Germline mutations in pediatric cancer cohort with mixed-ancestry Mexicans.

BACKGROUND: Childhood cancer is one of the primary causes of disease-related death in 5- to 14-year-old children and currently no prevention strategies exist to reduce the incidence of this disease. Childhood cancer has a larger hereditary component compared with cancer in adults. Few genetic studies have been conducted on children with cancer. Additionally, Latin American populations are underrepresented in genomic studies compared with other populations. Therefore, the aim of this study is to analyze germline mutations in a group of mixed-ancestry Mexican pediatric patients with solid and hematological cancers. METHODS: We analyzed genetic variants from 40 Mexican childhood cancer patients and their relatives. DNA from saliva or blood samples was used for whole-exome sequencing. All variants were identified following GATK best practices. RESULTS: We found that six patients (15%) were carriers of germline mutations in CDKN2A, CHEK2, DICER1, FANCA, MSH6, MUTYH, NF1, and SBDS cancer predisposition genes, and additional new variants predicted to be deleterious by in silico algorithms. A population genetics analysis detected five components consistent with the demographic models assumed for modern mixed-ancestry Mexicans. CONCLUSIONS: This report identifies potential genetic risk factors and provides a better understanding of the underlying mechanisms of childhood cancer in this population.

Long-term experience in treatment of acute promyelocytic leukemia in Mexican children in a tertiary care hospital.

Introduction: Acute promyelocytic leukemia (APL) is a rare myeloid leukemia subtype affecting adult and pediatric populations. APL constitutes 15-20% of all childhood AML in Latin America, compared to 7% in the non-Latino population. This leukemia has unique characteristics, such as its association with chromosomal translocations involving the retinoid acid receptor α (RARA) gene on chromosome 17. In addition, APL is also distinct from other AML subtypes due to its response to all-trans-retinoic acid (ATRA), which induces terminal granulocytic differentiation of blasts. Overall 5-year survival rates are generally reported to be greater than 80%. Materials and methods: A study was conducted from January 2008 to December 2022 applying the IC-APL 2006 treatment protocol. This case series reports the clinical results of 22 children with APL. In all cases, the diagnosis was made by bone marrow aspiration and evaluation of the t(15:17) or t(11:17) transcripts. Results: We identified 22 patients with APL, of whom 10 were female and 12 were male. Twelve patients debuted with coagulation abnormalities. The doses of anthracyclines varied according to the risk, with an average of 496.8 mgm2. The cardiological assessment was performed before and after chemotherapy, finding 2/22 patients with moderate sisto-diastolic dysfunction and one with mild pulmonary insufficiency at the end of treatment. There were 6/22 patients with complications related to ATRA treatment, the most frequent being pseudotumor cerebri. All complications were transitory and treated immediately without complications. In this series of cases, an overall survival of 90.6% and a relapse-free survival of 90.6% were recorded. The follow-up mean was 9.1 ± 3.8 years. Conclusion: APL is a highly curable disease when combined with ATRA and anthracyclines. In this series of cases, good long-term results were observed with the IC-APL 2006 protocol. However, in Latin America, the availability of drugs such as arsenic trioxide as the first line of treatment is an unresolved challenge.

Unravelling the genome of the brackish water malaria vector Anopheles aquasalis.

Malaria is a severe public health problem in several developing tropical and subtropical countries. Anopheles aquasalis is the primary coastal malaria vector in Central and South America and the Caribbean Islands, and it has the peculiar feature of living in water with large changes in salinity. Recent research has recognised An. aquasalis as an important model for studying the interactions of murine and human Plasmodium parasites. This study presents the complete genome of An. aquasalis and offers insights into its evolution and physiology. The genome is similar in size and gene content to other Neotropical anophelines, with 162 Mb and 12,446 protein-coding genes. There are 1387 single-copy orthologs at the Diptera level (eg. An. gambiae, An. darlingi and Drosophila melanogaster). An. aquasalis diverged from An. darlingi, the primary malaria vector in inland South America, nearly 20 million years ago. Proteins related to ion transport and metabolism belong to the most abundant gene families with 660 genes. We identified gene families relevant to osmosis control (e.g., aquaporins, vacuolar-ATPases, Na+/K+-ATPases, and carbonic anhydrases). Evolutionary analysis suggests that all osmotic regulation genes are under strong purifying selection. We also observed low copy number variation in insecticide resistance and immunity-related genes for all known classical pathways. The data provided by this study offers candidate genes for further studies of parasite-vector interactions and for studies on how anophelines of brackish water deal with the high fluctuation in water salinity. We also established data and insights supporting An. aquasalis as an emerging Neotropical malaria vector model for genetic and molecular studies.

