Fungal infections in pediatric patients with acute myeloid leukemia in a tertiary hospital.

Introduction: Acute leukemia accounts for more than 30% of all pediatric cancer cases, and of these, 15-20% are acute myeloid leukemia (AML). Children who super from AML are more likely to develop infections due to the humoral and cellular immune deficits generated by the disease and its treatment. The incidence of fungal infections is underestimated; reports show that up to 75% of fungal infections go undiagnosed until autopsy. In only 30 years, the incidence of invasive candidiasis has increased by 40-fold. Thus, the high morbidity and mortality associated with fungal infections in hematological patients make it necessary to adopt preventive measures. Methods: This work aimed to retrospectively identify pediatric patients with acute myeloid leukemia and invasive fungal diseases (IFDs) in a Latin American tertiary care hospital. A retrospective analysis of 36 clinical records of pediatric patients diagnosed with AML from 2007 to 2017 was carried out. Results: One hundred and twenty-nine hospitalizations were associated with infectious events. Thirteen patients in our study presented 15 infectious events associated with IFDs (11.6%). Two patients died because of complications related to IFDs (15.3%). The most frequent IFD type was aspergillosis, which was observed in 7 cases, followed by Candidemia, which was observed in 4 cases. The most frequent clinical manifestations were fever and respiratory distress. Discussion: Mortality due to IFD can be prevented with effective pharmacotherapy. An appropriate antifungal prophylaxis strategy still needs to be developed through larger prospective studies in Latin America.

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.

Human papillomavirus infection and seroprevalence among female university students in Mexico.

Human papillomavirus (HPV) is one of the most common causes of sexually transmitted diseases, and the main etiology of cervical cancer. This study was aimed to assess type-specific cervical HPV prevalence and their association with HPV-specific antibodies in a cohort of female university students. HPV genotyping was performed by amplifying and sequencing a fragment of the L1 protein. A BLAST search was performed to identify HPV types. HPV-specific IgG antibodies were measured by ELISA in serum samples. A total of 129 women participated, with an average age of 21.75 years. The prevalence of vaginal HPV infection was 74.42%. The most predominant high-risk HPV types were 18 (13.95%), 31 (10.85%), and 16 (9.3%). We found that early age at coitarche and a higher number of sexual partners were significantly associated with a high prevalence of HPV infection. In addition to sexual behavior, we observed that the presence of serum-specific IgG antibodies against HPV can impact the prevalence of the virus. Seropositivity to HPV-16 and HPV-18 was associated with a lower prevalence of HPV-16, but not for other HPV types. Of note, there was a lower proportion of HPV-specific seropositivity in women who had the presence of the same HPV type in a cervical specimen, suggesting an immunoregulatory mechanism associated with the viral infection. In conclusion, the prevalence of HPV in university women was higher than expected and it was associated with early age of sexual debut, an increasing number of sexual partners, and a low proportion of HPV seropositivity.

Acute myeloid leukemia associated with t(16:21)(p11;q22) in a pediatric patient / Leucemia mieloide aguda asociada con t(16:21)(p11;q22) en un paciente pediátrico

Abstract Background: Rare subgroups of pediatric patients with acute myeloid leukemia (AML), such as t(16:21) (p11;q22), require international cooperation to establish a proper stratification system to assign clinical risk. Case report: Here, we report a 13-year-old female who was admitted for asthenia, fatigue, and intermittent fever. The hematological data showed thrombocytopenia and anemia, and the bone marrow test showed 82.5% blast cells, which were positive for CD13, CD33, CD38, and CD117. Blast cells showed negative myeloperoxidase staining and positive periodic acid-Schiff staining. A diagnosis of AML M6 was made. Cells were positive for the fusion transcript FUS-ERG t(16;21)(p11;q22). The patient achieved morphological remission. However, molecular remission was not achieved, and she died 11 months after diagnosis. Conclusions: It is essential to report this sporadic case of AML to provide clinicians with data for clinical decision-making, such as for risk-group stratification. To the best of our knowledge, this is the first association between this translocation and this morphological subtype.

