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Hospital General Universitario Gregorio Marañón

HealthcareMadrid, 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.


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Journal ArticleDOI
TL;DR: Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipILimumab alone, and in patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone.
Abstract: The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with PD-L1–negative tumors, progression-free survival was longer with the combination therapy than with nivolumab alone (11.2 months [95% CI, 8.0 to not reached] vs. 5.3 months [95% CI, 2.8 to 7.1]). Treatment-related adverse events of grade 3 or 4 occurred in 16.3% of the patients in the nivolumab group, 55.0% of those in the nivolumab-plus-ipilimumab group, and 27.3% of those in the ipilimumab group. CONCLUSIONS Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1–negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 ClinicalTrials.gov number, NCT01844505.)

6,318 citations

Journal ArticleDOI
TL;DR: Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer (NSCLC) with activating EGFR mutations as discussed by the authors.
Abstract: Summary Background Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer (NSCLC) with activating EGFR mutations. We aimed to assess the safety and efficacy of erlotinib compared with standard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC. Methods We undertook the open-label, randomised phase 3 EURTAC trial at 42 hospitals in France, Italy, and Spain. Eligible participants were adults (>18 years) with NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease (neoadjuvant or adjuvant chemotherapy ending ≥6 months before study entry was allowed). We randomly allocated participants (1:1) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of standard intravenous chemotherapy of cisplatin 75 mg/m 2 on day 1 plus docetaxel (75 mg/m 2 on day 1) or gemcitabine (1250 mg/m 2 on days 1 and 8). Carboplatin (AUC 6 with docetaxel 75 mg/m 2 or AUC 5 with gemcitabine 1000 mg/m 2 ) was allowed in patients unable to have cisplatin. Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status (0 vs 1 vs 2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed safety in all patients who received study drug (≥1 dose). This study is registered with ClinicalTrials.gov, number NCT00446225. Findings Between Feb 15, 2007, and Jan 4, 2011, 174 patients with EGFR mutations were enrolled. One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy. The preplanned interim analysis showed that the study met its primary endpoint; enrolment was halted, and full evaluation of the results was recommended. At data cutoff (Jan 26, 2011), median PFS was 9·7 months (95% CI 8·4-12·3) in the erlotinib group, compared with 5·2 months (4·5–5·8) in the standard chemotherapy group (hazard ratio 0·37, 95% CI 0·25–0·54; p vs none of 82 patients in the chemotherapy group), neutropenia (none vs 18 [22%]), anaemia (one [1%] vs three [4%]), and increased amino-transferase concentrations (two [2%] vs 0). Five (6%) patients on erlotinib had treatment-related severe adverse events compared with 16 patients (20%) on chemotherapy. One patient in the erlotinib group and two in the standard chemotherapy group died from treatment-related causes. Interpretation Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors. Funding Spanish Lung Cancer Group, Roche Farma, Hoffmann-La Roche, and Red Tematica de Investigacion Cooperativa en Cancer.

4,791 citations

Journal ArticleDOI
TL;DR: In this article, the authors used a continuous wave Doppler (Doppler) to detect aortic regurgitation, MS mitral stenosis, MVA mitral valve area, DP pressure gradient, RV right ventricle, RVOT right ventricular outflow tract, SV stroke volume.
Abstract: Abbreviations: AR aortic regurgitation, AS aortic stenosis, AVA aortic valve area, CSA cross sectional area, CWD continuous wave Doppler, D diameter, HOCM hypertrophic obstructive cardiomyopathy, LV left ventricle, LVOT left ventricular outflow tract, MR mitral regurgitation, MS mitral stenosis, MVA mitral valve area, DP pressure gradient, RV right ventricle, RVOT right ventricular outflow tract, SV stroke volume, TEE transesophageal echocardiography, T1/2 pressure half-time, TR tricuspid regurgitation, TS tricuspid stenosis, V velocity, VSD ventricular septal defect, VTI velocity time integral

