Factors Influencing Mortality in Children with Central Nervous System Tumors: A Cohort Study on Clinical Characteristics and Genetic Markers.

Multidrug resistance (MDR) commonly leads to cancer treatment failure because cancer cells often expel chemotherapeutic drugs using ATP-binding cassette (ABC) transporters, which reduce drug levels within the cells. This study investigated the clinical characteristics and single nucleotide variant (SNV) in ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2, and their association with mortality in pediatric patients with central nervous system tumors (CNST). Using TaqMan probes, a real-time polymerase chain reaction genotyped 15 SNPs in 111 samples. Patients were followed up until death or the last follow-up day using the Cox proportional hazards model. An association was found between the rs1045642 (ABCB1) in the recessive model (HR = 2.433, 95% CI 1.098-5.392, p = 0.029), and the ICE scheme in the codominant model (HR = 9.810, 95% CI 2.74-35.06, p ≤ 0.001), dominant model (HR = 6.807, 95% CI 2.87-16.103, p ≤ 0.001), and recessive model (HR = 6.903, 95% CI 2.915-16.544, p = 0.038) significantly increased mortality in this cohort of patients. An association was also observed between the variant rs3114020 (ABCG2) and mortality in the codominant model (HR = 5.35, 95% CI 1.83-15.39, p = 0.002) and the dominant model (HR = 4.421, 95% CI 1.747-11.185, p = 0.002). A significant association between the ICE treatment schedule and increased mortality risk in the codominant model (HR = 6.351, 95% CI 1.831-22.02, p = 0.004, HR = 9.571, 95% CI 2.856-32.07, p ≤ 0.001), dominant model (HR = 6.592, 95% CI 2.669-16.280, p ≤ 0.001), and recessive model (HR = 5.798, 95% CI 2.411-13.940, p ≤ 0.001). The genetic variants rs3114020 in the ABCG2 gene and rs1045642 in the ABCB1 gene and the ICE chemotherapy schedule were associated with an increased mortality risk in this cohort of pediatric patients with CNST.

Evidence of spatial clustering of childhood acute lymphoblastic leukemia cases in Greater Mexico City: report from the Mexican Inter-Institutional Group for the identification of the causes of childhood leukemia.

Background: A heterogeneous geographic distribution of childhood acute lymphoblastic leukemia (ALL) cases has been described, possibly, related to the presence of different environmental factors. The aim of the present study was to explore the geographical distribution of childhood ALL cases in Greater Mexico City (GMC). Methods: A population-based case-control study was conducted. Children <18 years old, newly diagnosed with ALL and residents of GMC were included. Controls were patients without leukemia recruited from second-level public hospitals, frequency-matched by sex, age, and health institution with the cases. The residence address where the patients lived during the last year before diagnosis (cases) or the interview (controls) was used for geolocation. Kulldorff's spatial scan statistic was used to detect spatial clusters (SCs). Relative risks (RR), associated p-value and number of cases included for each cluster were obtained. Results: A total of 1054 cases with ALL were analyzed. Of these, 408 (38.7%) were distributed across eight SCs detected. A relative risk of 1.61 (p<0.0001) was observed for the main cluster. Similar results were noted for the remaining seven ones. Additionally, a proximity between SCs, electrical installations and petrochemical facilities was observed. Conclusions: The identification of SCs in certain regions of GMC suggest the possible role of environmental factors in the etiology of childhood ALL.

Perinucleolar Compartment (PNC) Prevalence as an Independent Prognostic Factor in Pediatric Ewing Sarcoma: A Multi-Institutional Study.

The perinucleolar compartment (PNC) is a small nuclear body that plays important role in tumorigenesis. PNC prevalence correlates with poor prognosis and cancer metastasis. Its expression in pediatric Ewing sarcoma (EWS) has not previously been documented. In this study, we analyzed 40 EWS tumor cases from Caucasian and Hispanic patients for PNC prevalence by immunohistochemical detection of polypyrimidine tract binding protein and correlated the prevalence with dysregulated microRNA profiles. EWS cases showed staining ranging from 0 to 100%, which were categorized as diffuse (≥77%, n = 9, high PNC) or not diffuse (<77%, n = 31) for low PNC. High PNC prevalence was significantly higher in Hispanic patients from the US (n = 6, p = 0.017) and in patients who relapsed with metastatic disease (n = 4; p = 0.011). High PNC was associated with significantly shorter disease-free survival and early recurrence compared to those with low PNC. Using NanoString digital profiling, high PNC tumors revealed upregulation of eight and downregulation of 18 microRNAs. Of these, miR-320d and miR-29c-3p had the most significant differential expression in tumors with high PNC. In conclusion, this is the first study that demonstrates the presence of PNC in EWS, reflecting its utility as a predictive biomarker associated with tumor metastasis, specific microRNA profile, Hispanic ethnic origin, and poor prognosis.

