Publications by authors named "Rocío Cárdenas-Cardos"

29 Publications

  • Page 1 of 1

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

Bol Med Hosp Infant Mex 2021 Jan 26. Epub 2021 Jan 26.

Division of Hematology/Oncology. Instituto Nacional de Pediatría, Mexico City, Mexico.

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.
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http://dx.doi.org/10.24875/BMHIM.20000043DOI Listing
January 2021

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.

Bioelectromagnetics 2020 Dec 23;41(8):581-597. Epub 2020 Sep 23.

Unidad de Investigación Médica en Epidemiología Clínica, Unidad Médica de Alta Especialidad (UMAE), Hospital de Pediatría, Centro Médico Nacional (CMN) "Siglo XXI," Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico.

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.
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http://dx.doi.org/10.1002/bem.22295DOI Listing
December 2020

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

Asia Pac J Clin Oncol 2021 Feb 10;17(1):60-67. Epub 2020 Aug 10.

Experimental Oncology Laboratory, Research Department, National Institute of Pediatrics, Mexico City, Mexico.

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 . 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.
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http://dx.doi.org/10.1111/ajco.13406DOI Listing
February 2021

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

Cancer Epidemiol 2020 08 19;67:101731. Epub 2020 May 19.

Coordinación de Investigación en Salud, CMN "Siglo XXI", IMSS. Av. Cuauhtemoc 330, Delegación Cuauhtémoc, Mexico City, 06720, Mexico; Unidad de Investigación Médica en Epidemiología Clínica, Unidad Médica de AltaEspecialidad (UMAE) Hospital de Pediatría, Centro Médico Nacional (CMN) "Siglo XXI", Instituto Mexicano del Seguro Social (IMSS). Av. Cuauhtemoc 330, Delegación Cuauhtémoc, Mexico City, 06720, Mexico; Laboratorio de Biología Molecular de las Leucemias, Unidad de Investigación en Genética Humana, UMAE, Hospital de Pediatría, CMN "Siglo XXI", IMSS. Av. Cuauhtemoc 330, Delegación Cuauhtémoc, Mexico City, 06720, Mexico. Electronic address:

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.
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http://dx.doi.org/10.1016/j.canep.2020.101731DOI Listing
August 2020

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

Biomarkers 2020 Jun 30;25(4):331-340. Epub 2020 Apr 30.

Department of Biomedical Oncology Laboratory, National Institute of Respiratory Diseases, Mexico City, Mexico.

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. The aim of this study was to determine whether the presence of certain allelic variants of genes , , and increases the risk of toxicity in children with solid tumours treated with ifosfamide. 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. The rs3745274 allelic variant in was associated with haematological toxicity, affecting neutrophils; variant rs2740574 was also associated with toxicity, affecting both leukocytes and neutrophils. Additionally, the gene variant rs776746 was found to affect haemoglobin. Our results show that allelic variants rs3745274 (, rs2740574 ( and rs776746 ( increase the risk for high haematological toxicity. 068/2013.
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http://dx.doi.org/10.1080/1354750X.2020.1754913DOI Listing
June 2020

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

Genes (Basel) 2019 09 16;10(9). Epub 2019 Sep 16.

Experimental Oncology Laboratory, Research Department, National Institute of Pediatrics, Mexico City 04530, Mexico.

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.
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http://dx.doi.org/10.3390/genes10090716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771147PMC
September 2019

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

Ann Hematol 2019 Oct 21;98(10):2379-2388. Epub 2019 Jun 21.

Laboratorio de Genética y Cáncer, Instituto Nacional de Pediatría, Insurgentes Sur 3700-C, Colonia Insurgentes Cuicuilco, C.P. 04530, Mexico City, Mexico.

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.
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http://dx.doi.org/10.1007/s00277-019-03730-xDOI Listing
October 2019

Feeding difficulties and eating disorders in pediatric patients with cancer.

Bol Med Hosp Infant Mex 2019 ;76(3):113-119

Subdirección de Hematología/Oncología Instituto Nacional de Pediatría, Mexico City, Mexico.

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.
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http://dx.doi.org/10.24875/BMHIM.19000072DOI Listing
February 2020

Pediatric mature B-cell NHL, early referral and supportive care problems in a developing country.

