ALL is the most frequent hematological tumor in children, so during remission induction chemotherapy protocol (RICP) adverse events (AEs) may appear. The public program in Mexico in charge of ...financial support to oncologic children without social security delivered a fix amount for ALL chemotherapy, but additional money needed to treat any other unexpected condition should be taken from the budget of the oncologic healthcare providers. So the purpose of our study was to estimate and evaluate the direct medical costs associated to EAs during RICP in children with ALL.
This study was retrospective, longitudinal, and observational based on medical records review of patients in RICP. The CTCAE was used to identify and classify AEs according to a SOC category. We focused on extracting resources data that were consumed both for inpatients and outpatients AEs. A micro-costing approach was adopted which involve quantification of each healthcare resource consumed by the hospital multiplying them by unit cost. The probability distributions of data were evaluated to identify the appropriated statistical tests to be used for comparisons between groups that were performed with Wilcoxon rank sum test. Generalized linear models (GLM) were adjusted to evaluate the effects of patient characteristics on total cost.
Forty patients accumulated 204 inpatient and 81 outpatient AEs during RICP. Comparison of total costs between groups showed an incremental cost of $7,460.23 likewise attributable to AEs. The total cost of a pediatric patient undergoing RICP without adverse events was $3,078.36 and the total cost of a patient with AEs exceeds it threefold.
The costs associated with AEs during RICP in Mexican children with ALL representing a high burden for the healthcare provider. Generalized linear models showed that variables such as sex, risk category and alive status are associated with the total costs of AEs. This is the first study aiming to analyze the effect of ALL-related AEs on health care costs in pediatric population, so our results may help not only to local decision making but also it may contribute to the research agenda in this field.
Evidence shows that medical education includes a variety of basic and clinical skills. Ethical and human values are not typically considered in medical school curricula, and this is evident in ...medical practice in certain scenarios such as decision-making at pediatric cancer patients' end of life.
This study explores a bioethical approach to address complex decision-making at the end of life in children and adolescents with cancer. We are a cross-functional group of scientists from several academic disciplines who conducted a systematic review of the literature using our newly developed meta-bioethical analysis and synthesis of findings. The search was carried out in five databases, resulting in 10 research papers. Following quality screening, seven articles were ultimately selected for further analysis.
Our focus is on the state of the art to better understand the bioethical deliberation at the end of life in pediatric oncology. Here, we report a systematic review that includes (i) classification of the screened articles by the type of decision-making they use, ii) the system values that are at the core of the decision-making at the end of life, and iii) bioethical and ethical discernment queries. We conclude with a discussion regarding the best practices of ethical discernment and decision-making at the end of life.This study highlights the need to develop more research to better understand the influence and origin of these multidimensional factors determining critical decisions that define the quality of life of patients in a highly sensitive moment.
We conclude that personal aspects of the physician define their actions more than knowledge or organized structure. It is thus necessary that pediatric oncologists receive ethics and humanistic education.
There is evidence that high circulating levels of IL-6 and IL-8 are markers of a poor prognosis in various types of cancer, including NB. The participation of these cytokines in the tumor ...microenvironment has been described to promote progression and metastasis. Our objective was to evaluate the prognostic role of genetic polymorphisms and serum levels of IL-6 and IL-8 in a cohort of Mexican pediatric patients with NB. The detection of the SNPs rs1800795 IL-6 and rs4073 and rs2227306 IL-8 was carried out by PCR-RFLP and the levels of cytokines were determined by the ELISA method. We found elevated circulating levels of IL-8 and IL-6 in NB patients compared to the control group. The genotype frequencies of the rs1800795 IL-6 and rs4073 IL-8 variants were different between the patients with NB and the control group. Likewise, the survival analysis showed that the GG genotypes of rs1800795 IL-6 (
= 0.014) and AA genotypes of rs4073 IL-8 (
= 0.002), as well as high levels of IL-6 (
= 0.009) and IL-8 (
= 0.046), were associated with lower overall survival. We confirmed the impact on an adverse prognosis in a multivariate model. This study suggests that the SNPs rs1800795 IL-6 and rs4073 IL-8 and their serum levels could be promising biomarkers of a poor prognosis, associated with overall survival, metastasis, and a high risk in Mexican children with NB.
•Vascular endothelial growth factor.•Pediatric hematopoietic stem cell transplantation.•Real-time Polymerase Chain Reaction.