Triple-hit explanation for the worse prognosis of pediatric acute lymphoblastic leukemia among Mexican and Hispanic children.

Acute lymphoblastic leukemia (ALL) is the most common malignancy among Mexican and Hispanic children and the first cause of death by disease in Mexico. We propose a "triple-hit" explanation for the survival gap affecting this population. The first hit can be attributed to epidemiology and social, cultural, and economic burdens. The second hit refers to cancer biology, with a high incidence of unfavorable genetic characteristics associated with an unfavorable response to treatment and, subsequently, poor survival. Finally, the third hit relates to sub-optimal treatment and support. Society and culture, leukemia biology, and treatment approach limitations are key factors that should not be seen apart and must be considered comprehensively in any strategy to improve the prognosis of Mexican and Hispanic children with ALL.

Persistently high incidence rates of childhood acute leukemias from 2010 to 2017 in Mexico City: A population study from the MIGICCL.

Introduction: Over the years, the Hispanic population living in the United States has consistently shown high incidence rates of childhood acute leukemias (AL). Similarly, high AL incidence was previously observed in Mexico City (MC). Here, we estimated the AL incidence rates among children under 15 years of age in MC during the period 2010-2017. Methods: The Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia conducted a study gathering clinical and epidemiological information regarding children newly diagnosed with AL at public health institutions of MC. Crude age incidence rates (cAIR) were obtained. Age-standardized incidence rates worldwide (ASIRw) and by municipalities (ASIRm) were calculated by the direct and indirect methods, respectively. These were reported per million population <15 years of age; stratified by age group, sex, AL subtypes, immunophenotype and gene rearrangements. Results: A total of 903 AL cases were registered. The ASIRw was 63.3 (cases per million) for AL, 53.1 for acute lymphoblastic leukemia (ALL), and 9.4 for acute myeloblastic leukemia. The highest cAIR for AL was observed in the age group between 1 and 4 years (male: 102.34 and female: 82.73). By immunophenotype, the ASIRw was 47.3 for B-cell and 3.7 for T-cell. The incidence did not show any significant trends during the study period. The ASIRm for ALL were 68.6, 66.6 and 62.8 at Iztacalco, Venustiano Carranza and Benito Juárez, respectively, whereas, other municipalities exhibited null values mainly for AML. Conclusion: The ASIRw for childhood AL in MC is among the highest reported worldwide. We observed spatial heterogeneity of rates by municipalities. The elevated AL incidence observed in Mexican children may be explained by a combination of genetic background and exposure to environmental risk factors.

Clinical characteristics and mortality predictors of patients with cancer hospitalized by COVID-19 in a pediatric third-level referral center.

Background: More than 135 million COVID-19 cases (coronavirus disease 2019) have been reported worldwide until today, with over 2.9 million deaths. Several studies have demonstrated that disease severity is lower in the pediatric population than in adults; however, differences are described in patients with chronic diseases, including oncological patients. Current world literature suggests patients with comorbidities, including cancer, have an increased risk of unfortunate outcomes. Therefore, our objective was to describe the clinical characteristics and epidemiological factors associated with mortality in a cohort of pediatric cancer patients hospitalized for COVID-19. Methods: This is a retrospective, descriptive study of the cases of patients with cancer hospitalized for COVID-19. A total of 40 pediatrics were included in the analysis. Data from pediatric patients with COVID-19 included clinical and epidemiological records, laboratory, imaging studies, COVID-19 diagnostic methods, and medical treatment. Results: Of the 40 pediatric patients admitted with cancer with a confirmed diagnosis of COVID-19, 42.5% were solid tumors, 40% leukemias, and 17.5% lymphomas. The clinical parameters associated with mortality were stage IV tumor (p = 0.029) and intubation (p < 0.001). The biochemical factors associated with lower survival were thrombocytopenia under 25,000 cells/mm3 (p < 0.001), D-dimer over 1 µg/ml (p = 0.003), clinical malnutrition (p = 0.023), and disseminated intravascular coagulation (p = 0.03). Conclusion: Our findings showed that the fever was the most frequent symptom, and the clinical parameters associated with mortality were stage IV tumor, intubation, saturation percentage, RDW, platelets, creatinine, ALT, D-dimer, ferritin, and FiO2 percentage. The thrombocytopenia, D-dimer, nutritional status, and disseminated intravascular coagulation were significantly associated with lower survival.

Expression of Cytochrome P450 Enzymes in Pediatric Non-Rhabdomyosarcoma Soft Tissue Sarcomas: Possible Role in Carcinogenesis and Treatment Response.

