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Background: Recurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL. Methods: A total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation. Results: We identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed. Discussion: Our findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome.
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The main objective of the National Project for Research and Incidence of Childhood Leukemias is to reduce early mortality rates for these neoplasms in the vulnerable regions of Mexico. This project was conducted in the states of Oaxaca, Puebla, and Tlaxcala. A key strategy of the project is the implementation of an effective roadmap to ensure that leukemia patients are the target of maximum benefit of interdisciplinary collaboration between researchers, clinicians, surveyors, and laboratories. This strategy guarantees the comprehensive management of diagnosis and follow-up samples of pediatric patients with leukemia, centralizing, managing, and analyzing the information collected. Additionally, it allows for a precise diagnosis and monitoring of the disease through immunophenotype and measurable residual disease (MRD) studies, enhancing research and supporting informed clinical decisions for the first time in these regions through a population-based study. This initiative has significantly improved the diagnostic capacity of leukemia in girls, boys, and adolescents in the regions of Oaxaca, Puebla, and Tlaxcala, providing comprehensive, high-quality care with full coverage in the region. Likewise, it has strengthened collaboration between health institutions, researchers, and professionals in the sector, which contributes to reducing the impact of the disease on the community.
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Introduction: Acute leukemias (AL) are the main types of cancer in children worldwide. In Mexico, they represent one of the main causes of death in children under 20 years of age. Most of the studies on the incidence of AL in Mexico have been developed in the urban context of Greater Mexico City and no previous studies have been conducted in the central-south of the country through a population-based study. The aim of the present work was to identify the general and specific incidence rates of pediatric AL in three states of the south-central region of Mexico considered as some of the marginalized populations of Mexico (Puebla, Tlaxcala, and Oaxaca). Methods: A population-based study was conducted. Children aged less than 20 years, resident in these states, and newly diagnosed with AL in public/private hospitals during the period 2021-2022 were identified. Crude incidence rates (cIR), standardized incidence rates (ASIRw), and incidence rates by state subregions (ASIRsr) were calculated. Rates were calculated using the direct and indirect method and reported per million children under 20 years of age. In addition, specific rates were calculated by age group, sex, leukemia subtype, and immunophenotype. Results: A total of 388 cases with AL were registered. In the three states, the ASIRw for AL was 51.5 cases per million (0-14 years); in Puebla, it was 53.2, Tlaxcala 54.7, and Oaxaca de 47.7. In the age group between 0-19 years, the ASIRw were 44.3, 46.4, 48.2, and 49.6, in Puebla, Tlaxcala, and Oaxaca, respectively. B-cell acute lymphoblastic leukemia was the most common subtype across the three states. Conclusion: The incidence of childhood AL in the central-south region of Mexico is within the range of rates reported in other populations of Latin American origin. Two incidence peaks were identified for lymphoblastic and myeloid leukemias. In addition, differences in the incidence of the disease were observed among state subregions which could be attributed to social factors linked to the ethnic origin of the inhabitants. Nonetheless, this hypothesis requires further investigation.
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BACKGROUND: A variety of bacterial and fungal co-infections may be attributed to the coronavirus disease 2019 (COVID-19), particularly in people who already have a medical condition such diabetes mellitus or those who received large dosages of steroids. CASE REPORT: We described a 52-year-old diabetic man who was receiving high doses of dexamethasone and antibiotics while receiving ambulatory care for COVID-19 pneumonia. His anterior rhinoscopy revealed a necrotic scab, and a sample confirmed Mucor spp. He underwent surgery and was given amphotericin as a result of the severity of the condition, palpebral ptosis, and right ocular palsy he was experiencing. The patien Ìs progression was satisfactory. CONCLUSIONS: pre-existing diabetes mellitus, previous steroid and antimicrobial use, as well as SARS-CoV-2 infection are some of the risk factors associated with Mucor spp. infection. Prompt detection of mucormycosis is important in the management of these affected patients.
