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.

Bootstrap tests: how many bootstraps?

Abstract: In practice, bootstrap tests must use a finite number of bootstrap samples. This means that the outcome of the test will depend on the sequence of random numbers used to generate the bootstrap samples, and it necessarily results in some loss of power. We examine the extent of this power loss and propose a simple pretest procedure for choosing the number of bootstrap samples so as to minimize experimental randomness. Simulation experiments suggest that this procedure will work very well in practice.

A prospective, randomized study of computer-assisted and conventional total knee arthroplasty. Three-dimensional evaluation of implant alignment and rotation.

Abstract: Background: Despite the use of modern instruments in total knee arthroplasty, component malalignment remains a problem. Whether a computer-assisted implantation technique can improve the accuracy of the spatial positioning of an implant is a matter of debate. The objective of this study was to determine whether computer-assisted total knee arthroplasty is superior to the conventional surgical method with regard to the precision of implant positioning. Methods: The spatial positioning of the implant in sixty total knee arthroplasties (thirty-two imageless computer-assisted and twenty-eight conventional implantations) was determined three-dimensionally with use of computed tomographic measurement, which allowed derotation and full extension of the knee in order to avoid projection-related imaging errors. Results: The overall mechanical axis showed a range of between 4.8° of valgus and 6.6° of varus alignment in the frontal plane for conventionally implanted arthroplasty components compared with a significantly smaller range of between 2.9° of valgus and 3.1° of varus alignment for computer-assisted implantations (p = 0.004). In relation to the tibial implant, the mean deviation (and standard deviation) from the mechanical axis was 2.0° ± 1.7° for the conventional surgical method and 1.4° ± 0.9° for the navigated implantation. The rotational deviation from the referenced axis of the femoral component was between 3.3° of internal rotation and 5.0° of external rotation for the conventional implantation method, with a mean deviation of 0.1° ± 2.2°. Femoral components implanted with computer assistance showed a deviation of between 4.7° of internal rotation and 2.2° of external rotation, with a mean deviation of 0.3° ± 1.4°. Conclusions: In this study, with our technique of filtering out projection-related imaging errors, computer-assisted implantation of total knee replacements improved the frontal and sagittal alignment of the femoral component but not of the tibial component. We found that the rotational alignment of the component was not improved through navigation by solely referencing to the epicondylar axis for the femur and the tuberosity for the tibia. Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

Cachexia as a major underestimated and unmet medical need: facts and numbers

Abstract: Cachexia is a serious, however underestimated and underrecognised medical consequence of malignant cancer, chronic heart failure (CHF), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), cystic fibrosis, rheumatoid arthritis, Alzheimer's disease, infectious diseases, and many other chronic illnesses. The prevalence of cachexia is high, ranging from 5% to 15% in CHF or COPD to 60% to 80% in advanced cancer. By population prevalence, the most frequent cachexia subtypes are in order: COPD cachexia, cardiac cachexia (in CHF), cancer cachexia, and CKD cachexia. In industrialized countries (North America, Europe, Japan), the overall prevalence of cachexia (due to any disease) is growing and currently about 1%, i.e., about nine million patients. The relative prevalence of cachexia is somewhat less in Asia, but is a growing problem there as well. In absolute terms, cachexia is, in Asia (due to the larger population), as least as big a problem as in the Western world. Cachexia is also a big medical problem in South America and Africa, but data are scarce. A consensus statement recently proposed to diagnose cachexia in chronic diseases when there is weight loss exceeding 5% within the previous 3–12 months combined with symptoms characteristic for cachexia (e.g., fatigue), loss of skeletal muscle and biochemical abnormalities (e.g., anemia or inflammation). Treatment approaches using anabolics, anti-catabolic therapies, appetite stimulants, and nutritional interventions are under development. A more thorough understanding of the pathophysiology of cachexia development and progression is needed that likely will lead to combination therapies being developed. These efforts are greatly needed as presence of cachexia is always associated with high-mortality and poor-symptom status and dismal quality of life. It is thought that in cancer, more than 30% of patients die due to cachexia and more than 50% of patients with cancer die with cachexia being present. In other chronic illnesses, one can estimate that up to 30% of patients die with some degree of cachexia being present. Mortality rates of patients with cachexia range from 10% to 15% per year (COPD), to 20% to 30% per year (CHF, CKD) to 80% in cancer.

Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance

Abstract: The recognition and elimination of tumours by T cells, a process termed cancer immunosurveillance, is effective against certain virus-associated cancers. Spontaneous tumours often induce a specific immune response and are therefore also immunogenic. However, it is not clear whether they can be controlled by T cells. The immunosurveillance hypothesis postulates that tumours, if they eventually grow, escaped T-cell recognition by losing immunogenicity. Here we show, by generating a mouse model of sporadic cancer based on rare spontaneous activation of a dormant oncogene, that immunogenic tumours do not escape their recognition but induce tolerance. In this model, tumours derive from single cells and express a tumour-specific transplantation rejection antigen. Whereas vaccinated mice remain tumour-free throughout their lifetime, naive mice always develop a progressively growing tumour. We also show that despite specific recognition by T cells, the tumours do not lose their intrinsic immunogenicity and are rejected after transplantation in T-cell-competent recipients. Furthermore, in the primary host tumour-induced tolerance is associated with the expansion of non-functional T cells. Together, our data argue against immunosurveillance of spontaneous cancer.