The 5-year relative survival rate estimate of treated patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) is ∼50% since they generally present with tumor progression, relapse, metastasis, and/or chemoresistance. The expression of cytochrome P450 (CYP) enzymes in malignancies can affect the pharmacology of drugs commonly used in chemotherapy or confer susceptibility to development of chemical carcinogenesis; in addition, their specific tumor expression can be used as a therapeutic target. Using qPCR and Western blot assays, the expression of CYP1B1, CYP2E1, CYP3A4, and CYP3A5 were analyzed in a cohort of tumor tissue paired with non-malignant adjacent tissue of patients with NRSTS. The mRNA and protein expression of CYP1B1, CYP2E1, and CYP3A4 were significantly increased in tumor tissue. We propose that the expression of these isoforms is related to carcinogenesis and chemoresistance frequently observed in these neoplasms.

Does the Human Development Index relate with acute lymphoblastic leukemia incidence? / ¿Existe relación entre el Índice de Desarrollo Humano y la incidencia de leucemia linfoblástica aguda?

Abstract Background: The association between childhood cancer and socioeconomic status has been widely studied. However, none of the results are conclusive. This study aimed to analyze the association between the Human Development Index (HDI) and the acute lymphoblastic leukemia (ALL) incidence in children under the Popular Medical Insurance Care. Methods: We conducted an observational, descriptive, and population-based study covering 55% of the Mexican population (58 million). Results: The most impoverished states were located in the south east region of Mexico, while the north was more homogeneous, with HDIs varying between 0.73 and 0.79. Our findings emphasize that the metropolitan area of Mexico City and the State of Nuevo Leon have the highest levels of HDI. Regions were graded from I to IV according to their HDIs in ascending order. The HDIs varied from 0.667 to 0.830/100,000 children/year, with a national average of 0.746. The leukemia incidence for regions I, II, III, and IV was 6.12, 6.53, 4.96, and 9.95. An analysis of ALL incidence in Mexico showed significant differences for region IV in comparison with the other regions based on the HDI values (p = 0.0001). Conclusions: Further in-depth studies, including the economic aspects of the different geographic regions and their ethnographic characteristics, would give a more comprehensive panorama.

Resumen Introducción: Se ha estudiado la relación entre el nivel socioeconómico y el cáncer en niños. Sin embargo, aún no existen resultados concluyentes. El objetivo de este trabajo fue analizar la asociación entre el Índice de Desarrollo Humano (IDH) y la incidencia de leucemia linfoblástica aguda en niños atendidos por el Seguro Popular. Métodos: Se realizó un estudio observacional y descriptivo. La población estudiada representa el 55% de la población mexicana (58 millones). Resultados: Los Estados más pobres se localizaron en la región sureste de México, mientras que el norte del país fue más homogéneo, con un IDH que varió entre 0.73 y 0.79. Los hallazgos muestran que el área metropolitana de la Ciudad de México y el Estado de Nuevo León tienen un IDH más alto. Las regiones se graduaron del I al IV en orden ascendente de acuerdo con su IDH. El IDH varió de 0.667 a 0.830 por 100,000 niños por año, con un promedio nacional de 0.746. La incidencia de leucemia por 100,000 niños por año en las regiones I, II, III y IV fue de 6.12, 6.53, 4.96 y 9.95, respectivamente. El análisis de variabilidad de la incidencia de leucemia linfoblástica aguda en México muestra diferencias entre la región IV y el resto de las regiones de acuerdo con los valores del IDH (p = 0.0001). Conclusiones: Se deben realizar estudios más profundos que consideren no solo los aspectos económicos de las diferentes regiones, sino también sus características etnográficas, lo cual podría dar un panorama más amplio.

Importancia de la cardiooncología. Cómo detectar la insuficiencia cardiaca subclínica / Importance of cardio-oncology. How to detect suclinical heart failure

Resumen Hoy una de las principales causas de mortalidad es el cáncer. La supervivencia en pacientes con cáncer ha incrementado de 1970 (25%) a la actualidad (80%). A raíz de la introducción de las antraciclinas como tratamiento de cáncer desde 1960-1970, más del 60% de los pacientes son tratados con estos agentes; sin embargo, la exposición de quimioterápicos conlleva las enfermedades cardiovasculares como la principal causa de mortalidad en enfermos supervivientes de cáncer en el s. XXI. Hay múltiples factores que incrementan la sensibilidad de cardiotoxicidad inducida por antracíclicos. En 1970 el estándar de oro para la detección de disfunción ventricular era la biopsia endomiocárdica, en forma posterior la detección y manejo de la cardiotoxicidad fue guiada por los síntomas, en 1981 la detección de cardiotoxicidad fue reportada con la determinación de la fracción de expulsión del ventrículo izquierdo (FEVI) por ecocardiografía 2D. En la actualidad el ecocardiograma 3D para FEVI y volúmenes sistólico y diastólico han presentado una alta correlación de los valores obtenidos por resonancia magnética para la evaluación de la función cardiaca. Hoy en día la ecocardiografía strain, strain-rate y speckle tracking se utilizan para determinar la función miocárdica regional y global. Para una valoración integral estos resultados se pueden complementar con biomarcadores cardiacos (troponinas y propéptido natriurético tipo B) y cambios electrocardiográficos. De esta forma se puede detectar insuficiencia cardiaca subclínica y dar un tratamiento oportuno.

