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Concept: Radboud University Nijmegen

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Gait and cognition have been related to mortality in population-based studies. This association is possibly mediated by cerebral small vessel disease (SVD), which has been associated with mortality as well. It is unknown which factors can predict mortality in individuals with SVD. Identification of high-risk patients may provide insight into factors that reflect their vital health status.

Concepts: Epidemiology, Demography, Actuarial science, Radboud University Nijmegen, Nijmegen, Dries van Agt, Hogeschool van Arnhem en Nijmegen

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Traditional remedies for common disorders have been known for centuries, but insight into their mechanism of action is often limited. In this issue of the JCI, Joost Schalkwijk’s research group at the Radboud University Nijmegen Medical Centre in The Netherlands advances our understanding of why topical coal tar is an effective treatment for atopic dermatitis (AD), both rationalizing the use of this traditional medicine, and providing the scientific basis for new therapeutic approaches.

Concepts: Medicine, Atopy, Netherlands, Eczema, Psoriasis, Atopic dermatitis, Radboud University Nijmegen, Nijmegen

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The relation between progression of cerebral small vessel disease (SVD) and gait decline is uncertain, and diffusion tensor imaging (DTI) studies on gait decline are lacking. We therefore investigated the longitudinal associations between (micro) structural brain changes and gait decline in SVD using DTI. 275 participants were included from the Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort (RUN DMC), a prospective cohort of participants with cerebral small vessel disease aged 50-85 years. Gait (using GAITRite) and magnetic resonance imaging measures were assessed during baseline (2006-2007) and follow-up (2011 - 2012). Linear regression analysis was used to investigate the association between changes in conventional magnetic resonance and diffusion tensor imaging measures and gait decline. Tract-based spatial statistics analysis was used to investigate region-specific associations between changes in white matter integrity and gait decline. 56.2% were male, mean age was 62.9 years (SD8.2), mean follow-up duration was 5.4 years (SD0.2) and mean gait speed decline was 0.2 m/s (SD0.2). Stride length decline was associated with white matter atrophy (β = 0.16, p = 0.007), and increase in mean white matter radial diffusivity and mean diffusivity, and decrease in mean fractional anisotropy (respectively, β = - 0.14, p = 0.009; β = - 0.12, p = 0.018; β = 0.10, p = 0.049), independent of age, sex, height, follow-up duration and baseline stride length. Tract-based spatial statistics analysis showed significant associations between stride length decline and fractional anisotropy decrease and mean diffusivity increase (primarily explained by radial diffusivity increase) in multiple white matter tracts, with the strongest associations found in the corpus callosum and corona radiata, independent of traditional small vessel disease markers. White matter atrophy and loss of white matter integrity are associated with gait decline in older adults with small vessel disease after 5 years of follow-up. These findings suggest that progression of SVD might play an important role in gait decline.

Concepts: Linear regression, Statistics, Medical imaging, Magnetic resonance imaging, White matter, Diffusion MRI, Corpus callosum, Radboud University Nijmegen

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In medical school selection, non-cognitive performance in particular correlates with performance in clinical practice. It is arguable, therefore, that selection should focus on non-cognitive aspects despite the predictive value of prior cognitive performance for early medical school performance. The aim of this study at Radboud University Medical Center, the Netherlands, is to determine the effects of admitting students through an autonomous non-cognitive procedure on early medical school performance. We compared their performance to the performance of students selected through an autonomous cognitive selection procedure, enrolling in the Bachelor’s curriculum simultaneously. 574 students (2013 and 2014 cohorts), admitted through non-cognitive selection (based on portfolio, CASPer and MMI, n = 135) or cognitive selection (curriculum sample selection, n = 439) were included in the study. We compared dropout rates, course credits and grades, using logistic and linear regression. The dropout rate was the highest in the non-cognitive selection group (p < 0.001). Students admitted through non-cognitive selection more often obtained the highest grade for the nursing attachment (p = 0.02) and had a higher mean grade for the practical clinical course in year 3 (p = .04). No differences in course grades were found. The results indicate that students perform best on the elements of the curriculum that are represented most strongly in the selection procedure they had participated in. We recommend the use of curriculum sample procedures, resembling the early medical school curriculum,-whether it has a more cognitive or a more non-cognitive focus-, to select the students who are likely to be successful in the subsequent curriculum.