Hematology 2019 Dec 27;24(1):79-83. Epub 2018 Aug 27.

i Servicio de Oncología, Instituto Nacional de Pediatría , México City , México.

Objective: Mature B-cell non-Hodgkin lymphoma (B-NHL) comprises more than 50% of all non-Hodgkin lymphoma (NHL) in children and adolescents. An official report published by the Mexican National Center for the Control and Prevention of Cancer in the Pediatric and Adolescent Populations, reported a lymphoma OS of 71% (including all Hodgkin and NHL). The Mexican Association of Pediatric Oncology and Hematology conducted a retrospective study to analyze the clinical characteristics and outcomes of children with diagnosis of B-NHL in Mexico, in order to perceive the main areas of improvement in the health care.

Methods: From 1 January 2000 to 31 December 2016, 166 pediatric patients were diagnosed with B-cell NHL at the participant institutions.

Results: According to histology the outcomes were 5-year EFS 63%, for BL/BLL, and 80% DLBCL, (P = .051), 5-year PFS 81%, for BL/BLL, and 91% for DLBCL, (P = .126), and 5-year OS 71%, for BL/BLL, and 83% for DLBCL, (P = .095).

Discussion: Overall, 18 patients died due to acute treatment toxicity, resulting in a cumulative incidence of toxic death of 10.84% and an early death rate of 7.23%, defined as <30 days after initial treatment. In conclusion, there is an urgent need to establish an academic collaboration to create strategies to improve pediatric cancer care according to our resources, especially in diseases with expected excellent prognosis as B-NHL. These strategies must include comprehensive supportive care, early referral, and the creation of easy communication between pediatric and adults centers as well as late-effects clinics.
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http://dx.doi.org/10.1080/10245332.2018.1510087DOI Listing
December 2019

MDR1 not CYP3A4 gene expression is the predominant mechanism of innate drug resistance in pediatric soft tissue sarcoma patients.

Cancer Biomark 2018 ;22(2):317-324

Laboratory of Genetic Toxicology, National Institute of Pediatrics, Mexico City, Mexico.

Background: Intratumoral up-regulation of genes coding for drug transporters and metabolizing enzymes, such as MDR1 and CYP3A4, after chemotherapy are linked to cancer drug resistance. However their expression in primary soft tissue sarcomas (STS) prior to drug treatment and their role in innate resistance remain unclear.

Objective: The aim of this study was characterize MDR1 and CYP3A4 expression pattern before to chemotherapy and its clinical implication in pediatric STS.

Methods: In this prospective study we analyzed MDR1 and CYP3A4 mRNA expression in both normal and tumor tissues from 28 newly diagnosed STS pediatric and then compared with patients' clinical-pathological data, including chemotherapy response.

Results: Our data showed that the expression of the MDR1 gene was significantly higher in malignant tissue than in the normal tissues of patients with STS. In addition, high MDR1 expression was significantly associated with local advances, as well as poor response to treatment. In contrast, CYP3A4 expression level was negligible in both tumoral and non-tumoral tissues.

Conclusions: These results suggest that a significant mRNA level of MDR1 gene was intrinsically present in STS before exposure to chemotherapeutic drugs, suggesting that MDR1 may be important contributors of innate chemoresistance of this tumor type.
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http://dx.doi.org/10.3233/CBM-171027DOI Listing
October 2018

A greater birthweight increases the risk of acute leukemias in Mexican children-experience from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia (MIGICCL).

Cancer Med 2018 04 13;7(4):1528-1536. Epub 2018 Mar 13.

Health Research Coordination, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico.

In Mexico, due to the high rates of diabetes, overweight, and obesity, there has also been noted an increased newborn weight, which may be contributing to the elevated incidence rate of childhood acute leukemia (AL). We conducted a case-control study in public hospitals of Mexico City aimed to know whether a greater weight at birth is associated with a higher risk of developing leukemia. We included incident cases with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) diagnosed between 2010 and 2015. Controls were frequency-matched to the cases by age, sex, and health institution. Logistic regression analysis was performed adjusting risks by child's sex, overcrowding index, birth order, and mother's age at the time of pregnancy. Adjusted odds ratios (aORs) and 95% confidence intervals were calculated. A total of 1455 cases and 1455 controls were included. An evident association between ALL and child's birthweight ≥2500 g was found (aOR 2.06; 95% CI: 1.59, 2.66) and also, in those with birthweight ≥3500 g (aOR 1.19; 95% CI: 1.00, 1.41). In AML patients with birthweight ≥2500 g and ≥3500 g, an aOR of 1.77 (95% CI: 1.07, 2.94) and 1.42 (95% CI: 1.03-1.95) was observed, respectively. No association was noticed with either type of AL and a birthweight ≥4000 g. To sum up, we found a moderate association between not having a low birthweight and an increased risk of acute leukemias. Birthweight ≥3500 g was also a risk factor for both types of leukemia. This suggests that a greater birthweight may increase the risk of acute leukemias in Mexican children.
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http://dx.doi.org/10.1002/cam4.1414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911591PMC
April 2018

