Breast Cancer in Pregnant Young Women: Clinicopathological Profile, Survival, and Pregnancy Outcomes.

Background Breast cancer is one of the most common cancer types diagnosed during pregnancy; the presence of any neoplasm in pregnant women faces clinical dilemmas and challenges in cancer and pregnancy management. Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during pregnancy or within one year after delivery. The aim of this study was to describe tumor clinicopathological characteristics and pregnancy outcomes in PABC patients. Materials and methods This is a retrospective cohort assessing PABC patients. Qualitative variables were compared using Fisher's exact test. Kaplan-Meier method was used to calculate survival. Cox regression and logistic regression methods were used to estimate the hazard ratio (HR) and odds ratio (OR), respectively. Results We assessed 16 PABC patients. Women ≤ 35 years of age were mainly diagnosed at advanced stage (88.8%) with ER-negative disease (77.8%). Patients with >4 pathological lymph nodes (25%; p = 0.001) and ER-negative disease (50%; p = 0.646) showed poor five-year overall survival (OS). In the multivariate analysis, nodal involvement was the main predictor associated with poorer OS (HR = 1.4, 90% confidence interval [CI]: 1.14 to 1.8). The following risk factors might influence the risk of preterm delivery: maternal older age, gestational age at diagnosis, and intrauterine exposure to chemotherapy, but an adjusted OR of 0.61 (90% CI: 0.34 to 1), 0.80 (90% CI: 0.66 to 0.9), and 0.013 (90% CI: 0.00 to 0.9), respectively, did not statistically support such an effect. Conclusions Younger women with PABC had a more aggressive pathological profile that might partly explain the poor OS. Obstetrical adverse events related to preterm delivery should be avoided with better planning of specialized strategies.

Infections and risk factors for infection-related mortality after pediatric allogeneic hematopoietic stem cell transplantation in Mexico: A single center retrospective study.

OBJECTIVE: To identify the type of infections and risk factors for infection-related mortality (IRM) after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: Retrospective cohort study of patients <16 years of age treated in 2010-2019 was conducted. Unadjusted hazard ratios (HR) and adjusted hazard ratios (aHR) with 95% confidence intervals (95% CIs) were estimated using Cox regression. Cumulative incidence was calculated. RESULTS: Data for 99 pediatric patients were analyzed. The myeloablative conditioning was the most used regimen (78.8%) and the hematopoietic stem cell source was predominantly peripheral blood (80.8%). Primary graft failure occurred in 19.2% of patients. Frequency of acute graft-versus-host disease was 46.5%. Total of 136 infectious events was recorded, the most common of which were bacterial (76.4%) followed by viral infection (15.5%) and then fungal infection (8.1%). The best predictors for infection subtypes where the following: a) for bacterial infection (the age groups of 10.1-15 years: aHR = 3.33; 95% CI: 1.62-6.85 and. >15 years: aHR = 3.34; 95% CI: 1.18-9.45); b) for viral infection (graft versus host disease: aHR = 5.36; 95% CI: 1.62-17.68), however, for fungal infection statistically significant predictors were not identified. Related mortality was 30% (n = 12). Increased risk for infection-related mortality was observed in patients with unrelated donor and umbilical cord stem cells recipients (HR = 3.12; 95% CI: 1.00-9.85). CONCLUSIONS: Frequencies of infections and infection-related mortality appear to be similar to those reported. Unrelated donors and stem cells from umbilical cord recipients were associated with a high risk of mortality.

[Associating prognostic factors with clinical results in locally advanced breast cancer]. / Asociando factores pronósticos con resultados clínicos en cáncer de mama localmente avanzado.

