Assuntos
Anticorpos Antivirais/sangue , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/imunologia , Transplante de Células-Tronco Hematopoéticas , Transplantados , Aloenxertos , Afinidade de Anticorpos , Transfusão de Sangue , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/transmissão , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Reação em Cadeia da Polimerase/métodos , Testes SorológicosAssuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Aspergilose Pulmonar/epidemiologia , Corticosteroides/uso terapêutico , Antifúngicos/uso terapêutico , Betacoronavirus , Líquido da Lavagem Broncoalveolar/microbiologia , Broncoscopia , COVID-19 , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , Infecções por Coronavirus/tratamento farmacológico , Humanos , Fatores Imunológicos/uso terapêutico , Unidades de Terapia Intensiva , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/epidemiologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/tratamento farmacológico , Fatores de Risco , SARS-CoV-2 , Ventilação , Tratamento Farmacológico da COVID-19RESUMO
Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL). It has been postulated that ATLL cells might act as regulatory T cells (T(regs)) which, in common with ATLL cells, express both CD25 and FoxP3, and so contribute to the severe immune suppression typical of ATLL. We report here that the frequency of CD25(+) cells varied independently of the frequency of FoxP3(+) cells in both a cross-sectional study and in a longitudinal study of 2 patients with chronic ATLL. Furthermore, the capacity of ATLL cells to suppress proliferation of heterologous CD4(+)CD25(-) cells correlated with the frequency of CD4(+) FoxP3(+) cells but was independent of CD25 expression. Finally, the frequency of CD4(+)FoxP3(+) cells was inversely correlated with the lytic activity of HTLV-1-specific CTLs in patients with ATLL. We conclude that ATLL is not a tumor of FoxP3(+) regulatory T cells, and that a population of FoxP3(+) cells distinct from ATLL cells has regulatory functions and may impair the cell-mediated immune response to HTLV-1 in patients with ATLL.
Assuntos
Fatores de Transcrição Forkhead/metabolismo , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Leucemia-Linfoma de Células T do Adulto/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Proliferação de Células , Doença Crônica , Feminino , Citometria de Fluxo , Seguimentos , Infecções por HTLV-I/complicações , Infecções por HTLV-I/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologiaRESUMO
OBJECTIVE: To evaluate the cost-effectiveness of caspofungin vs. liposomal amphotericin B in the treatment of suspected fungal infections in the UK. METHODS: The cost-effectiveness of caspofungin vs. liposomal amphotericin B was evaluated using a decision-tree model. The decision tree was populated using both data and clinical definitions from published clinical studies. Model outcomes included success in terms of resolution of fever, baseline infection, absence of breakthrough infection, survival and quality adjusted life years (QALYs) saved. Discontinuation due to nephrotoxicity or other adverse events were included in the model. Efficacy and safety data were based on additional analyses of a randomised, double blind, multinational trial of caspofungin compared with liposomal amphotericin B. Information on life expectancy, quality of life, medical resource consumption and costs were obtained from peer-reviewed published data. RESULTS: The caspofungin mean total treatment cost was 9762 pounds (95% uncertainty interval 6955-12,577), which was 2033 pounds (-2489; 6779) less than liposomal amphotericin B. Treatment with caspofungin resulted in 0.40 (-0.12; 0.94) additional QALYs saved in comparison with liposomal amphotericin B. Probabilistic sensitivity analysis found a 95% probability of the incremental cost per QALY saved being within the generally accepted threshold for cost-effectiveness (30,000 pounds). Additional analyses with varying dose of caspofungin and liposomal amphotericin B confirmed these findings. CONCLUSION: Given the underlying assumptions, caspofungin is cost-effective compared with liposomal amphotericin B in the treatment of suspected fungal infections in the UK.