RESUMEN
AIM: The aim of this study was to compare changes in serum hepcidin levels in paediatric patients with inflammatory bowel disease during therapy and correlate them with markers of iron metabolism, inflammation and type of treatment. METHODS: Children with newly diagnosed Crohn's disease (CD) and ulcerative colitis (UC) were included in this longitudinal study. Blood and stool samples were collected to assess levels of serum hepcidin and markers of iron metabolism parameters and inflammation. The parameters were examined before treatment (baseline levels) and compared with levels in the follow-up period during maintenance therapy (mean follow-up of 39 months after diagnosis). RESULTS: Patients with CD (n = 30) had higher serum hepcidin levels (expressed as a median and interquartile range) at diagnosis than subjects with UC (n = 13). These levels significantly decreased during the follow-up (from 36.5 (11.5-79.6) to 2.1 (0.9-6.7) ng/mL). In contrast, no significant serum hepcidin level changes were observed in the UC patients (5.4 (3.4-16.6) vs. 4.8 (0.9-8.1) ng/mL). While hepcidin level changes correlated with disease activity and inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein), in CD patients, they correlated only with serum iron levels in patients with UC. Biological therapy was accompanied by a significant decrease in C-reactive protein and interleukin-6 compared to conventional anti-inflammatory therapy in CD patients. CONCLUSIONS: Children with CD had higher serum hepcidin levels on diagnosis compared to subjects with UC. During an anti-inflammatory therapy, serum hepcidin decreased in the CD group but remained consistently low in children with UC.
Asunto(s)
Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Antiinflamatorios/uso terapéutico , Biomarcadores , Estudios de Casos y Controles , Niño , Colitis Ulcerosa/tratamiento farmacológico , Hepcidinas , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Estudios LongitudinalesRESUMEN
OBJECTIVES: Therapeutic drug monitoring of thiopurine erythrocyte levels is not available in all centers and it usually requires quite a long time to obtain the results. The aims of this study were to build a model predicting low levels of 6-thioguanine and 6-methylmercaptopurine in pediatric inflammatory bowel disease (IBD) patients and to build a model to predict nonadherence in patients treated with azathioprine (AZA). METHODS: The study consisted of 332 observations in 88 pediatric IBD patients. Low AZA dosing was defined as 6-thioguanine levels <125âpmol/8â×â10 erythrocytes and 6-methylmercaptopurine levels <5700âpmol/8â×â10 erythrocytes. Nonadherence was defined as undetectable levels of 6-thioguanine and 6-methylmercaptopurine <240âpmol/8â×â10 erythrocytes. Data were divided into training and testing part. To construct the model predicting low 6-thioguanine levels, nonadherence, and the level of 6-thioguanine, the modification of random forest method with cross-validation and resampling was used. RESULTS: The final models predicting low 6-thioguanine levels and nonadherence had area under the curve, 0.87 and 0.94; sensitivity, 0.81 and 0.82; specificity, 0.80 and 86; and distance, 0.31 and 0.21, respectively, when applied on the testing part of the dataset. When the final model for prediction of 6-thioguanine values was applied on testing dataset, a root-mean-square error of 110 was obtained. CONCLUSIONS: Using easily obtained laboratory parameters, we constructed a model with sufficient accuracy to predict patients with low 6-thioguanine levels and a model for prediction of AZA treatment nonadherence (web applications: https://hradskyo.shinyapps.io/6TG_prediction/ and https://hradskyo.shinyapps.io/Non_adherence/).
Asunto(s)
Inmunosupresores/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Cumplimiento de la Medicación , Mercaptopurina/análogos & derivados , Adolescente , Área Bajo la Curva , Niño , Monitoreo de Drogas , Eritrocitos/metabolismo , Femenino , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/farmacocinética , Enfermedades Inflamatorias del Intestino/sangre , Enfermedades Inflamatorias del Intestino/metabolismo , Masculino , Mercaptopurina/administración & dosificación , Mercaptopurina/farmacocinética , Mercaptopurina/uso terapéutico , Modelos Biológicos , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Tioguanina/metabolismoRESUMEN
INTRODUCTION: Glucocorticoids, particularly prednisone/ prednisolone and dexamethasone, play a prominent role in the treatment of pediatric patients with acute lymphoblastic leukemia due to their ability to induce apoptosis in susceptible cells. Current therapeutic protocols use prednisone for both the prophase and the induction phase of the therapy because the greater antileukemic activity of dexamethasone is compromised by its high frequency of serious adverse reactions. AIM: To compare, for the first time, the in vitro antileukemic activity of prednisolone alone to that of a combination of prednisolone and dexamethasone using dexamethasone at a very low and presumably safe dosage (1/50 w/w). METHODS: Lymphoblasts were isolated from bone marrow and/or blood samples from children with newly diagnosed acute lymphoblastic leukemia. The cytotoxic activity of prednisolone, dexamethasone and the prednisolone/dexamethasone combination against isolated leukemia cells was analyzed using the MTT cytotoxicity assay. RESULTS: We observed differences in the in vitro antileukemic activity of prednisolone and dexamethasone in 21% of the tested patients. 3% of the children were prednisolone sensitive but dexamethasone resistant, while 18% were prednisolone resistant and dexamethasone sensitive. 32% were sensitive to both glucocorticoids and 18% were resistant to both. Cells from patients with good in vivo responses to prednisone monotherapy were more responsive to prednisolone in vitro than were cells from patients with poor prednisone responses (P<0.07). Importantly, we demonstrated that the use of even a minimal dose (1/50 w/w) of dexamethasone with prednisolone dramatically increases the in vitro anti-leukemic activity of prednisolone (P<0.0006). CONCLUSION: The high inter-individual variability of acute lymphoblastic leukemia responses to glucocorticoids suggest that either patients should be selected for prednisone or dexamethasone treatment on the basis of predictive biomarkers or that prednisone should be used directly in combination with a very low and safe dose of dexamethasone to potentiate its antileukemic activity. The latter option is likely to be cheaper and more efficient, and therefore warrants further clinical investigation to assess its efficacy and safety in treating childhood acute lymphoblastic leukemia.
Asunto(s)
Dexametasona/farmacología , Resistencia a Antineoplásicos , Glucocorticoides/farmacología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Prednisolona/farmacología , Niño , Dexametasona/administración & dosificación , Quimioterapia Combinada , Glucocorticoides/administración & dosificación , Humanos , Técnicas In Vitro , Prednisolona/administración & dosificaciónRESUMEN
Pharyngeal perforation caused by non-penetrating cervical trauma is an extremely rare clinical entity both in adults and children. Data concerning management of this type of injury are quite rare in surgical and even scarcer in pediatric literature. Since delay in treatment may be associated with life-threatening complications, prompt diagnosis coupled with appropriate therapy is essential for achieving favorable clinical outcome. To the best of authors' knowledge, the present study illustrates for the first time the experience with successful treatment of pharyngeal perforation caused by a blunt cervical trauma in a child.