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Rodriguez-Pardo D.,Hospital Universitari Vall dHebron | Pigrau C.,Hospital Universitari Vall dHebron | Corona P.S.,Hospital Universitari Vall ebron | Almirante B.,Hospital Universitari Vall dHebron
Expert Review of Anti-Infective Therapy | Year: 2015

Periprosthetic joint infection (PJI) is a devastating complication that can occur following any arthroplasty procedure. Approximately half of these infections develop within the first year after arthroplasty, mainly in the first 1 to 3 months. These infections are known as early PJI. It is widely accepted that many early PJIs can be successfully managed by debridement, irrigation, and prosthetic retention, followed by a course of biofilm-effective antibiotics (debridement, antibiotics, implant retention procedure), but candidate patients should meet the requirements set down in Zimmerli's algorithm. The best antibiotic regimen for acute PJI treated without implant removal remains uncertain. Rifampin-containing regimens, when feasible, are recommended in gram-positive infections, and fluoroquinolones in gram-negative cases. The duration, dosage, and administration route of antibiotics and the use of combined therapy are matters that requires further clarification, as the current level of evidence is low and most recommendations are based on experimental data, studies in small series, and expert experience. © 2015 Informa UK, Ltd.


Marin J.M.,Hospital Universitario Miguel Servet | Alfageme I.,University of Seville | Almagro P.,Hospital Universitari Mutua Of Terrassa | Casanova C.,Hospital Nuestra Senora Of La Candelaria | And 7 more authors.
European Respiratory Journal | Year: 2013

Guidelines recommend defining chronic obstructive pulmonary disease (COPD) by airflow obstruction and other factors, but no studies have evaluated the ability of existing multicomponent indices to predict mortality up to 10 years. We conducted a patient-based pooled analysis. Survival analysis and C statistics were used to determine the best COPD index/indices according to several construct variables and by varying time-points. Individual data of 3633 patients from 11 COPD cohorts were collected, totalling the experience of 15 878 person-years. Overall, there were 1245 death events within our cohorts, with a Kaplan'Meier survival of 0.963 at 6 months, which was reduced to 0.432 at 10 years. In all patients, ADO (age, dyspnoea and forced expiratory volume in 1 s), BODE (body mass index, airflow obstruction, dyspnoea and exercise capacity) and e-BODE (BODE plus exacerbations) were the best indices to predict 6-month mortality. The ADO index was the best to predict 12-month (C statistic 0.702), 5-year (C statistic 0.695) and 10-year mortality (C statistic 0.698), and was significantly better than BODE (all p<0.05). The best indices to predict death by C statistics when adjusting by age were e-BODE, BODEx (substitution of exacerbations for exercise capacity) and BODE. No index predicts short-term survival of COPD well. All BODE modifications scored better than ADO after age adjustment. The ADO and BODE indices are overall the most valid multicomponent indices to predict time to death in all COPD patients. Copyright © ERS 2013.


Garcia-Martinez R.,Hospital Vall dHebron | Garcia-Martinez R.,Autonomous University of Barcelona | Cordoba J.,Hospital Vall dHebron | Cordoba J.,Autonomous University of Barcelona | And 2 more authors.
Current Opinion in Critical Care | Year: 2011

Purpose of review: Brain disturbances, which are considered a form of hepatic encephalopathy, are common in acute-on-chronic liver failure. Recent findings: Patients with hepatic encephalopathy exhibit sings of energy impairment that may participate in the development of disturbances in neurotransmission. Ammonia participates in the genesis of brain edema and in the development of oxidative stress injury to astrocytes. Neuroinflammation is a new element that has been described in experimental models. These mechanisms are involved in the genesis of cognitive sequels that may persist after liver transplantation. Clinical trials have demonstrated the value of drugs that decrease the production of ammonia in the intestines to prevent encephalopathy. In addition, improvement of circulatory dysfunction with the use of albumin and vasoconstrictors may prevent hepatic encephalopathy in acute-on-chronic liver failure. New drugs that act by enhancing ammonia disposal through the synthesis of nitrogenous metabolites have shown promising results. Summary: A better knowledge of the pathogenesis of brain disturbances in acute-on-chronic liver failure provides the rationale for using ammonia-focused therapy in the prevention and treatment of encephalopathy. New therapies addressed to correct brain edema, circulatory dysfunction and inflammation may also be useful for encephalopathy and may improve the neurological outcome. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Vandenbroeck K.,University of the Basque Country | Vandenbroeck K.,Ikerbasque | Urcelay E.,Hospital Clnico San Carlos | Comabella M.,Hospital Universitari Vall ebron
Pharmacogenomics | Year: 2010

