Showing papers by "University of Barcelona published in 2007"
University of Manchester1, University of Barcelona2, St George's Hospital3, University of Marburg4, University of Texas Health Science Center at San Antonio5, Imperial College London6, University of Modena and Reggio Emilia7, University of Michigan8, Hokkaido University9, University of British Columbia10
TL;DR: It is recommended that spirometry is required for the clinical diagnosis of COPD to avoid misdiagnosis and to ensure proper evaluation of severity of airflow limitation.
Abstract: Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.
17,023 citations
McMaster University1, Northwestern University2, University of Texas Health Science Center at San Antonio3, Johns Hopkins University4, University of Mississippi5, University of Utah6, LDS Hospital7, Centers for Disease Control and Prevention8, Baylor College of Medicine9, United States Department of Veterans Affairs10, Winthrop-University Hospital11, Stony Brook University12, University of Barcelona13
TL;DR: This work presents a meta-analyses of the immune system’s response to chronic obstructive pulmonary disease and shows clear patterns of decline in the immune systems of elderly patients with compromised immune systems.
Abstract: Lionel A. Mandell, Richard G. Wunderink, Antonio Anzueto, John G. Bartlett, G. Douglas Campbell, Nathan C. Dean, Scott F. Dowell, Thomas M. File, Jr. Daniel M. Musher, Michael S. Niederman, Antonio Torres, and Cynthia G. Whitney McMaster University Medical School, Hamilton, Ontario, Canada; Northwestern University Feinberg School of Medicine, Chicago, Illinois; University of Texas Health Science Center and South Texas Veterans Health Care System, San Antonio, and Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi School of Medicine, Jackson; Division of Pulmonary and Critical Care Medicine, LDS Hospital, and University of Utah, Salt Lake City, Utah; Centers for Disease Control and Prevention, Atlanta, Georgia; Northeastern Ohio Universities College of Medicine, Rootstown, and Summa Health System, Akron, Ohio; State University of New York at Stony Brook, Stony Brook, and Department of Medicine, Winthrop University Hospital, Mineola, New York; and Cap de Servei de Pneumologia i Allergia Respiratoria, Institut Clinic del Torax, Hospital Clinic de Barcelona, Facultat de Medicina, Universitat de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer, CIBER CB06/06/0028, Barcelona, Spain.
5,558 citations
Ewan Birney, John A. Stamatoyannopoulos1, Anindya Dutta2, Roderic Guigó3 +317 more•Institutions (44)
TL;DR: Functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project are reported, providing convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts.
Abstract: We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
5,091 citations
Istanbul University1, University of Bergen2, Stavanger University Hospital3, King's College London4, Newcastle University5, Pierre-and-Marie-Curie University6, Juntendo University7, University of New South Wales8, University of California, Los Angeles9, Mayo Clinic10, McGill University11, Rush University Medical Center12, Tel Aviv University13, French Institute of Health and Medical Research14, University of Louisville15, Icahn School of Medicine at Mount Sinai16, Innsbruck Medical University17, University of Lisbon18, University of Barcelona19
TL;DR: Clinical diagnostic criteria for probable and possible PD‐D are proposed, characterized by impairment in attention, memory, executive and visuo‐spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent.
Abstract: Dementia has been increasingly more recognized to be a common feature in patients with Parkinson's disease (PD), especially in old age. Specific criteria for the clinical diagnosis of dementia associated with PD (PD-D), however, have been lacking. A Task Force, organized by the Movement Disorder Study, was charged with the development of clinical diagnostic criteria for PD-D. The Task Force members were assigned to sub-committees and performed a systematic review of the literature, based on pre-defined selection criteria, in order to identify the epidemiological, clinical, auxillary, and pathological features of PD-D. Clinical diagnostic criteria were then developed based on these findings and group consensus. The incidence of dementia in PD is increased up to six times, point-prevelance is close to 30%, older age and akinetic-rigid form are associated with higher risk. PD-D is characterized by impairment in attention, memory, executive and visuo-spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent. There are no specific ancillary investigations for the diagnosis; the main pathological correlate is Lewy body-type degeneration in cerebral cortex and limbic structures. Based on the characteristic features associated with this condition, clinical diagnostic criteria for probable and possible PD-D are proposed.
