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Garcia-Martinez R.,Servei de Medicina Interna Hepatologia | Garcia-Martinez R.,Autonomous University of Barcelona | Cordoba J.,Servei de Medicina Interna Hepatologia | 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.

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.

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.

Marin J.M.,Hospital Universitario Miguel Servet | Alfageme I.,University of Seville | Almagro P.,Hospital Universitari Mutua Of Terrassa | Casanova C.,Hospital Nuestra Senora de la Candelaria | And 6 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.

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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