Resumen Introducción: La leucemia mieloide aguda (LMA) infantil es una enfermedad heterogénea, por lo que existen subgrupos de rara presentación, como aquellos con t(16;21)(p11;q22). Para establecer el riesgo clínico y la estratificación pronóstica adecuada es necesaria la cooperación internacional. Caso clínico: Se reporta el caso de una adolescente de 13 años, admitida por astenia, adinamia y fiebre intermitente. Los datos hematológicos mostraron trombocitopenia y anemia, con un 82.5% de blastos en médula ósea, los cuales fueron positivos para CD13, CD33, CD38 y CD 117. Los blastos fueron negativos para mieloperoxidasa y positivos para ácido peryódico de Schiff. Se realizó el diagnóstico morfológico de LMA M6. Las células fueron positivas para el transcrito FUS-ERG t(16;21)(p11;q22). La paciente alcanzó la remisión morfológica; sin embargo, no fue posible la remisión molecular y falleció 11 meses después del diagnóstico. Conclusiones: Es importante reportar casos en los que se identifique un subtipo muy raro de LMA infantil para incrementar la evidencia clínica y contribuir con elementos que ayuden a tomar decisiones clínicas y lograr la estratificación en grupos de riesgo. Hasta la fecha, este el primer caso reportado en que se asocia el transcrito t(16;21)(p11;q22) con el subtipo morfológico LMA M6.

Acute myeloid leukemia associated with t(16:21)(p11;q22) in a pediatric patient.

Background: Background">Rare subgroups of pediatric patients with acute myeloid leukemia (AML), such as t(16:21) (p11;q22), require international cooperation to establish a proper stratification system to assign clinical risk. Case report: Here, we report a 13-year-old female who was admitted for asthenia, fatigue, and intermittent fever. The hematological data showed thrombocytopenia and anemia, and the bone marrow test showed 82.5% blast cells, which were positive for CD13, CD33, CD38, and CD117. Blast cells showed negative myeloperoxidase staining and positive periodic acid-Schiff staining. A diagnosis of AML M6 was made. Cells were positive for the fusion transcript FUS-ERG t(16;21)(p11;q22). The patient achieved morphological remission. However, molecular remission was not achieved, and she died 11 months after diagnosis. Conclusions: It is essential to report this sporadic case of AML to provide clinicians with data for clinical decision-making, such as for risk-group stratification. To the best of our knowledge, this is the first association between this translocation and this morphological subtype.

Introducción: La leucemia mieloide aguda (LMA) infantil es una enfermedad heterogénea, por lo que existen subgrupos de rara presentación, como aquellos con t(16;21)(p11;q22). Para establecer el riesgo clínico y la estratificación pronóstica adecuada es necesaria la cooperación internacional. Caso clínico: Se reporta el caso de una adolescente de 13 años, admitida por astenia, adinamia y fiebre intermitente. Los datos hematológicos mostraron trombocitopenia y anemia, con un 82.5% de blastos en médula ósea, los cuales fueron positivos para CD13, CD33, CD38 y CD 117. Los blastos fueron negativos para mieloperoxidasa y positivos para ácido peryódico de Schiff. Se realizó el diagnóstico morfológico de LMA M6. Las células fueron positivas para el transcrito FUS-ERG t(16;21)(p11;q22). La paciente alcanzó la remisión morfológica; sin embargo, no fue posible la remisión molecular y falleció 11 meses después del diagnóstico. Conclusiones: Es importante reportar casos en los que se identifique un subtipo muy raro de LMA infantil para incrementar la evidencia clínica y contribuir con elementos que ayuden a tomar decisiones clínicas y lograr la estratificación en grupos de riesgo. Hasta la fecha, este el primer caso reportado en que se asocia el transcrito t(16;21)(p11;q22) con el subtipo morfológico LMA M6.