2,454 citations
TL;DR: These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution.
Abstract: Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
2,057 citations
TL;DR: The parmbsc0 force field as mentioned in this paper is a refinement of the AMBER parm99 force field, where emphasis has been made on the correct representation of the a/g concerted rotation in nucleic acids (NAs).
1,982 citations
TL;DR: A modified version of the Celera assembler is developed to facilitate the identification and comparison of alternate alleles within this individual diploid genome, and a novel haplotype assembly strategy is used, able to span 1.5 Gb of genome sequence in segments >200 kb, providing further precision to the diploids nature of the genome.
Abstract: Presented here is a genome sequence of an individual human. It was produced from ∼32 million random DNA fragments, sequenced by Sanger dideoxy technology and assembled into 4,528 scaffolds, comprising 2,810 million bases (Mb) of contiguous sequence with approximately 7.5-fold coverage for any given region. We developed a modified version of the Celera assembler to facilitate the identification and comparison of alternate alleles within this individual diploid genome. Comparison of this genome and the National Center for Biotechnology Information human reference assembly revealed more than 4.1 million DNA variants, encompassing 12.3 Mb. These variants (of which 1,288,319 were novel) included 3,213,401 single nucleotide polymorphisms (SNPs), 53,823 block substitutions (2–206 bp), 292,102 heterozygous insertion/deletion events (indels)(1–571 bp), 559,473 homozygous indels (1–82,711 bp), 90 inversions, as well as numerous segmental duplications and copy number variation regions. Non-SNP DNA variation accounts for 22% of all events identified in the donor, however they involve 74% of all variant bases. This suggests an important role for non-SNP genetic alterations in defining the diploid genome structure. Moreover, 44% of genes were heterozygous for one or more variants. Using a novel haplotype assembly strategy, we were able to span 1.5 Gb of genome sequence in segments >200 kb, providing further precision to the diploid nature of the genome. These data depict a definitive molecular portrait of a diploid human genome that provides a starting point for future genome comparisons and enables an era of individualized genomic information.
1,843 citations
Duke University1, University of Lausanne2, University of Zurich3, Vita-Salute San Raffaele University4, University of Modena and Reggio Emilia5, University College London6, Catholic University of the Sacred Heart7, King's College London8, Murdoch University9, University of Barcelona10, University of Copenhagen11, University of Geneva12, Harvard University13, John Radcliffe Hospital14
TL;DR: Using a whole-genome association strategy, polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set-point period of infection are identified.
Abstract: Understanding why some people establish and maintain effective control of HIV-1 and others do not is a priority in the effort to develop new treatments for HIV/AIDS. Using a whole-genome association strategy, we identified polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set-point period of infection. One of these is found within an endogenous retroviral element and is associated with major histocompatibility allele human leukocyte antigen (HLA)-B*5701, whereas a second is located near the HLA-C gene. An additional analysis of the time to HIV disease progression implicated two genes, one of which encodes an RNA polymerase I subunit. These findings emphasize the importance of studying human genetic variation as a guide to combating infectious agents.
1,230 citations
Duke University1, Johns Hopkins University2, University of Florence3, Leiden University4, Stanford University5, University of Vienna6, University of California, San Francisco7, University of Texas Health Science Center at Houston8, University of Barcelona9, University of Wisconsin-Madison10, University of Zurich11, University of Helsinki12, Yale University13, Mayo Clinic14, University of Turin15, Humboldt University of Berlin16, University of Paris17, St Thomas' Hospital18
TL;DR: These revisions are made to incorporate advances related to tumor cell biology and diagnostic techniques as pertains to mycosis fungoides and Sézary syndrome to clarify certain variables that currently impede effective interinstitution and interinvestigator communication and/or the development of standardized clinical trials in MF and SS.