Abstract Today one of the main causes of mortality is cancer. Survival in cancer patients has increased from 1970 (25%) to the present (80%). Following the introduction of anthracyclines as a cancer treatment since 1960-70, more than 60% of patients are treated with these agents, although chemotherapeutic exposure leads to cardiovascular diseases as the main cause of mortality in surviving patients. of cancer in the 21st Century. There are multiple factors that increase the sensitivity of anthracyclic-induced cardiotoxicity. In 1970 the gold standard for the detection of ventricular dysfunction was endomyocardial biopsy, subsequently the detection and management of cardiotoxicity was guided by symptoms, in 1981 the detection of cardiotoxicity was reported with the determination of the ejection fraction of the left ventricle (LVEF), by 2D echocardiography. Currently, the 3D echocardiogram for LVEF and systolic and diastolic volumes have presented a high correlation of the values obtained by magnetic resonance imaging for the evaluation of cardiac function. Today strain, strain-rate and speckle tracking echocardiography are used to determine regional and global myocardial function. For a comprehensive assessment, these results can be complemented with cardiac biomarkers (troponins) and electrocardiographic changes. In this way, subclinical heart failure can be detected and timely treatment can be given.

Importance of cardio-oncology. How to detect suclinical heart failure.

Today one of the main causes of mortality is cancer. Survival in cancer patients has increased from 1970 (25%) to the present (80%). Following the introduction of anthracyclines as a cancer treatment since 1960-70, more than 60% of patients are treated with these agents, although chemotherapeutic exposure leads to cardiovascular diseases as the main cause of mortality in surviving patients. of cancer in the 21st Century. There are multiple factors that increase the sensitivity of anthracyclic-induced cardiotoxicity. In 1970 the gold standard for the detection of ventricular dysfunction was endomyocardial biopsy, subsequently the detection and management of cardiotoxicity was guided by symptoms, in 1981 the detection of cardiotoxicity was reported with the determination of the ejection fraction of the left ventricle (LVEF), by 2D echocardiography. Currently, the 3D echocardiogram for LVEF and systolic and diastolic volumes have presented a high correlation of the values obtained by magnetic resonance imaging for the evaluation of cardiac function. Today strain, strain-rate and speckle tracking echocardiography are used to determine regional and global myocardial function. For a comprehensive assessment, these results can be complemented with cardiac biomarkers (troponins) and electrocardiographic changes. In this way, subclinical heart failure can be detected and timely treatment can be given.

Hoy una de las principales causas de mortalidad es el cáncer. La supervivencia en pacientes con cáncer ha incrementado de 1970 (25%) a la actualidad (80%). A raíz de la introducción de las antraciclinas como tratamiento de cáncer desde 1960-1970, más del 60% de los pacientes son tratados con estos agentes; sin embargo, la exposición de quimioterápicos conlleva las enfermedades cardiovasculares como la principal causa de mortalidad en enfermos supervivientes de cáncer en el s. XXI. Hay múltiples factores que incrementan la sensibilidad de cardiotoxicidad inducida por antracíclicos. En 1970 el estándar de oro para la detección de disfunción ventricular era la biopsia endomiocárdica, en forma posterior la detección y manejo de la cardiotoxicidad fue guiada por los síntomas, en 1981 la detección de cardiotoxicidad fue reportada con la determinación de la fracción de expulsión del ventrículo izquierdo (FEVI) por ecocardiografía 2D. En la actualidad el ecocardiograma 3D para FEVI y volúmenes sistólico y diastólico han presentado una alta correlación de los valores obtenidos por resonancia magnética para la evaluación de la función cardiaca. Hoy en día la ecocardiografía strain, strain-rate y speckle tracking se utilizan para determinar la función miocárdica regional y global. Para una valoración integral estos resultados se pueden complementar con biomarcadores cardiacos (troponinas y propéptido natriurético tipo B) y cambios electrocardiográficos. De esta forma se puede detectar insuficiencia cardiaca subclínica y dar un tratamiento oportuno.

CRLF2 and IKZF1 abnormalities in Mexican children with acute lymphoblastic leukemia and recurrent gene fusions: exploring surrogate markers of signaling pathways.

