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- ItemAcesso aberto (Open Access)Análise de diferentes pontos de corte de carga viral para suspender o tratamento do citomegalovírus em receptores de transplante renal sob estratégia preemptiva(Universidade Federal de São Paulo, 2024-10-13) Miehrig, Arthur Heinz [UNIFESP]; Lucio, Roberto Requião Moura [UNIFESP]; http://lattes.cnpq.br/9161729200802261; http://lattes.cnpq.br/3474011302931604Objetivo: Avaliar dois diferentes pontos de corte de carga viral (CV) para suspender a medicação antiviral durante o tratamento da infecção pelo citomegalovírus (CMV) em receptores de transplante de rim (RTR) sob estratégia preemptiva. Métodos: estudo de coorte retrospectiva, incluindo RTR CMV IgG+, transplantados entre março/2018 a julho/2020 no Hospital do Rim, que receberam indução timoglobulina, e manutenção com tacrolimo, micofenolato e prednisona. A estratégia preemptiva foi utilizada para redução de riscos, com monitoramento semanal de CV por PCR e tratamento com ganciclovir EV se CV>5.000 UI/ml, ou se CMV doença. Até agosto/2019, o antiviral era interrompido com a supressão completa da CV (grupo 1, n=664) e após essa data o ponto de corte para suspensão foi modificado para < 200 UI/ml (grupo 2, n=384). Desfecho primário: recidiva de CMV, definida como necessidade de retratamento. Desfechos secundários: taxa de infecção e doença pelo CMV e função renal ao final de um ano (TFGe, CKD-EPI). As variáveis associadas com as chances de recidiva foram avaliadas por regressão de Cox. A TFGe foi avaliada ao longo do tempo por estimativas de equação generalizada e ajustadas por Bonferroni. Resultados: Na comparação entre os grupos, os pacientes no grupo 1 eram com mais frequência brancos (55,7 vs. 41,9%, p<0,001) e portadores do vírus C (4,1 vs. 1,85%, p=0,048) e com menos frequência do vírus B (0.6 vs. 2,3%, p=0,01); os doadores eram mais jovens (52 vs. 54 anos, p=0,003), com menos frequência eram doadores falecidos (90,2 vs. 94,3%, p=0,02), de morte cerebrovascular (68,1 vs. 71,3%, p=0,01) e com histórico de hipertensão (40,7 vs. 50,8%, p=0,001). Não houve diferenças nas outras variáveis. As taxas de infecção assintomática foram semelhantes (30,1 vs. 31,3%, p=0,70), mas houve uma tendência de menos doença pelo CMV no grupo 2 (20,3 vs. 15,6%, p=0,06), e uma redução significativa do tempo de tratamento de 27 para 23 dias, p<0,001. A frequência de recidivas foi semelhante (12,2 vs. 10,8%, p=0,24), não havendo diferença nos espectros de infecção e doença (p=0,34). A TFGe ao longo do primeiro ano foi em média 3,84 (IC95%=1,38 a 6,29) ml/min maior no grupo 1 (p=0,002), alcançando 52,6 e 48,9 ml/min no grupo 1 e 2, respectivamente. Entre os 515 pacientes que necessitaram de tratamento de um primeiro evento relacionado ao CMV (infecção ou doença), 119 apresentaram critério para um segundo tratamento, com uma frequência de recidiva de 23,1% (11,3% do total). As variáveis associadas com a probabilidade de recidiva foram: idade do doador (HR=1,024; IC95%= 1,008-1,041) e o tempo de ocorrência do primeiro evento relacionado ao CMV (HR= 0.968; IC95%= 0,956-0,979; p<0,001). Conclusão: a redução da CV do CMV para a interrupção do tratamento antiviral na estratégia preemptiva não aumentou o risco de recidiva, mas houve redução significativa no tempo de tratamento, sem impactos nos espectros da infecção.
