Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por Citomegalovirus/diagnóstico , Citomegalovirus/inmunología , Trasplante de Células Madre Hematopoyéticas , Receptores de Trasplantes , Aloinjertos , Afinidad de Anticuerpos , Transfusión Sanguínea , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/transmisión , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Reacción en Cadena de la Polimerasa/métodos , Pruebas SerológicasAsunto(s)
Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Aspergilosis Pulmonar/epidemiología , Corticoesteroides/uso terapéutico , Antifúngicos/uso terapéutico , Betacoronavirus , Líquido del Lavado Bronquioalveolar/microbiología , Broncoscopía , COVID-19 , Coinfección/diagnóstico , Coinfección/tratamiento farmacológico , Coinfección/epidemiología , Infecciones por Coronavirus/tratamiento farmacológico , Humanos , Factores Inmunológicos/uso terapéutico , Unidades de Cuidados Intensivos , Aspergilosis Pulmonar Invasiva/diagnóstico , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Aspergilosis Pulmonar Invasiva/epidemiología , Pandemias , Neumonía Viral/tratamiento farmacológico , Aspergilosis Pulmonar/diagnóstico , Aspergilosis Pulmonar/tratamiento farmacológico , Factores de Riesgo , SARS-CoV-2 , Ventilación , Tratamiento Farmacológico de COVID-19RESUMEN
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.
Asunto(s)
Factores de Transcripción Forkhead/metabolismo , Infecciones por HTLV-I/inmunología , Virus Linfotrópico T Tipo 1 Humano/inmunología , Leucemia-Linfoma de Células T del Adulto/inmunología , Linfocitos T Reguladores/inmunología , Adulto , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/patología , Proliferación Celular , Enfermedad Crónica , Femenino , Citometría de Flujo , Estudios de Seguimiento , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/genética , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Leucemia-Linfoma de Células T del Adulto/genética , Leucemia-Linfoma de Células T del Adulto/patología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/patologíaRESUMEN
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.
