Institution
Hospital General Universitario Gregorio Marañón
Healthcare•Madrid, Spain•
About: Hospital General Universitario Gregorio Marañón is a healthcare organization based out in Madrid, Spain. It is known for research contribution in the topics: Population & Transplantation. The organization has 11975 authors who have published 12386 publications receiving 244847 citations.
Topics: Population, Transplantation, Medicine, Myocardial infarction, Cancer
Papers published on a yearly basis
Papers
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TL;DR: The available evidence for the use of AFS and their impact on health economics is reviewed, and the AFS program, the successive steps followed and the main difficulties found are described.
Abstract: During recent years, inappropriate antifungal use has contributed to the global increase in antifungal resistance and has played a role in the shift in the aetiology of invasive fungal infections. Moreover, overuse of antifungals may also lead to higher toxicity associated with unnecessary medication exposure and to increased healthcare costs. Antifungal stewardship (AFS) programmes consist of multidisciplinary interventions, led by specialists in infectious disease, microbiology and pharmacy that cooperate and communicate with the major prescribing departments in order to optimise antifungal therapies evaluating the indication, dose, streamlining and duration. Herein, we review the available evidence for the use of AFS and their impact on health economics. We also describe our AFS program, the successive steps we followed and the main difficulties we found.
78 citations
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TL;DR: Cognitive impairment in first-episode early-onset psychosis (FE-EOP) soon after their stabilisation seems to be non-specific to differential diagnosis and potential differences according to specific diagnostic sub-groups of patients are searched for.
Abstract: The aims of this study were to examine the nature and extent of cognitive impairment in first-episode early-onset psychosis (FE-EOP) soon after their stabilisation and to search for potential differences according to specific diagnostic sub-groups of patients. As part of a Spanish multicentre longitudinal study, 107 FE-EOP patients and 98 healthy controls were assessed on the following cognitive domains: attention, working memory, executive functioning, and verbal learning and memory. Three diagnostic categories were established in the patient sample: schizophrenia (n = 36), bipolar disorder (n = 19), and other psychosis (n = 52). Patients performed significantly worse than controls in all cognitive domains. The three diagnostic sub-groups did not differ in terms of impaired/preserved cognitive functions or degree of impairment. FE-EOP patients show significant cognitive impairment that, during this early phase, seems to be non-specific to differential diagnosis.
78 citations
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Autonomous University of Barcelona1, University of Zurich2, University of Münster3, University of Freiburg4, University of Murcia5, Spanish National Research Council6, Ikerbasque7, University of the Basque Country8, Hospital Clínico San Carlos9, Hospital General Universitario Gregorio Marañón10, University of Barcelona11, University of Queensland12, University of Toronto13
TL;DR: Results point to a role of IL1B and the NLRP3 inflammasome as prognostic biomarker and potential therapeutic target, respectively, in patients with primary progressive multiple sclerosis.
Abstract: Primary progressive multiple sclerosis is a poorly understood disease entity with no specific prognostic biomarkers and scarce therapeutic options. We aimed to identify disease activity biomarkers in multiple sclerosis by performing an RNA sequencing approach in peripheral blood mononuclear cells from a discovery cohort of 44 untreated patients with multiple sclerosis belonging to different clinical forms and activity phases of the disease, and 12 healthy control subjects. A validation cohort of 58 patients with multiple sclerosis and 26 healthy control subjects was included in the study to replicate the RNA sequencing findings. The RNA sequencing revealed an interleukin 1 beta (IL1B) signature in patients with primary progressive multiple sclerosis. Subsequent immunophenotyping pointed to blood monocytes as responsible for the IL1B signature observed in this group of patients. Functional experiments at baseline measuring apoptosis-associated speck-like protein containing a CARD (ASC) speck formation showed that the NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome was overactive in monocytes from patients with primary progressive multiple sclerosis, and canonical NLRP3 inflammasome activation with a combination of ATP plus lipopolysaccharide was associated with increased IL1B production in this group of patients. Primary progressive multiple sclerosis patients with high IL1B gene expression levels in peripheral blood mononuclear cells progressed significantly faster compared to patients with low IL1B levels based on the time to reach an EDSS of 6.0 and the Multiple Sclerosis Severity Score. In agreement with peripheral blood findings, both NLRP3 and IL1B expression in brain tissue from patients with primary progressive multiple sclerosis was mainly restricted to cells of myeloid lineage. Treatment of mice with a specific NLRP3 inflammasome inhibitor attenuated established experimental autoimmune encephalomyelitis disease severity and improved CNS histopathology. NLRP3 inflammasome-specific inhibition was also effective in reducing axonal damage in a model of lipopolysaccharide-neuroinflammation using organotypic cerebellar cultures. Altogether, these results point to a role of IL1B and the NLRP3 inflammasome as prognostic biomarker and potential therapeutic target, respectively, in patients with primary progressive multiple sclerosis.