1,167 citations
University of Alberta1, Harvard University2, Johns Hopkins University3, University of Manitoba4, Mayo Clinic5, University of Pittsburgh6, University of Maryland, Baltimore7, University of California, San Diego8, Katholieke Universiteit Leuven9, Washington University in St. Louis10, National Institutes of Health11, Hannover Medical School12, University of Basel13, University of Sydney14, University of North Carolina at Chapel Hill15, John Radcliffe Hospital16, Saint Louis University17, Scripps Research Institute18, University of Barcelona19, Royal London Hospital20, University of Amsterdam21
TL;DR: The 8th Banff Conference on Allograft Pathology was held in Edmonton, Canada, 15–21 July 2005, and major outcomes included the elimination of the non‐specific term ‘chronic allograft nephropathy’ (CAN) and the recognition of the entity of chronic antibody‐mediated rejection.
1,036 citations
University of Paris1, Newcastle University2, Rush University Medical Center3, University of Bergen4, Stavanger University Hospital5, King's College London6, Prince of Wales Medical Research Institute7, Mayo Clinic8, Pierre-and-Marie-Curie University9, University of California, Los Angeles10, McGill University11, Tel Aviv University12, French Institute of Health and Medical Research13, University of Louisville14, Juntendo University15, Icahn School of Medicine at Mount Sinai16, Innsbruck Medical University17, Instituto de Medicina Molecular18, University of Barcelona19, Istanbul University20
TL;DR: The main focus of this article is to operationalize the diagnosis of PD‐D and to propose pratical guidelines based on a two level process depending upon the clinical scenario and the expertise of the evaluator involved in the assessment.
Abstract: A preceding article described the clinical features of Parkinson's disease dementia (PD-D) and proposed clinical diagnostic criteria for "probable" and "possible" PD-D. The main focus of this article is to operationalize the diagnosis of PD-D and to propose practical guidelines based on a two level process depending upon the clinical scenario and the expertise of the evaluator involved in the assessment. Level I is aimed primarily at the clinician with no particular expertise in neuropsychological methods, but who requires a simple, pragmatic set of tests that are not excessively time-consuming. Level I can be used alone or in concert with Level II, which is more suitable when there is the need to specify the pattern and the severity on the dementia of PD-D for clinical monitoring, research studies or pharmacological trials. Level II tests can also be proposed when the diagnosis of PD-D remains uncertain or equivocal at the end of a Level I evaluation. Given the lack of evidence-based standards for some tests when applied in this clinical context, we have tried to make practical and unambiguous recommendations, based upon the available literature and the collective experience of the Task Force. We accept, however, that further validation of certain tests and modifications in the recommended cut off values will be required through future studies.
TL;DR: Ozonation was the oxidation process most studied, gives the best expectatives to be applied with successful results.
TL;DR: Chemoembolization using DEBs is an effective procedure with a favorable pharmacokinetic profile and after a median follow-up of 27.6 months, 1- and 2-year survival is 92.5% and 88.9%, respectively.
Mayo Clinic1, University of Cologne2, Indiana University3, University of Texas MD Anderson Cancer Center4, Uppsala University5, Royal Hallamshire Hospital6, Medical University of Vienna7, University of Florence8, University of Barcelona9, University of Illinois at Chicago10, Harvard University11, Ohio State University12, University of Chicago13
TL;DR: In this paper, the authors proposed a revision of the current World Health Organization (WHO) diagnostic criteria for polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), which was subsequently presented by an international expert panel of pathologists and clinical investigators in myeloproliferative disorders.
TL;DR: Findings reveal how aggressive primary tumorigenic functions can be mechanistically coupled to greater lung metastatic potential, and how such biological activities may be therapeutically targeted with specific drug combinations.
Abstract: Metastasis entails numerous biological functions that collectively enable cancerous cells from a primary site to disseminate and overtake distant organs. Using genetic and pharmacological approaches, we show that the epidermal growth factor receptor ligand epiregulin, the cyclooxygenase COX2, and the matrix metalloproteinases 1 and 2, when expressed in human breast cancer cells, collectively facilitate the assembly of new tumour blood vessels, the release of tumour cells into the circulation, and the breaching of lung capillaries by circulating tumour cells to seed pulmonary metastasis. These findings reveal how aggressive primary tumorigenic functions can be mechanistically coupled to greater lung metastatic potential, and how such biological activities may be therapeutically targeted with specific drug combinations.