- ItemAcesso aberto (Open Access)Citomegalovirose congênita: relato de caso(Federação Brasileira das Sociedades de Ginecologia e Obstetrícia, 2005-12-01) Azevedo, Patrícia de Fátima; Souza, Alex Sandro Rolland de; Noronha Neto, Carlos; Lima, Marcelo Marques de Souza [UNIFESP]; Cardoso, Alexandre Silva; Porto, Ana Maria Feitosa; Instituto Materno Infantil Prof. Fernando Figueira IMIP; Universidade Federal de São Paulo (UNIFESP)Congenital cytomegalovirus infection is an important clinical entity, due to its sonographic symptomatology. In Brazil, in utero diagnosis is not accomplished despite the improvements in diagnostic methods. We report a congenital infection including: splenomegaly and hepatomegaly, hypoplasia of the cerebellar vermis, intracranial calcifications, hyperechoic kidneys, hyperechoic bowel, cardiomegaly, lung hypoplasia, ascites, and pericardial effusion. Fetal magnetic resonance imaging confirmed the sonographic findings. Amniocentesis was performed for cytomegalovirus PCR in amniotic fluid, which confirmed fetal infection. Fetal loss occurred in the 31st week of pregnancy. Necropsy studies confirmed the sonographic findings. The diagnostic methods have been useful to confirm congenital cytomegalovirus infection and to establish fetal outcome.
- ItemAcesso aberto (Open Access)Clinical features and outcomes of AIDS-related cytomegalovirus retinitis in the era of highly active antiretroviral therapy(Conselho Brasileiro de Oftalmologia, 2010-02-01) Arantes, Tiago Eugênio Faria E [UNIFESP]; Garcia, Claudio Renato [UNIFESP]; Saraceno, Janaína Jamile Ferreira [UNIFESP]; Muccioli, Cristina [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)PURPOSE: To describe the features and outcomes of patients with AIDS-related cytomegalovirus retinitis after highly active antiretroviral therapy availability. METHODS: Retrospective chart review of 30 consecutive patients (44 eyes) with AIDS and newly diagnosed, active AIDS-related cytomegalovirus retinitis, examined from January 2005 to December 2007. RESULTS: The mean age was 34.8 years, 18 patients (60.0%) were male and median duration of AIDS was 90 months. Nineteen patients (63.3%) had evidence of highly active antiretroviral therapy failure and median CD4+ lymphocyte count was 12.5 cells/µl. Visual acuity at presentation was 20/40 or better in 27 eyes (61.4%). Retinitis involved Zone 1 in 13 eyes (39.5%). Despite specific anti-AIDSrelated cytomegalovirus therapy, 16 eyes (36.4%) presented relapse of retinitis and 10 eyes (22.7%) lost at least three lines of vision. When compared to highly active antiretroviral therapy responsive patients, eyes of highly active antiretroviral therapy failure patients were more likely to develop relapse of retinitis (p=0.03) and loss of at least three lines of vision (p=0.03). CONCLUSION: The patients in this series are essentially young men with longstanding AIDS, non-responsive to highly active antiretroviral therapy and with a similar immunological profile as noted before highly active antiretroviral therapy era. These findings have implications for the management of the disease and confirm the magnitude of rational periodic screening after diagnosis of AIDS.
- ItemAcesso aberto (Open Access)Comparação da eficácia e segurança do uso de sirolimo, everolimo e micofenolato de sódio de novo em receptores de transplante renal induzidos com globulina antitimócito, tacrolimo e prednisona(Universidade Federal de São Paulo, 2023-10-25) Freschi, Juliana Toniato de Rezende [UNIFESP]; Silva Junior, Helio Tedesco [UNIFESP]; http://lattes.cnpq.br/1621797721074970; http://lattes.cnpq.br/4877593559634267Objetivos: Os inibidores do alvo da rapamicina nos mamíferos (mTORi), sirolimo (SRL) e everolimo (EVR), apresentam propriedades farmacocinéticas e farmacodinâmicas distintas. Não existem estudos que comparem a eficácia e a segurança da utilização de novo de SRL versus EVR em combinação com o inibidor da calcineurina em dose reduzida. Métodos: Este estudo prospectivo, randomizado e de centro único incluiu receptores de primeiro transplante renal que receberam dose única de globulina antitimócito de coelho 3mg/Kg, tacrolimo e prednisona, sem profilaxia farmacológica para infecção por citomegalovírus (CMV). Os pacientes foram randomizados em três grupos: SRL, EVR ou micofenolato (MPS). As doses de SRL e EVR foram ajustadas para manter as concentrações sanguíneas entre 4-8 ng/ml. O objetivo primário foi