Impairments in fine motor skills in children with Acute Lymphoblastic Leukaemia. A cross-sectional study.

AIM: We evaluated fine motor skills; precision, motor integration, manual dexterity, and upper-limb coordination according to sex and risk stratification in children with Acute Lymphoblastic Leukaemia (ALL). METHODS: We evaluated twenty-nine children in the maintenance phase aged 6 to 12 years with the Bruininks-Oseretsky Test of Motor Proficiency-second edition (BOT-2), and sex and age-specific norm values of BOT-2 were used to compare our results. RESULTS: We found lower scores on the upper-limb coordination subtest, p = 0.003 and on the manual coordination composite, p = 0.008, than normative values. Most boys performed "average" on both the subtests and the composites, but girls showed lower scores with a mean difference of 7.69 (95%CI; 2.24 to 3.14), p = 0.009. Girls' scale scores on the upper-limb coordination subtest were lower than normative values, with mean difference 5.08 (95%CI; 2.35 to 7.81), p = 0.006. The mean standard score difference in high-risk patients was lower than normative on the manual coordination composite, 8.18 (95%CI; 2.26 to 14.1), p = 0.015. High-risk children also performed below the BOT-2 normative on manual dexterity 2.82 (95%CI; 0.14 to 5.78), p = 0.035 and upper limb coordination subtest 4.10 (95%CI; 1.13 to 7.05), p = 0.028. We found a decrease in fine motor precision in children with a higher BMI, rho= -0.87, p = 0.056 and a negative correlation between older age and lower manual dexterity, r= -0.41 p = 0.026; however, we did not find any correlation with the weeks in the maintenance phase. CONCLUSIONS: Fine motor impairments are common in children with ALL in the maintenance phase; it is important to identify these impairments to early rehabilitation.

Self-sampling monkeypox virus testing in high-risk populations, asymptomatic or with unrecognized Mpox, in Spain.

The recent monkeypox virus (MPXV) outbreak was of global concern and has mainly affected gay, bisexual and other men who have sex with men (GBMSM). Here we assess prevalence of MPXV in high-risk populations of GBMSM, trans women (TW) and non-binary people without symptoms or with unrecognized monkeypox (Mpox) symptoms, using a self-sampling strategy. Anal and pharyngeal swabs are tested by MPXV real-time PCR and positive samples are tested for cytopathic effect (CPE) in cell culture. 113 individuals participated in the study, 89 (78.76%) were cis men, 17 (15.04%) were TW. The median age was 35.0 years (IQR: 30.0-43.0), 96 (85.02%) individuals were gay or bisexual and 72 (63.72%) were migrants. Seven participants were MPXV positive (6.19% (95% CI: 1.75%-10.64%)). Five tested positive in pharyngeal swabs, one in anal swab and one in both. Six did not present symptoms recognized as MPXV infection. Three samples were positive for CPE, and showed anti-vaccinia pAb staining by FACS and confocal microscopy. This suggests that unrecognized Mpox cases can shed infectious virus. Restricting testing to individuals reporting Mpox symptoms may not be sufficient to contain outbreaks.

The contradictory relationship between security and human rights / La contradictoria relación entre seguridad y derechos humanos / A relação contraditória entre segurança e direitos humanos

Security and human rights have a contradictory relationship. The crux of the problem lies in the tension that exists between the different approaches to security and the protection of human rights in different contexts and periods, in which fear plays a fundamental role. This review article describes how the public security, citizen security and human security perspectives can be manipulated so that they do not fulfil the objective of guaranteeing human rights and citizen freedoms and actually end up promoting the violation or limitation of these. In other words, these approaches exhibit the oppositional logic that states that what is gained in security is lost in rights, a perspective which ignores the dynamics that should accompany democratic regimes, where security is not an end in itself, but rather a means by which the state and its institutions can guarantee the effective enjoyment of human rights and civil liberties.

