ABSTRACT
Our study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients' clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children's Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.
Subject(s)
Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Myeloid-Derived Suppressor Cells/immunology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/etiology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Adolescent , Age Factors , Biomarkers , Case-Control Studies , Child , Child, Preschool , Disease Susceptibility , Female , Humans , Immunophenotyping , Infant , Lymphocytes, Tumor-Infiltrating/pathology , Male , Myeloid-Derived Suppressor Cells/metabolism , Myeloid-Derived Suppressor Cells/pathology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Prognosis , T-Lymphocytes, Regulatory/pathology , Tumor MicroenvironmentABSTRACT
OBJECTIVES: The administration of ketamine as nebulized inhalation is relatively new and studies on nebulized ketamine are scarce. We aimed to investigate the analgesic efficacy of nebulized ketamine (1 and 2mg.kg-1) administered 30min before general anesthesia in children undergoing elective tonsillectomy in comparison with intravenous ketamine (0.5mg.kg-1) and saline placebo. METHODS: One hundred children aged (7-12) years were randomly allocated in four groups (n=25) receive; Saline Placebo (Group C), Intravenous Ketamine 0.5mg.kg-1 (Group K-IV), Nebulized Ketamine 1mg.kg-1 (Group K-N1) or 2mg.kg-1 (Group K-N2). The primary endpoint was the total consumption of rescue analgesics in the first 24h postoperative. RESULTS: The mean time to first request for rescue analgesics was prolonged in K-N1 (400.9±60.5min, 95% CI 375.9-425.87) and K-N2 (455.5±44.6min, 95% CI 437.1-473.9) groups compared with Group K-IV (318.5±86.1min, 95% CI 282.9-354.1) and Group C (68.3±21.9min, 95% CI 59.5-77.1; p<0.001), with a significant difference between K-N1 and K-N2 Groups (p<0.001). The total consumption of IV paracetamol in the first 24h postoperative was reduced in Group K-IV (672.6±272.8mg, 95% CI 559.9-785.2), Group K-N1 (715.6±103.2mg, 95% CI 590.4-840.8) and Group K-N2 (696.6±133.3mg, 95% CI 558.8-834.4) compared with Control Group (1153.8±312.4mg, 95% CI 1024.8-1282.8; p<0.001). With no difference between intravenous and Nebulized Ketamine Groups (p=0.312). Patients in intravenous and Nebulized Ketamine Groups showed lower postoperative VRS scores compared with Group C (p<0.001), no differences between K-IV, K-N1 or K-N2 group and without significant adverse effects. CONCLUSION: Preemptive nebulized ketamine was effective for post-tonsillectomy pain relief. It can be considered as an effective alternative route to IV ketamine.
Subject(s)
Analgesics/administration & dosage , Ketamine/administration & dosage , Pain, Postoperative/prevention & control , Tonsillectomy/methods , Acetaminophen/administration & dosage , Administration, Inhalation , Administration, Intravenous , Anesthesia, General/methods , Child , Double-Blind Method , Female , Humans , Male , Nebulizers and VaporizersABSTRACT