analisar a incidência do primeiro episódio de infecção/doença por CMV em 12 meses. Resultados: Foram incluídos no estudo 266 pacientes (SRL, n = 86; EVR, n = 90; MPS, n = 90). A incidência do primeiro evento por CMV foi menor nos grupos mTORi comparado ao MPS (10,5% vs. 7,8% vs. 43,3%, p < 0,0001). Não houve diferença na incidência de viremia por poliomavírus (8,2% vs. 10,1% vs. 15,1%, p = 0,360). Não foi observada diferença na sobrevida livre de falha do tratamento (87,8% vs. 88,8% vs. 93,3%, p = 0,421) e na incidência de anticorpos específicos contra o doador de novo. Aos 12 meses, não se registaram diferenças na função renal (75 ± 23 vs. 78 ± 24 vs. 77 ± 24 ml/min/1,73m2, p = 0,736), na proteinúria e na histologia das biopsias protocolares. Descontinuação definitiva foi maior nos grupos SRL e EVR (18,6% vs. 15,6% vs. 6,7%, p=0,054). Conclusão: O uso de novo de SRL ou EVR, visando concentrações sanguíneas terapêuticas semelhantes, apresenta eficácia e segurança comparáveis. A incidência reduzida de infecção/doença por CMV e o perfil de segurança distinto dos mTORi versus MPS foram confirmados neste estudo.
- ItemAcesso aberto (Open Access)Comparação de métodos convencionais e reação em cadeia da polimerase em tempo real na detecção de infecção pelo citomegalovírus in vitro(Universidade Federal de São Paulo (UNIFESP), 2009-09-30) Cezar, Amanda Cristina [UNIFESP]; Pacheco-Silva, Alvaro [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction: Clinical isolates of Cytomegalovirus (CMV) are easily spread in vitro resulting in impairment of the monolayer cell where the virus was inoculated, thus evidencing the presence or absence of infection. The cell culture is a classic method for detection of CMV and it was widely used in the past. Antigenemia assay, which detects CMV pp65 antigen, is the method most used currently in clinical practice, because it is faster and specific for detection of the active infection. Recently, the real-time PCR has been used in monitoring of the infection through the quantification of viral load for being a high sensitivity and specificity method to viral DNA. Therefore, the aim of the study was employing tests used in diagnosis and monitoring of infection to the standard CMV strain as a protocol for implantation in experiments in vitro. Methods: Quiescent human fibroblasts in confluent monolayer were inoculated with samples of infected cells by the adapted CMV AD169 strain. The effect of the virus on culture was monitored at 1 hour, 24 hours, 48 hours and 72 hours post infection (h.p.i) by observation of cytopathic effect. The same samples were analyzed by antigenemia being estimate the mean of positive cells in 2x105 cells and by real-time PCR being estimate the mean of copies of viral DNA/Log10 present in samples. Results: Cytopathic effect was first noticed 24 h.p.i, showing that the initiation of morphological changes occurred early. This effect became more intense after 72 h.p.i. Antigenemia assay showed the presence of active infection through pattern of labeling of the pp65 viral antigen found on nucleus of infected cells, while the real-time PCR showed the number of copies of viral DNA in different times of infection. Antigenemia showed an mean of 57 ±56 positive cells 1h.p.i. The peak of the infection was reached 24h.p.i with a significant increase in the mean 2.381 ±168 (P<0.05 versus 1h.p.i) and remained high 48h.p.i, showing an mean of 2.012 ±352 positive cells. However, the mean of antigenemia decrease 72h.p.i to 262 ±5 (P<0.05 versus 48h.p.i). As well as in antigenemia, a significant increase of th viral load was observed of 1h.p.i to 24h.p.i, being the mean of viral DNA detected 11.30 ±0.30 and 11.96 ±0.09, respectively (P<0.05). The levels of viral DNA stayed high 48h.p.i, being detected a mean of 12.33 ±0.26. After this period, viral load decreased significantly to 11.57 ±0.06 (P<0.05 versus 48h.p.i). No correlation was found between the quantitative methods of antigenemia and real-time PCR. Conclusion: The three methods, virus isolation, antigenemia and real-time PCR, showed the success of the CMV infection “in vitro” by cyto-morphological changes, detection of viral antigen specific and viral load by virus DNA detection, respectively. PCR method was more sensitive in detecting virus in relation the other methods. Although sensitive and specific, we consider the need for viral titration in any experimental studies in vitro.
