Institution
Charité
Healthcare•Berlin, Germany•
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.
Topics: Population, Transplantation, Immune system, Heart failure, Cancer
Papers published on a yearly basis
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TL;DR: Chronic heart failure is a multisystem disorder in which intestinal morphology, permeability, and absorption are modified, and increased intestinal permeability and an augmented bacterial biofilm may contribute to the origin of both chronic inflammation and malnutrition.
505 citations
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TL;DR: The hypothesis was that the omission of whole brain radiotherapy does not compromise overall survival, with a non-inferiority margin of 0·9, and the primary hypothesis was not proven.
Abstract: Summary Background High-dose methotrexate is the standard of care for patients with newly diagnosed primary CNS lymphoma. The role of whole brain radiotherapy is controversial because delayed neurotoxicity limits its acceptance as a standard of care. We aimed to investigate whether first-line chemotherapy based on high-dose methotrexate was non-inferior to the same chemotherapy regimen followed by whole brain radiotherapy for overall survival. Methods Immunocompetent patients with newly diagnosed primary CNS lymphoma were enrolled from 75 centres and treated between May, 2000, and May, 2009. Patients were allocated by computer-generated block randomisation to receive first-line chemotherapy based on high-dose methotrexate with or without subsequent whole brain radiotherapy, with stratification by age ( vs ≥60 years) and institution (Berlin vs Tubingen vs all other sites). The biostatistics centre assigned patients to treatment groups and informed local centres by fax; physicians and patients were not masked to treatment group after assignment. Patients enrolled between May, 2000, and August, 2006, received high-dose methotrexate (4 g/m 2 ) on day 1 of six 14-day cycles; thereafter, patients received high-dose methotrexate plus ifosfamide (1·5 g/m 2 ) on days 3–5 of six 14-day cycles. In those assigned to receive first-line chemotherapy followed by radiotherapy, whole brain radiotherapy was given to a total dose of 45 Gy, in 30 fractions of 1·5 Gy given daily on weekdays. Patients allocated to first-line chemotherapy without whole brain radiotherapy who had not achieved complete response were given high-dose cytarabine. The primary endpoint was overall survival, and analysis was per protocol. Our hypothesis was that the omission of whole brain radiotherapy does not compromise overall survival, with a non-inferiority margin of 0·9. This trial is registered with ClinicalTrials.gov, number NCT00153530. Findings 551 patients (median age 63 years, IQR 55–69) were enrolled and randomised, of whom 318 were treated per protocol. In the per-protocol population, median overall survival was 32·4 months (95% CI 25·8–39·0) in patients receiving whole brain radiotherapy (n=154), and 37·1 months (27·5–46·7) in those not receiving whole brain radiotherapy (n=164), hazard ratio 1·06 (95% CI 0·80–1·40; p=0·71). Thus our primary hypothesis was not proven. Median progression-free survival was 18·3 months (95% CI 11·6–25·0) in patients receiving whole brain radiotherapy, and 11·9 months (7·3–16·5; p=0·14) in those not receiving whole brain radiotherapy. Treatment-related neurotoxicity in patients with sustained complete response was more common in patients receiving whole brain radiotherapy (22/45, 49% by clinical assessment; 35/49, 71% by neuroradiology) than in those who did not (9/34, 26%; 16/35, 46%). Interpretation No significant difference in overall survival was recorded when whole brain radiotherapy was omitted from first-line chemotherapy in patients with newly diagnosed primary CNS lymphoma, but our primary hypothesis was not proven. The progression-free survival benefit afforded by whole brain radiotherapy has to be weighed against the increased risk of neurotoxicity in long-term survivors. Funding German Cancer Aid.
505 citations
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TL;DR: Human body burdens of these chemicals are detected with high prevalence, and concentrations in young children, a group particularly sensitive to exogenous insults, are typically higher, indicating the need to decrease exposure to these compounds.