Vascular endothelial growth factors are proteins that participate in ...processes related to normal physiology, solid tumors and hematologic malignancies; however, their role in hematopoietic stem cell transplantation (HSCT) requires further investigation. To better define the role and changes in vascular endothelial growth factor-A (VEGF-A) in the context of HSCT, we conducted an observational prospective analysis of VEGF-A expression during the early period after HSCT in pediatric patients. Thirty-seven pediatric patients who underwent hematopoietic stem cell transplantation at the Federico Gómez Children's Hospital in Mexico between June 2016 and July 2018 were prospectively enrolled in this study. Ribonucleic acid was isolated from the venous blood of these patents on Days 0, +7, +14, +21, +28, and +35 after transplantation, and TaqMan reverse transcription-polymerase chain reaction was performed using specific primers and a probe for VEGF-A. The concentration of VEGF-A was determined using a complementary deoxyribonucleic acid control. Data were analyzed using one-way ANOVA and Dunnett post hoc tests. Statistical analysis was performed using SPSS version 25. There were significant differences in the concentrations of VEGF-A between Day 0 vs. Day +28 (p = 0.009 95% CI=0.02–0.24), Day 0 vs. Day +35 (p = 0.006; 95% CI=0.03–0.28) and Day 7 vs. Day + 35 (p = 0.006; 95% CI=0.03–0.24) after allogeneic HSCT. We observed significant increases in the VEGF-A concentration during the early period after stem cell transplantation in pediatric patients. Our results provide important insights that should be considered a basis for future clinical trials of pediatric HSCT, including the monitoring of VEGF-A concentrations, proteins and in vitro analysis.
Background
Childhood cancer is one of the primary causes of disease‐related death in 5‐ to 14‐year‐old children and currently no prevention strategies exist to reduce the incidence of this disease. ...Childhood cancer has a larger hereditary component compared with cancer in adults. Few genetic studies have been conducted on children with cancer. Additionally, Latin American populations are underrepresented in genomic studies compared with other populations. Therefore, the aim of this study is to analyze germline mutations in a group of mixed‐ancestry Mexican pediatric patients with solid and hematological cancers.
Methods
We analyzed genetic variants from 40 Mexican childhood cancer patients and their relatives. DNA from saliva or blood samples was used for whole‐exome sequencing. All variants were identified following GATK best practices.
Results
We found that six patients (15%) were carriers of germline mutations in CDKN2A, CHEK2, DICER1, FANCA, MSH6, MUTYH, NF1, and SBDS cancer predisposition genes, and additional new variants predicted to be deleterious by in silico algorithms. A population genetics analysis detected five components consistent with the demographic models assumed for modern mixed‐ancestry Mexicans.
Conclusions
This report identifies potential genetic risk factors and provides a better understanding of the underlying mechanisms of childhood cancer in this population.
We found that 15% of confirmed mixed‐ancestry Mexican patients were carriers of germline mutations in CDKN2A, CHEK2, DICER1, FANCA, MSH6, MUTYH, NF1, and SBDS. This first report identifies potential genetic risk factors and provides a better understanding of the underlying mechanisms of childhood cancer in this population.
Late adverse events (LAEs) are an important cause of illness and disability in childhood cancer survivors (CCSs) and increase the risk of mortality. The aim of this cross-sectional study was to ...describe the frequency and severity of treatment-related LAEs in Mexican CCSs. The study period was between September 2018 and April 2019. We tested a sample of 82 CCSs at the Hospital Infantil de México Federico Gómez. We considered an LAE to be any medical effect related to treatment after ending cancer therapy. All LAEs were classified according to severity (using the grades of Common Terminology Criteria for Adverse Events v.5.0), diagnosis and time of occurrence after treatment. The treatment-related LAE frequency was 11.0% (95% CI; 4.2–17.8%). A total of 11 LAEs were identified in nine patients. Slightly over half of the patients were male (54.9%). The most frequent diagnosis was acute lymphoblastic leukemia (45.1%). The body systems involved in LAEs were the endocrine (55.6%), neurological (22.2%), auditory (11.1%) and renal (11.1%) systems. Obesity was the most frequent LAE (45.4%). Most LAEs were classified as grade 1 and 2 (60%). The median follow-up was 6.5 years. The odds ratio was used as a measure of association to identify characteristics associated with the LAEs. We identified that the age at diagnosis (OR = 0.71, 95% CI, 0.51–0.99; p = 0.046) and chemotherapy-only group (OR = 0.03, 95% CI, 0.00–0.86, p = 0.040) were associated with LAEs. This is the first study that describes the frequency and severity of LAEs in Mexican childhood cancer survivors.