- ItemSomente MetadadadosComparação Entre Everolimo E Micofenolato De Sódio Em Receptores De Transplante Renal Com Doadores Falecidos De Critérios Expandidos(Universidade Federal de São Paulo (UNIFESP), 2018-12-04) Ferreira, Alexandra Nicolau [UNIFESP]; Silva Junior, Helio Tedesco [UNIFESP]Introduction. The Use Of Expanded Criteria Donors (Ecd) For Kidney Transplantation Has Been A New Strategy To Increase The Number Of Deceased Donor Kidneys Available In The World. However, The Incidence Of Delayed Graft Function (Dgf), Acute Rejection And Nephrotoxic Events Is More Often In Ecd Kidneys Recipients Than Standard Criteria Donor Kidneys Recipients. The Optimal Immunosuppressive Regimen For Recipients Of Ecd Kidneys Has Not Been Defined. Methods. In This Single-Center Study, 171 Recipients Of Ecd Kidney Transplants Were Randomized To Receive Antithymocyte Globulin Induction, Delayed Introduction Of Reduced Dose Tacrolimus, Prednisone And Everolimus (R-Atg/Evr, N=88) Or Mycophenolate (R-Atg/Mps, N=83). No Cytomegalovirus (Cmv) Pharmacological Prophylaxis Was Used. The Primary End-Point Was The Incidence Of Cmv Infection/Disease In The Intention-To-Treat Population At 12 Months. Secondary Endpoints Included Treatment Failure (First Biopsy Proven Acute Rejection [Bpar], Graft Loss Or Death) And Safet
- ItemAcesso aberto (Open Access)Efeito Da Globulina Anti-Timócito E Do Everolimo Na Cinética Da Carga Viral Do Citomegalovírus Em Pacientes Transplantados Renais Soropositivos E Sem Quimioprofilaxia(Universidade Federal de São Paulo (UNIFESP), 2018-06-28) Basso, Geovana [UNIFESP]; Silva Junior, Helio Tedesco [UNIFESP]; http://lattes.cnpq.br/1621797721074970; http://lattes.cnpq.br/1695195960247950; Universidade Federal de São Paulo (UNIFESP)Introduction: Cytomegalovirus Is The Most Common Infection After Organ Solid Transplants And It Is Related With Major Morbidity, Mortality And Costs. The Use Of Mtor Inhibitors Is Associated With Lower Incidence Of Cmv Infections But Its Effect On Viral Load Has Not Been Investigated. Objective And Methods: The Aim Of This Analysis Was To Investigate And Compare The Kinetics Of Cmv Replication Using A Quantitative Nucleic Acid Amplification Testing (Qnat) During The First 6 Months After Kidney Transplantation In The Absence Of Pharmacological Prophylaxis. Results: Weekly And Simultaneously, It Was Collected Plasma Samples To Measure Pp65 Antigenemia And Cmv Qnat In 273 Cmv Positive Kidney Transplant Recipients Receiving Ragt/Tac/Evr (N=81), Bas/Tac/Evr (N=97) Or Bas/Tac/Mps (N=95) And No Pharmacological Prophylaxis. Preemptive Therapy Was Used To Prevent Cmv Disease With Pp65 Antigenemia. Qnat Was Collected Exclusively For This Analyses. The Incidence Of First Cmv Infection/Disease (2.5 Vs. 7.2 Vs. 33.7%, P=0
- ItemAcesso aberto (Open Access)Genotipagem do citomegalovírus humano para pesquisa de resistência primária aos antivirais em transplantados renais(Sociedade Brasileira de Patologia ClínicaSociedade Brasileira de PatologiaSociedade Brasileira de Citopatologia, 2004-02-01) Carraro, Emerson [UNIFESP]; Granato, Celso Francisco Hernandes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The aim of this study was to detect by PCR/RFLP HCMV strains containing specific UL97 or UL54 mutation in patients without previous therapy. Samples from 20 renal transplant recipients with HCMV infection at the moment of the diagnosis. From all the patients blood, saliva and urine samples were collected to investigate the possible occurrence of distinct mutations in different body sites. Although no HCMV strains with mutations conferring drug resistance were detected, the PCR/RFLP methodology was considered an adequate and practical tool to detect alterations in viral genes from different body fluids. The absence of drug resistant viral strains in the analyzed samples do not preclude its appearance in the near future, since the use of antiviral drugs in this setting is more widespread in the recent years. We suggest a periodic evaluation of the sensitivity pattern to antiviral drugs in order to monitor its occurrence.