Dasatinib in Pediatric Patients With Chronic Myeloid Leukemia in Chronic Phase: Results From a Phase II Trial.

J Clin Oncol 2018 05 2;36(13):1330-1338. Epub 2018 Mar 2.

Lia Gore, University of Colorado School of Medicine/Children's Hospital Colorado, Aurora, CO; Pamela R. Kearns, University of Birmingham, Birmingham, West Midlands; Donna Lancaster, Royal Marsden Hospital, Sutton, Surrey, United Kingdom; Maria Lucia de Martino Lee, Support Group for Children and Adolescents with Cancer; Carmino Antonio De Souza, University of Campinas, São Paulo, Brazil; Yves Bertrand, L'Institut d'Hématologie et d'Oncologie Pédiatrique, Lyon, France; Nobuko Hijiya, Ann and Robert H. Lurie Children's Hospital of Chicago, and Northwestern University Feinberg School of Medicine, Chicago, IL; Linda C. Stork, Oregon Health & Science University, Portland, OR; Nack-Gyun Chung, The Catholic University of Korea, Seoul St. Mary's Hospital; Jong Jin Seo, University of Ulsan College of Medicine, and Asan Medical Center, Seoul, Republic of Korea; Rocio Cardenas Cardos, Instituto Nacional De Pediatria, Mexico City, Mexico; Tapan Saikia, Prince Aly Khan Hospital, Mumbai, India; Franca Fagioli, Regina Margherita Hospital, Turin, Italy; Judith Landman-Parker, Hôpital Enfants Armand-Trousseau, Paris, France; Andrew E. Place, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA; Karen R. Rabin, Texas Children's Cancer Center, and Baylor College of Medicine, Houston, TX; Mariana Sacchi and Rene Swanink, Bristol-Myers Squibb, Princeton, NJ; C. Michel Zwaan, Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands; Pamela R. Kearns and C. Michel Zwaan, Innovative Therapies for Children with Cancer Consortium, European Union.

Purpose Safe, effective treatments are needed for pediatric patients with chronic myeloid leukemia in chronic phase (CML-CP). Dasatinib is approved for treatment of adults and children with CML-CP. A phase I study determined suitable dosing for children with Philadelphia chromosome-positive (Ph+) leukemias. Methods CA180-226/NCT00777036 is a phase II, open-label, nonrandomized prospective trial of patients < 18 years of age receiving dasatinib. There are three cohorts: (1) imatinib-resistant/intolerant CML-CP, (2) imatinib-resistant/intolerant CML in accelerated/blast phase or Ph+ acute lymphoblastic leukemia (n = 17), and (3) newly diagnosed CML-CP treated with tablets or powder for oral suspension. Major cytogenetic response > 30% for imatinib-resistant/intolerant patients and complete cytogenetic response (CCyR) > 55% for newly diagnosed patients were of clinical interest. Results Of 113 patients with CML-CP, 14 (48%) who were imatinib-resistant/intolerant and 61 (73%) who were newly diagnosed remained on treatment at time of analysis. Major cytogenetic response > 30% was reached by 3 months in the imatinib-resistant/intolerant group and CCyR > 55% was reached by 6 months in the newly diagnosed CML-CP group. CCyR and major molecular response by 12 months, respectively, were 76% and 41% in the imatinib-resistant/intolerant group and 92% and 52% in newly diagnosed CML-CP group. Progression-free survival by 48 months was 78% and 93% in the imatinib-resistant/intolerant and newly diagnosed CML-CP groups, respectively. No dasatinib-related pleural or pericardial effusion, pulmonary edema, or pulmonary arterial hypertension were reported. Bone growth and development events were reported in 4% of patients. Conclusion In the largest prospective trial to date in children with CML-CP, we demonstrate that dasatinib is a safe, effective treatment of pediatric CML-CP. Target responses to first- or second-line dasatinib were met early, and deep molecular responses were observed. Safety of dasatinib in pediatric patients was similar to that observed in adults; however, no cases of pleural or pericardial effusion or pulmonary arterial hypertension were reported.
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http://dx.doi.org/10.1200/JCO.2017.75.9597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929218PMC
May 2018

Current outlook of childhood cancer epidemiology in a middle-income country under a public health insurance program.