TL;DR: The results support the idea that the cell interior is at once a crowded chemical space and a fragile soft material in which the effects of biochemistry, molecular crowding and physical forces are complex and inseparable, yet conspire nonetheless to yield remarkably simple phenomenological laws.
Abstract: With every beat of the heart, inflation of the lung or peristalsis of the gut, cell types of diverse function are subjected to substantial stretch. Stretch is a potent stimulus for growth, differentiation, migration, remodelling and gene expression. Here, we report that in response to transient stretch the cytoskeleton fluidizes in such a way as to define a universal response class. This finding implicates mechanisms mediated not only by specific signalling intermediates, as is usually assumed, but also by non-specific actions of a slowly evolving network of physical forces. These results support the idea that the cell interior is at once a crowded chemical space and a fragile soft material in which the effects of biochemistry, molecular crowding and physical forces are complex and inseparable, yet conspire nonetheless to yield remarkably simple phenomenological laws. These laws seem to be both universal and primitive, and thus comprise a striking intersection between the worlds of cell biology and soft matter physics.
TL;DR: The use of anti-TNF agents has been associated with an increasing number of cases of autoimmune diseases, principally cutaneous vasculitis, lupus-like syndrome, SLE, and interstitial lung disease.
TL;DR: In this article, the properties of cerium oxides have been studied in the framework of the LDA+\mathrm{U} and GGA+\Mathrm{GGA} implementations of density functional theory, and the dependence of selected observables on the effective U parameter has been investigated in detail.
Abstract: The electronic structure and properties of cerium oxides ($\mathrm{Ce}{\mathrm{O}}_{2}$ and ${\mathrm{Ce}}_{2}{\mathrm{O}}_{3}$) have been studied in the framework of the $\mathrm{LDA}+\mathrm{U}$ and $\mathrm{GGA}(\mathrm{PW}91)+\mathrm{U}$ implementations of density functional theory. The dependence of selected observables of these materials on the effective U parameter has been investigated in detail. The examined properties include lattice constants, bulk moduli, density of states, and formation energies of $\mathrm{Ce}{\mathrm{O}}_{2}$ and ${\mathrm{Ce}}_{2}{\mathrm{O}}_{3}$. For $\mathrm{Ce}{\mathrm{O}}_{2}$, the $\mathrm{LDA}+\mathrm{U}$ results are in better agreement with experiment than the $\mathrm{GGA}+\mathrm{U}$ results whereas for the computationally more demanding ${\mathrm{Ce}}_{2}{\mathrm{O}}_{3}$ both approaches give comparable accuracy. Furthermore, as expected, ${\mathrm{Ce}}_{2}{\mathrm{O}}_{3}$ is much more sensitive to the choice of the U value. Generally, the PW91 functional provides an optimal agreement with experiment at lower U energies than LDA does. In order to achieve a balanced description of both kinds of materials, and also of nonstoichiometric $\mathrm{Ce}{\mathrm{O}}_{2\ensuremath{-}x}$ phases, an appropriate choice of U is suggested for $\mathrm{LDA}+\mathrm{U}$ and $\mathrm{GGA}+\mathrm{U}$ schemes. Nevertheless, an optimum value appears to be property dependent, especially for ${\mathrm{Ce}}_{2}{\mathrm{O}}_{3}$. Optimum U values are found to be, in general, larger than values determined previously in a self-consistent way.
TL;DR: The MAGIC telescope was used to observe the blazar Markarian 501 (Mrk 501) at energies above 100 GeV from May through July 2005 as mentioned in this paper, and the high sensitivity of the instrument enabled the determination of the flux and spectrum of the source on a night-by-night basis.