Entre seguridad y derechos humanos existe una contradictoria relación. El quid del problema radica en la tensión manifiesta entre los enfoques de seguridad ­con el miedo como un elemento fundamental­ y la protección de los derechos humanos en diferentes contextos y periodos. Este artículo de revisión describe cómo la seguridad pública, la seguridad ciudadana y la seguridad humana son perspectivas que pueden ser manipuladas de tal forma que no cumplen con el objetivo de garantizar los derechos humanos y las libertades ciudadanas, sino que terminan promoviendo la violación o limitación de estos. Es decir, se deja en evidencia la lógica contrapuesta que afirma que lo que se gana en seguridad se pierde en derechos, lo que implica ignorar la dinámica que debería acompañar a los regímenes democráticos, donde la seguridad no es un fin en sí misma, sino un medio con el cual el Estado y sus instituciones pueden garantizar el goce efectivo de los derechos humanos y de las libertades ciudadanas.

Existe uma relação contraditória entre segurança e direitos humanos. O cerne do problema está na tensão manifesta entre as abordagens de segurança - com o medo como elemento fundamental - e a proteção dos direitos humanos em diferentes contextos e períodos. Este artigo de revisão descreve como a segurança pública, a segurança cidadã e a segurança humana são perspectivas que podem ser manipuladas de tal forma que não cumprem o objetivo de garantir os direitos humanos e as liberdades do cidadão, mas acabam promovendo a violação ou a limitação desses direitos. Em outras palavras, evidencia-se a lógica oposta que afirma que o que se ganha em segurança se perde em direitos, o que implica ignorar a dinâmica que debe acompanhar os regimes democráticos, nos quais a segurança não é um fim em si mesma, mas um meio pelo qual o Estado e suas instituições podem garantir o gozo efetivo dos direitos humanos e das liberdades civis.

Egg-laying by female Aedes aegypti shapes the bacterial communities of breeding sites.

BACKGROUND: Aedes aegypti, the main arboviral mosquito vector, is attracted to human dwellings and makes use of human-generated breeding sites. Past research has shown that bacterial communities associated with such sites undergo compositional shifts as larvae develop and that exposure to different bacteria during larval stages can have an impact on mosquito development and life-history traits. Based on these facts, we hypothesized that female Ae. aegypti shape the bacteria communities of breeding sites during oviposition as a form of niche construction to favor offspring fitness. RESULTS: To test this hypothesis, we first verified that gravid females can act as mechanical vectors of bacteria. We then elaborated an experimental scheme to test the impact of oviposition on breeding site microbiota. Five different groups of experimental breeding sites were set up with a sterile aqueous solution of larval food, and subsequently exposed to (1) the environment alone, (2) surface-sterilized eggs, (3) unsterilized eggs, (4) a non-egg laying female, or (5) oviposition by a gravid female. The microbiota of these differently treated sites was assessed by amplicon-oriented DNA sequencing once the larvae from the sites with eggs had completed development and formed pupae. Microbial ecology analyses revealed significant differences between the five treatments in terms of diversity. In particular, between-treatment shifts in abundance profiles were detected, showing that females induce a significant decrease in microbial alpha diversity through oviposition. In addition, indicator species analysis pinpointed bacterial taxa with significant predicting values and fidelity coefficients for the samples in which single females laid eggs. Furthermore, we provide evidence regarding how one of these indicator taxa, Elizabethkingia, exerts a positive effect on the development and fitness of mosquito larvae. CONCLUSIONS: Ovipositing females impact the composition of the microbial community associated with a breeding site, promoting certain bacterial taxa over those prevailing in the environment. Among these bacteria, we found known mosquito symbionts and showed that they can improve offspring fitness if present in the water where eggs are laid. We deem this oviposition-mediated bacterial community shaping as a form of niche construction initiated by the gravid female.

Microbial communities in the water surface microlayer and associations with microbes in aerosols, beach sand, and bulk water.

