Ferenci P.,Medical University of Vienna |
Lalezari J.,Quest Clinical Research |
Cohen D.,AbbVie |
Luo Y.,AbbVie |
And 24 more authors.
New England Journal of Medicine | Year: 2014
BACKGROUND: The interferon-free regimen of ABT-450 with ritonavir (ABT-450/r), ombitasvir, and dasabuvir with or without ribavirin has shown efficacy in inducing a sustained virologic response in a phase 2 study involving patients with hepatitis C virus (HCV) genotype 1 infection. We conducted two phase 3 trials to examine the efficacy and safety of this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis. METHODS: We randomly assigned 419 patients with HCV genotype 1b infection (PEARL-III study) and 305 patients with genotype 1a infection (PEARL-IV study) to 12 weeks of ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), dasabuvir (250 mg twice daily), and ribavirin administered according to body weight or to matching placebo for ribavirin. The primary efficacy end point was a sustained virologic response (an HCV RNA level of <25 IU per milliliter) 12 weeks after the end of treatment. RESULTS: The study regimen resulted in high rates of sustained virologic response among patients with HCV genotype 1b infection (99.5% with ribavirin and 99.0% without ribavirin) and among those with genotype 1a infection (97.0% and 90.2%, respectively). Of patients with genotype 1b infection, 1 had virologic failure, and 2 did not have data available at post-treatment week 12. Among patients with genotype 1a infection, the rate of virologic failure was higher in the ribavirin-free group than in the ribavirin group (7.8% vs. 2.0%). In both studies, decreases in the hemoglobin level were significantly more common in patients receiving ribavirin. Two patients (0.3%) discontinued the study drugs owing to adverse events. The most common adverse events were fatigue, headache, and nausea. CONCLUSIONS: Twelve weeks of treatment with ABT-450/r-ombitasvir and dasabuvir without ribavirin was associated with high rates of sustained virologic response among previously untreated patients with HCV genotype 1 infection. Rates of virologic failure were higher without ribavirin than with ribavirin among patients with genotype 1a infection but not among those with genotype 1b infection. Copyright © 2014 Massachusetts Medical Society.
Moura R.A.,University of Lisbon |
Graca L.,University of Lisbon |
Fonseca J.E.,University of Lisbon |
Fonseca J.E.,Centro Hospitalar Lisbon Norte
Clinical Reviews in Allergy and Immunology | Year: 2012
Rheumatoid arthritis (RA) is a chronic, systemic immune-mediated inflammatory disorder that mainly targets the joints. Several lines of evidence have pointed to B cell function as a critical factor in the development of RA. B cells play several roles in the pathogenesis of RA, such as autoantibody production, antigen presentation and T cell activation, cytokine release, and ectopic lymphoid organogenesis. The success of B cell depletion therapy in RA further supports the relevance of these cells in RA progression. In addition, recent studies have also highlighted the B cell role in the first weeks of RA onset. The present article is a review focused in the immunopathogenic B celldependent mechanisms associated with RA development and chronicity and the importance of the recent discoveries documented in untreated very early RA patients with less than 6 weeks of disease duration. © Springer Science+Business Media, LLC 2012.
Arinto-Garcia R.,University of Lisbon |
Pinho M.D.,University of Lisbon |
Carrico J.A.,University of Lisbon |
Melo-Cristino J.,University of Lisbon |
And 2 more authors.
Journal of Clinical Microbiology | Year: 2015
The heterogeneity of members of the Streptococcus anginosus group (SAG) has traditionally hampered their correct identification. Recently, the group was subdivided into 6 taxa whose prevalence among human infections is poorly described. We evaluated the accuracy of the Rapid ID32 Strep test, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and a PCR multiplex method to identify 212 SAG isolates recovered from human infections to the species and subspecies level by using multilocus sequence analysis (MLSA) as the gold standard. We also determined the antimicrobial susceptibilities of the isolates. Representatives of all SAG taxa were found among our collection. MALDI-TOF MS and the Rapid ID32 Strep test correctly identified 92% and 68% of the isolates to the species level, respectively, but showed poor performance at the subspecies level, and the latter was responsible for major identification errors. The multiplex PCR method results were in complete agreement with the MLSA identifications but failed to distinguish the subspecies Streptococcus constellatus subsp. pharyngis and S. constellatus subsp. viborgensis. A total of 145 MLSA sequence types were present in our collection, indicating that within each taxon a number of different lineages are capable of causing infection. Significant antibiotic resistance was observed only to tetracycline, erythromycin, and clindamycin and was present in most taxa. MALDI-TOF MS is a reliable method for routine SAG species identification, while the need for identification to the subspecies level is not clearly established. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Conceicao I.,Centro Hospitalar Lisbon Norte |
Conceicao I.,University of Lisbon
Amyloid | Year: 2012
Familial amyloid polyneuropathy (FAP) is an autosomal dominant disorder characterized by the extracellular deposition of transthyretin (TTR) fibrils in several tissues, particularly in the peripheral nervous system. The largest focus of the disease is in Portugal where the age of disease onset shows a wide range (1778 years), with 80% of cases developing symptoms before age 40. The characteristic fiber length-dependent sensory-motor and autonomic neuropathy are the neurological hallmark of TTR-FAP. Additional cardiovascular, gastrointestinal (GI), renal and ocular symptoms are the main systemic manifestations that account for phenotypic heterogeneity. © 2012 Informa UK, Ltd.
