Browsing by Author "Gomes, P"
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- Acute Bivalvular Left-Sided Methicillin-Resistant Staphylococcus Aureus Endocarditis with Cardiac, Cerebral, Renal and Septic ComplicationsPublication . Póvoas, D; Figueiredo, M; Murinello, A; Damásio, H; Ramos, A; Rodrigues, N; Sousa, J; Carvalho, F; Peres, H; Gomes, PInfective endocarditis (IE) is now rare in developed countries, but its prevalence is higher in elderly patients with prosthetic valves, diabetes, renal impairment, or heart failure. An increase in health-care associated IE (HCAIE) has been observed due to invasive maneuvers (30% of cases). Methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus are the most common agents in HCAIE, causing high mortality and morbidity. We review complications of IE and its therapy, based on a patient with acute bivalvular left-sided MRSA IE and a prosthetic aortic valve, aggravated by congestive heart failure, stroke, acute immune complex glomerulonephritis, Candida parapsilosis fungémia and death probably due to Serratia marcescens sepsis. The HCAIE was assumed to be related to three temporally associated in-hospital interventions considered as possible initial etiological mechanisms: overcrowding in the hospital environment,iv quinolone therapy and red blood cell transfusion. Later in the clinical course,C. parapsilosis and S. marcescens septicemia were considered to be possible secondary etiological mechanisms of HCAIE.
- Um Caso de Esófago Negro em Doente AlcoólicoPublication . Mendes, M; Bentes, T; David Marques, A; Gomes, P; Lima, C; Bettencourt, MJA necrose esofágica aguda é uma entidade raramente descrita na literatura, caracterizada endoscopicamente por uma coloração negra da mucosa do esófago. Tem sido associada à ingestão de cáusticos, à hipersensibilidade a fármacos, a infecções locais da mucosa e, mais frequentemente, a fenómenos da isquémia por instabilidade hemodinâmica. Recentemente, foram detectados alguns casos em doentes com ingestão alcoólica aguda e crónica e suas complicações, admitindo-se uma relação entre as duas entidades. Os autores descrevem um caso de esófago negro num doente internado por intoxicação alcoólica aguda, hematemeses, choque hipovolémico e pneumonia de aspiração. Atribui-se uma etiopatogénese multifactorial, que inclui a lesão directa e indirecta do álcool sobre a mucosa esofágica, assim como fenómenos de isquémia secundários ao choque hipovolémico e à pneumonia.
- Doença de Horton. A Propósito de 40 CasosPublication . Pinheiro, S; Horta, A; Gomes, P; Febra, C; Ricardo, A; Oliveira, S; Goes, MJ; Rolo, J; Serra, MJ; Castro, ASApresentamos uma casuística de 40 casos de Doença de Horton observados no Serviço de Medicina 2 e na Consulta de Doenças Autoimunes do Hospital de Santo António dos Capuchos, entre 1984 e 2002. Pretendemos comentar e destacar os aspectos práticos, clínicos, de diagnóstico e de terapêutica, relacionados com o adequado controle da doença, através da análise comparativa da literatura com os nossos dados.
- Evolution of the Human Immunodeficiency Virus Type 2 Envelope in the First Years of Infection is Associated with the Dynamics of the Neutralizing Antibody ResponsePublication . Rocha, C; Calado, R; Borrego, P; Marcelino, JM; Bártolo, I; Rosado, L; Cavaco-Silva, P; Gomes, P; Família, C; Quintas, A; Skar, H; Leitner, T; Barroso, H; Taveira, NBackground: Differently from HIV-1, HIV-2 disease progression usually takes decades without antiretroviral therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4+ T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected at birth. Results: CD4+ T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4+ T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a β-hairpin structure were related with rate of escape from the neutralizing antibodies. Conclusion: Our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs play an important role in HIV-2 pathogenesis.