Background: Breast cancer is the most frequent malignant tumor in women. Objective: To identify clinico-pathological and molecular markers as predictors of survival in patients with locally advanced breast cancer (LABC). Methods: Retrospective and observational study. The clinical factors of clinico-pathological and molecular predictors in relation with overall survival (OS) were assessed by the survival function, baseline hazard with smoothing and Cox regression. Results: 126 patients were assessed. OS at five years was significantly superior in patients with clinical stage IIIA (87%; p < 0.001), grade 2 tumor (81%; p < 0.001), pathological node stage (ypN0: 90%; p < .001), low-risk Nottingham prognostic index (86%; p < 0.001) and luminal A subtype (88%; p = 0.022). Baseline hazard with smoothing exhibited an increase in the mortality rate at 50 months for the luminal B/ HER2+ subtype compared with other subtypes. The multivariate analysis ascertained that the stage ypN2-3 (hazard ratio [HR] = 7.3; 95% confidence interval [95% CI]: 2.2 to 23.9) and the HER2+ nonluminal (HR = 7.8; 95% CI: 2 to 29.6) and triple negative (HR = 5.4; 95% CI: 1.7 to 17.2) subtypes were associated with a poor OS. Conclusions: The comprehensive evaluation of the molecular marker and clinico-pathological factors provides more accurate predictive and prognostic information. The nodal stage and molecular subtype are suitable clinical parameters on survival for LABC patients.

Introducción: el cáncer de mama es el tumor maligno más frecuente en las mujeres. Objetivo: identificar marcadores clínico-patológicos y moleculares como predictores de la supervivencia en pacientes con cáncer de mama localmente avanzado (CMLA). Material y métodos: estudio retrospectivo y observacional. Los factores clínico-patológicos y moleculares fueron evaluados en relación con la supervivencia global (SG) mediante la función de supervivencia, riesgo basal con suavizamiento y regresión de Cox. Resultados: 126 pacientes fueron evaluadas. La SG a cinco años fue significativamente superior en pacientes con estadio clínico IIIA (87%; p < 0.001), tumor de grado 2 (81%; p < 0.001), ausencia de ganglios patológicos (ypN0: 90%; p < 0.001) y en el subtipo luminal A (88%; p = 0.022). El riesgo basal con suavizamiento exhibió un incremento en la tasa de mortalidad a los 50 meses para el subtipo luminal B/ HER2+ comparado con los otros subtipos. En el análisis multivariado, el estadio ypN2-3 (razón de riesgo [RR] = 7.3; intervalo de confianza del 95% [IC 95%]: 2.2 a 23.9) y los subtipos HER2+ (RR = 7.8; IC 95%: 2 a 29.6) y triple negativo (RR= 5.4; IC 95%: 1.7 a 17.2) se asociaron con una pobre SG. Conclusiones: la evaluación integral del marcador molecular y de los factores clínico-patológicos proporciona información predictiva y pronóstica más precisa. El estadio ganglionar y subtipo molecular son parámetros adecuados con un impacto pronóstico en la SG para las pacientes con CMLA.

Is colostomy closure without mechanical bowel preparation safe in pediatric patients? A randomized clinical trial.

BACKGROUND: Mechanical bowel preparation (MBP) is largely used worldwide prior to colostomy closure in children, although its benefits are questioned by scientific evidence, and its use can cause adverse reactions. We hypothesized that colostomy closure procedures in children are not associated with increased complications (surgical site infection [SSI] and anastomotic leakage) when performed without MBP. Thus, we conducted a noninferiority trial to compare the safety and efficacy of colostomy takedown with and without MBP. METHODS: A randomized noninferiority clinical trial was conducted at Hospital Infantil de Mexico in Mexico City from 2015 to 2019, in which the experimental group did not receive MBP prior to colostomy closure. A total of 79 patients were analyzed, and the primary outcomes were safety-related. Data were analyzed using the chi-squared test, Student's t-test, or Mann-Whitney U test as appropriate. RESULTS: The demographics in both groups were comparable. Statistical analysis revealed equivalence in safety outcomes (superficial SSI, 22.5% vs 15.3% p = 0.420; deep SSI, 7.5% vs 0% p = 0.081; reoperation, p = 0.320; intestinal occlusion, p = 0.986); no anastomotic leakage was observed in any group. Secondary outcomes such as fasting time and length of hospital stay after surgery were also similar between the groups. However, patients who received MBP were admitted 2 days before surgery. CONCLUSIONS: Our findings indicate that withholding MBP prior to colostomy takedowns in children is not associated with increased complications. Omitting MBP also leads to less discomfort and shortens hospital length of stay, suggesting that it has safer and more effective procedures. LEVEL OF EVIDENCE: Randomized controlled clinical trial with adequate statistical power.

Costs associated with adverse events from remission induction for children with Acute Lymphoblastic Leukemia (ALL).