The gene fusions BCR-ABL1, TCF3-PBX1, and ETV6-RUNX1 are recurrent in B-cell acute lymphoblastic leukemia (B-ALL) and are found with low frequency in coexistence with CRLF2 (cytokine receptor-like factor 2) rearrangements and overexpression. There is limited information regarding the CRLF2 abnormalities and dominant-negative IKZF1 isoforms associated with surrogate markers of Jak2, ABL, and Ras signaling pathways. To assess this, we evaluated 24 Mexican children with B-ALL positive for recurrent gene fusions at diagnosis. We found CRLF2 rearrangements and/or overexpression, dominant-negative IKZF1 isoforms, and surrogate phosphorylated markers of signaling pathways coexisting with recurrent gene fusions. All the BCR-ABL1 patients expressed CRLF2 and were positive for pCrkl (ABL); most of them were also positive for pStat5 (Jak2/Stat5) and negative for pErk (Ras). TCF3-PBX1 patients with CRLF2 abnormalities were positive for pStat5, most of them were also positive for pCrkl, and two patients were also positive for pErk. One patient with ETV6-RUNX1 and intracellular CRLF2 protein expressed pCrkl. In some cases, the activated signaling pathways were reverted in vitro by specific inhibitors. We further analyzed a TCF3-PBX1 patient at relapse, identifying a clone with the recurrent gene fusion, P2RY8-CRLF2, rearrangement, and phosphorylation of the three surrogate markers that we studied. These results agree with the previous reports regarding resistance to treatment observed in patients with recurrent gene fusions and coexisting CRLF2 gene abnormalities. A marker phosphorylation signature was identified in BCR-ABL1 and TCF3-PBX1 patients. To obtain useful information for the assessment of treatment in B-ALL patients with recurrent gene fusions, we suggest that they should be evaluated at diagnosis for CRLF2 gene abnormalities and dominant-negative IKZF1 isoforms, in addition to the analyses of activation and inhibition of signaling pathways.

Does the Human Development Index relate with acute lymphoblastic leukemia incidence?

BACKGROUND: The association between childhood cancer and socioeconomic status has been widely studied. However, none of the results are conclusive. This study aimed to analyze the association between the Human Development Index (HDI) and the acute lymphoblastic leukemia (ALL) incidence in children under the Popular Medical Insurance Care. METHODS: We conducted an observational, descriptive, and population-based study covering 55% of the Mexican population (58 million). RESULTS: The most impoverished states were located in the south east region of Mexico, while the north was more homogeneous, with HDIs varying between 0.73 and 0.79. Our findings emphasize that the metropolitan area of Mexico City and the State of Nuevo Leon have the highest levels of HDI. Regions were graded from I to IV according to their HDIs in ascending order. The HDIs varied from 0.667 to 0.830/100,000 children/year, with a national average of 0.746. The leukemia incidence for regions I, II, III, and IV was 6.12, 6.53, 4.96, and 9.95. An analysis of ALL incidence in Mexico showed significant differences for region IV in comparison with the other regions based on the HDI values (p = 0.0001). CONCLUSIONS: Further in-depth studies, including the economic aspects of the different geographic regions and their ethnographic characteristics, would give a more comprehensive panorama.

v-myb avian myeloblastosis viral oncogene homolog expression is a potential molecular diagnostic marker for B-cell acute lymphoblastic leukemia.

BACKGROUND: B-cell acute lymphoblastic leukemia (B-ALL) is the most commonly diagnosed childhood malignancy worldwide and is especially common in Mexico. Additionally, the number of cases has increased in recent years. Thus, it is very important to develop molecular strategies to diagnose leukemia. The aim of this study was to investigate MYB expression and to determine its impact on the diagnosis of B-ALL. METHODS: We analyzed the B-ALL gene expression profile by microarray data mining. Bioinformatics analysis was performed to identify the genes that are overexpressed in leukemia. We determined that MYB was highly expressed in leukemia. Then, we validated MYB expression in 70 patients with B-ALL and in 16 healthy controls (HCs) using qRT-PCR. The results were statistically analyzed using the Kolmogorov-Smirnov Z test, Mann-Whitney U test, receiver operating characteristic curves, and the Youden index. RESULTS: The microarrays showed that MYB was overexpressed in B-ALL patients with a fold change of 57.8728 and a P value of 2.56-195 . MYB expression showed great variability among the patients analyzed. However, compared to the HCs, the B-ALL patients had a P value < .0001, an area under the curve of 0.813, and a Youden index of 1.46, indicating the statistical significance. CONCLUSION: MYB expression in B-ALL cells could be a potential molecular marker for childhood leukemia.

Extremely Low-Frequency Magnetic Fields and the Risk of Childhood B-Lineage Acute Lymphoblastic Leukemia in a City With High Incidence of Leukemia and Elevated Exposure to ELF Magnetic Fields.