Multiple sclerosis (MS) is a condition of the CNS marked by inflammation and neurodegeneration. Interferon (IFN)-β was the first, and still is the main, immunomodulatory treatment for MS. Its clinical efficacy is limited, and a proportion of patients, ranging between 20-55%, do not respond to the therapy. Identification and subsequently, implementation in the clinic of biomarkers predictive for individual therapeutic response would facilitate improved patient care in addition to ensuring a more rational provision of this therapy. In this article, we summarize the main findings from studies addressing the pharmacogenomics of clinical response to IFN-β in MS by either whole-genome association scans, candidate gene or transcriptomics studies. Whole-genome DNA association screens have revealed a high representation of brain-specific genes, and have hinted toward both extracellular ligand-gated ion channels and type I IFNs pathway genes as important categories of genetic IFN-β response modifiers. One hit, glypican 5 (GPC5), was recently replicated in an independent study of IFN-β responsiveness. Recent RNA transcriptomics studies have revealed the occurrence of a pre-existing type I IFN gene-expression signature, composed of genes that are predominantly induced by type I IFNs, as a potential contributing feature of poor response to therapy. Thus, while the outlines of a complex polygenic mechanism are gradually being uncovered, the main challenges for the near future will reside in the robust validation of identified response-modifying genes as well as in the decipherment of the mechanistic relationships between these genes and clinical response to IFN-β. © 2010 Future Medicine Ltd.


Gimenez-Barcons M.,Hospital Universitari Vall ebron | Casteras A.,Hospital Universitari Vall ebron | Del Pilar Armengol M.,Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | Porta E.,Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | And 6 more authors.
Journal of Immunology | Year: 2014

Down syndrome (DS), or trisomy of chromosome 21, is the most common genetic disorder associated with autoimmune diseases. Autoimmune regulator protein (AIRE), a transcription factor located on chromosome 21, plays a crucial role in autoimmunity by regulating promiscuous gene expression (pGE). To investigate if autoimmunity in DS is promoted by the reduction of pGE owing to dysregulation of AIRE, we assessed the expression of AIRE and of several peripheral tissue-restricted Ag genes by quantitative PCR in thymus samples from 19 DS subjects and 21 euploid controls. Strikingly, despite the 21 trisomy, AIRE expression was significantly reduced by 2-fold in DS thymuses compared with controls, which was also confirmed by fluorescent microscopy. Allele-specific quantification of intrathymic AIRE showed that despite its lower expression, the three copies are expressed. More importantly, decreased expression of AIRE was accompanied by a reduction of pGE because expression of tissue-restricted Ags, CHRNA1, GAD1, PLP1, KLK3, SAG, TG, and TSHR, was reduced. Of interest, thyroid dysfunction (10 cases of hypothyroidism and 1 of Graves disease) developed in 11 of 19 (57.9%) of the DS individuals and in none of the 21 controls. The thymuses of these DS individuals contained significantly lower levels of AIRE and thyroglobulin, to which tolerance is typically lost in autoimmune thyroiditis leading to hypothyroidism. Our findings provide strong evidence for the fundamental role of AIRE and pGE, namely, central tolerance, in the predisposition to autoimmunity of DS individuals. Copyright © 2014 by The American Association of Immunologists, Inc.