BACKGROUND: ALL is the most frequent hematological tumor in children, so during remission induction chemotherapy protocol (RICP) adverse events (AEs) may appear. The public program in Mexico in charge of financial support to oncologic children without social security delivered a fix amount for ALL chemotherapy, but additional money needed to treat any other unexpected condition should be taken from the budget of the oncologic healthcare providers. So the purpose of our study was to estimate and evaluate the direct medical costs associated to EAs during RICP in children with ALL. METHODS: This study was retrospective, longitudinal, and observational based on medical records review of patients in RICP. The CTCAE was used to identify and classify AEs according to a SOC category. We focused on extracting resources data that were consumed both for inpatients and outpatients AEs. A micro-costing approach was adopted which involve quantification of each healthcare resource consumed by the hospital multiplying them by unit cost. The probability distributions of data were evaluated to identify the appropriated statistical tests to be used for comparisons between groups that were performed with Wilcoxon rank sum test. Generalized linear models (GLM) were adjusted to evaluate the effects of patient characteristics on total cost. RESULTS: Forty patients accumulated 204 inpatient and 81 outpatient AEs during RICP. Comparison of total costs between groups showed an incremental cost of $7,460.23 likewise attributable to AEs. The total cost of a pediatric patient undergoing RICP without adverse events was $3,078.36 and the total cost of a patient with AEs exceeds it threefold. CONCLUSIONS: The costs associated with AEs during RICP in Mexican children with ALL representing a high burden for the healthcare provider. Generalized linear models showed that variables such as sex, risk category and alive status are associated with the total costs of AEs. This is the first study aiming to analyze the effect of ALL-related AEs on health care costs in pediatric population, so our results may help not only to local decision making but also it may contribute to the research agenda in this field.

HP0953 - hypothetical virulence factor overexpresion and localization during Helicobacter pylori infection of gastric epithelium.

BACKGROUND: The high prevalence and persistence of Helicobacter pylori (H. pylori) infection, as well as the diversity of pathologies related to it, suggest that the virulence factors used by this microorganism are varied. Moreover, as its proteome contains 340 hypothetical proteins, it is important to investigate them to completely understand the mechanisms of its virulence and survival. We have previously reported that the hypothetical protein HP0953 is overexpressed during the first hours of adhesion to inert surfaces, under stress conditions, suggesting its role in the environmental survival of this bacterium and perhaps as a virulence factor. AIM: To investigate the expression and localization of HP0953 during adhesion to an inert surface and against gastric (AGS) cells. METHODS: Expression analysis was performed for HP0953 during H. pylori adhesion. HP0953 expression at 0, 3, 12, 24, and 48 h was evaluated and compared using the Kruskal-Wallis equality-of-populations rank test. Recombinant protein was produced and used to obtain polyclonal antibodies for immunolocalization. Immunogold technique was performed on bacterial sections during adherence to inert surfaces and AGS cells, which was analyzed by transmission electron microscopy. HP0953 protein sequence was analyzed to predict the presence of a signal peptide and transmembrane helices, both provided by the ExPASy platform, and using the GLYCOPP platform for glycosylation sites. Different programs, via, I-TASSER, RaptorX, and HHalign-Kbest, were used to perform three-dimensional modeling. RESULTS: HP0953 exhibited its maximum expression at 12 h of infection in gastric epithelium cells. Immunogold technique revealed HP0953 localization in the cytoplasm and accumulation in some peripheral areas of the bacterial body, with greater expression when it is close to AGS cells. Bioinformatics analysis revealed the presence of a signal peptide that interacts with the transmembrane region and then allows the release of the protein to the external environment. The programs also showed a similarity with the Tip-alpha protein of H. pylori. Tip-alpha is an exotoxin that penetrates cells and induces tumor necrosis factor alpha production, and HP0953 could have a similar function as posttranslational modification sites were found; modifications in turn require enzymes located in eukaryotic cells. Thus, to be functional, HP0953 may necessarily need to be translocated inside the cell where it can trigger different mechanisms producing cellular damage. CONCLUSION: The location of HP0953 around infected cells, the probable posttranslational modifications, and its similarity to an exotoxin suggest that this protein is a virulence factor.

Association of Genetic Polymorphisms and Serum Levels of IL-6 and IL-8 with the Prognosis in Children with Neuroblastoma.