ANTECEDENTES: A la enfermedad por coronavirus (COVID-19) se le han atribuido diversas coinfecciones bacterianas y fúngicas, especialmente en sujetos con enfermedades preexistentes (diabetes mellitus) o en quienes han recibido altas dosis de corticosteroides. REPORTE DE CASO: Paciente masculino de 52 años, con antecedente de diabetes mellitus, quien recibió altas dosis de dexametasona y antibióticos mientras recibía atención ambulatoria por neumonía secundaria a COVID-19. La rinoscopia anterior reveló una costra necrótica, y una muestra de exudado confirmó la coexistencia de Mucor spp. Debido a la complicación del cuadro clínico, ptosis palpebral y parálisis ocular derecha, se le administró anfotericina B y fue intervenido quirúrgicamente. La evolución del paciente fue satisfactoria. CONCLUSIONES: La diabetes mellitus preexistente, el consumo de corticosteroides y antimicrobianos, además de la infección por SARS-CoV-2 son factores de riesgo asociados con la infección por Mucor spp. Es importante la detección oportuna de mucormicosis en el tratamiento de estos pacientes.
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COVID-19 , Mucormicose , Masculino , Humanos , Pessoa de Meia-Idade , Mucormicose/complicações , Mucormicose/diagnóstico , COVID-19/complicações , SARS-CoV-2 , NarizRESUMO
Traditional fermented foods and beverages play an important role in a range of human diets, and several experimental studies have shown their potential positive effects on human health. Studies from different continents have revealed strong associations between the microorganisms present in certain fermented foods (e.g., agave fructans, kefir, yeats, kombucha, chungkookjang, cheeses and vegetables, among others) and weight maintenance, reductions in the risk of cardiovascular disease, antidiabetic and constipation benefits, improvement of glucose and lipids levels, stimulation of the immunological system, anticarcinogenic effects and, most importantly, reduced mortality. Accordingly, the aim of this review is to corroborate information reported in experimental studies that comprised interventions involving the consumption of traditional fermented foods or beverages and their association with human health. This work focuses on studies that used fermented food from 2014 to the present. In conclusion, traditional fermented foods or beverages could be important in the promotion of human health. Further studies are needed to understand the mechanisms involved in inflammatory, immune, chronic and gastrointestinal diseases and the roles of fermented traditional foods and beverages in terms of preventing or managing those diseases.
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Cancer is the first cause of death by disease in childhood globally. The most frequent types of cancers in children and adolescents are leukemias, followed by brain and central nervous system tumors and lymphomas. The recovery rate of cancer in children is around 80% in developed countries and up to 30% in developing countries. Some of the main causes of complications in children and adolescents with cancer are respiratory viral infections, mainly in bone marrow-transplanted patients. Respiratory viruses have been detected in the bronchoalveolar lavage or nasal wash specimens from cancer patients with or without respiratory illness symptoms. Human metapneumovirus (HMPV) is within the ten most common viruses that are encountered in samples from pediatric patients with underlying oncology conditions. In most of cases, HMPV is found as the only viral agent, but co-infection with other viruses or with bacterial agents has also been reported. The discrepancies between the most prevalent viral agents may be due to the different populations studied or the range of viral agents tested. Some of the cases of infection with HMPV in cancer patients have been fatal, especially in those who have received a hematopoietic stem cell transplant. This review seeks to show a general view of the participation of HMPV in respiratory illness as a complication of cancer in childhood and adolescence.
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A reverse genetics system for human astrovirus (HAstV) was established previously; however, it has not been exploited mainly because cells used for virus packaging are not permissive, requiring several rounds of replication to obtain acceptable infectious virus. In this work, in the search for alternative permissive cell lines to be used as packaging cells, Hek-293 and Huh7.5.1 were tested. Given that HAstV infection in Hek-293 showed differences with that in Caco-2, the gold standard for HAstV growth but scarcely transfectable, and it was more similar to that observed in the hepatoma Huh7.5.1 cell line, these last cells were further used to transfect viral RNA. Virus titers near to 10(8) infectious particles per ml (ffu/ml) were obtained at 16-20 h after transfection with RNA from infected cells. However, virus titers close to 10(6) ffu/ml were obtained by using in vitro transcribed RNA from a cDNA HAstV-1 clone. In contrast, virus recovery in BHK-21, reported previously as the packaging cells, from this RNA was of about 10(4) ffu/ml, two logarithms less than in Huh7.5.1. Apparently, the 5'-end modification of the viral RNA determined its specific infectivity, since virus recovery was abolished when the total RNA was treated with proteinase-K, probably by removing a protein-linked genome protein, but it increased when capping of the in vitro transcribed RNA was more efficient. Thus, an alternative and more efficient reverse genetics system for HAstV was established by using Huh7.5.1 cells.