Abstract: The blazar Markarian 501 (Mrk 501) was observed at energies above 100 GeV with the MAGIC telescope from May through July 2005. The high sensitivity of the instrument enabled the determination of the flux and spectrum of the source on a night-by-night basis. Throughout our observational campaign, the flux from Mrk 501 was found to vary by an order of magnitude, and to be correlated with spectral changes. Intra-night flux variability with flux-doubling times down to 2 minutes was also observed. The strength of variability increased with the energy of the {gamma}-ray photons. The energy spectra were found to harden significantly with increasing flux, and a spectral peak clearly showed up during very active states. The position of the spectral peak seems to be correlated with the source luminosity.
Heidelberg University1, University of Texas MD Anderson Cancer Center2, University of Bologna3, Hammersmith Hospital4, Oregon Health & Science University5, Hackensack University Medical Center6, University of Barcelona7, Cornell University8, Harvard University9, Bristol-Myers Squibb10, University of California, San Francisco11
TL;DR: Dasatinib induces notable responses in imatinib-resistant or -intolerant CML-CP, is well tolerated, and represents a promising therapeutic option for these patients.
University of California, San Francisco1, Sahlgrenska University Hospital2, University of Tromsø3, University of Barcelona4, Indiana University – Purdue University Indianapolis5, University of Pisa6, Akdeniz University7, Catholic University of the Sacred Heart8, Medical University of Silesia9, Royal Prince Alfred Hospital10, University of Southern California11, Humboldt University of Berlin12
TL;DR: The incidence of NODAT or IFG at 6 months post‐transplant is significantly lower with CsA‐ME than with tacrolimus without a significant difference in short‐term outcome, and the profile and incidence of adverse events were similar between treatments.
TL;DR: In patients with few remaining treatment options, raltegravir at all doses studied provided better viral suppression than placebo when added to an optimised background regimen.
TL;DR: An examination of the evolution of the design of videogames is a good way to analyze the main contributions and characteristics of games-based learning environments and the main obstacles and challenges to the use of games for learning.
Abstract: In recent years, electronic games have assumed an important place in the lives of children and adolescents. Children acquire digital literacy informally, through play, and neither schools nor other educational institutions take sufficient account of this important aspect. We consider that multimedia design for training and education should combine the most powerful features of interactive multimedia design with the most effective principles of technologically-mediated learning. An examination of the evolution of the design of videogames is a good way to analyze the main contributions and characteristics of games-based learning environments. At the same time, we will discuss the main obstacles and challenges to the use of games for learning.
Journal Article•
National Institutes of Health1, Leipzig University2, Harvard University3, University of Ibadan4, University of Barcelona5, Peking University6, Israel Ministry of Health7, Nagasaki University8, Monash University9, Utrecht University10, University of Hong Kong11, University of Michigan12, World Health Organization13
TL;DR: In this article, the authors present data on patterns of failure and delay in making initial treatment contact after first onset of a mental disorder in 15 countries in the World Health Organization (WHO)'s World Mental Health Surveys.
TL;DR: A meta-analysis of trials randomizing patients with colon cancer to laparoscopically assisted or open colectomy to enhance the power in determining whether laparoscopic coLECTomy for cancer is oncologically safe was performed.
Abstract: OBJECTIVE: To perform a meta-analysis of trials randomizing patients with colon cancer to laparoscopically assisted or open colectomy to enhance the power in determining whether laparoscopic colect ...
Harvard University1, Rotterdam University of Applied Sciences2, NewYork–Presbyterian Hospital3, University of Pennsylvania4, Emory University5, Heidelberg University6, University of Salamanca7, University of Barcelona8, University of Turin9, St Bartholomew's Hospital10, Mayo Clinic11, University of Michigan12, Millennium Pharmaceuticals13, Genentech14
TL;DR: The activity of bortezomib is confirmed and support extended treatment in relapsed multiple myeloma patients tolerating therapy and among responding patients, 56% improved response with longer therapy beyond initial response, leading to continued improvement in overall quality of response.
TL;DR: The Neandertals, the authors' closest extinct relatives, share with modern humans two evolutionary changes in FOXP2, a gene that has been implicated in the development of speech and language, and these changes lie on the common modern human haplotype, which previously was shown to have been subject to a selective sweep.