Pediatr Hematol Oncol 2017 Feb 13;34(1):43-50. Epub 2017 Mar 13.

b Department of Pediatric Oncology , National Institute of Pediatrics (NIP) , Mexico City , Mexico.

In Mexico, childhood cancer (0-18 years) is treated in a multidisciplinary way while providing care for more than half of the affected children through a public medical insurance. This insurance is given to all children who do not have any health care coverage in Mexico. This program is offered to the poorest of all Mexicans. All the children with this disease are submitted to pathology diagnosis and treatment according to national treatment protocols from 57 accredited medical institutions. From 2007 to 2015, a total of 24,039 children with cancer have been registered; the male gender predominates by 55%. The highest incidence was in the group aged between 0 and 4 years. Every year, there has been an increment in registration. In 2015, there were 3,433 new patients with an incidence of 150.1/million. In the same year, the incidence for all types of leukemia increased to 89.5/million. But for acute lymphoblastic leukemia, the incidence was found to be 79.8/million, which is extremely high. The mortality rate for all these patients in 2015 was 5.3/100,000. However, with regard to children aged between 15 and 18 years, the mortality rate was 8.5/100,000. Abandonment rate was 10%, and there were nine state institutions that had a mortality rate between 25% and 50% among their patients. Coincidentally, as per the Human Development Index, the parameters for education, health, and income were low for those nine institutions. The purpose of this work is to show the epidemiology and the burden we are facing due to this disease.
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http://dx.doi.org/10.1080/08880018.2016.1276236DOI Listing
February 2017

The burden of childhood cancer in Mexico: Implications for low- and middle-income countries.

Pediatr Blood Cancer 2017 06 1;64(6). Epub 2016 Dec 1.

Department of Pediatric Oncology, National Institute of Pediatrics (NIP), Mexico City, Mexico.

In Mexico, childhood cancer incidence and mortality have increased in the last decade. Through government actions since 2005, the Popular Medical Insurance (PMI) program for childhood cancer was created. The objective of PMI was to offer early cancer diagnosis, standardized treatment regimens, and numerous pediatric oncology residency programs. It has also accredited 55 national hospitals for the care of these children. Current problems still present under the PMI include shortage of pediatric oncologists and nurses and high rate of abandonment of treatment. Our aim is to describe the current scenario of childhood cancer care in Mexico, especially from the perspective of the PMI and how it has impacted human resources, infrastructure, and medical education.
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http://dx.doi.org/10.1002/pbc.26366DOI Listing
June 2017

[Descriptive epidemiology of children with acute myeloid leukemia residing in Mexico City: a report from the Mexican Inter-Institutional Group for Identifying Childhood Leukemia Causes].

Gac Med Mex 2016 Oct;152(Suppl 2):66-77

Coordinación de Investigación en Salud, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México.

Introduction: Acute myeloid leukemias represent the second most common childhood leukemia subtype. In Mexico, there are few studies on descriptive epidemiology for this disease.

Aims: To report acute myeloid leukemia incidence for children less than 15 years of age in the Metropolitan Area of the Valley of Mexico for a period of five years (2010-2014) and to analyze whether there are differences in the incidence of acute myeloid leukemia by regions.

Material And Methods: A descriptive study was conducted in nine public hospitals in Mexico City. The crude annual average incidence rate and adjusted average annual incidence rate were calculated.

Results: A total of 190 patients with diagnosis of de novo acute myeloid leukemia were analyzed. Male sex (57.2%) and acute myeloid leukemia-M3 subtype (25.3%) were more frequent. The adjusted average annual incidence rates for Mexico City and for the Metropolitan Area of the Valley of Mexico were 8.18 and 7.74 per million children under 15 years old, respectively.

