Charité

About: Charité is a healthcare organization based out in Berlin, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 30624 authors who have published 64507 publications receiving 2437322 citations. The organization is also known as: Charite & Charité – University Medicine Berlin.

Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study

Abstract: Summary Background Imaging with amyloid-β PET can potentially aid the early and accurate diagnosis of Alzheimer's disease. Florbetaben ( 18 F) is a promising 18 F-labelled amyloid-β-targeted PET tracer in clinical development. We aimed to assess the sensitivity and specificity of florbetaben ( 18 F) PET in discriminating between patients with probable Alzheimer's disease and elderly healthy controls. Methods We did a multicentre, open-label, non-randomised phase 2 study in 18 centres in Australia, Germany, Switzerland, and the USA. Imaging with florbetaben ( 18 F) PET was done on patients with probable Alzheimer's disease (age 55 years or older, mini-mental state examination [MMSE] score=18–26, clinical dementia rating [CDR]=0·5–2·0) and age-matched healthy controls (MMSE ≥28, CDR=0). Our primary objective was to establish the diagnostic efficacy of the scans in differentiating between patients with probable disease and age-matched healthy controls on the basis of neocortical tracer uptake pattern 90–110 min post-injection. PET images were assessed visually by three readers masked to the clinical diagnosis and all other clinical findings, and quantitatively by use of pre-established brain volumes of interest to obtain standard uptake value ratios (SUVRs), taking the cerebellar cortex as the reference region. This study is registered with ClinicalTrials.gov, number NCT00750282. Findings 81 participants with probable Alzheimer's disease and 69 healthy controls were assessed. Independent visual assessment of the PET scans showed a sensitivity of 80% (95% CI 71–89) and a specificity of 91% (84–98) for discriminating participants with Alzheimer's disease from healthy controls. The SUVRs in all neocortical grey-matter regions in participants with Alzheimer's disease were significantly higher (p r −0·27 to −0·33, p≤0·021). APOE ɛ4 was more common in participants with positive PET images compared with those with negative scans (65% vs 22% [p=0·027] in patients with Alzheimer's disease; 50% vs 16% [p=0·074] in healthy controls). No safety concerns were noted. Interpretation We provide verification of the efficacy, safety, and biological relevance of florbetaben ( 18 F) amyloid-β PET and suggest its potential as a visual adjunct in the diagnostic algorithm of dementia. Funding Bayer Schering Pharma AG.

Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans

Abstract: Identifying transplant recipients in whom immunological tolerance is established or is developing would allow an individually tailored approach to their posttransplantation management. In this study, we aimed to develop reliable and reproducible in vitro assays capable of detecting tolerance in renal transplant recipients. Several biomarkers and bioassays were screened on a training set that included 11 operationally tolerant renal transplant recipients, recipient groups following different immunosuppressive regimes, recipients undergoing chronic rejection, and healthy controls. Highly predictive assays were repeated on an independent test set that included 24 tolerant renal transplant recipients. Tolerant patients displayed an expansion of peripheral blood B and NK lymphocytes, fewer activated CD4+ T cells, a lack of donor-specific antibodies, donor-specific hyporesponsiveness of CD4+ T cells, and a high ratio of forkhead box P3 to alpha-1,2-mannosidase gene expression. Microarray analysis further revealed in tolerant recipients a bias toward differential expression of B cell-related genes and their associated molecular pathways. By combining these indices of tolerance as a cross-platform biomarker signature, we were able to identify tolerant recipients in both the training set and the test set. This study provides an immunological profile of the tolerant state that, with further validation, should inform and shape drug-weaning protocols in renal transplant recipients.

Connectivity Predicts deep brain stimulation outcome in Parkinson disease.

Abstract: Objective: The benefit of deep brain stimulation (DBS) for Parkinson's disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remains unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort. Methods: A training dataset of 51 PD patients with STN DBS was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of Unified Parkinson's Disease Rating Scale). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients from a different center. Results: In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex (p < 0.001). This same connectivity profile predicted response in an independent patient cohort (p < 0.01). Structural and functional connectivity were independent predictors of clinical improvement (p < 0.001) and estimated response in individual patients with an average error of 15% UPDRS improvement. Results were similar using connectome data from normal subjects or a connectome age, sex, and disease-matched to our DBS patients. Interpretation: Effective STN-DBS for PD is associated with a specific connectivity profile that can predict clinical outcome across independent cohorts. This prediction does not require specialized imaging in PD patients themselves. This article is protected by copyright. All rights reserved.

Functional roles of social support within the stress and coping process: A theoretical and empirical overview

Abstract: This article reports four longitudinal field studies and one experimental study designed to shed light on the functional roles of social support within the stress and coping context. First, the enabling hypothesis is examined that assumes a facilitating effect of support on self‐efficacy, which, in turn, promotes coping with the aftermath of cardiac surgery. Second, we discuss the support cultivation hypothesis that regards support as a mediator between self‐efficacy and various outcomes, such as depressive mood, as illustrated by a finding on the experience of macrosocial stress during the East German transition. Third, support is highlighted as a coping resource by specifying provided partner support as a predictor of patients' coping with cancer. It was found that the direct effect of provided support on coping needs to be mediated by received support in order to become effective. Fourth, coping efforts of a target person are found to be predictive of support intentions of a potential provider. The bet...

Contrast-induced nephropathy: a clinical and evidence-based approach.

Abstract: Contrast medium–induced nephropathy (CIN) is a common cause of acute renal dysfunction. During the past few years, several publications have provided clinical and experimental data on this topic. Our review focuses on 4 major concerns of CIN relevant in clinical practice: (1) What is the evidence that CIN is a clinically relevant and a dangerous condition for the patient? (2) Is there a difference in CIN rate among different contrast media, and how is that related to the physicochemical properties of different available contrast media? (3) What is the evidence that periprocedural hydration is an effective, appropriate, and safe method to prevent CIN? (4) What is the evidence for the use of a drug, in particular acetylcysteine, to prevent CIN? CIN has gained increased attention in the clinical setting, particularly during cardiac intervention but also in many other radiological procedures in which iodinated contrast media are used. There is at present good clinical evidence from well-controlled randomized studies that CIN is a common cause of acute renal dysfunction.1,2 CIN is the acute deterioration of renal function after parenteral administration of radiocontrast media in the absence of other causes. CIN is generally defined as an increase in serum creatinine concentration of >0.5 mg/dL (>44 μmol/L) or 25% above baseline within 48 hours after contrast administration.3–7 Although the exact mechanisms of CIN have yet to be fully elucidated, several causes have been described. Increased adenosine-, endothelin-, and free radical–induced vasoconstriction and reduced nitric oxide– and prostaglandin-induced vasodilatation have been observed. These mechanisms cause ischemia in the deeper portion of the outer medulla, an area with high oxygen requirements and remote from the vasa recta supplying the renal medulla with blood. Contrast agents also have direct toxic effects on renal tubular cells, causing vacuolization, altered mitochondrial function, and apoptosis.8 Atopy …