It is important to study the relationship between extremely low-frequency magnetic fields (ELF-MFs) and childhood leukemia, particularly in locations with a high incidence of this neoplasm in children and an elevated exposure to ELF-MF, such as Mexico City. The aim was to investigate the association between ELF-MF exposure and the risk of B-lineage acute lymphoblastic leukemia (B-ALL). A case-control study was conducted in Mexico City during the period from 2010 to 2011. Residential 24-h ELF-MF measurements were obtained for 290 incident B-ALL patients and 407 controls, aged less than 16 years. Controls were frequency-matched by sex, age (±18 months), and health institution. The adjusted odds ratios (aOR) and 95% confidence intervals (CIs) were calculated. ELF-MF exposure at <0.2 µT was used to define the reference group. ELF-MF exposure at ≥0.3 µT was observed in 11.3% of the controls. Different ELF-MF intensity cutoff values were used to define the highest exposure category; the highest exposure category for each cutoff value was associated with an increased risk of B-ALL compared with the corresponding lower exposure categories. The aORs were as follows: ≥0.2 µT = 1.26 (95% CI: 0.84-1.89); ≥0.3 µT = 1.53 (95% CI: 0.95-2.48); ≥0.4 µT = 1.87 (95% CI: 1.04-3.35); ≥0.5 µT = 1.80 (95% CI 0.95-3.44); ≥0.6 µT = 2.32 (95% CI: 1.10-4.93). ELF-MF exposure as a continuous variable (per 0.2 µT intervals) was associated with B-ALL risk (aOR = 1.06; 95% CI: 1.01-1.12). In the present study, the proportion of children exposed to ≥0.3 µT is among the highest reported worldwide. Additionally, an ELF-MF exposure ≥0.4 µT may be associated with the risk of B-ALL. Bioelectromagnetics. © 2020 Bioelectromagnetics Society.

Maternal and paternal ages at conception of index child and risk of childhood acute leukaemia: A multicentre case-control study in Greater Mexico City.

BACKGROUND: The parental age at conception has been reported to be a risk factor for childhood acute leukaemia (AL); however, the relationship is controversial. The aim of the present study was to investigate the association between parental age at conception and the risk of AL in Mexican children, a population with a high incidence of the disease and a high prevalence of pregnancies in adolescents and young adults. METHODS: A multicentre case-control study was conducted. Incident AL cases younger than 17 years of age diagnosed between 2010 and 2015 were included. Controls were matched with cases according to age, sex, and health institution. Using logistic regression analysis, adjusted odds ratios (aOR) and 95 % confidence intervals (95 % CI) were calculated for each maternal stratum after adjusting for paternal age at conception of index child. The maternal age between 25 and 29.99 years was selected as the reference category. RESULTS: In most strata where maternal and paternal ages were assessed, no association was found with the risk of developing acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in their offspring. An increased risk for AML was observed when the mother was between 20 and 24.99 years of age and the father aged 25-29.99 years (aOR, 1.94; 95 % CI, 1.03-3.67). In addition, there was a positive association for ALL when the mother´s age was between 20 and 24.99 years and the father was <20 years of age, however, a very wide confidence interval was noted (aOR, 12.26; 95 % CI, 1.41-106.83). CONCLUSION: In the present study, maternal and paternal ages assessed in different strata showed little association with risk of developing ALL and AML in children. Positive associations between risk of both types of childhood AL were observed with younger paternal and maternal ages.

Analysis of CYP450 gene allelic variants can predict ifosfamide toxicity in Mexican paediatric patients.

Context: Ifosfamide (IFA) is an effective antineoplastic for solid tumours in children, although it is associated with high levels of systemic toxicity and causes death in some cases. Objective: The aim of this study was to determine whether the presence of certain allelic variants of genes CYP2B6, CYP2C9, CYP3A4 and CYP3A5 increases the risk of toxicity in children with solid tumours treated with ifosfamide.Materials and methods: A total of 131 DNA samples were genotyped by real-time polymerase chain reaction (RT-PCR) using TaqMan probes. Toxicity was assessed using WHO criteria, and survival analysis was performed using Kaplan-Meier curves.Results: The rs3745274 allelic variant in CYP2B6 was associated with haematological toxicity, affecting neutrophils; CYP3A4 variant rs2740574 was also associated with toxicity, affecting both leukocytes and neutrophils. Additionally, the CYP3A5 gene variant rs776746 was found to affect haemoglobin.Conclusions: Our results show that allelic variants rs3745274 (CYP2B6), rs2740574 (CYP34) and rs776746 (CYP3A5) increase the risk for high haematological toxicity.Clinical trial registration: 068/2013.

Expression of ZNF695 Transcript Variants in Childhood B-Cell Acute Lymphoblastic Leukemia.