- FavismoPublication . Oliveira, S; Pinheiro, S; Gomes, P; Bayão Horta, A; Santos Castro, AO favismo é um síndrome hemolítico agudo que ocorre em indivíduos com deficiência de glucose-6-fosfato desidrogenase (G6PD), após o consumo de favas. Os autores apresentam o caso clínico de um doente do sexo masculino, de 16 anos de idade, internado no Serviço 2 de Medicina do Hospital dos Capuchos por um quadro de hemólise aguda, vindo-se a constatar uma diminuição marcada de G6PD, e tendo sido a ingesta de favas o factor desencadeante. A propósito do caso clínico, é feito um estudo da família e uma breve revisão teórica acerca do favismo.
- HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019Publication . Pingarilho, M; Pimentel, V; Miranda, M; Silva, AR; Diniz, A; Ascenção, B; Piñeiro, C; Koch, C; Rodrigues, C; Caldas, C; Morais, C; Faria, D; Gomes da Silva, E; Teófilo, E; Monteiro, F; Roxo, F; Maltez, F; Rodrigues, F; Gaião, G; Ramos, H; Costa, I; Germano, I; Simões, J; Oliveira, J; Ferreira, J; Poças, J; Saraiva da Cunha, J; Soares, J; Henriques, J; Mansinho, K; Pedro, L; Aleixo, MJ; Gonçalves, MaJ; Manata, MJ; Mouro, M; Serrado, M; Caixeiro, M; Marques, N; Costa, O; Pacheco, P; Proença, P; Rodrigues, P; Pinho, R; Tavares, R; Correia de Abreu, R; Côrte-Real, R; Serrão, R; Sarmento e Castro, R; Nunes, S; Faria, T; Baptista, T; Martins, MR; Gomes, P; Mendão, L; Simões, D; Abecasis, AObjective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (p for-trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.
- HIV-2 Integrase Polymorphisms and Longitudinal Genotypic Analysis of HIV-2 Infected Patients Failing a Raltegravir-Containing RegimenPublication . Cavaco-Silva, J; Abecasis, A; Miranda, AC; Poças, J; Narciso, J; Águas, MJ; Maltez, F; Almeida, I; Germano, I; Diniz, A; Gonçalves, MF; Gomes, P; Cunha, C; Camacho, RJTo characterize the HIV-2 integrase gene polymorphisms and the pathways to resistance of HIV-2 patients failing a raltegravir-containing regimen, we studied 63 integrase strand transfer inhibitors (INSTI)-naïve patients, and 10 heavily pretreated patients exhibiting virological failure while receiving a salvage raltegravir-containing regimen. All patients were infected by HIV-2 group A. 61.4% of the integrase residues were conserved, including the catalytic motif residues. No INSTI-major resistance mutations were detected in the virus population from naïve patients, but two amino acids that are secondary resistance mutations to INSTIs in HIV-1 were observed. The 10 raltegravir-experienced patients exhibited resistance mutations via three main genetic pathways: N155H, Q148R, and eventually E92Q - T97A. The 155 pathway was preferentially used (7/10 patients). Other mutations associated to raltegravir resistance in HIV-1 were also observed in our HIV-2 population (V151I and D232N), along with several novel mutations previously unreported. Data retrieved from this study should help build a more robust HIV-2-specific algorithm for the genotypic interpretation of raltegravir resistance, and contribute to improve the clinical monitoring of HIV-2-infected patients.
- In Vitro Evaluation of Novel Reverse Transcriptase Inhibitors TAF (Tenofovir Alafenamide) and OBP-601 (2,3-didehydro-3-deoxy-4-ethynylthymidine) Against Multi-Drug Resistant Primary Isolates of HIV-2Publication . Bártolo, I; Borrego, P; Gomes, P; Gonçalves, F; Caixas, U; Pinto, IV; Taveira, NNew antiretroviral drugs are needed to treat HIV-2 infected patients failing therapy. Herein, we evaluate the activity of novel reverse transcriptase inhibitors tenofovir alafenamide (TAF) and OBP-601(2,3-didehydro-3-deoxy-4-ethynylthymidine) against primary isolates from HIV-2 infected patients experiencing virologic failure. TAF and OBP-601 were tested against twelve primary isolates obtained from nine drug-experienced patients failing therapy and three drug naïve patients using a single-round infectivity assay in TZM-bl cells. The RT-coding region of pol was sequenced and the GRADE algorithm was used to identify resistance profiles and mutations. TAF and OBP-601 inhibited the replication of almost all isolates at a median EC50 of 0.27 nM and 6.83 nM, respectively. Two isolates showed moderate-level resistance to OBP-601 or TAF and two other isolates showed high-level resistance to OBP-601 or to both drugs. With one exception, all resistant viruses had canonical nucleoside reverse transcriptase inhibitors (NRTIs)-associated resistance mutations (K65R, N69S, V111I, Y115F, Q151M and M184V). Our results show that TAF has potent activity against most multi-drug resistant HIV-2 isolates and should be considered for the treatment of HIV-2 infected patients failing therapy.
