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Institution

Charité

HealthcareBerlin, 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.


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Journal ArticleDOI
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

Journal ArticleDOI
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

Journal ArticleDOI
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

Journal ArticleDOI
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

Journal ArticleDOI
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

NameH-indexPapersCitations
JoAnn E. Manson2701819258509
Yi Chen2174342293080
David J. Hunter2131836207050
Raymond J. Dolan196919138540
John P. A. Ioannidis1851311193612
Stefan Schreiber1781233138528
Kenneth C. Anderson1781138126072
Eric J. Nestler178748116947
Klaus Rajewsky15450488793
Charles B. Nemeroff14997990426
Andreas Pfeiffer1491756131080
Rinaldo Bellomo1471714120052
Jean Bousquet145128896769
Christopher Hill1441562128098
Holger J. Schünemann141810113169
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202339
2022317
20214,865
20204,577
20194,042
20183,718