There is evidence that high circulating levels of IL-6 and IL-8 are markers of a poor prognosis in various types of cancer, including NB. The participation of these cytokines in the tumor microenvironment has been described to promote progression and metastasis. Our objective was to evaluate the prognostic role of genetic polymorphisms and serum levels of IL-6 and IL-8 in a cohort of Mexican pediatric patients with NB. The detection of the SNPs rs1800795 IL-6 and rs4073 and rs2227306 IL-8 was carried out by PCR-RFLP and the levels of cytokines were determined by the ELISA method. We found elevated circulating levels of IL-8 and IL-6 in NB patients compared to the control group. The genotype frequencies of the rs1800795 IL-6 and rs4073 IL-8 variants were different between the patients with NB and the control group. Likewise, the survival analysis showed that the GG genotypes of rs1800795 IL-6 (p = 0.014) and AA genotypes of rs4073 IL-8 (p = 0.002), as well as high levels of IL-6 (p = 0.009) and IL-8 (p = 0.046), were associated with lower overall survival. We confirmed the impact on an adverse prognosis in a multivariate model. This study suggests that the SNPs rs1800795 IL-6 and rs4073 IL-8 and their serum levels could be promising biomarkers of a poor prognosis, associated with overall survival, metastasis, and a high risk in Mexican children with NB.

Ocular preservation in patients with bilateral retinoblastoma before chemotherapy in situ era: A report from a Mexican Retinoblastoma Reference Hospital.

BACKGROUND: Bilateral retinoblastoma (Rb) treatment remains a challenge for ophthalmologists and pediatric oncologists despite new therapeutic strategies for eye preservation. The purpose of this work is to evaluate treatment outcomes in patients who underwent eye salvage treatment at a single-center prior to the chemotherapy in situ era. PROCEDURE: We followed a cohort of 88 consecutive Rb patients diagnosed at Hospital Infantil de México between November 2000 and June 2014. Eye salvage treatment consisted of systemic chemotherapy plus focal therapy planned by a multidisciplinary team. Unresponsive tumors were treated with episcleral brachytherapy and external beam radiotherapy (EBRT). RESULTS: A total of 96 eyes underwent eye salvaging therapy. Seventy-eight eyes (81%) were salvaged. Seven patients (8%) required brachytherapy and 34 patients (39%) underwent EBRT. Thirty-three of 78 preserved eyes (42%) achieved normal visual acuity: 5/27 (20%) in radiated patients and 28/51 (61%) in nonradiated patients. Eight patients developed secondary primary malignancies; however, those treated with EBRT did not have a significantly increased risk when compared with nonirradiated patients (OR: 1.66; P = 0.492). The overall survival rate was 86% (95% CI, 76%-92%) after a mean follow-up of 10 years. CONCLUSIONS: Eye preservation, long-term tumor control, and functional visual acuity could be maintained in many child and adolescent Rb survivors. Our data suggest that ocular radiotherapy can be used as consolidation treatment when other recently developed therapies with potentially fewer side effects are not available. Multidisciplinary management of Rb is mandatory to obtain cancer control during eye salvage treatment.

Safety and efficacy of step-down to oral outpatient treatment versus inpatient antimicrobial treatment in pediatric cancer patients with febrile neutropenia: A noninferiority multicenter randomized clinical trial.

BACKGROUND: It has been suggested that low-risk febrile neutropenia (FN) episodes can be treated in a step-down manner in the outpatient setting. This recommendation has been limited to implementation in middle-income countries due to concerns about infrastructure and lack of trained personnel. We aimed to determine whether early step-down to oral antimicrobial outpatient treatment is not inferior in safety and efficacy to inpatient intravenous treatment in children with low-risk FN. PROCEDURE: A noninferiority randomized controlled clinical trial was conducted in three hospitals in Mexico City. Low-risk FN was identified in children younger than 18 years. After 48 to 72 hours of intravenous treatment, children were randomly allocated to receive outpatient oral treatment (experimental arm, cefixime) or to continue inpatient treatment (standard of care, cefepime). Daily monitoring was performed until neutropenia resolution. The presence of any unfavorable clinical outcome was the endpoint of interest. We performed a noninferiority test for comparison of proportions. RESULTS: We identified 1237 FN episodes; 117 cases were randomized: 60 to the outpatient group and 57 for continued inpatient treatment. Of the FN episodes, 100% in the outpatient group and 93% in the inpatient group had a favorable outcome (P < 0.001). The mean duration of antibiotics was 4.1 days (SD 2.5; 95% CI, 3.4-4.8 days) in the outpatient group and 4.4 days (SD 2.5; 95% CI, 3.7-5.0 days) in the inpatient group (P = 0.70). CONCLUSIONS: In our population, step-down oral outpatient treatment of low-risk FN was as safe and effective as inpatient intravenous treatment. Clinical Trials Identifier: NCT04000711.