Abstract Objectives The administration of ketamine as nebulized inhalation is relatively new and studies on nebulized ketamine are scarce. We aimed to investigate the analgesic efficacy of nebulized ketamine (1 and 2 mg.kg-1) administered 30 min before general anesthesia in children undergoing elective tonsillectomy in comparison with intravenous ketamine (0.5 mg.kg-1) and saline placebo. Methods One hundred children aged (7-12) years were randomly allocated in four groups (n = 25) receive; Saline Placebo (Group C), Intravenous Ketamine 0.5 mg.kg-1 (Group K-IV), Nebulized Ketamine 1 mg.kg-1 (Group K-N1) or 2 mg.kg-1 (Group K-N2). The primary endpoint was the total consumption of rescue analgesics in the first 24 h postoperative. Results The mean time to first request for rescue analgesics was prolonged in K-N1 (400.9 ± 60.5 min, 95% CI 375.9-425.87) and K-N2 (455.5 ± 44.6 min, 95% CI 437.1-473.9) groups compared with Group K-IV (318.5 ± 86.1 min, 95% CI 282.9-354.1) and Group C (68.3 ± 21.9 min, 95% CI 59.5-77.1; p < 0.001), with a significant difference between K-N1 and K-N2 Groups (p < 0.001). The total consumption of IV paracetamol in the first 24 h postoperative was reduced in Group K-IV (672.6 ± 272.8 mg, 95% CI 559.9-785.2), Group K-N1 (715.6 ± 103.2 mg, 95% CI 590.4-840.8) and Group K-N2 (696.6 ± 133.3 mg, 95% CI 558.8-834.4) compared with Control Group (1153.8 ± 312.4 mg, 95% CI 1024.8-1282.8; p < 0.001). With no difference between intravenous and Nebulized Ketamine Groups (p = 0.312). Patients in intravenous and Nebulized Ketamine Groups showed lower postoperative VRS scores compared with Group C (p < 0.001), no differences between K-IV, K-N1 or K-N2 group and without significant adverse effects. Conclusion Preemptive nebulized ketamine was effective for post-tonsillectomy pain relief. It can be considered as an effective alternative route to IV ketamine.
Resumo Objetivos A administração de cetamina por via inalatória através de nebulizador é relativamente nova e os estudos sobre este assunto são escassos. Nosso objetivo foi investigar a eficácia analgésica da cetamina nebulizada (1 e 2 mg.kg-1) administrada 30 minutos antes da anestesia geral em crianças submetidas à amigdalectomia eletiva, em comparação com cetamina intravenosa (0,5 mg.kg-1) e placebo (soro fisiológico). Métodos Cem crianças entre 7-12 anos foram randomicamente alocadas em quatro grupos (n = 25) e receberam: soro fisiológico para controle (Grupo C); 0,5 mg.kg-1 de cetamina intravenosa (Grupo C-IV); 1 mg.kg-1 de cetamina nebulizada (Grupo C-N1); 2 mg.kg-1 de cetamina nebulizada (Grupo C-N2). O desfecho primário foi o consumo total de analgésicos de resgate nas primeiras 24 horas de pós-operatório. Resultados O tempo médio para a primeira solicitação de analgésicos de resgate foi prolongado nos grupos C-N1 (400,9 ± 60,5 min, IC 95% 375,9-425,87) e C-N2 (455,5 ± 44,6 min, IC 95% 437,1-473,9) em comparação com o Grupo C-IV (318,5 ± 86,1 min, IC 95% 282,9-354,1) e o Grupo C (68,3 ± 21,9 min, IC 95% 59,5-77,1; p < 0,001), com uma diferença significativa entre os grupos C-N1 e C-N2 (p < 0,001). O consumo total de paracetamol IV nas primeiras 24 horas de pós-operatório foi reduzido no Grupo C-IV (672,6 ± 272,8 mg, IC 95% 559,9-785,2), Grupo C-N1 (715,6 ± 103,2 mg, IC 95% 590,4-840,8) e Grupo C-N2 (696,6 ± 133,3 mg, IC 95% 558,8-834,4) em comparação com o Grupo C (1153,8 ± 312,4 mg, IC 95% 1024,8-1282,8; p < 0,001). Não houve diferença entre os grupos de cetamina intravenosa e nebulizada (p = 0,312). Os pacientes dos grupos de cetamina intravenosa e nebulizada apresentaram escores VRS pós-operatórios menores, em comparação com o Grupo C (p < 0,001), sem diferenças entre os grupos C-IV, C-N1 ou C-N2 e sem efeitos adversos significativos. Conclusão A administração preventiva de cetamina nebulizada foi eficaz no alívio da dor pós-amigdalectomia. Cetamina nebulizada pode ser considerada como uma via alternativa eficaz à cetamina IV.