- In Vitro Evaluation of Novel Reverse Transcriptase Inhibitors TAF (Tenofovir Alafenamide) and OBP-601 (2,3-Didehydro-3-Deoxy-4-Ethynylthymidine) Against Multi-Drug Resistant Primary Isolates of HIV-2Publication . Bártolo, I; Borrego, P; Gomes, P; Gonçalves, F; Caixas, U; Pinto, I; Taveira, NNew antiretroviral drugs are needed to treat HIV-2 infected patients failing therapy. Herein, we evaluate the activity of novel reverse transcriptase inhibitors tenofovir alafenamide (TAF) and OBP-601(2,3-didehydro-3-deoxy-4-ethynylthymidine) against primary isolates from HIV-2 infected patients experiencing virologic failure. TAF and OBP-601 were tested against twelve primary isolates obtained from nine drug-experienced patients failing therapy and three drug naïve patients using a single-round infectivity assay in TZM-bl cells. The RT-coding region of pol was sequenced and the GRADE algorithm was used to identify resistance profiles and mutations. TAF and OBP-601 inhibited the replication of almost all isolates at a median EC50 of 0.27 nM and 6.83 nM, respectively. Two isolates showed moderate-level resistance to OBP-601 or TAF and two other isolates showed high-level resistance to OBP-601 or to both drugs. With one exception, all resistant viruses had canonical nucleoside reverse transcriptase inhibitors (NRTIs)-associated resistance mutations (K65R, N69S, V111I, Y115F, Q151M and M184V). Our results show that TAF has potent activity against most multi-drug resistant HIV-2 isolates and should be considered for the treatment of HIV-2 infected patients failing therapy.
- In vitro evaluation of novel reverse transcriptase inhibitors TAF (tenofovir alafenamide) and OBP-601 (2,3-didehydro-3-deoxy-4-ethynylthymidine) against multi-drug resistant primary isolates of HIV-2Publication . Bártolo, I; Borrego, P; Gomes, P; Gonçalves, F; Caixas, U; Pinto, IV; Taveira, NNew antiretroviral drugs are needed to treat HIV-2 infected patients failing therapy. Herein, we evaluate the activity of novel reverse transcriptase inhibitors tenofovir alafenamide (TAF) and OBP-601(2,3-didehydro-3-deoxy-4-ethynylthymidine) against primary isolates from HIV-2 infected patients experiencing virologic failure. TAF and OBP-601 were tested against twelve primary isolates obtained from nine drug-experienced patients failing therapy and three drug naïve patients using a single-round infectivity assay in TZM-bl cells. The RT-coding region of pol was sequenced and the GRADE algorithm was used to identify resistance profiles and mutations. TAF and OBP-601 inhibited the replication of almost all isolates at a median EC50 of 0.27 nM and 6.83 nM, respectively. Two isolates showed moderate-level resistance to OBP-601 or TAF and two other isolates showed high-level resistance to OBP-601 or to both drugs. With one exception, all resistant viruses had canonical nucleoside reverse transcriptase inhibitors (NRTIs)-associated resistance mutations (K65R, N69S, V111I, Y115F, Q151M and M184V). Our results show that TAF has potent activity against most multi-drug resistant HIV-2 isolates and should be considered for the treatment of HIV-2 infected patients failing therapy.