The water surface microlayer (SML) serves as a boundary through which microbes can be exchanged. To evaluate exchanges of microbes, this study compared microbial communities within different reservoirs, with an emphasis on the water SML and aerosols. Additionally, the microbial communities during a sewage spill and perigean tides were evaluated and the results were compared to times without these events. Results show that during perigean tides and during the sewage spill, levels of culturable bacteria were highest and showed an increase via sequencing in potential pathogenic bacteria (Corynebacterium and Vibrio, which increased from 3.5%-1800% depending on sample type). In the aerosol samples, Corynebacterium (average of 2.0%), Vibrio (1.6%), and Staphylococcus (10%), were the most abundant genera. Aerosolization factors, which were used to examine the transfer of the microbes, were high for these three genera. Measurements of general marine bacteria (GMB) by culture showed a weak but significant correlation between culturable GMB in aerosol samples versus in water and in the SML. More research is needed to evaluate the exchange of pathogens between the SML and air, given the increase in potentially pathogenic microbes within the SML during rare events and evidence that suggests that microbes maintain viability during transfers across reservoirs.

Bacterial communities of Aedes aegypti mosquitoes differ between crop and midgut tissues.

Microbiota studies of Aedes aegypti and other mosquitoes generally focus on the bacterial communities found in adult female midguts. However, other compartments of the digestive tract maintain communities of bacteria which remain almost entirely unstudied. For example, the Dipteran crop is a food storage organ, but few studies have looked at the microbiome of crops in mosquitoes, and only a single previous study has investigated the crop in Ae. aegypti. In this study, we used both culture-dependent and culture-independent methods to compare the bacterial communities in midguts and crops of laboratory reared Ae. aegypti. Both methods revealed a trend towards higher abundance, but also higher variability, of bacteria in the midgut than the crop. When present, bacteria from the genus Elizabethkingia (family Weeksellaceae) dominated midgut bacterial communities. In crops, we found a higher diversity of bacteria, and these communities were generally dominated by acetic acid bacteria (family Acetobacteriaceae) from the genera Tanticharoenia and Asaia. These three taxa drove significant community structure differences between the tissues. We used FAPROTAX to predict the metabolic functions of these communities and found that crop bacterial communities were significantly more likely to contain bacteria capable of methanol oxidation and methylotrophy. Both the presence of acetic acid bacteria (which commonly catabolize sugar to produce acetic acid) and the functional profile that includes methanol oxidation (which is correlated with bacteria found with natural sources like nectar) may relate to the presence of sugar, which is stored in the mosquito crop. A better understanding of what bacteria are present in the digestive tract of mosquitoes and how these communities assemble will inform how the microbiota impacts mosquito physiology and the full spectrum of functions provided by the microbiota. It may also facilitate better methods of engineering the mosquito microbiome for vector control or prevention of disease transmission.

Chemsex in Barcelona: A qualitative study of factors associated with the practice, the perception of the impact on health and prevention needs. / Chemsex en Barcelona: Estudio cualitativo sobre factores asociados a la práctica, percepción del impacto en salud y necesidades de prevención.

Chemsex is defined as use of psychoactive drugs with the aim of having sexual relations between gay men, bisexuals and men who have sex with men for a long period of time. To study this phenomenon, this qualitative descriptive study was proposed with the objective of describing the practice of chemsex from the perspective of users, to determine the main factors associated with its practice, the perception of the impact on their health and to establish prevention needs. Data were obtained using conversational techniques: 12 semi-structured interviews and 3 focus groups. The purposive sample was made up of GBMSM with a mean age of 40.1 years, 78% born in Spain, and 68% with completed university studies. The qualitative analysis focused on three thematic areas: factors associated with the practice of chemsex, the impact of chemsex on health, and prevention and risk reduction needs. It is concluded that the practice of chemsex should be understood as multifactorial and multicausal, associated with the sociocultural context. Sexual satisfaction, increased libido and the search for more intense pleasure are identified as key factors among people who practice it. These men are still scared of being judged, even by specialists who may lack knowledge or training. A reanalysis and rethinking of the interventions and policies directed towards this population is necessary, putting the focus of action on shared decision-making, self-care, cultural competence and the humanization of care.

