Institution
Hospital Universitario La Paz
Healthcare•Madrid, Spain•
About: Hospital Universitario La Paz is a healthcare organization based out in Madrid, Spain. It is known for research contribution in the topics: Population & Medicine. The organization has 8960 authors who have published 11499 publications receiving 191509 citations.
Topics: Population, Medicine, Cancer, Transplantation, Haemophilia
Papers published on a yearly basis
Papers
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TL;DR: The immunoreactivity of E‐ and P‐cadherin, β‐ and γ‐catenin, and p120ctn in premalignant and malignant endometrial lesions and to correlate their membranous expression with clinicopathological features was evaluated.
Abstract: Abnormal expression of cadherins and catenins plays a critical role in the initiation and progression of multiple human tumours. This study aimed to evaluate the immunoreactivity of E- and P-cadherin, beta- and gamma-catenin, and p120ctn in premalignant and malignant endometrial lesions and to correlate their membranous expression with clinicopathological features. In addition, we examined whether or not LOH and promoter hypermethylation of the CDH1 gene were associated with E-cadherin expression and clinicopathological variables. Finally, we studied the frequency of beta-catenin mutations in premalignant endometrial lesions. Immunohistochemical staining was performed in 21 atypical endometrial hyperplasias (AEHs), 95 endometrioid carcinomas (EECs), and 33 non-endometrioid carcinomas (NEECs). Reduced E-cadherin expression was observed in 57.8% of the cases, being more frequent in NEECs (87.1%, p = 0.001) and carcinomas of more advanced stage (85.7% of stage III-IV carcinomas, p = 0.01). LOH of CDH1 gene was found in 57.1% of NEECs but only in 22.5% of EECs (p = 0.011) and showed a trend towards association with reduced E-cadherin expression (p = 0.089). CDH1 promoter hypermethylation was found in 21.2% of endometrial carcinomas but was not associated with clinicopathological or immunohistochemical variables. Reduced expression of beta- and gamma-catenin and p120ctn was found in 76.1%, 94.3%, and 63.6% of the cases, respectively, being more frequent in lesions with reduced E-cadherin expression. In addition, beta-catenin, but not gamma-catenin or p120ctn expression, was associated with the histology of the lesion, since it was reduced in 35% of AEHs, 80.3% of EECs, and 96.9% of NEECs (p = 0.000). Mutations in exon 3 of the beta-catenin gene, associated with beta-catenin nuclear expression, were detected in 3 (14.0%) AEH, a frequency similar to that previously reported in this series of ECs. Finally, upregulation of P-cadherin was observed in 28.6% of cases. This alteration was associated with the histology of the lesion, since it was found in 9.5% of AEHs, 27.7% of EECs, and 46.2% of NEECs (p = 0.021).
127 citations
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TL;DR: 1,25(OH)2D3 has protective effects against CRC through the regulation of stromal fibroblasts, and treatment of patients with CRC with VDR agonists could be explored even in the absence of VDR expression in carcinoma cells.
Abstract: Objective Colorectal cancer (CRC) is a major health concern. Vitamin D deficiency is associated with high CRC incidence and mortality, suggesting a protective effect of vitamin D against this disease. Given the strong influence of tumour stroma on cancer progression, we investigated the potential effects of the active vitamin D metabolite 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) on CRC stroma. Design Expression of vitamin D receptor (VDR) and two 1,25(OH) 2 D 3 target genes was analysed in 658 patients with CRC with prolonged clinical follow-up. 1,25(OH) 2 D 3 effects on primary cultures of patient-derived colon normal fibroblasts (NFs) and cancer-associated fibroblasts (CAFs) were studied using collagen gel contraction and migration assays and global gene expression analyses. Publicly available data sets (n=877) were used to correlate the 1,25(OH) 2 D 3 -associated gene signature in CAFs with CRC outcome. Results High VDR expression in tumour stromal fibroblasts was associated with better overall survival (OS) and progression-free survival in CRC, independently of its expression in carcinoma cells. 1,25(OH) 2 D 3 inhibited the protumoural activation of NFs and CAFs and imposed in CAFs a 1,25(OH) 2 D 3 -associated gene signature that correlated with longer OS and disease-free survival in CRC. Furthermore, expression of two genes from the signature, CD82 and S100A4, correlated with stromal VDR expression and clinical outcome in our cohort of patients with CRC. Conclusions 1,25(OH) 2 D 3 has protective effects against CRC through the regulation of stromal fibroblasts. Accordingly, expression of VDR and 1,25(OH) 2 D 3 -associated gene signature in stromal fibroblasts predicts a favourable clinical outcome in CRC. Therefore, treatment of patients with CRC with VDR agonists could be explored even in the absence of VDR expression in carcinoma cells.
127 citations
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Hebrew University of Jerusalem1, Charité2, National and Kapodistrian University of Athens3, Shaare Zedek Medical Center4, University of Bern5, The Chinese University of Hong Kong6, University of Ioannina7, University of Basel8, Katholieke Universiteit Leuven9, Mater Misericordiae University Hospital10, University of Liège11, Agostino Gemelli University Polyclinic12, Aarhus University Hospital13, Hospital Universitario La Paz14, University of Texas MD Anderson Cancer Center15, Cleveland Clinic16, Royal Berkshire Hospital17, Utrecht University18
TL;DR: Significantly more treatment limitations occurred in the 2015-2016 cohort compared with data reported from the same ICUs in 1999-2000, limitations in life-prolonging therapies occurred significantly more frequently and death without limitations in Life Prolonging Therapy occurred significantly less frequently.