Conclusions: It seems that childhood acute myeloid leukemia incidence is increasing in Mexico City, which makes the identification of associated risk factors imperative.
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October 2016

Early mortality in children with acute lymphoblastic leukemia in a developing country: the role of malnutrition at diagnosis. A multicenter cohort MIGICCL study.

Leuk Lymphoma 2017 04 26;58(4):898-908. Epub 2016 Aug 26.

b Unidad de Investigación Médica en Epidemiologia Clínica, UMAE Hospital de Pediatría, Centro Médico Nacional (CMN) 'Siglo XXI' , Instituto Mexicano del Seguro Social (IMSS) , México D.F , México.

The role of malnutrition at diagnosis as a predictor of early mortality in Mexican leukemia children remains controversial. The objective of present study was to investigate whether malnutrition was a predictor of early mortality during the first year of treatment in Mexican acute lymphoblastic leukemia (ALL) children through the first population-based study. A total of 794 newly diagnosed ALL pediatric patients from public hospitals of Mexico City were enrolled. A multivariate Cox proportional hazards regression model was constructed and adjusted by patient's age at diagnosis, gender, hospital of treatment, and socioeconomic status. Early mortality was high (12.1%) and malnutrition by different indicators was not associated with mortality at induction phase and at 6th month; a high risk of dying (RR = 2.08; 95% CI: 1.08-4.01) was observed in the group of malnourished children with a high-risk ALL.
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http://dx.doi.org/10.1080/10428194.2016.1219904DOI Listing
April 2017

Indurated papules and plaques on left hemithorax: a clinicopathologic challenge.

Int J Dermatol 2016 Mar 31;55(3):e123-5. Epub 2015 Oct 31.

Department of Dermatology, National Institute of Pediatrics, Mexico City, Mexico.

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http://dx.doi.org/10.1111/ijd.13142DOI Listing
March 2016

Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma.

Proc Natl Acad Sci U S A 2014 Dec 15;111(51):E5564-73. Epub 2014 Dec 15.

Department of Pediatric Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215; Department of Pediatrics,

Osteosarcoma is the most common primary bone tumor, yet there have been no substantial advances in treatment or survival in three decades. We examined 59 tumor/normal pairs by whole-exome, whole-genome, and RNA-sequencing. Only the TP53 gene was mutated at significant frequency across all samples. The mean nonsilent somatic mutation rate was 1.2 mutations per megabase, and there was a median of 230 somatic rearrangements per tumor. Complex chains of rearrangements and localized hypermutation were detected in almost all cases. Given the intertumor heterogeneity, the extent of genomic instability, and the difficulty in acquiring a large sample size in a rare tumor, we used several methods to identify genomic events contributing to osteosarcoma survival. Pathway analysis, a heuristic analytic algorithm, a comparative oncology approach, and an shRNA screen converged on the phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway as a central vulnerability for therapeutic exploitation in osteosarcoma. Osteosarcoma cell lines are responsive to pharmacologic and genetic inhibition of the PI3K/mTOR pathway both in vitro and in vivo.
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http://dx.doi.org/10.1073/pnas.1419260111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280630PMC
December 2014

Descriptive Epidemiology in Mexican children with cancer under an open national public health insurance program.

BMC Cancer 2014 Oct 29;14:790. Epub 2014 Oct 29.

Head of the Division of Pediatric Hem/Oncology, National Institute of Pediatrics (NIP), Coordinator for the Technical Committee of the National Council for the Prevention and Treatment of Childhood Cancer, Mexico City, Mexico.

Background: All the children registered at the National Council for the Prevention and Treatment of Childhood Cancer were analyzed. The rationale for this Federal Government Council is to financially support the treatment of all children registered into this system. All patients are within a network of 55 public certified hospitals nationwide.

Methods: In the current study, data from 2007 to 2012 are presented for all patients (0-18 years) with a pathological diagnosis of leukemia, lymphoma and solid tumors. The parameters analyzed were prevalence, incidence, mortality, and abandonment rate.

Results: A diagnosis of cancer was documented in 14,178 children. The incidence was of 156.9/million/year (2012). The median age was 4.9. The most common childhood cancer is leukemia, which occurs in 49.8% of patients (2007-2012); and has an incidence rate of 78.1/million/year (2012). The national mortality rate was 5.3/100,000 in 2012, however in the group between 15 to 18 years it reaches a level of 8.6.