B-cell acute lymphoblastic leukemia is the most commonly diagnosed childhood malignancy worldwide; more than 50% of these cases are diagnosed in Mexico. Although the five-year survival rate is >80%, 30% of patients experience relapse with poor prognosis. Cancer-associated gene expression profiles have been identified in several malignancies, and some transcripts have been used to predict disease prognosis. The human transcriptome is incompletely elucidated; moreover, more than 80% of transcripts can be processed via alternative splicing (AS), which increases transcript and protein diversity. The human transcriptome is divided; coding RNA accounts for 2%, and the remaining 98% is noncoding RNA. Noncoding RNA can undergo AS, promoting the diversity of noncoding transcripts. We designed specific primers to amplify previously reported alternative transcript variants of ZNF695 and showed that six ZNF695 transcript variants are co-expressed in cancer cell lines. The amplicons were sequenced and identified. Additionally, we analyzed the expression of these six transcript variants in bone marrow from B-cell acute lymphoblastic leukemia patients and observed that ZNF695 transcript variants one and three were the predominant variants expressed in leukemia. Moreover, our results showed the co-expression of coding and long noncoding RNA. Finally, we observed that long noncoding RNA ZNF695 expression predicted survival rates.

Variants in ARID5B gene are associated with the development of acute lymphoblastic leukemia in Mexican children.

A high impact of ARID5B SNPs on acute lymphoblastic leukemia (ALL) susceptibility has been described in Hispanic children; therefore, it is relevant to know if they influence the high incidence of childhood-ALL in Mexicans. Seven SNPs (rs10821936, rs10994982, rs7089424, rs2393732, rs2393782, rs2893881, rs4948488) of ARID5B were analyzed in 384 controls and 298 ALL children using genomic DNA and TaqMan probes. The SNPs were analyzed for deviation of Hardy-Weinberg equilibrium; Fisher's exact test was used to compare the genotypic and allelic frequencies between controls and patients. The association between SNPs and ALL susceptibility was calculated, and haplotype and ancestry analyses were conducted. All SNPs were associated with ALL, pre-B ALL, and hyperdiploid-ALL susceptibility (p < 0.05). No association with T-ALL and gene fusions was found (p > 0.05). The seven SNPs were associated with risk of pre-B ALL in younger children; however, rs2393732, rs2393782, rs2893881, and rs4948488 were not associated with susceptibility in older children and adolescents. The CAG haplotype (rs10821936, rs10994982, rs7089424) was strongly associated with ALL risk in our population (p < 0.00001). The frequency of all risk alleles in our ALL, pre-B, and hyperdiploid-ALL patients was higher than that in Hispanic children reported. This is the first report showing the association between rs2393732, rs2393782, and rs4948488 with pre-B hyperdiploid-ALL children. The G allele at rs2893881 confers major risk for pre-B hyperdiploid-ALL in Mexican (OR, 2.29) than in Hispanic children (OR, 1.71). The genetic background of our population could influence the susceptibility to ALL and explain its high incidence in Mexico.

Feeding difficulties and eating disorders in pediatric patients with cancer / Trastornos y dificultades en la alimentación en pacientes pediátricos con cáncer

Abstract Background Feeding difficulties and disorders are a common problem in the pediatric population, which involve a series of deficient behaviors about nutrition processes that can adversely affect psychomotor, psychosocial, and physical development of children. This study aimed to describe the frequency of feeding difficulties or disorders in pediatric patients with cancer. Methods A prospective study which included 125 children from 1-19 years treated at the Department of Oncology of the Instituto Nacional de Pediatría, Mexico City, was conducted. The diagnosis of eating disorders and feeding difficulties was determined during the first 48 h since admission, and the age of the patient influenced the type of disorder and feeding difficulties. Results Children older than 11 years presented more frequently an intense resistance of feeding because of discomfort pain (fear of feeding) than younger children (11.4 ± 4.7 vs. 7.4 ± 4.9, p ≤ 0.001). The most frequent alteration associated with malnutrition was loss of appetite (odds ratio [OR]: 8.8, confidence interval [CI] 95% 2.9-26.9, p<0.001), followed by fear of feeding (OR: 3.14, CI 95% 1.24-7.9, p=0.015), and the organic causes showed the highest risk for malnutrition (OR: 3.1, CI 95% 0.98-9.7, p=0.054). Conclusions Over 90% of the studied population demonstrated at least one eating disorder or feeding difficulty. The principal effect is inadequate nutritional intake due to limited appetite and fear of feeding, which can result in undernutrition. For this reason, the identification of alterations in nutrition processes should be part of the comprehensive assessment of cancer patients.