Casellas F.,Hospital Universitari Vall ebron | Ginard D.,Hospital Universitari Son Espases | Vera I.,Hospital Universitario Puerta Of Hierro | Torrejon A.,Hospital Universitari Vall ebron
Inflammatory Bowel Diseases | Year: 2013

Background: Currently, there is no tool to evaluate satisfaction of patients with inflammatory bowel disease (IBD) with health care services. The objective of this study was to develop and test a new specific instrument to measure satisfaction with health care in patients with IBD. Methods: The questionnaire was developed using a literature review, a focus group with clinical experts, and administration of a provisional version to 20 patients with IBD. The final version of the questionnaire was validated in a longitudinal multicenter study in adult patients with IBD. The instrument's underlying dimension structure was analyzed using factor analysis, and its feasibility, reliability, and validity were assessed. Results: The final version of the CACHE questionnaire contains 31 items scored on a 5-point Likert-type scale. Scores were standardized to a range from 0 (minimum satisfaction) to 100 (maximum satisfaction). Factor analysis revealed 6 factors (staff care, clinician care, facilities, information, center accessibility, and support received), which explained 56% of variance. Overall, 91% of patients answered all items. Cronbach's alpha for the overall score was 0.93. There were no statistically significant correlations between the overall score and sociodemographic and clinical variables, but there was a statistically significant correlation between the time spent in the waiting room and the item measuring satisfaction with that aspect. There were no statistically significant changes in the overall score between the visits. The effect size was 0.016. Conclusions: The CACHE questionnaire covers aspects relevant to the assessment of health care quality in patients with IBD and has proved to be feasible, reliable, and valid. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.


Teixido-Tura G.,Hospital Universitari Vall ebron | Redheuil A.,University of Paris Descartes | Rodriguez-Palomares J.,Hospital Universitari Vall ebron | Gutierrez L.,Hospital Universitari Vall ebron | And 5 more authors.
International Journal of Cardiology | Year: 2014

Background Previous studies demonstrated the usefulness of MRI in the evaluation of aortic biomechanics in Marfan patients with aortic dilatation. However, these parameters have not been well studied in earlier stages of aortic disease. The present work aimed to study aortic biomechanics: aortic distensibility (AD) and pulse wave velocity (PWV), by MRI in Marfan patients without advanced aortic disease. Methods Eighty consecutive Marfan patients were compared with 36 age- and sex-matched controls. MRI images at the level of ascending, descending and abdominal aorta were used to determine AD and PWV. Results Marfan patients (27 men; age: 32.0 ± 10.5 years; mean aortic root diameter: 37.2 ± 4.6 mm) had lower AD at all levels (ascending 2.6 ± 2.1 vs. 6.2 ± 3.7 mm Hg- 1 · 10- 3, p < 0.001; descending 3.1 ± 2.0 vs. 8.3 ± 4.2, p < 0.001; and abdominal 4.5 ± 2.2 vs. 14.0 ± 5.2, p < 0.001), higher aortic arch PWV (8.1 ± 6.5 vs. 4.3 ± 1.8 m/s, p < 0.01) and ascending-to-abdominal PWV (6.1 ± 3.0 vs. 4.7 ± 1.5 m/s, p < 0.01) compared with controls. Thirty-five Marfan patients had a non-dilated aortic root (mean aortic root diameter: 34.5 ± 3.8 mm). In multivariable analyses, after adjustment for age, pulse pressure and aortic dimensions, AD remained lower and PWV higher in Marfan patients; even Marfan patients with non-dilated aortic root showed impaired aortic biomechanics compared with controls. Z-score for ascending AD < - 3.5 distinguished Marfan patients from controls with 82.5% sensitivity and 86.1% specificity. Conclusions Aortic biomechanics by MRI were abnormal in the entire aorta in Marfan patients. Moreover, Marfan patients without dilated aortic root showed clear impairment of aortic biomechanics, which suggests that they may be used as early markers of aortic involvement in these patients. © 2013 Elsevier Ireland Ltd.