- ItemSomente MetadadadosO impacto dos métodos de antigenemia pp65 e reação em cadeia da polimerase quantitativo para o diagnóstico de infecção por citomegalovírus em receptores de transplante renal em eras distintas(Universidade Federal de São Paulo (UNIFESP), 2020-12-18) Nakamura, Monica Rika [UNIFESP]; Bonato, Claudia Rosso Felipe [UNIFESP]; Universidade Federal de São PauloIntroduction: Cytomegalovirus (CMV) infection is one of the post- most common transplants (20 to 60%), with a possible negative impact on the survival of graft, increased morbidity, and occasionally mortality. Strategies for risk reduction should be adopted after kidney transplantation, such as prophylaxis pharmacological or preemptive treatment. The main laboratory methods for detection of CMV viremia after transplantation are the antigenemia for pp65 and the real-time polymerase chain reaction (PCR). In many Brazilian services, the strategy adopted is preemptive treatment, and the methodology for detecting viremia has varied between services and over time. Objective: To assess the impact of the pp65 (AgCMV) and PCR antigenemia methods used for the detection of viremia in the preemptive treatment of patients at high risk to develop CMV infection or disease, in different eras of transplantation renal. Methodology: This is a quasi-experimental, open, longitudinal study, observational, without intervention by the researchers, with historical control, center (Hospital do Rim - Fundação Oswaldo Ramos), designed to to compare two eras, in which different diagnostic methods of detection of CMV infection. Consecutive kidney transplants were analyzed, between 23/03/2016 to 13/08/2018: 193 patients in the AgCMV era and 198 patients in the AgCMV era PCRCMV. Incidence of infection and disease and duration of treatment were compared between the ages, in addition to an indirect measure of adherence for preemptive treatment. Multivariate analysis for the risk of infection and disease was performed in each of the ages. Results: The population selected for the study (391 patients) had an average of 48 years old, 55.5% male and 54.4% Caucasian, with a predominance of chronic kidney disease of undetermined etiology (43.2%). In the comparison between the two ages (AgCMV vs. PCRCMV), significant differences (P & lt; 0.05) were observed in the following variables: ethnicity of the recipient (45.6 vs. 63.1% Caucasians), time on dialysis pre-transplant (47 vs. 34 months), donor age (53 vs. 50 years), donor gender (47.2 vs. 58.6% male), frequency of KDPI & gt; 80% (49.7 vs. 36.9%) and PRA of class I & gt; 80% (11.4 vs. 4.5%), cold ischemia time (24.3 vs. 21.9 hours), frequency of late graft function (58.5 vs. 41.4%) and, consequently, renal function (CKD-EPI) in 30 days after transplantation (33.99 vs. 41.48 ml / min). There was no difference in the incidence of first episode of infection or disease in the two ages (52.2% vs. 47.8%, P = 0.30) or time to diagnosis (47 vs. 48 days, P = 0.92), however the treatment time was significantly shorter in the AGCMV era (20 vs. 28 days, P & lt; 0.001). There was no statistical difference in the incidence of CMV recurrence the two ages. In a multivariate analysis in the AgCMV era, renal function in 30 days was the only variable that interfered with the risk of developing infection or disease (HR = 0.98, CI- 95% 0.97-0.99, P & lt; 0.001). In the PCRCMV era, the variables related to this risk were donor age (HR = 1.02, 95% CI 1.00-1.03, P = 0.044), late graft function (HR = 1.65, 95% CI 1.07-2.54, P = 0.023) and acute rejection in the first 30 days (HR = 2.13, 95% CI 1.05-4.34, P = 0.037). Conclusion: there was no difference in the incidence of CMV infection and disease and nor in the time to detect viremia, between the two ages. Treatment time, however, it was superior in the PCRCMV era, with no difference in recurrence of infection or illness. Renal function at 30 days interfered with the risk of developing CMV infection or disease in the AgCMV era, as donor age, late function of the graft and acute rejection in the first 30 days were independent factors for the risk of infection or disease in the PCRCMV era.