[Diffusion-weighted MR imaging characterization of progressive multifocal leucoencefalopathy (PML) lesions]. [Caracterização das lesões de leucoencefalopatia multifocal progressiva por imagem de ressonância magnética ponderada em difusão.]
Barata Tavares J.,Centro Hospitalar Lisbon Norte
Acta médica portuguesa | Year: 2012
Progressive multifocal leucoencefalopathy (PML) is a subacute demielinating disease of the Central Nervous System caused by the neurotropic virus John Cunningham (JC), common in immunodeficient patients, namely in HIV infection. PML encephalic lesions have a progressive nature that needs characterization and progressive study, especially for evaluating the therapeutic response. The authors reviewed diffusion-weight MR imaging of PML lesions in four patients, characterizing the different lesional areas in DWI and ADC maps, and correlating these data with previous published studies, namely regarding histological correlation and lesion time course. The four cases studied showed heterogeneity in DWI and ADC maps, with restriction in water diffusion in the periphery of each lesion. Diffusion-weighted MR images allows characterization of PML lesions, highlighting their heterogeneity and asynchrony. These data allow important knowledge on lesions temporal evolution and treatment response.
Braga-Tavares H.,Centro Hospitalar Lisbon Norte |
Fonseca H.,Centro Hospitalar Lisbon Norte
European Journal of Pediatrics | Year: 2010
In order to determine the prevalence of metabolic syndrome (MS) in a Portuguese pediatric overweight population according to three different sets of criteria, 237 overweight and obese adolescents were evaluated at engagement in a specific multidisciplinary program. Two of the used definitions were based on the National Cholesterol Education Program (ATPIII) guidelines modified for pediatric age and were proposed by Cook et al. (Arch Pediatr Adolesc Med 157(8):821-827, 2003) and de Ferranti et al. (Circulation 110(16):2494-2497, 2004). The third definition used resulted from a consensus of the International Diabetes Federation (IDF 2005). All of them include five components: waist circumference, blood pressure, high-density lipoprotein cholesterol, triglycerides, and fasting glucose values, with different cut-off points. Of the studied sample, 53% were girls, median age 13.4 years, 89% classified as obese, and the remaining as overweight. MS prevalence was 15.6%, 34.9%, and 8.9% according to Cook's, de Ferranti's, and IDF definitions, respectively. No adolescent fulfilled the five MS criteria, and only three (1.2%), 15 (6%), and 13 (5.1%) had no criteria at all, according to the three definitions used. Waist circumference was the most prevalent component (89.5%, 98.7%, and 93.2%), and high fasting glucose the least (1.3% for the two first and 2.5% according to the IDF definition). A significant correlation between increased body mass index and MS was found, using the two first definitions (Cook et al. p<0.05; de Ferranti et al. p<0.01), but not when using the third one. Considerable prevalence differences were found using three different MS criteria. It is urgent to establish a consensus on MS definition to allow early identification of adolescents at risk and the development of prospective studies to define what cut-offs are the best indicators of future morbidity. © 2010 Springer-Verlag.