Molina C.A.,Hospital Universitari Vall ebron
Stroke | Year: 2011

Background and Purpose: Arterial recanalization and subsequent reperfusion have extensively demonstrated their ability to restore the brain function when performed shortly after acute ischemic stroke. However, arterial recanalization does not necessarily lead to brain tissue reperfusion. Summary of Report: This review provides an update of current approaches to improve the efficacy profile of brain tissue reperfusion within and beyond the therapeutic window, including the use of novel thrombolytic agents, bridging intravenous and intra-arterial therapies, and mechanical clot retrieval or aspiration. Conclusions: There are still several challenges in the near future of reperfusion therapy for acute ischemic stroke, such as improving the ultra-early access to treatment within the "golden hour," extending the therapeutic window beyond the current 4.5-hour time window, and developing novel thrombolitics or combined approaches to improve treatment efficacy. © 2010 American Heart Association, Inc.


Rovira A.,Hospital Universitari Vall ebron | Auger C.,Hospital Universitari Vall ebron | Alonso J.,Hospital Universitari Vall ebron
Therapeutic Advances in Neurological Disorders | Year: 2013

Disease activity in multiple sclerosis (MS) is strongly linked to the formation of new lesions, which involves a complex sequence of inflammatory, degenerative, and reparative processes. Conventional magnetic resonance imaging (MRI) techniques, such as T2-weighted and gadolinium-enhanced T1-weighted sequences, are highly sensitive in demonstrating the spatial and temporal dissemination of demyelinating plaques in the brain and spinal cord. Hence, these techniques can provide quantitative assessment of disease activity in patients with MS, and they are commonly used in monitoring treatment efficacy in clinical trials and in individual cases. However, the correlation between conventional MRI measures of disease activity and the clinical manifestations of the disease, particularly irreversible disability, is weak. This has been explained by a process of exhaustion of both structural and functional redundancies that increasingly prevents repair and recovery, and by the fact that these imaging techniques do not suffice to explain the entire spectrum of the disease process and lesion development. Nonconventional MRI techniques, such as magnetization transfer imaging, diffusion-weighted imaging, and proton magnetic resonance spectroscopy, which can selectively measure the more destructive aspects of MS pathology and monitor the reparative mechanisms of this disease, are increasingly being used for serial analysis of new lesion formation and provide a better approximation of the pathological substrate of MS plaques. These nonconventional MRI-based measures better assess the serial changes in newly forming lesions and improve our understanding of the relationship between the damaging and reparative mechanisms that occur in MS. © 2013 The Author(s).


Curran A.,Hospital Universitari Vall ebron | Curran A.,Autonomous University of Barcelona | Perez-Valero I.,Hospital Universitario La Paz | Molto J.,Hospital Universitari Germans Trias i Pujol | Molto J.,Autonomous University of Barcelona
AIDS Reviews | Year: 2015

Rezolsta® (darunavir/cobicistat) is the first boosted protease inhibitor in a fixed-dose combination to be approved for the treatment of HIV infection. It contains darunavir, a protease inhibitor with a well-known safety and efficacy profile, and the new pharmacokinetic enhancer cobicistat. The convenience of this combination makes boosted darunavir easier to take, thus improving adherence. Exposure to darunavir is equivalent when it is administered with cobicistat or with ritonavir. Darunavir/cobicistat-based antiretroviral therapy has shown considerable efficacy and good tolerability in several clinical trials. Data from the single-Arm, open-label, phase III GS-US-216-130 trial showed virological efficacy rates comparable to those from ARTEMIS and ODIN. Darunavir/cobicistat was well tolerated; most adverse events were mild and consisted of gastrointestinal disturbances. Cobicistat inhibits transporters of creatinine in kidney tubules, thus causing a minimal and reversible reduction in estimated glomerular filtration rate. Like ritonavir, cobicistat is a strong CYP3A4 inhibitor and, as such, shares most of its drug interactions. However, inhibition by cobicistat seems to be more specific than with ritonavir, and cobicistat has no inducer effect; therefore, differences in its drug interaction profile may be observed.

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