Conclusions: The study demonstrates that there is a high incidence of childhood cancer in Mexico. In particular, the results reveal an elevated incidence and prevalence of leukemia especially from 0 to 4 years. Only 4.7% of these patients abandoned treatment. The clinical outcome for all of the children studied improved since the establishment of this national program.
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http://dx.doi.org/10.1186/1471-2407-14-790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4228174PMC
October 2014

Differential expression of cytochrome P450 enzymes in normal and tumor tissues from childhood rhabdomyosarcoma.

PLoS One 2014 3;9(4):e93261. Epub 2014 Apr 3.

Instituto Nacional de Pediatría, Mexico City, Mexico.

Intratumoral expression of genes encoding Cytochrome P450 enzymes (CYP) might play a critical role not only in cancer development but also in the metabolism of anticancer drugs. The purpose of this study was to compare the mRNA expression patterns of seven representative CYPs in paired tumor and normal tissue of child patients with rabdomyosarcoma (RMS). Using real time quantitative RT-PCR, the gene expression pattern of CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2W1, CYP3A4, and CYP3A5 were analyzed in tumor and adjacent non-tumor tissues from 13 child RMS patients. Protein concentration of CYPs was determined using Western blot. The expression levels were tested for correlation with the clinical and pathological data of the patients. Our data showed that the expression levels of CYP1A1 and CYP1A2 were negligible. Elevated expression of CYP1B1 mRNA and protein was detected in most RMS tumors and adjacent normal tissues. Most cancerous samples exhibit higher levels of both CYP3A4 and CYP3A5 compared with normal tissue samples. Expression of CYP2E1 mRNA was found to be significantly higher in tumor tissue, however no relation was found with protein levels. CYP2W1 mRNA and/or protein are mainly expressed in tumors. In conclusion, we defined the CYP gene expression profile in tumor and paired normal tissue of child patients with RMS. The overexpression of CYP2W1, CYP3A4 and CYP3A5 in tumor tissues suggests that they may be involved in RMS chemoresistance; furthermore, they may be exploited for the localized activation of anticancer prodrugs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0093261PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974704PMC
January 2015

Consolidation treatment for high risk solid tumors in children with myeloablative chemotherapy and autologous hematopoietic progenitor stem cell transplantation.

Rev Bras Hematol Hemoter 2013 ;35(5):343-6

National Institute of Pediatrics - INP, Mexico City, AC, Mexico.

Background: In childhood cancer, consolidation treatment with chemotherapy followed by autologous hematopoietic progenitor stem cell transplantation is currently an accepted treatment modality in patients with high-risk solid tumors or in patients who have relapsed after conventional treatment.

Objectives: The objective of this study was to describe the results of transplantation of a group of children who had high-risk solid tumors or relapsed after conventional chemotherapy regimens.

Methods: A retrospective analysis was conducted from January 1998 to October 2004 of all children with pathologic diagnoses of high-risk solid tumors or children that had previously relapsed after conventional chemotherapy and that were subsequently submitted to autologous hematopoietic progenitor stem cell transplantation. The analysis included overall survival rates, event-free survival rates, mortality rates and chemotherapy complications.

Results: Nineteen patients were submitted to this approach. The age range was from 27 to 196 months with a median age of 52 months. The overall survival rate at 100 days was observed in 79%, the three-year event-free survival rate was 63%. The mortality rate secondary to the myeloablative chemotherapy regimen was 21% (n = 4). Only three patients (15.8%) relapsed with tumor progression after transplant.

Conclusion: Autologous hematopoietic progenitor stem cell transplantation is still a successful procedure in patients with solid tumors refractory to conventional chemotherapy.
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http://dx.doi.org/10.5581/1516-8484.20130099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832315PMC
November 2013

Incidence of childhood cancer among Mexican children registered under a public medical insurance program.

Int J Cancer 2013 Apr 28;132(7):1646-50. Epub 2012 Aug 28.

Division of Pediatric Hem/Oncology, Coordinator for the Technical Committee of the National Council for the Prevention and Treatment of Childhood Cancer, National Institute of Pediatrics, Mexico City, Mexico.