Stent Placement for the Treatment of Malignant Superior Vena Cava Syndrome - A Single-Center Series of 56 Patients [Implantación de endoprótesis para el tratamiento del síndrome de vena cava superior maligno: Serie de 56 pacientes de un solo centro]
Sobrinho G.,Centro Hospitalar Lisbon Norte |
Aguiar P.,New University of Lisbon
Archivos de Bronconeumologia | Year: 2014
Objective: To report a series of stenting procedures for the treatment of malignant superior vena cava (SVC) syndrome. Material and methods: A review conducted from October 2005 to July 2013 retrieved 56 consecutive patients treated for symptomatic malignant SVC syndrome with stenting. Results: SVC stenting was attempted in 56 patients (46 males, 10 females), aged 34-84. years (mean 59.3).The success rate was 49/57 (86%). Success was associated with the type of obstruction classified as: group. 1 (a -SVC stenosis, or b -unilateral innominate vein occlusion with contralateral innominate vein stenosis and normal SVC), group. 2 (SVC occlusion excluding bilateral innominate vein occlusion) and group. 3 (bilateral innominate vein occlusion irrespective of SVC status). Success rates were 100% (39/39), 75% (9/12) and 16.6% (1/6), respectively. These differences were significant for group. 1 versus group. 2. +. 3 (p. <. 0.001) and for group. 2 versus group. 3 (p. = 0.032). Acute complications occurred in 9 patients. Patients in whom acute complications occurred were older than the others (67.8 vs. 57.6 years, p. = 0.019). The procedure-related death rate was 3.5% (n. = 2). Stent occlusion occurred in 3.5% (n. = 2). The patient survival was poor (median 2.6; range <. 1-29.6. months), independently of the success of stenting. Conclusions: Stenting for malignant SVC syndrome provides immediate and sustained symptomatic relief that lasts until death in this set of patients with a short life expectancy and restores the central venous access for administration of chemotherapy. Technical failure was associated with SVC occlusions and primarily with bilateral innominate vein occlusion. © 2013 SEPAR.
Lopes J.A.,Centro Hospitalar Lisbon Norte |
Jorge S.,Centro Hospitalar Lisbon Norte |
Neves M.,Centro Hospitalar Lisbon Norte
Bone Marrow Transplantation | Year: 2016
Acute kidney injury (AKI) is highly prevalent whether the patients undergo myeloablative or non-myeloablative hematopoietic cell transplantation (HCT); however, the pathogenesis and risk factors leading to AKI can differ between the two. The prognosis of AKI in patients receiving HCT is poor. In fact, AKI following HCT is associated not only with increased short-and long-term mortality, but also with progression to chronic kidney disease. Herein, the authors provide a comprehensive and up-to-date review of the definition and diagnosis, as well as of the incidence, pathogenesis and outcome of AKI in patients undergoing HCT, centering on the differences between myeloablative and non-myeloablative regimens. © 2016 Macmillan Publishers Limited.
Maltez F.,Hospital Of Curry Cabral |
Doroana M.,Centro Hospitalar Lisbon Norte |
Branco T.,Medical Service |
Valente C.,Centro Hospitalar Of Coimbra
Current Opinion in HIV and AIDS | Year: 2011
Purpose of review: To discuss new antiretroviral agents (ARVs) and alternative ARV treatment strategies that are currently being evaluated, and to provide an overview of the most recent advances in HIV vaccine development. RECENT FINDINGS: There is a continuous need for improvements in ARV therapy (ART) and several new ARVs are currently undergoing clinical investigation, including the non-nucleoside reverse transcriptase inhibitor rilpivirine, the integrase inhibitor elvitegravir, the chemokine receptor 5 co-receptor antagonist vicriviroc and the maturation inhibitor bevirimat. Strategies to optimize ART, such as treatment interruption, induction-maintenance and class-sparing regimens, are also being evaluated and have had varying success to date. However, vaccination still remains the optimal solution, and one second-generation preventative HIV vaccine has produced encouraging results in a recent phase III trial. SUMMARY: Global prevention and treatment with ARVs that are effective, well tolerated and have high barriers to the development of HIV resistance are the main strategies to fight HIV/AIDS while we await the development of an effective vaccine. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Mendes Dos Santos C.,Centro Hospitalar Lisbon Norte
Acta médica portuguesa | Year: 2012
Rasmussen's encephalitis is a chronic inflammatory encephalitis of unknown etiology. Clinical, imaging and electroencephalographic characteristic findings allow its diagnosis. Serial brain MRI evaluation of these patients has a characteristic pattern of temporal evolution. Regarding a clinical case, the authors make a brief review of this pathology, with particular emphasis on the MRI findings. Female child, seven years old, who started a drug-resistant focal epilepsy at the age of four. The video-EEG revealed a left fronto-temporal epileptogenic focus. The serial MRI evaluation showed a left fronto-temporal and insular lesion with variation of its imaging features over time. After thorough investigation, the diagnosis of exclusion was that of Rasmussen's encephalitis. MRI plays an important role in the diagnosis and monitoring of Rasmussen's encephalitis. Regarding a clinical case, we review this pathology, specially its MRI findings.