Concepts: Regression analysis, Medicine, Grade, Education, Performance, Medical school, Selection, Radboud University Nijmegen

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Metastatic infection is an important complication of Staphylococcus aureus bacteremia (SAB). Early diagnosis of metastatic infection is crucial, as specific treatment is required. However, metastatic infection can be asymptomatic and difficult to detect. In this study, we investigated the role of (18)F-FDG-PET/CT in patients with SAB for detection of metastatic infection and its consequences for treatment and outcome. Methods: All patients with SAB at Radboud university medical center were included between January 2013 and April 2016. Clinical data and results of (18)F-FDG-PET/CT and other imaging techniques, including echocardiography, were collected. Primary outcomes were newly diagnosed metastatic infection by (18)F-FDG-PET/CT, subsequent treatment modifications, and outcome. Results: A total of 184 patients were included and (18)F-FDG-PET/CT was performed in 105 patients of whom 99 had a high-risk bacteremia. (18)F-FDG-PET/CT detected metastatic infectious foci in 73.7% of these high-risk patients. In 71.2% of patients with metastatic infection, no signs and symptoms suggesting metastatic complications were present before (18)F-FDG-PET/CT was performed. (18)F-FDG-PET/CT led to a total of 104 treatment modifications in 74 patients. Three-month mortality was higher in high-risk bacteremia patients without (18)F-FDG-PET/CT performed compared to those in whom (18)F-FDG-PET/CT was performed (32.7% versus 12.4%, P = 0.003). In multivariate analysis, (18)F-FDG-PET/CT was the only factor independently associated with reduced mortality (P = 0.005; OR, 0.204; 95% CI, 0.066-0.624). A higher co-morbidity score was independently associated with increased mortality (P = 0.003; OR, 1.254; 95% CI, 1.078-1.457). Conclusion:(18)F-FDG-PET/CT is a valuable technique for early detection of metastatic infectious foci, often leading to treatment modification. Performing(18)F-FDG-PET/CT is associated with significantly reduced three-month mortality.

Concepts: Staphylococcus aureus, Infection, Staphylococcus, Multivariate statistics, Transmission and infection of H5N1, Outcome, Radboud University Nijmegen, 2016

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This article reviews the development of multidisciplinary osseointegration treatment in the Netherlands since its start in 2009. People experiencing limitations due to their socket prosthesis after a leg amputation present to the Radboud University Nijmegen Medical Centre for an osseointegration implant or “bone-anchored” prosthesis. In this article we share our experience with the first 100 patients regarding referral pattern, selection criteria, available osseointegration systems, preoperative planning, surgical treatment, the rehabilitation protocol, outcome measurement, revision surgery, and future developments.

Concepts: Surgery, Netherlands, Amputation, Osseointegration, Radboud University Nijmegen, Nijmegen, Dries van Agt, Rita Verdonk

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Now that genome sequencing prices are dropping fast and genome/exome sequencing is increasingly offered in a diagnostic setting, the ability to counsel patients on having their genome or exome sequence = is becoming increasingly important. Additionally, an increasing number of healthy individuals is having their genome sequenced, either out of curiosity or because they think that there may be a gain for their own health. With the underlying hypothesis that personal experience improves counseling skills, the statement “Should clinical geneticists have their genome sequenced?” was discussed during an interactive debate session on June 9(th) 2015, during the European Society for Human Genetics (ESHG) meeting in Glasgow, United Kingdom. The discussion was chaired by Joris Veltman (Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands) and Martina Cornel (VU University Medical Center, Amsterdam, The Netherlands), and the panel consisted of Carsten Bergmann (University Freiburg Medical Center, Freiburg, Germany), Kate Bushby (Newcastle University, Newcastle upon Tyne, UK), Heidi Howard (Uppsala University, Uppsala, Sweden) and Gijs Santen (Leiden University Medical Center, Leiden, The Netherlands). This article is protected by copyright. All rights reserved.

Concepts: European Union, Biotechnology, Europe, Netherlands, Newcastle upon Tyne, Radboud University Nijmegen, Nijmegen, Amsterdam

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Poor inter-professional collaboration might negatively influence adequate planning of operative procedures. Interventions capable of improving inter-professional collaboration will positively impact professional practice and health care outcomes. Radboud University Medical Center (UMC) redesigned their operating room (OR) scheduling method by implementing cross-functional teams (CFTs). In this center, positive effects of CFTs were already demonstrated in a mono-center study. This study aims to confirm these effects by comparing the Radboud data with data from 6 other similar centers using a nationwide OR benchmark collaborative.

Concepts: Health care, Medicine, Health, Improve, Urgent care, Collaboration, Collaborative software, Radboud University Nijmegen

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Ipilimumab is a fully human monoclonal antibody that binds cytotoxic T-lymphocyte antigen 4 to enhance antitumour immunity. Our aim was to assess the use of ipilimumab after radiotherapy in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel chemotherapy.

Concepts: Cancer, Chemotherapy, Prostate cancer, Netherlands, Paclitaxel, Bristol-Myers Squibb, Radboud University Nijmegen, University of Utah

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Traditionally, antirejection therapy in organ transplantation has mainly been directed at T cells. During recent years, the role of B cells in acute rejection has attracted more attention. In the Radboud university medical center (Nijmegen, The Netherlands) we performed a randomized, placebocontrolled study to assess the efficacy and safety of rituximab as induction therapy after renal transplantation. In parallel we investigated the effects of rituximab on the numbers and function of B and T cells. An overview of the results, which have largely been published in peer reviewed papers, is presented below.

Concepts: Stem cell, Organ, Organ transplant, Kidney transplantation, Transplant rejection, Netherlands, Radboud University Nijmegen, Nijmegen