78 citations
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TL;DR: Her2 inhibition can enhance or restore ER expression with parallel Bcl2 upregulation, representing an ER-dependent survival mechanism potentially leading to anti-HER2 resistance.
Abstract: Purpose: To investigate the direct effect and therapeutic consequences of epidermal growth factor receptor 2 (HER2)-targeting therapy on expression of estrogen receptor (ER) and Bcl2 in preclinical models and clinical tumor samples. Experimental design: Archived xenograft tumors from two preclinical models (UACC812 and MCF7/HER2-18) treated with ER and HER2-targeting therapies and also HER2+ clinical breast cancer specimens collected in a lapatinib neoadjuvant trial (baseline and week 2 posttreatment) were used. Expression levels of ER and Bcl2 were evaluated by immunohistochemistry and Western blot analysis. The effects of Bcl2 and ER inhibition, by ABT-737 and fulvestrant, respectively, were tested in parental versus lapatinib-resistant UACC812 cells in vitro . Results: Expression of ER and Bcl2 was significantly increased in xenograft tumors with acquired resistance to anti-HER2 therapy compared with untreated tumors in both preclinical models (UACC812: ER P = 0.0014; Bcl2 P P = 0.0007; Bcl2 P = 0.0306). In the neoadjuvant clinical study, lapatinib treatment for 2 weeks was associated with parallel upregulation of ER and Bcl2 (Spearman coefficient: 0.70; P = 0.0002). Importantly, 18% of tumors originally ER-negative (ER − ) converted to ER + upon anti-HER2 therapy. In ER − /HER2 + MCF7/HER2-18 xenografts, ER reexpression was primarily observed in tumors responding to potent combination of anti-HER2 drugs. Estrogen deprivation added to this anti-HER2 regimen significantly delayed tumor progression ( P = 0.018). In the UACC812 cells, fulvestrant, but not ABT-737, was able to completely inhibit anti–HER2-resistant growth ( P Conclusions: HER2 inhibition can enhance or restore ER expression with parallel Bcl2 upregulation, representing an ER-dependent survival mechanism potentially leading to anti-HER2 resistance. Clin Cancer Res; 21(17); 3995–4003. ©2015 AACR .
78 citations
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TL;DR: It is shown that LFA-1 induces a potent and transient increase in the activity of the small GTPase Rac-1 in T cells and that T cells with a sustained Rac activity have impaired capacity to elongate onto ICAM-1.
78 citations
Authors
Showing all 12014 results
Name | H-index | Papers | Citations |
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David H. Adams | 155 | 1613 | 117783 |
Stefanie Dimmeler | 147 | 574 | 81658 |
Stuart J. Pocock | 145 | 684 | 143547 |
M. I. Martínez | 134 | 1251 | 79885 |
Guy A. Rouleau | 129 | 884 | 65892 |
Jose L. Jimenez | 124 | 654 | 64226 |
Antoni Torres | 120 | 1238 | 65049 |
Paul P. Tak | 112 | 591 | 57689 |
Luis A. Diaz | 111 | 596 | 75036 |
Frans Van de Werf | 109 | 747 | 63537 |
José Luis Zamorano | 105 | 695 | 133396 |
Francisco Sánchez-Madrid | 102 | 527 | 43418 |
Francesco Locatelli | 99 | 820 | 42454 |
Roberto M. Lang | 96 | 823 | 56638 |
Carlos Simón | 95 | 589 | 31147 |