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

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.

Differential expression of miRNA-146a and miRNA-155 in gastritis induced by Helicobacter pylori infection in paediatric patients, adults, and an animal model.

BACKGROUND: Helicobacter pylori is a major aetiologic agent associated with gastritis. H. pylori infections increase the expression of the Toll-like receptor (TLR), which in turn modulates the expression of microRNA (miRNA)-146a and miRNA-155. The objective of this study was to compare the expression of miRNA-146a and miRNA-155 in gastric lesions of paediatric and adult patients with different pathologies and in Mongolian gerbils (Meriones unguiculatus) infected with H. pylori 26,695. METHODS: Quantification of miRNA expression was performed by quantitative real-time polymerase chain reaction (qRT-PCR) of paraffin-embedded gastric lesions of children with or without an infection (n = 25), adults with follicular gastritis and metaplasia (n = 32) and eight-week-old M. unguiculatus males (Hsd:MON) infected with H. pylori 26,695 for 0, 3, 6, 12 and 18 months (n = 25). The genes RNU48 and RNU6 were used as endogenous controls for data normalization. Statistical analyses were performed using Kruskal-Wallis, Mann-Whitney, ANOVA and Student's t-test. RESULTS: The expression of miRNA-146a and miRNA-155 in infected children increased by 247.6- and 79.4-fold (on average), respectively, compared to that observed in the control group. However, these results were not significant (p = 0.12 and p = 0.07 respectively). In some children a gradual increase in expression was observed, while in others, expression was very high. Additionally, the expression levels of miRNA-146a and miRNA-155 increased by an average of 21.7- and 62-fold, respectively, in adult patients with follicular gastritis when compared to those of the controls. In M. unguiculatus infected with H. pylori 26,695, the expression of both miRNAs increased as the infection progressed. CONCLUSION: This is the first report to show differences in the expression of miRNA-146a and miRNA-155 in paediatric and adult patients with gastritis who were infected with H. pylori. In addition, in M. unguiculatus infected with H. pylori, miRNA expression was associated with the progression of infection and the ability of the bacteria to adapt to the host.

Delivery of Pediatric Cancer Care in Mexico: A National Survey.

Purpose Limited data describe the delivery of pediatric cancer care in Mexico. We report a nationwide survey of pediatric cancer units. Methods An electronic survey was distributed to 74 pediatric cancer units in Mexico to describe case volumes; organization of care; and availability of medical/surgical specialists, supportive care, complex therapies, and diagnostic services. Centers were classified as low (< 30 new patients/year), medium (30 to 59/year) and high (≥ 60/year). Results Sixty-two centers completed the survey (response rate, 84%). The median annual new case volume per center was 50 (interquartile range [IQR], 23 to 81). Thirty-four percent (n = 21), 26% (n = 16), and 40% (n = 25) of units were low-, medium-, and high-volume centers, respectively. Treatment units reported a median of two pediatric oncologists (IQR, 2) and one pediatric hematologist (IQR, 1 to 2). Availability of medical and surgical subspecialists varied by center size, with substantially more specialist support at higher-volume centers ( P < .01). Multidisciplinary tumor boards are available at 29% (six of 21), 56% (nine of 16), and 76% (19 of 25) of low- to high-volume centers, respectively ( P = .005). Radiation and palliative care services are available at 42% (n = 26) and 63% (n = 36) of all centers, which did not vary by center volume. Educational support for hospitalized children and school reintegration programs are available at 56% (n = 36) and 58% (n = 36) of centers, respectively. One third (38% [n = 23]) of centers reported that at least one half of patients were lost to follow-up during the transition from pediatric to adult programs. Conclusion A large variation exists in annual case volumes across Mexican pediatric cancer centers. Additional efforts to increase access to multidisciplinary, supportive, and palliative care across all pediatric cancer units in Mexico are required.

Potential drug-drug interactions and their risk factors in pediatric patients admitted to the emergency department of a tertiary care hospital in Mexico.