TL;DR: The magnetic superelasticity and the inverse magnetocaloric effect in Ni-Mn-In and their association with the first-order structural transition are studied by magnetization, strain, and neutron-diffraction studies under magnetic field as mentioned in this paper.
Abstract: Applying a magnetic field to a ferromagnetic Ni{sub 50}Mn{sub 34}In{sub 16} alloy in the martensitic state induces a structural phase transition to the austenitic state. This is accompanied by a strain which recovers on removing the magnetic field, giving the system a magnetically superelastic character. A further property of this alloy is that it also shows the inverse magnetocaloric effect. The magnetic superelasticity and the inverse magnetocaloric effect in Ni-Mn-In and their association with the first-order structural transition are studied by magnetization, strain, and neutron-diffraction studies under magnetic field.
TL;DR: The first randomized, placebo-controlled, double-blind, multicenter trial of standardized treatment with glucocorticosteroids and adjunctive treatment with placebo or infliximab in patients with newly diagnosed giant cell arteritis found that inflIXimab did not reduce rates of relapse or any secondary end point.
Abstract: Background Tumor necrosis factor-alpha is present in arteries in giant cell arteritis. Objective To evaluate the efficacy of infliximab, an anti-tumor necrosis factor-alpha agent, in giant cell arteritis. Design Randomized, controlled trial. Setting 22 sites in the United States, the United Kingdom, Belgium, Italy, and Spain. Patients 44 patients with newly diagnosed giant cell arteritis that was in glucocorticosteroid-induced remission. Intervention Participants were randomly assigned in a 2:1 ratio to receive infliximab (5 mg/kg of body weight) or placebo. Sixteen patients were assigned to glucocorticosteroid plus placebo, and 28 patients to glucocorticosteroid plus infliximab. Measurements End points were measured through week 22, when an interim analysis resulted in early stopping of the planned 54-week trial. Primary end points were the number of patients who remained free of relapse through week 22 and adverse events. Secondary end points were time to first relapse, biomarkers, cumulative glucocorticosteroid dose, and the number of patients who remained relapse-free while the glucocorticosteroid dosage was tapered to 10 mg/d. Results Infliximab therapy did not increase the proportion of patients without relapse at week 22 compared with placebo (43% vs. 50%, respectively; difference, -7 percentage points [95% CI, -38 to 23 percentage points; P = 0.65), nor did it increase the proportion of patients whose glucocorticosteroid dosages were tapered to 10 mg/d without relapse (61% vs. 75%, respectively; difference, -14 percentage points [CI, -42 to 14 percentage points]; P = 0.31). The incidence of infection was 71% with infliximab and 56% with placebo (difference, 15 percentage points [CI, -14 to 45 percentage points]). Limitations The sample was too small to rule out modest effects of infliximab and included only patients with a new diagnosis. Only one dose of infliximab was evaluated, and the study was terminated early. Conclusions This trial is too small to draw definitive conclusions, but it provides evidence that using infliximab as maintenance therapy in patients in glucocorticoid-induced remission of newly diagnosed giant cell arteritis is of no benefit and may be harmful. If infliximab has benefit, it is unlikely to be great. ClinicalTrials.gov registration number: NCT00076726.
TL;DR: Understanding these mechanisms and how they affect tumour behaviour is providing the rationale for the identification of reliable predictors of clinical evolution and the design of innovative therapeutic strategies that could open new avenues for the treatment of patients with MCL.
Abstract: Mantle cell lymphoma, characterized by proliferation of mature B lymphocytes, is one of the most aggressive lymphomas. What molecular pathways are involved in its pathogenesis, and how can these be exploited to predict patient prognosis and design new therapies? Mantle cell lymphoma (MCL) is a well-defined lymphoid malignancy characterized by a rapid clinical evolution and poor response to current therapeutic protocols. The genetic and molecular mechanisms involved in its pathogenesis combine the dysregulation of cell proliferation and survival pathways with a high level of chromosome instability that seems related to the disruption of the DNA damage response pathway. Understanding these mechanisms and how they affect tumour behaviour is providing the rationale for the identification of reliable predictors of clinical evolution and the design of innovative therapeutic strategies that could open new avenues for the treatment of patients with MCL.