Prior to 2005, 51% of children in Mexico diagnosed with cancer received no standardized optimal multidisciplinary medical care. A government-subsidized national cancer treatment program was therefore created for these patients and a National Cooperative Childhood Cancer Treatment Group was consequently formed for these patients. Pediatric patients with a proven diagnosis of leukemia, lymphoma or solid tumor and who were registered in the Popular Medical Insurance (PMI) program from January 2007 to December 2010, are described in this report. These patients had been enrolled and registered in one of the 49 nationwide certified medical institutions in Mexico. The national incidence and frequency data for childhood cancers were analyzed for the whole program. At the end of a 4-year study, the analysis revealed that 8,936 children from across Mexico had been diagnosed with cancer. The incidence rate for the PMI patients was 150.3/million/year (2010) for children of 0-18 years. The highest age incidence rate was 51.9 between 0 and 4 years and boys were the predominant group for all types of cancer. The leukemia incidence was 75.3/million/year (2010), and an average frequency of 50.75% throughout the 4 years. The overall mortality rate was measured at 5.4/100,000/year (2010). This study demonstrates a high frequency and incidence of childhood cancer and a beneficial impact of the PMI program over the quality of life in these children.
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http://dx.doi.org/10.1002/ijc.27771DOI Listing
April 2013

Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology.

BMC Cancer 2011 Aug 17;11:355. Epub 2011 Aug 17.

Unidad de Investigación en Epidemiología Clínica, Unidad Médica de Alta Especialidad UMAE Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano de Seguridad Social, México DF, México.

Background: Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City.

Methods: Included in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR), and the standardized average annual incidence rates (SAAIR) per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level).

Results: Although a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3); acute lymphoblastic leukemia (ALL) was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million), followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million), and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million). The 1-4 years age group had the highest SAAIR for ALL (77.7 per million). For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million) and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million). The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8%) were classified as high risk. There was a positive correlation between the average number of persons per household and the incidence of the pre-B immunophenotype (Pearson's r, 0.789; P = 0.02).

Conclusions: The frequency of ALL in Mexico City is among the highest in the world, similar to those found for Hispanics in the United States and in Costa Rica.
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http://dx.doi.org/10.1186/1471-2407-11-355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171387PMC
August 2011

[Medulloblastoma in pediatrics. Current prognosis and treatment].

Gac Med Mex 2007 Sep-Oct;143(5):415-20

Hematooncología Pediátrica, Instituto Nacional de Pediatriá, SSA, México DF, México.

In Mexico, Central Nervous System (CNS) tumors are the third most common childhood cancers. Medulloblastoma constitutes 20% of the primary CNS tumors and 40% of all cerebellar tumors, the single most common brain tumor among children. It originates over the external granular layer that normally migrates from the vermis to the surface of the cerebellum hemispheres and from there to the deep portions of the internal granular layer. These tumors infiltrate profusely the cerebellar cortex. The dissemination process can occur through the spinal fluid with seeding along the subarachnoidal space and around the spinal chord They eventually produce metastasis mainly to bone, liver, and bone marrow. There is a group of well identified prognostic factors that are relevant for each individual patient and that can be applied for multidisciplinary treatment purposes. The objective of the present review is to emphasize on new research findings and the overall survival that can be achieved with modern treatment programs.
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May 2008

Early death in children with acute lymphoblastic leukemia: does malnutrition play a role?

Pediatr Hematol Oncol 2008 Jan-Feb;25(1):17-26

Division of Hem-Oncology, National Institute of Pediatrics (Instituto Nacional de Pediatría), Mexico City, Mexico.

The study aim was to correlate malnutrition and early death in children with acute lymphoblastic leukemia (ALL). A study was conducted in 100 consecutive children with ALL. An analysis included clinical and laboratory parameters as well as co-morbidity factors. Forty patients were standard risk and 60 high risk. Multivariate analysis showed variables of statistical importance, including female gender (p 010), ALL high-risk (p 04), and infection (p 036). Malnutrition (p 1.0) and poverty (p 0.5) did not influence. Early mortality was documented in 15/100 (15%) patients. The study shows that high-risk ALL and infection represent the leading causes of early mortality.
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http://dx.doi.org/10.1080/08880010701774132DOI Listing
April 2008

Detection of ETV6 and RUNX1 gene rearrangements using fluorescence in situ hybridization in Mexican patients with acute lymphoblastic leukemia: experience at a single institution.