El chemsex se define como el uso de drogas psicoactivas con el objetivo de mantener relaciones sexuales entre hombres gay, bisexuales y otros hombres que tienen sexo con hombres (GBHSH), por un largo periodo de tiempo. El objetivo de este estudio cualitativo exploratorio es describir la práctica del chemsex desde la perspectiva de los usuarios, determinar los principales factores asociados a su práctica, la percepción del impacto en su salud y establecer necesidades de prevención. Se obtuvieron los datos mediante técnicas conversacionales: 12 entrevistas semiestructuradas y 3 grupos focales. El análisis cualitativo se centró en tres áreas temáticas: factores asociados a la práctica de chemsex, impacto del chemsex en la salud y necesidades prevención y reducción de riesgos. La muestra intencionada fue conformada por hombres GBHSH con una edad media de 40,1 años, 78% nacidos en España, y 68% con estudios universitarios finalizados. Los resultados del estudio ponen de manifiesto que la práctica de chemsex debe comprenderse como multifactorial y multicausal, y asociada al contexto sociocultural. La satisfacción sexual, del aumento de la libido y de la búsqueda de placer más intenso se identifican como factores clave entre las personas que lo practican. Sigue existiendo miedo en estos hombres a ser juzgados, incluso por los especialistas que pueden carecer de conocimiento o formación. Es necesario un reanálisis y replanteamiento de las intervenciones y políticas dirigidas hacia esta población, poniendo el foco de acción en la toma de decisiones compartidas, el autocuidado, la competencia cultural y la humanización del cuidado.

Syndemic Conditions and Their Association with HIV/STI Sexual Risk Behaviors Among Transgender Women and Cisgender Men Sex Workers in Catalonia: The SexCohort Project.

BACKGROUND: Transgender women and cisgender men sex workers are vulnerable to HIV and sexually transmitted infections (STIs). This study aimed to explore in depth the prevalence of syndemic conditions and their association with the sexual risk behaviors for HIV/STI acquisition in cis men and trans women sex workers in Barcelona (Catalonia, Spain). METHOD: We conducted a study between 2014 and 2018 to determine whether syndemic conditions (frequent alcohol consumption and polydrug use (> 2) during sex with clients; experience of violence; and lack of healthcare access) are associated with HIV/STI sexual risk behaviors. A "syndemic index" was calculated based on the cumulative number of syndemic conditions (0 to 4). RESULTS: In the last year (2018), 78.8% of cisgender men and 68.1% of transgender women reported at least one syndemic condition. The most prevalent syndemic factor in both cisgender men and transgender women was violence (38.8% and 43.6% respectively). In multivariable analysis, an association was found between condomless anal sex and violence (aOR = 1.81), and frequent alcohol consumption and violence with reporting > 10 clients/week (aOR = 2.73 and 1.88, respectively). The higher the number of syndemic factors, the greater probability of having > 10 clients/week and reporting condomless anal sex with clients. CONCLUSION: Psychosocial conditions have a syndemic effect on risky sexual behaviors highlighting the need for a more holistic approach to HIV/STI prevention targeting these populations.

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.

Characterization of Philadelphia-like Pre-B Acute Lymphoblastic Leukemia: Experiences in Mexican Pediatric Patients.

Ph-like subtypes with CRLF2 abnormalities are frequent among Hispano-Latino children with pre-B ALL. Therefore, there is solid ground to suggest that this subtype is frequent in Mexican patients. The genomic complexity of Ph-like subtype constitutes a challenge for diagnosis, as it requires diverse genomic methodologies that are not widely available in diagnostic centers in Mexico. Here, we propose a diagnostic strategy for Ph-like ALL in accordance with our local capacity. Pre-B ALL patients without recurrent gene fusions (104) were classified using a gene-expression profile based on Ph-like signature genes analyzed by qRT-PCR. The expressions of the CRLF2 transcript and protein were determined by qRT-PCR and flow cytometry. The P2RY8::CRLF2, IGH::CRLF2, ABL1/2 rearrangements, and Ik6 isoform were screened using RT-PCR and FISH. Surrogate markers of Jak2-Stat5/Abl/Ras pathways were analyzed by phosphoflow. Mutations in relevant kinases/transcription factors genes in Ph-like were assessed by target-specific NGS. A total of 40 patients (38.5%) were classified as Ph-like; of these, 36 had abnormalities associated with Jak2-Stat5 and 4 had Abl. The rearrangements IGH::CRLF2,P2RY8::CRLF2, and iAMP21 were particularly frequent. We propose a strategy for the detection of Ph-like patients, by analyzing the overexpression/genetic lesions of CRLF2, the Abl phosphorylation of surrogate markers confirmed by gene rearrangements, and Sanger sequencing.

