Quantitative analysis of collagens and fibronectin expression in human right ventricular hypertrophy

One of the main features in human tetralogy of Fallot (TF) is right ventricular hypertrophy (RVH) due to pressure (sub-pulmonary stenosis) and volume overload (ventricular septal defect). Currently, primary correction at a young age is the treatment of choice. To unravel the role of extracellular matrix in RVH, we examined myocardial expression of collagens and fibronectin in TF patients with primary correction (TF1, age 0.7 ± 0.2 yr,), secondary surgery (TF2, age 36.9 ± 4.6 yr), and in age-matched control patients. Sirius red staining quantified by video imaging showed significantly increased interstitial staining for collagens in both TF1 and TF2 groups as compared to respective controls. Fibronectin was expressed in extracellular spaces, perivascular regions, and in some cardiomyocytes. Quantitative analysis of fibronectin revealed increased expression in only TF1 group as compared to respective control. Our results indicate an increased amount of myocardial extracellular matrix deposition as a sign of fibrosis during RVH in patients with TF

Evaluation of a Semi-automatic Right Ventricle Segmentation Method on Short-Axis MR Images

The purpose of this study was to evaluate a semi-automatic right ventricle segmentation method on short-axis cardiac cine MR images which segment all right ventricle contours in a cardiac phase using one seed contour. Twenty-eight consecutive short-axis, four-chamber, and tricuspid valve view cardiac cine MRI examinations of healthy volunteers were used. Two independent observers performed the manual and automatic segmentations of the right ventricles. Analyses were based on the ventricular volume and ejection fraction of the right heart chamber. Reproducibility of the manual and semi-automatic segmentations was assessed using intra- and inter-observer variability. Validity of the semi-automatic segmentations was analyzed with reference to the manual segmentations. The inter- and intra-observer variability of manual segmentations were between 0.8 and 3.2%. The semi-automatic segmentations were highly correlated with the manual segmentations (R2 0.79–0.98), with median difference of 0.9–4.8% and of 3.3% for volume and ejection fraction parameters, respectively. In comparison to the manual segmentation, the semi-automatic segmentation produced contours with median dice metrics of 0.95 and 0.87 and median Hausdorff distance of 5.05 and 7.35 mm for contours at end-diastolic and end-systolic phases, respectively. The inter- and intra-observer variability of the semi-automatic segmentations were lower than observed in the manual segmentations. Both manual and semi-automatic segmentations performed better at the end-diastolic phase than at the end-systolic phase. The investigated semi-automatic segmentation method managed to produce a valid and reproducible alternative to manual right ventricle segmentation

Comparison of the serious injury pattern of adult bicyclists, between South-West Netherlands and the State of Victoria, Australia 2001-2009

Background: Head injury is the leading cause of death and long term disability from bicycle injuries and may be prevented by helmet wearing. We compared the pattern of injury in major trauma victims resulting from bicyclist injury admitted to hospitals in the State of Victoria, Australia and South-West Netherlands, with respective high and low prevalence of helmet use among bicyclists. Methods: A cohort of bicycle injured patients with serious injury (defined as Injury Severity Score > 15) in South-West Netherlands, was compared to a cohort of serious injured bicyclists in the State of Victoria, Australia. Additionally, the cohorts of patients with serious injury admitted to a Dutch level 1 trauma centre in Rotterdam, the Netherlands and an Australian level 1 trauma centre in Melbourne, Australia were compared. Both cohorts included patients admitted between July 2001 and June 2009. Primary outcome was in-hospital mortality and secondary outcome was prevalence of severe injury per body region. Outcome was compared using univariate analysis and mortality outcomes were also calculated using multivariable logistic regression models. Results: A total of 219 cases in South-West Netherlands and 500 cases in Victoria were analyzed. Further analyses comparing the major trauma centres in each region, showed the percentage of bicycle-related death was higher in the Dutch population than in the Australian (n = 45 (24%) vs n = 13(7%); P < 0.001). After adjusting for age, mechanism of injury, GCS and head injury severity in both hospitals, there was no significant difference in mortality (adjusted odds ratio 1.4; 95% confidence interval = 0.6, 3.5). Patients in Netherlands trauma centre suffered from more serious head injuries (Abbreviated Injury Scale ≥ 3) than patients in the Australian trauma centre (n = 165 (88.2%) vs n = 121 (62.4%); P < 0.001). The other body regions demonstrated significant differences i

Application of an Imaging-Based Sum Score for Cerebral Amyloid Angiopathy to the General Population: Risk of Major Neurological Diseases and Mortality