Cancer Genet Cytogenet 2005 Oct;162(2):140-5

Department of Research in Human Genetics, Instituto Nacional de Pediatría Insurgentes Sur 3700-C, Col. Insurgentes Cuicuilco, México D.F. 04530, Mexico.

The t(12;21) produces the gene fusion ETV6/RUNX1 and is a frequent rearrangement in childhood ALL, associated with a good prognosis. In Mexico its prevalence has not been reported. This study evaluated a group of consecutive Mexican children with newly diagnosed ALL, to detect the fusion using fluorescence in situ hybridization (FISH). Seventy-one bone marrow samples were analyzed with FISH, using ETV6/RUNX1 DNA probes. Abnormalities of ETV6, RUNX1, or both were found in 31 of the 71 (44%) patients. Six showed ETV6/RUNX1 fusion and 17, with extra RUNX1 copies, presented an additional chromosome 21 or dup(21)(q22). Five patients had structural changes in ETV6, and three patients showed extra copies of ETV6 and RUNX1 from polysomy of chromosomes 12 and 21. Our results revealed a fusion in 8.5% of the 71 cases analyzed. This frequency is lower than that observed in other populations (9.5-32%). The structural rearrangements resulting in RUNX1 extra copies were found in 9.8% of patients, which is close to the range reported (1.5-9.7%) by other authors. Due to the prevalence of RUNX1 overrepresentation in our population and its unknown prognostic significance, further studies should be conducted in consecutive children with ALL, to correlate this abnormality with the patients' follow-up.
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http://dx.doi.org/10.1016/j.cancergencyto.2005.03.018DOI Listing
October 2005

Prognostic factors including neoadjuvant chemotherapy in Mexican children with neuroblastoma.

Clin Transl Oncol 2005 Jan-Feb;7(1):12-7

Department of Oncology, Instituto Nacional de Pediatría, Secretaría de Salud, 04530 Mexico City, Mexico.

Introduction: There are several prognostic factors in children with neuroblastoma that have been outlined in the international literature.

Material And Methods: A retrospective study was carried out analysing the medical records of patients with the pathological diagnosis of neuroblastoma seen at the Department of Oncology from the Instituto Nacional de Pediatriá (Mexico) between January 1984 to January 1997. A total of 32 clinical prognostic factors were assess in our population.

Results: Fifty five patients whose age ranged from 1 to 168 months old, mean of 35 months were included. Out of 32 prognostic factors only 6 including sex (p= 0.0039), metastatic disease to bone (p= 0.003), bone marrow involvement (p= 0.0027), staging system (p= 0.000015), surgical treatment (p 0,0022) and neoadjuvant chemotherapy (p.005) were the most significant.

Conclusions: It was concluded that besides the prognostic factors outlined, neoadjuvant chemotherapy is of utmost importance. It decreases tumor volume and allows surgery to be more successful, therefore believing that this variable represents a specific prognostic factor in cases of advanced neuroblastoma.
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http://dx.doi.org/10.1007/BF02710020DOI Listing
July 2005

Brain tumors in children under 1 year of age: emphasis on the relationship of prognostic factors.

Childs Nerv Syst 2003 Jun 6;19(5-6):311-4. Epub 2003 May 6.

Department of Oncology, Instituto Nacional de Pediatría, Insurgentes Sur 3700-C, 04530, Mexico City, Mexico.

Objects: Primary brain tumors in infants under 12 months of age have a different prognosis from older children.

Material: A retrospective analysis was done in all patients less than 12 months old with primary brain tumors.

Results: Out of 1682 children with primary brain tumors, 61 (3.6%) were infants under 12 months old. The mean age at diagnosis was 181.6 days (SD 128) with a range of 1 to 364 days. There were 37 males (60.6%). The most common tumor was astrocytoma ( n=22) (36%). Supratentorial tumors were present in 63.9% but this was not related to survival ( p=0.1095). Complete surgical resection ( n=14) was favorable for survival ( p=0.039). Intracranial hypertension at diagnosis did not influence survival ( p=0.89). The overall survival rate was 32%, mean 42.08 (SD 7.38). A total of 24 patients are alive and without evidence of disease.

Conclusion: Complete surgical resection was necessary for a favorable prognosis, and the long-term effects are a valid problem.
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http://dx.doi.org/10.1007/s00381-003-0738-9DOI Listing
June 2003