Mortality in children with cancer and SARS-CoV-2 in Latin America: A systematic review.

The new COVID-19 disease is caused by a novel coronavirus (SARS-CoV-2), that probably originated in Wuhan, China, and has currently infected 505,817,953 people and caused 6,213,876 deaths in the world. On the American continent, 152,265,980 cases and 2,717,108 deaths have been reported to WHO (World Health Organization). The Latin America and the Caribbean (LAC) region presents an epidemiological challenge due to its population's heterogeneity and socioeconomic inequality. A particularly vulnerable population is that of children with cancer, and their mortality from COVID-19 has been reported to be 3.6% globally. This work aimed to study the lethality of SARS-CoV-2 infection in children with cancer in the Latin American region. Our objective was to systematically review published scientific literature and search hospital databases in Latin America to explore mortality in this region. A median of mortality of 9.8% was found in the articles analyzed. In addition, we collected five databases from Latin American hospitals. We concluded that there was an underestimation in the mortality registry of this group of patients in the analyzed region. Therefore, although the causes are unknown, it is necessary to strengthen the case-reporting system to determine the reality in complex and particular areas such as Latin America.

Performance of Cervical Screening a Decade Following HPV Vaccination: The Costa Rica Vaccine Trial.

BACKGROUND: We investigated the impact of human papillomavirus (HPV) vaccination on the performance of cytology-based and HPV-based screening for detection of cervical precancer among women vaccinated as young adults and reaching screening age. METHODS: A total of 4632 women aged 25-36 years from the Costa Rica HPV Vaccine Trial were included (2418 HPV-vaccinated as young adults and 2214 unvaccinated). We assessed the performance of cytology- and HPV-based cervical screening modalities in vaccinated and unvaccinated women to detect high-grade cervical precancers diagnosed over 4 years and the absolute risk of cumulative cervical precancers by screening results at entry. RESULTS: We detected 95 cervical intraepithelial neoplasia grade 3 or worse (52 in unvaccinated and 43 in vaccinated women). HPV16/18/31/33/45 was predominant (69%) among unvaccinated participants, and HPV35/52/58/39/51/56/59/66/68 predominated (65%) among vaccinated participants. Sensitivity and specificity of cervical screening approaches were comparable between women vaccinated as young adults and unvaccinated women. Colposcopy referral rates were lower in the vaccinated group for HPV-based screening modalities, but the positive predictive value was comparable between the 2 groups. CONCLUSIONS: Among women approaching screening ages, vaccinated as young adults, and with a history of intensive screening, the expected reduction in the positive predictive value of HPV testing, associated with dropping prevalence of HPV-associated lesions, was not observed. This is likely due to the presence of high-grade lesions associated with nonvaccine HPV types, which may be less likely to progress to cancer.

High occurrence of CRLF2 abnormalities in Mexican children with B-cell acute lymphoblastic leukemia.