Abstract: Components used in plastics, such as phthalates, bisphenol A (BPA), polybrominated diphenyl ethers (PBDE) and tetrabromobisphenol A (TBBPA), are detected in humans. In addition to their utility in plastics, an inadvertent characteristic of these chemicals is the ability to alter the endocrine system. Phthalates function as anti-androgens while the main action attributed to BPA is oestrogen-like activity. PBDE and TBBPA have been shown to disrupt thyroid hormone homeostasis while PBDEs also exhibit anti-androgen action. Experimental investigations in animals indicate a wide variety of effects associated with exposure to these compounds, causing concern regarding potential risk to human health. For example, the spectrum of effects following perinatal exposure of male rats to phthalates has remarkable similarities to the testicular dysgenesis syndrome in humans. Concentrations of BPA in the foetal mouse within the range of unconjugated BPA levels observed in human foetal blood have produced effects in animal experiments. Finally, thyroid hormones are essential for normal neurological development and reproductive function. Human body burdens of these chemicals are detected with high prevalence, and concentrations in young children, a group particularly sensitive to exogenous insults, are typically higher, indicating the need to decrease exposure to these compounds.
505 citations
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University of Michigan1, University of Cologne2, Harvard University3, Medical University of Vienna4, University of Marburg5, Hacettepe University6, Tel Aviv University7, Rabin Medical Center8, University of Freiburg9, Technische Universität München10, Dokuz Eylül University11, Charité12, Hannover Medical School13, State University of New York Upstate Medical University14, University of Rochester15
TL;DR: These findings, together with the zebrafish model of human nephrotic syndrome generated by plce1 knockdown, open new inroads into pathophysiology and treatment mechanisms of nephrotsic syndrome.
Abstract: Nephrotic syndrome, a malfunction of the kidney glomerular filter, leads to proteinuria, edema and, in steroid-resistant nephrotic syndrome, end-stage kidney disease. Using positional cloning, we identified mutations in the phospholipase C epsilon gene (PLCE1) as causing early-onset nephrotic syndrome with end-stage kidney disease. Kidney histology of affected individuals showed diffuse mesangial sclerosis (DMS). Using immunofluorescence, we found PLCepsilon1 expression in developing and mature glomerular podocytes and showed that DMS represents an arrest of normal glomerular development. We identified IQ motif-containing GTPase-activating protein 1 as a new interaction partner of PLCepsilon1. Two siblings with a missense mutation in an exon encoding the PLCepsilon1 catalytic domain showed histology characteristic of focal segmental glomerulosclerosis. Notably, two other affected individuals responded to therapy, making this the first report of a molecular cause of nephrotic syndrome that may resolve after therapy. These findings, together with the zebrafish model of human nephrotic syndrome generated by plce1 knockdown, open new inroads into pathophysiology and treatment mechanisms of nephrotic syndrome.
505 citations
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Royal Free Hospital1, Institut Gustave Roussy2, University of Perugia3, University of Turin4, Imperial College London5, University of Milan6, University of Bern7, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico8, Memorial Sloan Kettering Cancer Center9, University of Marburg10, Autonomous University of Barcelona11, Erasmus University Rotterdam12, Uppsala University13, University of Genoa14, Churchill Hospital15, Kyushu University16, National Institutes of Health17, National and Kapodistrian University of Athens18, University of Reims Champagne-Ardenne19, University of Copenhagen20, Medical University of Silesia21, Curie Institute22, Aberdeen Royal Infirmary23, University College Dublin24, Charité25, Charles University in Prague26, University College London27, University of Freiburg28, Peking Union Medical College29
TL;DR: PCs are complex tumors which require a multidisciplinary approach and long-term follow-up, and may be considered as first-line systemic antiproliferative treatment in unresectable PCs, particularly of low-grade TC and AC.
505 citations
Authors
Showing all 30787 results
Name | H-index | Papers | Citations |
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JoAnn E. Manson | 270 | 1819 | 258509 |
Yi Chen | 217 | 4342 | 293080 |
David J. Hunter | 213 | 1836 | 207050 |
Raymond J. Dolan | 196 | 919 | 138540 |
John P. A. Ioannidis | 185 | 1311 | 193612 |
Stefan Schreiber | 178 | 1233 | 138528 |
Kenneth C. Anderson | 178 | 1138 | 126072 |
Eric J. Nestler | 178 | 748 | 116947 |
Klaus Rajewsky | 154 | 504 | 88793 |
Charles B. Nemeroff | 149 | 979 | 90426 |
Andreas Pfeiffer | 149 | 1756 | 131080 |
Rinaldo Bellomo | 147 | 1714 | 120052 |
Jean Bousquet | 145 | 1288 | 96769 |
Christopher Hill | 144 | 1562 | 128098 |
Holger J. Schünemann | 141 | 810 | 113169 |