BACKGROUND: Drug-drug interactions (DDIs) detected in a patient may not be clinically apparent (potential DDIs), and when they occur, they produce adverse drug reactions (ADRs), toxicity or loss of treatment efficacy. In pediatrics, there are only few publications assessing potential DDIs and their risk factors. There are no studies in children admitted to emergency departments (ED). The present study estimates the prevalence and describes the characteristics of potential DDIs in patients admitted to an ED from a tertiary care hospital in Mexico; in addition, potential DDI-associated risk factors are investigated. METHODS: A secondary analysis of data from 915 patients admitted to the ED of the Hospital Infantil de México "Federico Gómez" was conducted. The Medscape Drug Interaction Checker software was used to identify potential DDIs. The results are expressed as number of cases (%), means (95% CI) and medians (25-75th percentiles). Count data regressions for number of total and severity-stratified potential DDIs were performed adjusting for patient characteristics, number of administered drugs, days of stay, presence of ADRs and diagnoses. RESULTS: The prevalence of potential DDIs was 61%, with a median of 4 (2-8). A proportion of 0.2% of potential DDIs was "Contraindicated", 7.5% were classified as "Serious", 62.8% as "Significant" and 29.5% as "Minor". Female gender, age, days of stay, number of administered drugs and diagnoses of Neoplasms (C00-D48), Congenital malformations (Q00-Q99), Diseases of the Blood, Blood-forming Organs and Immunity (D50-D89) and Diseases of the nervous system (G00-G99) were significantly associated with potential DDIs. CONCLUSION: The prevalence of potential DDIs in the ED is high, and strategies should therefore be established to monitor patients' safety during their stay, in addition to conducting investigations to estimate the real harm potential DDIs inflict on patients.

Analysis of Normal Hematopoietic Stem and Progenitor Cell Contents in Childhood Acute Leukemia Bone Marrow.

BACKGROUND AND AIMS: Childhood acute leukemias (AL) are characterized by the excessive production of malignant precursor cells at the expense of effective blood cell development. The dominance of leukemic cells over normal progenitors may result in either direct suppression of functional hematopoiesis or remodeling of microenvironmental niches, contributing to BM failure and AL-associated mortality. We undertook this study to investigate the contents and functional activity of hematopoietic stem/progenitor cells (HSPC) and their relationship to immune cell production and risk status in AL pediatric patients. METHODS: Multiparametric flow cytometry of BM aspirates was performed to classify AL on the basis of lineage and differentiation stages and to analyze HSPC and immune cell frequencies. Controlled co-culture systems were conducted to evaluate functional lineage potentials of primitive cells. Statistical correlations and inter-group significant differences were established. RESULTS: Among 113 AL BM aspirates, 26.5% corresponded to ProB, 19.5% to PreB and 32% contain ProB and PreB differentiation stages, whereas nearly 9% of the cases were T- and 13% myeloid-lineage leukemias. We identified ProB-ALL as the subtype endowed with the highest relative contents of HSPC, whereas T-ALL and PreB-ALL showed a critically reduced size of both HSC and MLP compartments. Notably, lower cell frequencies of HSPC in ProB-ALL correlated to high-risk prognosis at disease debut. CONCLUSIONS: HSPC abundance at initial diagnosis may aid to predict the clinical course of ALL and to identify high-risk patients. A clearer understanding of their population dynamics and functional properties in the leukemia setting will potentially pave the way for targeted therapies.

Diseño de estudios clínicos y causalidad: ¿la vacuna oral contra rotavirus causa invaginación intestinal? / Clinical research design and causality: does oral rotavirus vaccine cause intussusception?

ResumenLos diseños de investigación clínica, cuyo propósito es responder preguntas sobre causalidad, se pueden clasificar en relación con cuatro ejes: el número de grupos de estudio, la aplicación de una maniobra experimental, la direccionalidad causa-efecto y la fuente de la que se recaban los datos. Los diseños básicos más utilizados en epidemiología son el ensayo clínico, el estudio de cohortes, el estudio de casos y controles y la encuesta transversal. Este texto pretende facilitar la identificación y comprensión de cada uno de estos diseños mediante ejemplos relacionados con la asociación entre la vacunación con rotavirus y la invaginación intestinal.