The α1D-adrenoreceptor antagonist BMY 7378 reverses cardiac hypertrophy in spontaneously hypertensive rats.

OBJECTIVE: The α1D-adrenoreceptor (α1D-AR) is involved in angiotensin II-induced vascular remodeling and hypertension. Whether α1D-AR plays a role in hypertension-associated cardiac hypertrophy is unclear. Here we investigated effects of BMY 7378, a selective α1D-AR antagonist, on cardiac status in aged spontaneously hypertensive rats (SHR). METHODS: Male SHR were studied during the phase of developing hypertension (5 and 10 weeks old) and once hypertension was established (20 and 30 weeks old) to assess the evolution of cardiac hypertrophy. Age-matched WKY rats were studied as controls. Thirty-week-old SHR were treated for 4 weeks with BMY 7378 (10 mg/kg per day, o.a.), or captopril (angiotensin-converting enzyme inhibitor, 40 mg/kg per day, o.a.) (as a positive control). Blood pressure and cardiac function were measured in vivo, cardiac hypertrophy by histology, and α1D-AR protein expression by immunofluorescence. RESULTS: By 30 weeks of age, SHR exhibited significant hypertension and cardiac hypertrophy. BMY 7378 and captopril decreased blood pressure and improved hemodynamic parameters and cardiac function in treated SHR vs. untreated SHR (P < 0.05). Histology showed increased cardiomyocyte size, fibrosis, and left ventricular hypertrophy in SHR hearts. BMY 7378 ameliorated fibrosis and cardiac hypertrophy, but had no effect on cardiomyocyte size in SHR. Effects of BMY 7378 were associated with increased α1D-AR protein expression in SHR. CONCLUSION: Our data indicate that pharmacological antagonism of α1D-AR reduces blood pressure and associated cardiac hypertrophy in aged SHR. These findings suggest that the α1D-AR plays a pathophysiological role in the development of hypertension and cardiac target organ damage in SHR.

[Osteogenesis of human vascular endothelial cells in culture]. / Osteogénesis en cultivo de endotelio vascular humano.

INTRODUCTION: Mesenchymal stem cells have the potential to differentiate into several types of cells including osteoblasts. These stem cells have cell surface markers found on cells of endothelial and subendothelial origin of the umbilical cord vein. Taking this into consideration we have postulated that human umbilical vein endothelial cells (HUVEC) could present osteogenic differentiation as well. Gene activation that could drive osteogenic differentiation is regulated by exogenous and endogenous factors. OBJECTIVE: The induction osteogenesis in HUVEC. MATERIAL AND METHODS: We used: a) an osteogenic medium containing 0.1 microM dexamethasone, 10 microM beta-glycerophosphate, 50 microM L-ascorbic-acid 2-phosphate, 20% MCGS serum; and b) a treatment with DNA demethylating agents hydralazine and 5'-aza-2'-deoxycytidine (0.39-200 microM). Phenotypic characteristics of HUVEC were their spindle and stellate shapes with fine homogenous cytoplasm, typically associated with fibroblast-like cells. RESULTS: The control cells (without osteogenic treatment) exhibited little extracellular matrix, whereas the osteogenically treated cells appeared shortened and flattened, and they were surrounded by extracellular matrix that subsequently became mineralized in vitro. After 28 days in culture, morphologic and histochemical studies confirmed that osteogenic medium had a strong stimulatory effect on the alkaline phosphatase activity of endothelial cells, a very early marker of cell differentiation into the osteogenic lineage. Hydralazine and 5'-aza-2'-deoxycytidine, two drugs utilized in chromatin remodeling leading to gene re-expression of inactivated DNA hypermethylated islands, did not favor osteoblast differentiation. CONCLUSION: Our study shows that HUVEC can differentiate along an osteogenic lineage and thus provide an alternative source for cell-based therapies and tissue engineering strategies.