Objective: To assess the relation between a sum score of imaging markers indicative of cerebral amyloid angiopathy (CAA) and cognitive impairment, stroke, dementia, and mortality in a general population. Methods: One thousand six hundred twenty-two stroke-free and dementia-free participants of the population-based Rotterdam Study (mean age 73.1 years, 54.3% women) underwent brain MRI (1.5 tesla) in 2005–2011 and were followed for stroke, dementia and death until 2016–2017. Four MRI markers (strictly lobar cerebral microbleeds, cortical superficial siderosis, centrum semiovale perivascular spaces, and white matter hyperintensities) were combined to construct the CAA sum score, ranging from 0 to 4. Neuropsychological testing measured during the research visit closest to scan date were used to assess general cognitive function and cognitive domains. The associations of the CAA sum score with cognition cross-sectionally and with stroke, dementia, and mortality longitudinally were determined using linear regression and Cox proportional hazard modeling adjusted for age, sex, hypertension, cholesterol, lipid lowering medication, atrial fibrillation, antithrombotic medication and APOE-ε2/ε4 carriership. Additionally, we accounted for competing risks of death due to other causes for stroke and dementia, and calculated absolute risk estimates. Results: During a mean follow-up of 7.2 years, 62 participants suffered a stroke, 77 developed dementia and 298 died. Participants with a CAA score of 1 showed a lower Mini-Mental-State-Exam (fully-adjusted mean difference −0.21, 9

External validation of four dementia prediction models for use in the general community-dwelling population: a comparative analysis from the Rotterdam Study

To systematically review the literature for dementia prediction models for use in the general population and externally validate their performance in a head-to-head comparison. We selected four prediction models for validation: CAIDE, BDSI, ANU-ADRI and DRS. From the Rotterdam Study, 6667 non-demented individuals aged 55 years and older were assessed between 1997 and 2001. Subsequently, participants were followed for dementia until 1 January, 2015. For each individual, we computed the risk of dementia using the reported scores from each prediction model. We used the C-statistic and calibration plots to assess the performance of each model to predict 10-year risk of all-cause dementia. For comparisons, we also evaluated discriminative accuracy using only the age component of these risk scores for each model separately. During 75,581 person-years of follow-up, 867 participants developed dementia. C-statistics for 10-year dementia risk prediction were 0.55 (95% CI 0.53–0.58) for CAIDE, 0.78 (0.76–0.81) for BDSI, 0.75 (0.74–0.77) for ANU-ADRI, and 0.81 (0.78–0.83) for DRS. Calibration plots showed that predicted risks were too extreme with underestimation at low risk and overestimation at high risk. Importantly, in all models age alone already showed nearly identical discriminative accuracy as the full model (C-statistics: 0.55 (0.53–0.58) for CAIDE, 0.81 (0.78–0.83) for BDSI, 0.77 (0.75–0.79) for ANU-ADRI, and 0.81 (0.78–0.83) for DRS). In this study, we found high variability in discriminative ability for predicting dementia in an elderly, community-dwelling population. All models showed similar discriminative ability when compared to prediction based on age alone. These findings highlight the urgent need for updated or new models to predict dementia risk in the general population

Enlarged perivascular spaces in brain MRI: Automated quantification in four regions

Enlarged perivascular spaces (PVS) are structural brain changes visible in MRI, are common in aging, and are considered a reflection of cerebral small vessel disease. As such, assessing the burden of PVS has promise as a brain imaging marker. Visual and manual scoring of PVS is a tedious and observer-dependent task. Automated methods would advance research into the etiology of PVS, could aid to assess what a “normal” burden is in aging, and could evaluate the potential of PVS as a biomarker of cerebral small vessel disease. In this work, we propose and evaluate an automated method to quantify PVS in the midbrain, hippocampi, basal ganglia and centrum semiovale. We also compare associations between (earlier established) determinants of PVS and visual PVS scores versus the automated PVS scores, to verify whether automated PVS scores could replace visual scoring of PVS in epidemiological and clinical studies. Our approach is a deep learning algorithm based on convolutional neural network regression, and is contingent on successful brain structure segmentation. In our work we used FreeSurfer segmentations. We trained and validated our method on T2-contrast MR images acquired from 2115 subjects participating in a population-based study. These scans were visually scored by an expert rater, who counted the number of PVS in each brain region. Agreement between visual and automated scores was found to be excellent for all four regions, with intraclass correlation coefficients (ICCs) between 0.75 and 0.88. These values were higher than the inter-observer agreement of visual scoring (ICCs between 0.62 and 0.80). Scan-rescan reproducibility was high (ICCs between 0.82 and 0.93). The association between 20 determinants of PVS, including aging, and the automated scores were similar to those between th

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Association of common genetic variants with brain microbleeds

OBJECTIVE: To identify common genetic variants associated with the presence of brain microbleeds (BMBs). METHODS: We performed geno