AbstractDesign of clinical research whose purpose is to answer questions about causality can be classified in relation to four axes: the number of study groups, the implementation of an experimental maneuver, cause-effect directionality and source from which the data are collected. The basic designs used in epidemiology are the clinical trial, the cohort study, the case-control study and the cross-sectional survey. This text aims to facilitate the identification and understanding of each of these designs through examples related to the association between rotavirus vaccination and intussusception.

[Treatment of Fallot tetralogy with a transannular patch. Six years follow-up]. / Tratamiento de la tetralogía de Fallot con parche transanular. Seguimiento a 6 años.

BACKGROUND: Primary repair of Fallot tetralogy has been performed successfully for the last 45 years. It has low surgical mortality (< 5%), with excellent long-term results. However, there are delayed adverse effects: progressive right ventricular dilation and dysfunction, arrhythmia, and sudden death. In our centre, Fallot tetralogy is the most common form of cyanotic congenital heart disease (including transannular patch) and accounts for 7.5% of all cardiovascular surgical procedures. The mid-term follow-up results are reported. MATERIAL AND METHODS: Case series. The study included patients who had complete repair of Fallot tetralogy with transannular patch from January 2000 to December 2009. An analysis was performed on the clinical variables, morbidity and mortality. RESULTS: There were 52 patients in the study, with mean age 4 ± 2 years. Perioperative mortality in 6 patients, with 5 associated with residual right ventricular obstruction and, 1 associated with further surgery. The survival rate was 88% (46) patients, with a follow-up 75 ± 26 months. Late morbidity occurred in 14, due to right ventricular dysfunction in 11, recurrent distal obstruction in 2, and residual ventricular septal defect in 1. Associated risk factors were severe pulmonary insufficiency (p=0.001); QRS > 160 ms, p=0.001); cardiothoracic > 0.60 index, (p=0.048), and tricuspid regurgitation (p=0.001). CONCLUSIONS: There was reasonable long-term survival and excellent quality of life after total correction of Fallot tetralogy; however, progressive right ventricular dysfunction requires continuous monitoring, as well as the choice of optimal timing of pulmonary valve replacement.

Role of Genetic Polymorphisms of Deoxycytidine Kinase and Cytidine Deaminase to Predict Risk of Death in Children with Acute Myeloid Leukemia.

Cytarabine is one of the most effective antineoplastic agents among those used for the treatment of acute myeloid leukemia. However, some patients develop resistance and/or severe side effects to the drug, which may interfere with the efficacy of the treatment. The polymorphisms of some Ara-C metabolizing enzymes seem to affect outcome and toxicity in AML patients receiving cytarabine. We conducted this study in a cohort of Mexican pediatric patients with AML to investigate whether the polymorphisms of the deoxycytidine kinase and cytidine deaminase enzymes are implicated in clinical response and toxicity. Bone marrow and/or peripheral blood samples obtained at diagnosis from 27 previously untreated pediatric patients with de novo AML were processed for genotyping and in vitro chemosensitivity assay, and we analyzed the impact of genotypes and in vitro sensitivity on disease outcome and toxicity. In the multivariate Cox regression analysis, we found that age at diagnosis, wild-type genotype of the CDA A79C polymorphism, and wild-type genotype of the dCK C360G polymorphism were the most significant prognostic factors for predicting the risk of death.

Bone Marrow Cells in Acute Lymphoblastic Leukemia Create a Proinflammatory Microenvironment Influencing Normal Hematopoietic Differentiation Fates.

B-cell acute lymphoblastic leukemia (B-ALL) is a serious public health problem in the pediatric population worldwide, contributing to 85% of deaths from childhood cancers. Understanding the biology of the disease is crucial for its clinical management and the development of therapeutic strategies. In line with that observed in other malignancies, chronic inflammation may contribute to a tumor microenvironment resulting in the damage of normal processes, concomitant to development and maintenance of neoplastic cells. We report here that hematopoietic cells from bone marrow B-ALL have the ability to produce proinflammatory and growth factors, including TNFα, IL-1ß, IL-12, and GM-CSF that stimulate proliferation and differentiation of normal stem and progenitor cells. Our findings suggest an apparently distinct CD13(+)CD33(+) population of leukemic cells contributing to a proinflammatory microenvironment that may be detrimental to long-term normal hematopoiesis within B-ALL bone marrow.