The P2RY8-CRLF2 and IGH-CRLF2 rearrangements induce the overexpression of cytokine receptor-like factor 2 (CRLF2) and have been associated with relapse and poor prognosis in B-cell acute lymphoblastic leukemia (B-ALL). Additionally, they are frequently documented in high-risk Hispanic populations. To better understand the potential causes of the adverse prognosis of childhood B-ALL in Mexico, we analyzed these rearrangements and the CRLF2 mRNA and protein levels in 133 Mexican children with B-ALL. We collected bone marrow samples at diagnosis and evaluated the CRLF2 gene expression by qRT-PCR and the total CRLF2 protein by flow cytometry. P2RY8-CRLF2 and IGH-CRLF2 were detected by RT-PCR and FISH, respectively. The median time of follow-up to determine the prognostic significance of the CRLF2 abnormalities was three years. In 82% of the participants, the mRNA levels correlated with the cell-surface and intracellular CRLF2 protein levels. The P2RY8-CRLF2 rearrangement was present in 31.5% (42/133) of the patients, while the IGH-CRLF2 rearrangement was detected in 13.5% (9/67) of patients with high expression of CRLF2 (6.8% of the total sample). CRLF2 copy number variations (gain) were also detected in 7.5% (5/67) of patients with high protein levels. The overall survival (OS) presented significantly lower rates in patients with high white blood cell count (≥50x109/L) regardless of CRLF2 expression, but high levels of CRLF2 gene expression appears to contribute to the reduction of OS within this group of patients. In conclusion, in our cohort, a high occurrence of CRLF2 abnormalities was documented, particularly the P2RY8-CRLF2 rearrangement, which might represent a characteristic of the Mexican population. Targeted therapy to treat this group of patients could improve OS.

Características clínico-patológicas de pacientes jóvenes con cáncer de mama en un centro oncológico en Medellín / Clinical and pathological characteristics of young patients with breast cancer at a cancer center in Medellin

Introducción: El cáncer de mama es la principal neoplasia en mujeres y se ha reportado un aumento de la incidencia en jóvenes menores a 40 años. El objetivo del presente estudio fue describir las características clínicas y patológicas, de pacientes con cáncer de mama invasor, ≤40 años, atendidas en un centro de referencia oncológico en Medellín-Colombia. Metodología: Se realizó un estudio transversal, realizado en la Clínica Vida (Fundación Colombiana de Cancerología), en el período enero del 2015 a diciembre del 2019. La muestra fue no probabilística, de pacientes con diagnóstico oncológico de cáncer de mama invasor. Se registró edad, tipo de cáncer, antecedentes familiares, recidivas y mortalidad. Se utiliza estadística descriptiva. Resultados: De 2332 casos de nuevos de cáncer de mama invasor, 261 se identificaron en mujeres ≤ 40 años, 11.19 % (IC 95 % 11.17-11.22 %), edad de 34.2 ± 4 años. 16.5 % en menores de 30 años, 40.2 % en edad de 30 a 45 años y 42.2 % en mujeres de 35 a 40 años. La presentación principal fue masa palpable auto detectada. El subtipo molecular Luminal A 16 %, Luminal B 48.3 %, Her2 enriquecido 11.2 % y Triple negativo 21.6 %. El 27 % tuvo algún antecedente familiar. La recidiva fue del 14 % y la mortalidad del 14.9 %. Conclusión: El 11 % de pacientes con cáncer de mama en esta serie corresponde a mujeres jóvenes, con una presentación en estadios más avanzados y biología molecular desfavorable, lo cual requirió un manejo más agresivo y radical. Esto resalta la importancia del diagnóstico oportuno en pacientes de lesiones mamarias en mujeres jóvenes.

Introduction: Breast cancer is the main neoplasm in women, and an increased incidence has been reported in young people under 40 years of age. The objective of the present study was to describe the clinical and pathological characteristics of patients with invasive breast cancer, ≤40 years old, treated at a reference oncology center in Medellín-Colombia. Methodology: A cross-sectional study was carried out by the Vida Clinic (Colombian Cancer Foun-dation) from January 2015 to December 2019. The sample was nonprobabilistic of patients with an oncological diagnosis of invasive breast cancer. Age, type of cancer, family history, recurrence, and mortality were recorded. Descriptive statistics are used. Results: Of 2332 cases of new invasive breast cancer, 261 were identified in women ≤ 40 years, 11.19% (95% CI 11.17-11.22%), age 34.2±4 years. 16.5% in those under 30 years of age, 40.2% in women between 30 and 45 years of age, and 42.2% in women between 35 and 40 years of age. The main presentation was a self-detected palpable mass. The molecular subtypes luminal A 16%, luminal B 48.3%, Her2 enriched 11.2%, and triple-negative 21.6%. A total of 27% had a family history. Recurrence was 14%, and mortality was 14.9%. Conclusion: Eleven percent of patients with breast cancer in this series were young women, with a presentation in more advanced stages and unfavorable molecular biology, which requires more aggressive and radical management. This highlights the importance of timely diagnosis in young women with breast injuries.