2,163 citations

Journal ArticleDOI
Hreinn Stefansson1, Hreinn Stefansson2, Roel A. Ophoff2, Roel A. Ophoff3, Roel A. Ophoff4, Stacy Steinberg1, Stacy Steinberg2, Ole A. Andreassen5, Sven Cichon6, Dan Rujescu7, Thomas Werge8, Olli Pietilainen9, Ole Mors10, Preben Bo Mortensen11, Engilbert Sigurdsson12, Omar Gustafsson1, Mette Nyegaard11, Annamari Tuulio-Henriksson13, Andres Ingason1, Thomas Hansen8, Jaana Suvisaari13, Jouko Lönnqvist13, Tiina Paunio, Anders D. Børglum11, Anders D. Børglum10, Annette M. Hartmann7, Anders Fink-Jensen8, Merete Nordentoft14, David M. Hougaard, Bent Nørgaard-Pedersen, Yvonne Böttcher1, Jes Olesen15, René Breuer16, Hans-Jürgen Möller7, Ina Giegling7, Henrik B. Rasmussen8, Sally Timm8, Manuel Mattheisen6, István Bitter17, János Réthelyi17, Brynja B. Magnusdottir12, Thordur Sigmundsson12, Pall I. Olason1, Gisli Masson1, Jeffrey R. Gulcher1, Magnús Haraldsson12, Ragnheidur Fossdal1, Thorgeir E. Thorgeirsson1, Unnur Thorsteinsdottir12, Unnur Thorsteinsdottir1, Mirella Ruggeri18, Sarah Tosato18, Barbara Franke19, Eric Strengman3, Lambertus A. Kiemeney19, Ingrid Melle5, Srdjan Djurovic5, Lilia I. Abramova20, Kaleda Vg20, Julio Sanjuán21, Rosa de Frutos21, Elvira Bramon22, Evangelos Vassos22, Gillian Fraser23, Ulrich Ettinger22, Marco Picchioni22, Nicholas Walker, T. Toulopoulou22, Anna C. Need24, Dongliang Ge24, Joeng Lim Yoon4, Kevin V. Shianna24, Nelson B. Freimer4, Rita M. Cantor4, Robin M. Murray22, Augustine Kong1, Vera Golimbet20, Angel Carracedo25, Celso Arango26, Javier Costas, Erik G. Jönsson27, Lars Terenius27, Ingrid Agartz27, Hannes Petursson12, Markus M. Nöthen6, Marcella Rietschel16, Paul M. Matthews28, Pierandrea Muglia29, Leena Peltonen9, David St Clair23, David Goldstein24, Kari Stefansson12, Kari Stefansson1, David A. Collier30, David A. Collier22 
06 Aug 2009-Nature
TL;DR: Findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.
Abstract: Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the 'genomic disorders', have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.

1,625 citations

Journal ArticleDOI
TL;DR: Patients with pCR after chemoradiation have better long-term outcome than do those without pCR, and pCR might be indicative of a prognostically favourable biological tumour profile with less propensity for local or distant recurrence and improved survival.
Abstract: Summary Background Locally advanced rectal cancer is usually treated with preoperative chemoradiation. After chemoradiation and surgery, 15–27% of the patients have no residual viable tumour at pathological examination, a pathological complete response (pCR). This study established whether patients with pCR have better long-term outcome than do those without pCR. Methods In PubMed, Medline, and Embase we identified 27 articles, based on 17 different datasets, for long-term outcome of patients with and without pCR. 14 investigators agreed to provide individual patient data. All patients underwent chemoradiation and total mesorectal excision. Primary outcome was 5-year disease-free survival. Kaplan-Meier survival functions were computed and hazard ratios (HRs) calculated, with the Cox proportional hazards model. Subgroup analyses were done to test for effect modification by other predicting factors. Interstudy heterogeneity was assessed for disease-free survival and overall survival with forest plots and the Q test. Findings 484 of 3105 included patients had a pCR. Median follow-up for all patients was 48 months (range 0–277). 5-year crude disease-free survival was 83·3% (95% CI 78·8–87·0) for patients with pCR (61/419 patients had disease recurrence) and 65·6% (63·6–68·0) for those without pCR (747/2263; HR 0·44, 95% CI 0·34–0·57; p Q test and forest plots did not suggest significant interstudy variation. The adjusted HR for pCR for failure was 0·54 (95% CI 0·40–0·73), indicating that patients with pCR had a significantly increased probability of disease-free survival. The adjusted HR for disease-free survival for administration of adjuvant chemotherapy was 0·91 (95% CI 0·73–1·12). The effect of pCR on disease-free survival was not modified by other prognostic factors. Interpretation Patients with pCR after chemoradiation have better long-term outcome than do those without pCR. pCR might be indicative of a prognostically favourable biological tumour profile with less propensity for local or distant recurrence and improved survival. Funding None.

1,459 citations


Authors

Showing all 12014 results

NameH-indexPapersCitations
Enric Carreras5723510427
Didier Blaise5759013905
Esperanza Naredo5622910303
Peter Dreger5642312241
Salut Brunet5630610622
Manuel Fresno552629894
Manuel Praga5533813573
Francisco Fernández-Avilés5549016439
Ibrahim Yakoub-Agha5548911649
Annamaria Iagnocco5432611547
Valeria Caso5423936440
Pilar Guallar-Castillón5422112407
Marco Solmi5426510773
Rafael Bañares5422910416
Carmen Martinez5313610885
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202317
202246
20211,186
20201,045
2019898
2018637