- ItemAcesso aberto (Open Access)Infecção pelo citomegalovírus em pacientes com síndrome da imunodeficiência adquirida (AIDS): relações clínico-virológicas e anatomopatológicas(Instituto de Medicina Tropical, 1991-08-01) Turchi, Marília Dalva [UNIFESP]; Pannuti, Claudio Sérgio; Sumita, Laura Masami; Vilas Boas, Lucy Santos; Weinberg, Adriana; Stávale, João Norberto [UNIFESP]; Borges, Antônio Fernando Allemand; Collarine, Diva Carvalho; Santos, Honória Virginia Brom dos; Kitadai, Silvia Prado Smit [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Instituto de Medicina Tropical de São Paulo; Hosp. Servidor Estadual Serviço de Anatomia PatológicaBetween April 1986 and June 1987, 50 patients meeting the CDC criteria for AIDS were studied for serological and virological evidence of CMV infection. Attempts for virus isolation from peripheral blood, urine and saliva were performed in cell culture lines of human foreskin fibroblasts and CMV specific IgG and IgM were assayed by IFI and IgG by ELISA. A total of 121 blood, 119 urine and 96 saliva samples were collected. During the study period viremia was noted at least once in 12,5%, viruria in 23,2%, and excretion in saliva in 21,9%. When admitted in the study, 20% (10/50) of the patients had anti-CMV IgM antibodies and 100% (50/50) of them had IgG anti-CMV antibodies (IFI). Five of the 40 patients IgM negative at admission presented anti-CMV IgM antibodies during the study, suggesting CMV reactivation or reinfection. Active CMV infection based on virus isolation and/or IgM positivity was demonstrated in 60% of the patients. Histopathological studies were performed in 24 patients. CMV was found in 50% of the autopsies, mainly in the digestive system, lungs and adrenals. There was no correlation between clinical, virological (serology and isolation) and histopathological diagnosis.
- ItemAcesso aberto (Open Access)Terapia preemptiva de acordo com a percepção do risco de infecção por CMV após o transplante renal(Universidade Federal de São Paulo (UNIFESP), 2016-10-31) Pinto, Cahuê Henrique Motta Coli [UNIFESP]; Pestana, José Osmar Medina de Abreu [UNIFESP]; http://lattes.cnpq.br/7250195328752808; http://lattes.cnpq.br/3016936926052392; Universidade Federal de São Paulo (UNIFESP)Background: The identification of the best strategy to manage CMV infection is hampered by uncertainties regarding the risk/benefit ratios of universal prophylaxis versus preemptive therapy, the impact of indirect CMV effects and the associated costs. This study investigated the efficacy and safety of targeted preemptive therapy according to perceived risk of CMV infection after kidney transplantation. Methods: 144 adult kidney transplant recipient were enrolled in this 12 month study. None received CMV pharmacological prophylaxis. Only high risk patients (D+/R-, use of induction therapy with antithymocyte globulin, treatment of rejection) received preemptive therapy using pp65 antigenemia test. When the low-risk patients had symptoms related to CMV , it was applied screening with pp65 antigenemia and treatment initiated if confirmed CMV disease. Blinded CMV DNAemia was collected weekly during the first 3 months. Results: The incidence of CMV infection was 34 % and CMV disease was 17 %. DNAemia was detected by week 3, was observed in 30% of patients who were not treated for CMV infection/disease, and ?2,384 copies/ml showed a sensitivity of 61% and specificity 85% to detect CMV disease (AUC=0.849±0.042, p<0.001). Using multivariable analysis, only antithymocyte globulin induction was associated with CMV infection/disease whereas only expanded donor criteria and renal function at 30 days were associated with renal function 12 months after transplantation. Conclusion: Targeted preemptive therapy in patients with perceived higher risk for CMV infection/disease was effective in preventing severe clinical presentation, including tissue invasive and late CMV infection. This strategy is associated with direct and indirect cost-savings.