Caracterización clínica y terapéutica del cáncer de mama, en mujeres mayores, atendidas en un centro oncológico de Medellín ­ Colombia / Clinical and therapeutic characterization of breast cancer, in older women, attended in a cancer center in Medellin ­ Colombia

Introducción: El cáncer de mama es el cáncer más frecuente en las mujeres colombianas y más de la mitad de la incidencia la aportan las adultas mayores de 60 años. El objetivo de este estudio fue caracterizar clínicamente a un grupo de pacientes ≥ 65 años, con diagnóstico de cáncer de mama primario. Metodología: Estudio descriptivo de 188 pacientes con edad ≥ 65 años, con cáncer de mama primario, atendidas en la Fundación Colombiana de Cancerología ­ Clínica Vida, entre enero de 2017 y diciembre de 2018. Se realizó un análisis descriptivo de datos sociodemográficos, comorbilidades, características de la enfermedad y tratamiento. Resultados: La población estudiada (188) presentó una edad promedio de 73 años y en el 79.8% de ellas se reportó al menos una comorbilidad. El 76.6% tuvo enfermedad con receptor hormonal positivo. El manejo primario con cirugía se hizo en el 58.5% de las pacientes, y la mayoría fueron procedimientos conservadores de la mama (70.9%). Conclusión: Las mujeres adultas mayores tienen características del cáncer de mama que pueden diferir de las pacientes jóvenes e influir en el tratamiento que se ofrece, impactando en su pronóstico oncológico, en el pronóstico de sus comorbilidades y en la calidad de vida.

Introduction: Breast cancer is the most frequent cancer in Colombian women and more than half of the incidence is contributed by adults over 60 years of age. The objective of this study was to clinically characterize a group of patients ≥ 65 years of age, diagnosed with primary breast cancer. Methodology: Descriptive study of 188 patients aged ≥ 65 years, with primary breast cancer, treated at the Colombian Cancer Foundation - Clínica Vida, between January 2017 and December 2018. A descriptive analysis of sociodemographic data, comorbidities, characteristics of the disease and treatment. Results: The studied population (188) had an average age of 73 years and in 79.8% of them at least one comorbidity was reported. 76.6% had hormone receptor positive disease. The primary manage-ment with surgery was done in 58.5% of the patients, and the majority were breast-conserving proce-dures (70.9%). Conclusion: Older women have characteristics of breast cancer that may differ from young pa-tients. This may influence the treatment offered, impacting on their oncological prognosis, on the prognosis of their comorbidities and on the quality of life.

Decision-Making at End-of-Life for Children With Cancer: A Systematic Review and Meta-Bioethical Analysis.

BACKGROUND: Evidence shows that medical education includes a variety of basic and clinical skills. Ethical and human values are not typically considered in medical school curricula, and this is evident in medical practice in certain scenarios such as decision-making at pediatric cancer patients' end of life. METHODS: This study explores a bioethical approach to address complex decision-making at the end of life in children and adolescents with cancer. We are a cross-functional group of scientists from several academic disciplines who conducted a systematic review of the literature using our newly developed meta-bioethical analysis and synthesis of findings. The search was carried out in five databases, resulting in 10 research papers. Following quality screening, seven articles were ultimately selected for further analysis. RESULTS: Our focus is on the state of the art to better understand the bioethical deliberation at the end of life in pediatric oncology. Here, we report a systematic review that includes (i) classification of the screened articles by the type of decision-making they use, ii) the system values that are at the core of the decision-making at the end of life, and iii) bioethical and ethical discernment queries. We conclude with a discussion regarding the best practices of ethical discernment and decision-making at the end of life.This study highlights the need to develop more research to better understand the influence and origin of these multidimensional factors determining critical decisions that define the quality of life of patients in a highly sensitive moment. CONCLUSION: We conclude that personal aspects of the physician define their actions more than knowledge or organized structure. It is thus necessary that pediatric oncologists receive ethics and humanistic education.