Abstract: Importance End-of-life decisions occur daily in intensive care units (ICUs) around the world, and these practices could change over time. Objective To determine the changes in end-of-life practices in European ICUs after 16 years. Design, Setting, and Participants Ethicus-2 was a prospective observational study of 22 European ICUs previously included in the Ethicus-1 study (1999-2000). During a self-selected continuous 6-month period at each ICU, consecutive patients who died or had any limitation of life-sustaining therapy from September 2015 until October 2016 were included. Patients were followed up until death or until 2 months after the first treatment limitation decision. Exposures Comparison between the 1999-2000 cohort vs 2015-2016 cohort. Main Outcomes and Measures End-of-life outcomes were classified into 5 mutually exclusive categories (withholding of life-prolonging therapy, withdrawing of life-prolonging therapy, active shortening of the dying process, failed cardiopulmonary resuscitation [CPR], brain death). The primary outcome was whether patients received any treatment limitations (withholding or withdrawing of life-prolonging therapy or shortening of the dying process). Outcomes were determined by senior intensivists. Results Of 13 625 patients admitted to participating ICUs during the 2015-2016 study period, 1785 (13.1%) died or had limitations of life-prolonging therapies and were included in the study. Compared with the patients included in the 1999-2000 cohort (n = 2807), the patients in 2015-2016 cohort were significantly older (median age, 70 years [interquartile range {IQR}, 59-79] vs 67 years [IQR, 54-75];P Conclusions and Relevance Among patients who had treatment limitations or died in 22 European ICUs in 2015-2016, compared with data reported from the same ICUs in 1999-2000, limitations in life-prolonging therapies occurred significantly more frequently and death without limitations in life-prolonging therapies occurred significantly less frequently. These findings suggest a shift in end-of-life practices in European ICUs, but the study is limited in that it excluded patients who survived ICU hospitalization without treatment limitations.
127 citations
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TL;DR: Dupilumab reduced severe exacerbation rates, improved FEV1 and asthma control, and suppressed type 2 inflammatory biomarkers in uncontrolled, moderate-to-severe asthma patients with or without evidence of allergic asthma, highlighting the key role of interleukin-4 and interleucin-13 in airway inflammation.
127 citations
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Rambam Health Care Campus1, Claude Bernard University Lyon 12, United Arab Emirates University3, University of Bologna4, University of Udine5, Scripps Health6, University of Milan7, University of Pisa8, Riverside University Health System - Medical Center9, University of Turin10, Cambridge University Hospitals NHS Foundation Trust11, National and Kapodistrian University of Athens12, Immanuel Kant Baltic Federal University13, University of Colorado Denver14, Hospital Universitario La Paz15, Universidad Nacional de Asunción16, Catholic University of the Sacred Heart17, Tan Tock Seng Hospital18, First Faculty of Medicine, Charles University in Prague19
TL;DR: A task force of experts met in Bertinoro, Italy, on June 28, 2018, for a specialist multidisciplinary consensus conference under the auspices of the World Society of Emergency Surgery (WSES) and the Surgical Infection Society Europe (SIS-E).
Abstract: Skin and soft-tissue infections (SSTIs) encompass a variety of pathological conditions that involve the skin and underlying subcutaneous tissue, fascia, or muscle, ranging from simple superficial infections to severe necrotizing infections. SSTIs are a frequent clinical problem in surgical departments. In order to clarify key issues in the management of SSTIs, a task force of experts met in Bertinoro, Italy, on June 28, 2018, for a specialist multidisciplinary consensus conference under the auspices of the World Society of Emergency Surgery (WSES) and the Surgical Infection Society Europe (SIS-E). The multifaceted nature of these infections has led to a collaboration among general and emergency surgeons, intensivists, and infectious disease specialists, who have shared these clinical practice recommendations.
127 citations
Authors
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Name | H-index | Papers | Citations |
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Jaakko Tuomilehto | 115 | 1285 | 210682 |
Vincent Soriano | 87 | 762 | 34084 |
Lina Badimon | 86 | 682 | 35774 |
Francisco J. Blanco | 84 | 789 | 33319 |
Michael A. Gatzoulis | 82 | 478 | 32562 |
Jose Lopez-Sendon | 81 | 460 | 41809 |
Victor Moreno | 80 | 635 | 31511 |
Joaquín Dopazo | 75 | 396 | 24790 |
Fernando Rodríguez-Artalejo | 74 | 512 | 23296 |
José R. Banegas | 74 | 421 | 28249 |
Michael Becker | 72 | 317 | 18189 |
Gianfranco Ferraccioli | 70 | 402 | 26515 |
Maria-Victoria Mateos | 66 | 480 | 24278 |
Manuel Romero-Gómez | 64 | 420 | 19006 |
Eulogio García | 63 | 270 | 15354 |