Multivariable analysis showed that higher MD at follow-up (>71.4 msec) was associated with VAs independent of whether final LVEF was below or above the guideline-reported cutoff of 35% (P<.05). Among ICD recipients, improvements in both left ventricular function and MD are associated with reduced risk for VAs. In patients whose follow-up LVEFs improved to >35%, risk for VAs, although substantially decreased, remained elevated in the presence of still elevated MD.

Widespread Disruptions of White Matter in Familial Multiple Sclerosis: DTI and NODDI Study.

Diffusion tensor imaging (DTI) is a noninvasive, quantitative MRI technique that measures white matter (WM) integrity. Many brain dimensions are heritable, including white matter integrity measured with DTI. Family studies are valuable to provide insights into the interactive effects of non-environmental factors on multiple sclerosis (MS). To examine the contribution of familial factors to the diffusion signals across WM microstructure, we performed DTI and calculated neurite orientation dispersion plus density imaging (NODDI) diffusion parameters in two patient groups comprising familial and sporadic forms of multiple sclerosis and their unaffected relatives. We divided 111 subjects (49 men and 62 women: age range 19–60) into three groups conforming to their MS history. The familial MS group included 30 participants (patients; n = 16, healthy relatives; n = 14). The sporadic group included 41 participants (patients; n = 10, healthy relatives; n = 31). Forty age-matched subjects with no history of MS in their families were defined as the control group. To study white matter integrity, two methods were employed: one for calculating the mean of DTI, FA, and MD parameters on 18 tracts using Tracts Constrained by Underlying Anatomy (TRACULA) and the other for whole brain voxel-based analysis using tract-based spatial statistics (TBSS) on NDI and ODI parameters derived from NODDI and DTI parameters. Voxel-based analysis showed considerable changes in FA, MD, NDI, and ODI in the familial group when compared with the control group, reflecting widespread impairment of white matter in this group. The analysis of 18 tracts with TRACULA revealed increased MD and FA reduction in more tracts (left and right ILF, UNC, and SLFT, forceps major and minor) in familial MS patients vs. the control group. There were no significant differences between the patient groups. We found no consequential changes in healthy relatives of both patient groups in voxel-based and tract analyses. Considering the multifactorial etiology of MS, familial studies are of great importance to clarify the effects of certain predisposing factors on demyelinating brain pathology.

The role of stress-induced dyssynchrony obtained from nuclear modalities in evaluation of high-risk patients after surgical treatment of ischemic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Background Mechanical dyssynchrony (MD) is a well-known parameter witch has prognostic value [1]. Stress tests can be used to unmask MD. However, stress-induced changes in left ventricle (LV) MD by data of nuclear imaging modalities are not well-understood, especially its predictive value [2]. Purpose. To assess the role of stress-induced changes of LV MD obtained by nuclear modalities in evaluating high-risk patients after surgical treatment of ischemic cardiomyopathy (ICM). Methods. Sixty-nine patients with ICM were enrolled. Before surgical treatment all patients underwent gated myocardial perfusion imaging (gMPI) (Tc99m-MIBI; 2 days stress-rest protocol, adenosine 140mkg/kg/min) and gated blood pool SPECT (gBPS) (rest – stress, dobutamine doses of 5/10/15 µg/kg/min). After surgical treatment patients were divided into 2 groups: with (n = 21) and without (n = 48) complicated course of early postoperative period (death, intra-aortic balloon pump, extra inotropic support). The following parameters were estimated: summed stress score (SSS), summed rest score (SRS), summed different score (SDS); phase mean, phase standard deviation (PSD) and histogram bandwidth (HBW) (% from cycle for MPI; degrees for gBPS); phase entropy (%, only by gBPS). Stress-induced changes (Δ) were calculated for MPI indices as [stress value-rest value], for gBPS indices as [value on each dobutamine dose-rest value]. For gBPS the maximum changes of MD were calculated as well. Results. Rest gBPS MD correlated with SRS better than rest gMPI (gMPI: PSD r = 0.31, p = 0.005; HBW r = 0.28, p = 0.008; gBPS: PSD r = 0.47, p &amp;lt; 0.001; HBW r = 0.36, p = 0.006; entropy r = 0.39, p = 0.003). Stress gBPS MD correlated better with post stress gMPI MD at the dobutamine dose of 5µg/kg/min. An following increase of the dobutamine dose led to a decrease in the r-value, but it remained significant for all indices (tab.1). Stress-induced MD changes didn’t correlate between gMPI and gBPS. Mann-Whitney test showed significant differences in SDS (p = 0.02) between the groups. Both methods didn’t show any differences at rest study. Stress-induced changes of MD showed differences between groups in only ΔEntropy rest-10µg/kg/min (p = 0.02) and maximum ΔEntropy (p = 0.01) by gBPS, as well as Δphase mean (p = 0.03) by gMPI. Logistic regression analysis showed that only maximum ΔEntropy has prognostic value in prediction of the course of early postoperative period (OR 1.2 95%CI 1.04; 1.37). ROC-analysis showed sensitivity of 80% and specificity of 55% with AUC of 0.7 for cut-off value &amp;gt;0. Conclusion. LVMD obtained from gBPS is associated with SRS better than those obtained from gMPI. Dyssynchrony indices obtained from gMPI with adenosine stress-test have a week to moderate correlation with those obtained from dobutamine gBPS, and correlation decrease with increasing of dobutamine dose. Only maximum ΔEntropy obtained from dobutamine gBPS is associated with the adverse course of early postoperative period in patients with ICM.

Mammographic density changes following BC treatment

BackgroundMammographic density (MD) reduction is associated with lower risk of breast cancer (BC) recurrence and may be used as a marker of treatment outcome; however, trends in MD following BC therapies and the factors associated with such trends are poorly understood. The aim of this study was to investigate MD changes following BC treatment and the factors associated with these changes. MethodsA total of 226 BC-affected patients who received BC treatments were examined. MD was assessed by the Laboratory for individualized Radiodensity Assessment (LIBRA) software. A Wilcoxon ranked signed test was used to investigate the differences in MD before and after treatment and median independent test to assess the associated factors. ResultsSignificant differences in MD between baseline and follow-up mammograms were observed for all MD measures: percent density (p ≤ 0.005), dense area (p ≤ 0.004), and nondense area (p ≤ 0.02). After adjustment, these differences were more pronounced among younger at BC diagnosis (p ≤ 0.001), premenopausal (p ≤ 0.003), and obese women (p ≤ 0.05). Changes in MD were evident regardless of the treatment regimen. MD reduction was observed among patients with high baseline MD (p < 0.001), younger at BC diagnosis (p ≤ 0.04), premenopausal (p < 0.001), and normal body mass index (p = 0.04). Patients who experienced an increase in nondense area had high percent density at baseline (p ≤ 0.001). ConclusionTwo different MD changes were observed over time: MD increase and decrease. Baseline MD, menopausal status, age at BC diagnosis, and body mass index influenced these changes.