INTRODUCCIÓN: la leucemia neonatal (o congénita) es aquella diagnosticada en los primeros 30 días tras el nacimiento. Su incidencia se reporta en 1 a 5 por cada millón de recién nacidos vivos ...(corresponde a menos del 1% de las leucemias en pediatría).OBJETIVO: describir los casos diagnosticados en el Hospital Infantil de México Federico Gómez (HIMFG).PRESENTACIÓN DE LA SERIE DE CASOS: se incluyó pacientes menores de 30 días a los cuales se les realizó el diagnóstico morfológico de leucemias entre el 1º de enero de 1990 y el 1º de junio del 2012 en el HIMFG.RESULTADOS: en los 12 años del estudio se identificaron 3,061 casos de leucemias, de los cuales sólo cinco expedientes correspondieron a leucemias neonatales. Se describen tres pacientes femeninos y dos masculinos, con edad media al diagnóstico de 21 días (17-26 días), tratándose con mayor frecuencia de leucemia mieloide (LMA) en tres casos (60%) y leucemia linfoide en dos pacientes. Un caso de LMA asociado a síndrome de Down. En ningún caso se encontraron translocaciones de riesgo. Cuatro pacientes (80%) recibieron manejo para síndrome de lisis tumoral. Cuatro pacientes fallecieron con una mediana de edad de 84 días (57-176 días). El paciente que sobrevivió recibió tratamiento con doxorrubicina y metotrexate al 50% y en suúltimo seguimiento a los tres años de edad continuaba en remisión.CONCLUSIONES: la presentación de los casos corresponde a la reportada en literatura con respecto a frecuencias de leucemias linfoides y mieloides. La supervivencia global a largo plazo fue del 20% (33% para las mieloides) con un solo paciente en remisión. Este padecimiento tiene un pronóstico fatal que puede mejorar con el diagnóstico oportuno (incluso prenatal) y manejo con quimioterapia intensiva. Ésta es la serie más grande de leucemias neonatales reportada en México.
Ovarian fibrosarcomas are extremely rare tumors with little genomic information available to date. In the present report we present the tumoral exome and transcriptome and the germinal exome of an ...ovarian fibrosarcoma from a 9-years old child. We found a paucity of mutations (0.77/Mb) and CNV alterations. Of these, the most relevant were a point mutation in the metal-binding site of the microRNA-processing DICER1 enzyme and a frame-shift alteration in the tumor suppressor gene NF1. We validated a germinal truncating mutation in DICER1, which was consistent with a DICER1 Syndrome diagnosis, providing the first example of an ovarian fibrosarcoma as the presenting neoplasia in this syndrome. Network and enrichment analyses showed that both a mesenchymal signature and a Hedgehog cascade could be driving the progression of this tumor. We were also able to find a global lincRNA deregulation, as the number of lincRNAs transcripts expressed in the tumor was decreased, with a concomitant upregulation of previously described non-coding transcripts associated with cancer, such as MALAT1, MIR181A1HG, CASC1, XIST and FENDRR. DICER1 Syndrome should be considered as a possible diagnosis in children ovarian fibrosarcoma. The role of lncRNAs in neoplasias associated with DICER1 alterations need to be studied in more detail.
Interleukin-1 receptor antagonist polymorphism (ILRN) 2 (ILRN*2) has been associated with a poor outcome in septic patients because of an elevated production of anti-inflammatory cytokines. In >70% ...of patients, morbidity and mortality in childhood acute lymphoblastic leukemia is caused by infections. The aim of this study was to determine the association between this polymorphism and the frequency of septic shock from the time of diagnosis until completion of treatment.
This cohort study was conducted in 57 consecutive children with acute lymphoblastic leukemia. At the end of follow-up, children were stratified according to their IL1RN polymorphism (ILRN*1/ILRN*2), evaluating the impact of genotype on the severity of febrile neutropenic events during their treatment.
Overall survival was 80% at 55 months after treatment. The average number of febrile neutropenic events in this cohort was 2.82 per patient. Genotype distribution was 50.9% for homozygote IL-1RN*1, 38.6% for heterozygote ILRN*1/ILRN*2 and 10.5% for homozygote IL-1RN*2. The risk of presenting septic shock for homozygote IL1RN*2/IL1RN*2 and heterozygote ILRN*1/ILRN*2 patients was significantly greater (odds ratio, 45; P = 0.001) adjusted for age, gender, risk of leukemia and presence of pathogenic bacteria. Genotype IL-1RN*2 is associated with the risk of development of septic shock in children with acute lymphoblastic leukemia. Further research in larger population-based studies is needed to replicate these findings.
This information would allow us to identify more predictive factors in this group of acute lymphoblastic leukemia patients in whom this information is lacking to establish an earlier and more aggressive approach.
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