Resumen Introducción Los trastornos y dificultades para la alimentación son problemas comunes en la edad pediátrica. Estas situaciones conllevan una serie de comportamientos inadecuados respecto de los procesos de nutrición que pueden afectar de manera adversa el desarrollo psicomotor, psicosocial y físico del niño. El objetivo de este trabajo fue describir la frecuencia de desórdenes y dificultades en la alimentación en niños con cáncer a través de un estudio prospectivo. Métodos Se incluyeron 125 niños de 1 a 19 años de edad del Servicio de Oncología del Instituto Nacional de Pediatría, Ciudad de México. El diagnóstico de desorden y dificultad en la alimentación se determinó en las primeras 48 horas del ingreso. Resultados Los niños mayores de 11 años presentan con mayor frecuencia resistencia a comer debido a dolor o malestar (miedo a comer) (11.4±4.7 años versus 7.4±4.9 años; p≤0.001). La alteración más frecuente asociada a malnutrición fue la disminución del apetito (razón de momios [RM]: 8.8; intervalo de confianza [IC] 95%: 2.9-26.9; p<0.001), seguido del miedo a comer (RM: 3.14; IC 95%: 1.24-7.9; p=0.015) y las causas con mayor riesgo de malnutrición fueron las orgánicas (RM: 3.1; IC 95%: 0.98-9.7; p=0.054). Conclusiones Se encontró que en más del 90% de esta población se presentó por lo menos un desorden alimentario o dificultad al alimentarse. El principal efecto es la ingesta nutricional inadecuada debida al apetito limitado y al miedo a alimentarse, lo que puede resultar en desnutrición. Por esta razón, la identificación de alteraciones en los procesos de nutrición deben ser parte de la valoración integral de los pacientes con cáncer.

Feeding difficulties and eating disorders in pediatric patients with cancer.

Background: Feeding difficulties and disorders are a common problem in the pediatric population, which involve a series of deficient behaviors about nutrition processes that can adversely affect psychomotor, psychosocial, and physical development of children. This study aimed to describe the frequency of feeding difficulties or disorders in pediatric patients with cancer. Methods: A prospective study which included 125 children from 1-19 years treated at the Department of Oncology of the Instituto Nacional de Pediatría, Mexico City, was conducted. The diagnosis of eating disorders and feeding difficulties was determined during the first 48 h since admission, and the age of the patient influenced the type of disorder and feeding difficulties. Results: Children older than 11 years presented more frequently an intense resistance of feeding because of discomfort pain (fear of feeding) than younger children (11.4 ± 4.7 vs. 7.4 ± 4.9, p ≤ 0.001). The most frequent alteration associated with malnutrition was loss of appetite (odds ratio [OR]: 8.8, confidence interval [CI] 95% 2.9-26.9, p<0.001), followed by fear of feeding (OR: 3.14, CI 95% 1.24-7.9, p=0.015), and the organic causes showed the highest risk for malnutrition (OR: 3.1, CI 95% 0.98-9.7, p=0.054). Conclusions: Over 90% of the studied population demonstrated at least one eating disorder or feeding difficulty. The principal effect is inadequate nutritional intake due to limited appetite and fear of feeding, which can result in undernutrition. For this reason, the identification of alterations in nutrition processes should be part of the comprehensive assessment of cancer patients.

Introducción: Los trastornos y dificultades para la alimentación son problemas comunes en la edad pediátrica. Estas situaciones conllevan una serie de comportamientos inadecuados respecto de los procesos de nutrición que pueden afectar de manera adversa el desarrollo psicomotor, psicosocial y físico del niño. El objetivo de este trabajo fue describir la frecuencia de desórdenes y dificultades en la alimentación en niños con cáncer a través de un estudio prospectivo. Métodos: Se incluyeron 125 niños de 1 a 19 años de edad del Servicio de Oncología del Instituto Nacional de Pediatría, Ciudad de México. El diagnóstico de desorden y dificultad en la alimentación se determinó en las primeras 48 horas del ingreso. Resultados: Los niños mayores de 11 años presentan con mayor frecuencia resistencia a comer debido a dolor o malestar (miedo a comer) (11.4±4.7 años versus 7.4±4.9 años; p≤0.001). La alteración más frecuente asociada a malnutrición fue la disminución del apetito (razón de momios [RM]: 8.8; intervalo de confianza [IC] 95%: 2.9-26.9; p<0.001), seguido del miedo a comer (RM: 3.14; IC 95%: 1.24-7.9; p=0.015) y las causas con mayor riesgo de malnutrición fueron las orgánicas (RM: 3.1; IC 95%: 0.98-9.7; p=0.054). Conclusiones: Se encontró que en más del 90% de esta población se presentó por lo menos un desorden alimentario o dificultad al alimentarse. El principal efecto es la ingesta nutricional inadecuada debida al apetito limitado y al miedo a alimentarse, lo que puede resultar en desnutrición. Por esta razón, la identificación de alteraciones en los procesos de nutrición deben ser parte de la valoración integral de los pacientes con cáncer.